93-31820. Occupational Safety and Health Standards for Cadmium in Shipyard Employment and Construction  

  • [Federal Register Volume 59, Number 1 (Monday, January 3, 1994)]
    [Unknown Section]
    [Page 0]
    From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
    [FR Doc No: 93-31820]
    
    
    [[Page Unknown]]
    
    [Federal Register: January 3, 1994]
    
    
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    Part III
    
    
    
    
    
    Department of Labor
    
    
    
    
    
    _______________________________________________________________________
    
    
    
    Occupational Safety and Health Administration
    
    
    
    _______________________________________________________________________
    
    
    
    29 CFR Parts 1915 and 1926
    
    
    
    Standard for Cadmium in Shipyard Employment and in Construction Work; 
    Reprint With Corrections and Technical Amendments; Final Rule
    DEPARTMENT OF LABOR
    
    Occupational Safety and Health Administration
    
    29 CFR Parts 1915 and 1926
    
     
    
    Occupational Safety and Health Standards for Cadmium in Shipyard 
    Employment and Construction
    
    AGENCY: Occupational Safety and Health Administration, Department of 
    Labor.
    
    ACTION: Final rule; miscellaneous corrections, technical amendments, 
    and redesignation.
    
    -----------------------------------------------------------------------
    
    SUMMARY: The Occupational Safety and Health Administration (OSHA) is 
    correcting an error stemming from the wording of the amendatory 
    language of the final rule that incorporated applicable General 
    Industry standards for toxic substances into the Occupational Safety 
    and Health Standards for Shipyard Employment. The final rule, which 
    appeared in the Federal Register on July 1, 1993, had the effect of 
    mistakenly inferring that the cadmium standard for shipyard employment 
    from the Code of Federal Regulations was being deleted though the 
    preamble made it clear it was retained. This correction reprints the 
    full text of the cadmium standard as published on September 14, 1992, 
    and incorporates changes from an April 23, 1993, document that made 
    corrections and amendments to the original publication. In addition, 
    several cross-references regarding employee records are being amended 
    to reflect the designation of a new section in the shipyard employment 
    standards, and a number of effective dates are being converted to dates 
    certain.
        In addition, OSHA is redesignating the cadmium standard for 
    construction employment, also published in the same September 14 
    document, into a different subpart. The redesignation merges it in with 
    the newly created subpart that contains specific toxic substance 
    standards for construction.
    
    EFFECTIVE DATE: July 1, 1993.
    
    FOR FURTHER INFORMATION CONTACT: Mr. James F. Foster, OSHA Office of 
    Public Affairs, Room N-3647, U.S. Department of Labor, 200 Constitution 
    Avenue NW., Washington, DC 20210, telephone (202) 219-8151.
    
    SUPPLEMENTARY INFORMATION:
    
    Background
    
        The final regulations which are the subject of this action was 
    published in the Federal Register on June 30 and July 1, 1993 (58 FR 
    35076 and 35512, respectively). Up until then, most health standards 
    applicable to shipyard employment and construction were not codified in 
    the parts of title 29 of the Code of Federal Regulations that contained 
    the bulk of the standards applicable to shipyards (part 1915) and 
    construction (part 1926). These toxic substance standards were made 
    applicable by cross-reference to subpart Z of the general industry 
    standards (part 1910) and other parts and documents.
        The Shipyard Employment Standard Advisory Committee (SESAC) 
    recommended that OSHA incorporate all toxic substance standards 
    covering shipyards into 29 CFR part 1915. As a first step to carry out 
    this recommendation, when OSHA issued the cadmium standard on September 
    14, 1992 (57 FR 42102), it created a subpart Z in part 1915 to include 
    health standards applicable to shipyards and included the cadmium 
    standard in subpart Z as Sec. 1915.1027. On April 23, 1993 (58 FR 
    21780), OSHA published a document that made corrections and amendments 
    to the September 14 document. As a second step, OSHA published a 
    technical amendment in the July 1, 1993, issue of the Federal Register, 
    which incorporated a comprehensive subpart Z into 29 CFR part 1915. The 
    July 1 document included the other toxic substance standards besides 
    cadmium, and added certain related standards applicable to shipyards.
        In similar fashion to what SESAC sought, the Advisory Committee for 
    Construction Safety and Health also asked that OSHA incorporate the 
    general industry standards deemed applicable to construction into 
    OSHA's construction standards. This incorporation of the pertinent 1910 
    standards into part 1926 was accomplished on June 30, 1993 (58 FR 
    35076), and in doing so, OSHA created a subpart Z in part 1926, for the 
    applicable specific toxic substance standards.
    
    Need for Correction
    
        As published, the July 1 final regulation contained amendatory 
    language that had the effect of removing the regulatory text and 
    appendixes of Sec. 1915.1027--Cadmium, by mistake. The preamble of that 
    document made it clear that the Cadmium standard remained applicable to 
    shipyard employment (58 FR 35513). This document reinserts the 
    regulatory text and appendices of Sec. 1915.1027 into subpart Z--Toxic 
    and Hazardous Substances of part 1915 along with the corrections and 
    amendments made on April 23, 1993.
        In addition, in the July 1 document, the text of existing 
    Sec. 1910.20, entitled ``Access to employee exposure and medical 
    records,'' was reprinted as an additional standard in part 1915, to add 
    it to the shipyard employment standards as new Sec. 1915.1120. OSHA is 
    changing cross-references in paragraphs (m) and (n) of the cadmium 
    standard to reflect the designation for the new section regarding 
    employee records within part 1915. These changes are to 
    Sec. 1915.1027(m)(4)(iii)(H), where the reference to ``Sec. 1910.20(g) 
    (1) and (2)'' is changed to read ``Sec. 1915.1120(g) (1) and (2)''; in 
    Sec. 1915.1027(n) (1)(iii), (3)(iii), and (5)(i), the reference to ``29 
    CFR 1910.20'' is changed to read ``Sec. 1915.1120 of this part''; and 
    in Sec. 1915.1027(n)(6), the reference to ``29 CFR 1910.20(h)'' is 
    changed to read ``Sec. 1915.1120(h) of this part.''
        In this document, OSHA is also converting a number of effective 
    dates that were not computed to dates certain. As published on 
    September 14, 1992, the standard included over a dozen effective dates 
    that were based on the effective dates of the cadmium document, such as 
    for 60 and 90 days after the section or standard became effective. 
    These dates, set out in paragraphs (p)(2)(i)-(viii) (57 FR 42399) are 
    being computed in this document. The following list details the 
    specific instances where these changes are made:
         In Sec. 1915.1027(p)(2)(i), the words ``60 days after the 
    effective date of this standard'' are changed to read ``February 12, 
    1993'';
         In Sec. 1915.1027(p)(2)(vi)(A), the words ``60 days after 
    the effective date of this section'' are changed to read ``February 12, 
    1993'';
         In Sec. 1915.1027(p)(2) (ii) and (iii), the words ``90 
    days after the effective date of this section'' are changed to read 
    ``March 15, 1993'';
         In Sec. 1915.1027(p)(2) (vii) and (viii), the words ``90 
    days after the effective date of this standard'' are changed to read 
    ``March 15, 1993'';
         In Sec. 1915.1027(p)(2)(i), the words ``120 days after the 
    effective date of this standard'' are changed to read ``April 14, 
    1993'';
         In Sec. 1915.1027(p)(2) (ii) and (iii), the words ``150 
    days after the effective date of this section'' are changed to read 
    ``May 14, 1993'';
         In Sec. 1915.1027(p)(2) (vii) and (viii), the words ``180 
    days after the effective date of this standard'' are changed to read 
    ``June 14, 1993'';
         In Sec. 1915.1027(p)(2) (iv) and (iv)(B), the words ``1 
    year after the effective date of this section'' are changed to read 
    ``December 14, 1993''; and
         In Sec. 1915.1027(p)(2)(v), the words ``two (2) years 
    after the effective date of this section'' are changed to read 
    ``December 14, 1994.''
        When it was published in the same September 14, 1992, document, at 
    57 FR 42452, the cadmium standard for construction was codified as 
    Sec. 1926.63 in subpart D, which covers occupational health and 
    environmental controls. With the publication of the June 30, 1993, 
    document that created a separate subpart Z for specific toxic 
    substances within OSHA's construction standards, it follows that the 
    cadmium standard belongs with the new subpart. Therefore, this document 
    is redesignating Sec. 1926.63 as Sec. 1926.1127, to place it in the 
    appropriate place subpart Z of the construction standards.
        In addition, in the June 30 document, the text of existing 
    Sec. 1910.20, entitled ``Access to employee exposure and medical 
    records,'' was reprinted as an additional standard in part 1926, to add 
    it to the construction standards as new Sec. 1926.33. OSHA is amending 
    cross-references in paragraphs (m) and (n) of the cadmium standard 
    (redesignated as Sec. 1926.1127) to reflect the designation for the new 
    section regarding employee records within part 1926. These changes are 
    to paragraph (m)(4)(iii)(H), where the reference to ``Sec. 1910.20(g) 
    (1) and (2)'' is changed to read ``Sec. 1926.33(g) (1) and (2)''; in 
    paragraphs (n) (1)(iii), (3)(iii), and (5)(i), where the reference to 
    ``29 CFR 1910.20'' is changed to read ``Sec. 1926.33 of this part''; 
    and in paragraph (n)(6), the reference to ``29 CFR 1910.20(h)'' is 
    changed to read ``Sec. 1926.33(h) of this part.''
        The corrections and technical amendments in this document are not 
    substantive regulatory actions, and therefore are not required to have 
    notice, comment, or an advance effective date. They are being made 
    retroactively effective, as of July 1, 1993, to make it clear that the 
    cadmium standard has been in effect covering shipyard employment since 
    December 14, 1992. The cadmium standard remained in effect subsequent 
    to the July 1, 1993, Federal Register document, as was OSHA's clearly 
    expressed intent.
    
    List of Subjects
    
    29 CFR Part 1915
    
        Air contaminants, Hazardous materials, Hazard communication, 
    Laboratories, Medical records, Occupational safety and health, 
    Recordkeeping, Shipyards, Shipbuilding, Ship repairing, Shipbreaking, 
    Toxic chemicals.
    
    29 CFR Part 1926
    
        Construction industry, Hazardous materials, Occupational safety and 
    health, Protective equipment.
    
    Authority and Signature
    
        This document was prepared under the direction of Joseph A. Dear, 
    Assistant Secretary of Labor for Occupational Safety and Health, U.S. 
    Department of Labor, 200 Constitution Avenue, NW., Washington, DC 
    20210.
        Accordingly, pursuant to sections 4, 6, and 8 of the Occupational 
    Safety and Health Act (29 U.S.C. 653, 655, and 657); section 107 of the 
    Contract Work Hours and Safety Standards Act (Construction Safety Act) 
    (40 U.S.C. 333); section 41 Longshore and Harbor Workers Compensation 
    Act (33 U.S.C. 941); section 4 of the Administrative Procedure Act (5 
    U.S.C. 553); and Secretary of Labor's Order No. 1-90 (55 FR 9033); OSHA 
    is issuing these corrections and technical amendments.
    
        Signed at Washington, DC, 17th day of December, 1993.
    Joseph A. Dear,
    Assistant Secretary of Labor.
        Accordingly, 29 CFR part 1915, subpart Z is corrected by the 
    following amendment:
    
    PART 1915--OCCUPATIONAL SAFETY AND HEALTH STANDARDS FOR SHIPYARD 
    EMPLOYMENT
    
        1. The authority citation for subpart Z of part 1915 continues to 
    read as follows:
    
        Authority: Sections 4, 6, 8 Occupational Safety and Health Act, 
    29 U.S.C. 653, 655, 657; Sec. 4 of the Administrative Procedure Act, 
    5 U.S.C. 553; Secretary of Labor's Orders 12-71 (36 FR 8754), 8-76 
    (41 FR 25059), 9-83 (48 FR 35736), or 1-90 (55 FR 9033), as 
    applicable; and 29 CFR part 1911.
    
    Subpart Z--Toxic and Hazardous Substances [Amended]
    
        2. Subpart Z of part 1915 is corrected by adding the text and 
    appendices of Sec. 1915.1027 as follows:
    
    
    Sec. 1915.1027  Cadmium.
    
        (a) Scope. This standard applies to all occupational exposures to 
    cadmium and cadmium compounds, in all forms, and in all industries 
    covered by the Occupational Safety and Health Act, except the 
    construction-related industries, which are covered under 29 CFR 
    1926.63.
        (b) Definitions.
        Action level (AL) is defined as an airborne concentration of 
    cadmium of 2.5 micrograms per cubic meter of air (2.5 g/m\3\), 
    calculated as an 8-hour time-weighted average (TWA).
        Assistant Secretary means the Assistant Secretary of Labor for 
    Occupational Safety and Health, U.S. Department of Labor, or designee.
        Authorized person means any person authorized by the employer and 
    required by work duties to be present in regulated areas or any person 
    authorized by the OSH Act or regulations issued under it to be in 
    regulated areas.
        Director means the Director of the National Institute for 
    Occupational Safety and Health (NIOSH), U.S. Department of Health and 
    Human Services, or designee.
        Employee exposure and similar language referring to the air cadmium 
    level to which an employee is exposed means the exposure to airborne 
    cadmium that would occur if the employee were not using respiratory 
    protective equipment.
        Final medical determination is the written medical opinion of the 
    employee's health status by the examining physician under paragraphs 
    (l)(3)-(12) of this section or, if multiple physician review under 
    paragraph (l)(13) of this section or the alternative physician 
    determination under paragraph (l)(14) of this section is invoked, it is 
    the final, written medical finding, recommendation or determination 
    that emerges from that process.
        High-efficiency particulate air (HEPA) filter means a filter 
    capable of trapping and retaining at least 99.97 percent of mono-
    dispersed particles of 0.3 micrometers in diameter.
        Regulated area means an area demarcated by the employer where an 
    employee's exposure to airborne concentrations of cadmium exceeds, or 
    can reasonably be expected to exceed the permissible exposure limit 
    (PEL).
        This section means this cadmium standard.
        (c) Permissible Exposure Limit (PEL). The employer shall assure 
    that no employee is exposed to an airborne concentration of cadmium in 
    excess of five micrograms per cubic meter of air (5 g/m\3\), 
    calculated as an eight-hour time-weighted average exposure (TWA).
        (d) Exposure monitoring--(1) General. (i) Each employer who has a 
    workplace or work operation covered by this section shall determine if 
    any employee may be exposed to cadmium at or above the action level.
        (ii) Determinations of employee exposure shall be made from 
    breathing zone air samples that reflect the monitored employee's 
    regular, daily 8-hour TWA exposure to cadmium.
        (iii) Eight-hour TWA exposures shall be determined for each 
    employee on the basis of one or more personal breathing zone air 
    samples reflecting full shift exposure on each shift, for each job 
    classification, in each work area. Where several employees perform the 
    same job tasks, in the same job classification, on the same shift, in 
    the same work area, and the length, duration, and level of cadmium 
    exposures are similar, an employer may sample a representative fraction 
    of the employees instead of all employees in order to meet this 
    requirement. In representative sampling, the employer shall sample the 
    employee(s) expected to have the highest cadmium exposures.
        (2) Specific. (i) Initial monitoring. Except as provided for in 
    paragraphs (d)(2)(ii) and (d)(2)(iii) of this section, the employer 
    shall monitor employee exposures and shall base initial determinations 
    on the monitoring results.
        (ii) Where the employer has monitored after September 14, 1991, 
    under conditions that in all important aspects closely resemble those 
    currently prevailing and where that monitoring satisfies all other 
    requirements of this section, including the accuracy and confidence 
    levels of paragraph (d)(6) of this section, the employer may rely on 
    such earlier monitoring results to satisfy the requirements of 
    paragraph (d)(2)(i) of this section.
        (iii) Where the employer has objective data, as defined in 
    paragraph (n)(2) of this section, demonstrating that employee exposure 
    to cadmium will not exceed the action level under the expected 
    conditions of processing, use, or handling, the employer may rely upon 
    such data instead of implementing initial monitoring.
        (3) Monitoring Frequency (periodic monitoring). (i) If the initial 
    monitoring or periodic monitoring reveals employee exposures to be at 
    or above the action level, the employer shall monitor at a frequency 
    and pattern needed to represent the levels of exposure of employees and 
    where exposures are above the PEL to assure the adequacy of respiratory 
    selection and the effectiveness of engineering and work practice 
    controls. However, such exposure monitoring shall be performed at least 
    every six months. The employer, at a minimum, shall continue these 
    semi-annual measurements unless and until the conditions set out in 
    paragraph (d)(3)(ii) of this section are met.
        (ii) If the initial monitoring or the periodic monitoring indicates 
    that employee exposures are below the action level and that result is 
    confirmed by the results of another monitoring taken at least seven 
    days later, the employer may discontinue the monitoring for those 
    employees whose exposures are represented by such monitoring.
        (4) Additional monitoring. The employer also shall institute the 
    exposure monitoring required under paragraphs (d)(2)(i) and (d)(3) of 
    this section whenever there has been a change in the raw materials, 
    equipment, personnel, work practices, or finished products that may 
    result in additional employees being exposed to cadmium at or above the 
    action level or in employees already exposed to cadmium at or above the 
    action level being exposed above the PEL, or whenever the employer has 
    any reason to suspect that any other change might result in such 
    further exposure.
        (5) Employee notification of monitoring results. (i) Within 15 
    working days after the receipt of the results of any monitoring 
    performed under this section, the employer shall notify each affected 
    employee individually in writing of the results. In addition, within 
    the same time period the employer shall post the results of the 
    exposure monitoring in an appropriate location that is accessible to 
    all affected employees.
        (ii) Wherever monitoring results indicate that employee exposure 
    exceeds the PEL, the employer shall include in the written notice a 
    statement that the PEL has been exceeded and a description of the 
    corrective action being taken by the employer to reduce employee 
    exposure to or below the PEL.
        (6) Accuracy of measurement. The employer shall use a method of 
    monitoring and analysis that has an accuracy of not less than plus or 
    minus 25 percent ( 25%), with a confidence level of 95 
    percent, for airborne concentrations of cadmium at or above the action 
    level, the permissible exposure limit (PEL), and the separate 
    engineering control air limit (SECAL).
        (e) Regulated areas--(1) Establishment. The employer shall 
    establish a regulated area wherever an employee's exposure to airborne 
    concentrations of cadmium is, or can reasonably be expected to be in 
    excess of the permissible exposure limit (PEL).
        (2) Demarcation. Regulated areas shall be demarcated from the rest 
    of the workplace in any manner that adequately establishes and alerts 
    employees of the boundaries of the regulated area.
        (3) Access. Access to regulated areas shall be limited to 
    authorized persons.
        (4) Provision of respirators. Each person entering a regulated area 
    shall be supplied with and required to use a respirator, selected in 
    accordance with paragraph (g)(2) of this section.
        (5) Prohibited activities. The employer shall assure that employees 
    do not eat, drink, smoke, chew tobacco or gum, or apply cosmetics in 
    regulated areas, carry the products associated with these activities 
    into regulated areas, or store such products in those areas.
        (f) Methods of compliance--(1) Compliance hierarchy. (i) Except as 
    specified in paragraphs (f)(1) (ii), (iii) and (iv) of this section the 
    employer shall implement engineering and work practice controls to 
    reduce and maintain employee exposure to cadmium at or below the PEL, 
    except to the extent that the employer can demonstrate that such 
    controls are not feasible.
        (ii) Except as specified in paragraphs (f)(1) (iii) and (iv) of 
    this section, in industries where a separate engineering control air 
    limit (SECAL) has been specified for particular processes (See Table 1 
    in this paragraph (f)(1)(ii)), the employer shall implement engineering 
    and work practice controls to reduce and maintain employee exposure at 
    or below the SECAL, except to the extent that the employer can 
    demonstrate that such controls are not feasible. 
    
       Table 1.--Separate Engineering Control Airborne Limits (SECALs) for  
                        Processes in Selected Industries                    
    ------------------------------------------------------------------------
                                                                    SECAL   
             Industry                      Process              (g/
                                                                     m3)    
    ------------------------------------------------------------------------
    Nickel cadmium battery....  Plate making, plate                      50 
                                 preparation.                               
                                All other processes...........           15 
    Zinc/Cadmium refining*....  Cadmium refining, casting,               50 
                                 melting, oxide production,                 
                                 sinter plant.                              
    Pigment manufacture.......  Calcine, crushing, milling,              50 
                                 blending.                                  
                                All other processes...........           15 
    Stabilizers*..............  Cadmium oxide charging,                  50 
                                 crushing, drying, blending.                
    Lead smelting*............  Sinter plant, blast furnace,             50 
                                 baghouse, yard area.                       
    Plating*..................  Mechanical plating............           15 
    ------------------------------------------------------------------------
    *Processes in these industries that are not specified in this table must
      achieve the PEL using engineering controls and work practices as      
      required in f(1)(i).                                                  
    
        (iii) The requirement to implement engineering and work practice 
    controls to achieve the PEL or, where applicable, the SECAL does not 
    apply where the employer demonstrates the following:
        (A) The employee is only intermittently exposed; and
        (B) The employee is not exposed above the PEL on 30 or more days 
    per year (12 consecutive months).
        (iv) Wherever engineering and work practice controls are required 
    and are not sufficient to reduce employee exposure to or below the PEL 
    or, where applicable, the SECAL, the employer nonetheless shall 
    implement such controls to reduce exposures to the lowest levels 
    achievable. The employer shall supplement such controls with 
    respiratory protection that complies with the requirements of paragraph 
    (g) of this section and the PEL.
        (v) The employer shall not use employee rotation as a method of 
    compliance.
        (2) Compliance program. (i) Where the PEL is exceeded, the employer 
    shall establish and implement a written compliance program to reduce 
    employee exposure to or below the PEL by means of engineering and work 
    practice controls, as required by paragraph (f)(1) of this section. To 
    the extent that engineering and work practice controls cannot reduce 
    exposures to or below the PEL, the employer shall include in the 
    written compliance program the use of appropriate respiratory 
    protection to achieve compliance with the PEL.
        (ii) Written compliance programs shall include at least the 
    following:
        (A) A description of each operation in which cadmium is emitted; 
    e.g., machinery used, material processed, controls in place, crew size, 
    employee job responsibilities, operating procedures, and maintenance 
    practices;
        (B) A description of the specific means that will be employed to 
    achieve compliance, including engineering plans and studies used to 
    determine methods selected for controlling exposure to cadmium, as well 
    as, where necessary, the use of appropriate respiratory protection to 
    achieve the PEL;
        (C) A report of the technology considered in meeting the PEL;
        (D) Air monitoring data that document the sources of cadmium 
    emissions;
        (E) A detailed schedule for implementation of the program, 
    including documentation such as copies of purchase orders for 
    equipment, construction contracts, etc.;
        (F) A work practice program that includes items required under 
    paragraphs (h), (i), and (j) of this section;
        (G) A written plan for emergency situations, as specified in 
    paragraph (h) of this section; and
        (H) Other relevant information.
        (iii) The written compliance programs shall be reviewed and updated 
    at least annually, or more often if necessary, to reflect significant 
    changes in the employer's compliance status.
        (iv) Written compliance programs shall be provided upon request for 
    examination and copying to affected employees, designated employee 
    representatives as well as to the Assistant Secretary, and the 
    Director.
        (3) Mechanical ventilation. (i) When ventilation is used to control 
    exposure, measurements that demonstrate the effectiveness of the system 
    in controlling exposure, such as capture velocity, duct velocity, or 
    static pressure shall be made as necessary to maintain its 
    effectiveness.
        (ii) Measurements of the system's effectiveness in controlling 
    exposure shall be made as necessary within five working days of any 
    change in production, process, or control that might result in a 
    significant increase in employee exposure to cadmium.
        (iii) Recirculation of air. If air from exhaust ventilation is 
    recirculated into the workplace, the system shall have a high 
    efficiency filter and be monitored to assure effectiveness.
        (iv) Procedures shall be developed and implemented to minimize 
    employee exposure to cadmium when maintenance of ventilation systems 
    and changing of filters is being conducted.
        (g) Respirator protection--(1) General. Where respirators are 
    required by this section, the employer shall provide them at no cost to 
    the employee and shall assure that they are used in compliance with the 
    requirements of this section. Respirators shall be used in the 
    following circumstances:
        (i) Where exposure levels exceed the PEL, during the time period 
    necessary to install or implement feasible engineering and work 
    practice controls;
        (ii) In those maintenance and repair activities and during those 
    brief or intermittent operations where exposures exceed the PEL and 
    engineering and work practice controls are not feasible or are not 
    required;
        (iii) In regulated areas, as prescribed in paragraph (e) of this 
    section;
        (iv) Where the employer has implemented all feasible engineering 
    and work practice controls and such controls are not sufficient to 
    reduce exposures to or below the PEL;
        (v) In emergencies;
        (vi) Wherever an employee who is exposed to cadmium at or above the 
    action level requests a respirator;
        (vii) Wherever an employee is exposed above the PEL in an industry 
    to which a SECAL is applicable; and
        (viii) Wherever an employee is exposed to cadmium above the PEL and 
    engineering controls are not required under paragraph (f)(1)(iii) of 
    this section.
        (2) Respirator selection. (i) Where respirators are required under 
    this section, the employer shall select and provide the appropriate 
    respirator as specified in Table 2 in this paragraph (g)(2)(i). The 
    employer shall select respirators from among those jointly approved as 
    acceptable protection against cadmium dust, fume, and mist by the Mine 
    Safety and Health Administration (MSHA) and by the National Institute 
    for Occupational Safety and Health (NIOSH) under the provisions of 30 
    CFR part 11. 
    
                                      Table 2.--Respiratory Protection for Cadmium                                  
    ----------------------------------------------------------------------------------------------------------------
    Airborne concentration or condition of usea                       Required respirator typeb                     
    ----------------------------------------------------------------------------------------------------------------
    10  x  or less.............................  A half mask, air-purifying respirator equipped with a HEPAc        
                                                  filter.d                                                          
    25  x  or less.............................  A powered air-purifying respirator (``PAPR'') with a loose-fitting 
                                                  hood or helmet equipped with a HEPA filter, or a supplied-air     
                                                  respirator with a loose-fitting hood or helmet facepiece operated 
                                                  in the continuous flow mode.                                      
    50  x  or less.............................  A full facepiece air-purifying respirator equipped with a HEPA     
                                                  filter, or a powered air-purifying respirator with a tight-fitting
                                                  half mask equipped with a HEPA filter, or a supplied air          
                                                  respirator with a tight-fitting half mask operated in the         
                                                  continuous flow mode.                                             
    250  x  or less............................  A powered air-purifying respirator with a tight-fitting full       
                                                  facepiece equipped with a HEPA filter, or a supplied-air          
                                                  respirator with a tight-fitting full facepiece operated in the    
                                                  continuous flow mode.                                             
    1000  x  or less...........................  A supplied-air respirator with half mask or full facepiece operated
                                                  in the pressure demand or other positive pressure mode.           
    >1000  x  or unknown concentrations........  A self-contained breathing apparatus with a full facepiece operated
                                                  in the pressure demand or other positive pressure mode, or a      
                                                  supplied-air respirator with a full facepiece operated in the     
                                                  pressure demand or other positive pressure mode and equipped with 
                                                  an auxiliary escape type self-contained breathing apparatus       
                                                  operated in the pressure demand mode.                             
    Fire fighting..............................  A self-contained breathing apparatus with full facepiece operated  
                                                  in the pressure demand or other positive pressure mode.           
    ----------------------------------------------------------------------------------------------------------------
    aConcentrations expressed as multiple of the PEL.                                                               
    bRespirators assigned for higher environmental concentrations may be used at lower exposure levels. Quantitative
      fit testing is required for all tight-fitting air purifying respirators where airborne concentration of       
      cadmium exceeds 10 times the TWA PEL (10 x 5 g/m3=50 g/m3). A full facepiece respirator is  
      required when eye irritation is experienced.                                                                  
    cHEPA means High Efficiency Particulate Air.                                                                    
    dFit testing, qualitative or quantitative, is required.                                                         
    SOURCE: Respiratory Decision Logic, NIOSH, 1987.                                                                
    
        (ii) The employer shall provide a powered, air-purifying respirator 
    (PAPR) in lieu of a negative pressure respirator wherever:
        (A) An employee entitled to a respirator chooses to use this type 
    of respirator; and
        (B) This respirator will provide adequate protection to the 
    employee.
        (3) Respirator program. (i) Where respiratory protection is 
    required, the employer shall institute a respirator protection program 
    in accordance with 29 CFR 1910.134.
        (ii) The employer shall permit each employee who is required to use 
    an air purifying respirator to leave the regulated area to change the 
    filter elements or replace the respirator whenever an increase in 
    breathing resistance is detected and shall maintain an adequate supply 
    of filter elements for this purpose.
        (iii) The employer shall also permit each employee who is required 
    to wear a respirator to leave the regulated area to wash his or her 
    face and the respirator facepiece whenever necessary to prevent skin 
    irritation associated with respirator use.
        (iv) If an employee exhibits difficulty in breathing while wearing 
    a respirator during a fit test or during use, the employer shall make 
    available to the employee a medical examination in accordance with 
    paragraph (l)(6)(ii) of this section to determine if the employee can 
    wear a respirator while performing the required duties.
        (v) No employee shall be assigned a task requiring the use of a 
    respirator if, based upon his or her most recent examination, an 
    examining physician determines that the employee will be unable to 
    continue to function normally while wearing a respirator. If the 
    physician determines the employee must be limited in, or removed from 
    his or her current job because of the employee's inability to wear a 
    respirator, the limitation or removal shall be in accordance with 
    paragraphs (l) (11) and (12) of this section.
        (4) Respirator fit testing. (i) The employer shall assure that the 
    respirator issued to the employee is fitted properly and exhibits the 
    least possible facepiece leakage.
        (ii) For each employee wearing a tight-fitting, air purifying 
    respirator (either negative or positive pressure) who is exposed to 
    airborne concentrations of cadmium that do not exceed 10 times the PEL 
    (10  x  5 g/m\3\ = 50 g/m\3\), the employer shall 
    perform either quantitative or qualitative fit testing at the time of 
    initial fitting and at least annually thereafter. If quantitative fit 
    testing is used for a negative pressure respirator, a fit factor that 
    is at least 10 times the protection factor for that class of 
    respirators (Table 2 in paragraph (g)(2)(i) of this section) shall be 
    achieved at testing.
        (iii) For each employee wearing a tight-fitting air purifying 
    respirator (either negative or positive pressure) who is exposed to 
    airborne concentrations of cadmium that exceed 10 times the PEL (10  x  
    5 g/m\3\ = 50 g/m\3\), the employer shall perform 
    quantitative fit testing at the time of initial fitting and at least 
    annually thereafter. For negative-pressure respirators, a fit factor 
    that is at least 10 times the protection factor for that class of 
    respirators (Table 2 in paragraph (g)(2)(i) of this section) shall be 
    achieved during quantitative fit testing.
        (iv) For each employee wearing a tight-fitting, supplied-air 
    respirator or self-contained breathing apparatus, the employer shall 
    perform quantitative fit testing at the time of initial fitting and at 
    least annually thereafter. This shall be accomplished by fit testing an 
    air purifying respirator of identical type facepiece, make, model, and 
    size as the supplied air respirator or self-contained breathing 
    apparatus that is equipped with HEPA filters and tested as a surrogate 
    (substitute) in the negative pressure mode. A fit factor that is at 
    least 10 times the protection factor for that class of respirators 
    (Table 2 in paragraph (g)(2)(i) of this section) shall be achieved 
    during quantitative fit testing. A supplied-air respirator or self-
    contained breathing apparatus with the same type facepiece, make, 
    model, and size as the air purifying respirator with which the employee 
    passed the quantitative fit test may then be used by that employee up 
    to the protection factor listed in Table 2 for that class of 
    respirators.
        (v) Fit testing shall be conducted in accordance with appendix C of 
    this section.
        (h) Emergency situations. The employer shall develop and implement 
    a written plan for dealing with emergency situations involving 
    substantial releases of airborne cadmium. The plan shall include 
    provisions for the use of appropriate respirators and personal 
    protective equipment. In addition, employees not essential to 
    correcting the emergency situation shall be restricted from the area 
    and normal operations halted in that area until the emergency is 
    abated.
        (i) Protective work clothing and equipment--(1) Provision and use. 
    If an employee is exposed to airborne cadmium above the PEL or where 
    skin or eye irritation is associated with cadmium exposure at any 
    level, the employer shall provide at no cost to the employee, and 
    assure that the employee uses, appropriate protective work clothing and 
    equipment that prevents contamination of the employee and the 
    employee's garments. Protective work clothing and equipment includes, 
    but is not limited to:
        (i) Coveralls or similar full-body work clothing;
        (ii) Gloves, head coverings, and boots or foot coverings; and
        (iii) Face shields, vented goggles, or other appropriate protective 
    equipment that complies with 29 CFR 1910.133.
        (2) Removal and storage. (i) The employer shall assure that 
    employees remove all protective clothing and equipment contaminated 
    with cadmium at the completion of the work shift and do so only in 
    change rooms provided in accordance with paragraph (j)(1) of this 
    section.
        (ii) The employer shall assure that no employee takes cadmium-
    contaminated protective clothing or equipment from the workplace, 
    except for employees authorized to do so for purposes of laundering, 
    cleaning, maintaining, or disposing of cadmium contaminated protective 
    clothing and equipment at an appropriate location or facility away from 
    the workplace.
        (iii) The employer shall assure that contaminated protective 
    clothing and equipment, when removed for laundering, cleaning, 
    maintenance, or disposal, is placed and stored in sealed, impermeable 
    bags or other closed, impermeable containers that are designed to 
    prevent dispersion of cadmium dust.
        (iv) The employer shall assure that bags or containers of 
    contaminated protective clothing and equipment that are to be taken out 
    of the change rooms or the workplace for laundering, cleaning, 
    maintenance or disposal shall bear labels in accordance with paragraph 
    (m)(3) of this section.
        (3) Cleaning, replacement, and disposal. (i) The employer shall 
    provide the protective clothing and equipment required by paragraph 
    (i)(1) of this section in a clean and dry condition as often as 
    necessary to maintain its effectiveness, but in any event at least 
    weekly. The employer is responsible for cleaning and laundering the 
    protective clothing and equipment required by this paragraph to 
    maintain its effectiveness and is also responsible for disposing of 
    such clothing and equipment.
        (ii) The employer also is responsible for repairing or replacing 
    required protective clothing and equipment as needed to maintain its 
    effectiveness. When rips or tears are detected while an employee is 
    working they shall be immediately mended, or the worksuit shall be 
    immediately replaced.
        (iii) The employer shall prohibit the removal of cadmium from 
    protective clothing and equipment by blowing, shaking, or any other 
    means that disperses cadmium into the air.
        (iv) The employer shall assure that any laundering of contaminated 
    clothing or cleaning of contaminated equipment in the workplace is done 
    in a manner that prevents the release of airborne cadmium in excess of 
    the permissible exposure limit prescribed in paragraph (c) of this 
    section.
        (v) The employer shall inform any person who launders or cleans 
    protective clothing or equipment contaminated with cadmium of the 
    potentially harmful effects of exposure to cadmium and that the 
    clothing and equipment should be laundered or cleaned in a manner to 
    effectively prevent the release of airborne cadmium in excess of the 
    PEL.
        (j) Hygiene areas and practices--(1) General. For employees whose 
    airborne exposure to cadmium is above the PEL, the employer shall 
    provide clean change rooms, handwashing facilities, showers, and 
    lunchroom facilities that comply with 29 CFR 1910.141.
        (2) Change rooms. The employer shall assure that change rooms are 
    equipped with separate storage facilities for street clothes and for 
    protective clothing and equipment, which are designed to prevent 
    dispersion of cadmium and contamination of the employee's street 
    clothes.
        (3) Showers and handwashing facilities. (i) The employer shall 
    assure that employees who are exposed to cadmium above the PEL shower 
    during the end of the work shift.
        (ii) The employer shall assure that employees whose airborne 
    exposure to cadmium is above the PEL wash their hands and faces prior 
    to eating, drinking, smoking, chewing tobacco or gum, or applying 
    cosmetics.
        (4) Lunchroom facilities. (i) The employer shall assure that the 
    lunchroom facilities are readily accessible to employees, that tables 
    for eating are maintained free of cadmium, and that no employee in a 
    lunchroom facility is exposed at any time to cadmium at or above a 
    concentration of 2.5 g/m\3\.
        (ii) The employer shall assure that employees do not enter 
    lunchroom facilities with protective work clothing or equipment unless 
    surface cadmium has been removed from the clothing and equipment by 
    HEPA vacuuming or some other method that removes cadmium dust without 
    dispersing it.
        (k) Housekeeping. (1) All surfaces shall be maintained as free as 
    practicable of accumulations of cadmium.
        (2) All spills and sudden releases of material containing cadmium 
    shall be cleaned up as soon as possible.
        (3) Surfaces contaminated with cadmium shall, wherever possible, be 
    cleaned by vacuuming or other methods that minimize the likelihood of 
    cadmium becoming airborne.
        (4) HEPA-filtered vacuuming equipment or equally effective 
    filtration methods shall be used for vacuuming. The equipment shall be 
    used and emptied in a manner that minimizes the reentry of cadmium into 
    the workplace.
        (5) Shoveling, dry or wet sweeping, and brushing may be used only 
    where vacuuming or other methods that minimize the likelihood of 
    cadmium becoming airborne have been tried and found not to be 
    effective.
        (6) Compressed air shall not be used to remove cadmium from any 
    surface unless the compressed air is used in conjunction with a 
    ventilation system designed to capture the dust cloud created by the 
    compressed air.
        (7) Waste, scrap, debris, bags, containers, personal protective 
    equipment, and clothing contaminated with cadmium and consigned for 
    disposal shall be collected and disposed of in sealed impermeable bags 
    or other closed, impermeable containers. These bags and containers 
    shall be labeled in accordance with paragraph (m)(2) of this section.
        (l) Medical surveillance--(1) General--(i) Scope. (A) Currently 
    exposed--The employer shall institute a medical surveillance program 
    for all employees who are or may be exposed to cadmium at or above the 
    action level unless the employer demonstrates that the employee is not, 
    and will not be, exposed at or above the action level on 30 or more 
    days per year (twelve consecutive months); and,
        (B) Previously exposed--The employer shall also institute a medical 
    surveillance program for all employees who prior to the effective date 
    of this section might previously have been exposed to cadmium at or 
    above the action level by the employer, unless the employer 
    demonstrates that the employee did not prior to the effective date of 
    this section work for the employer in jobs with exposure to cadmium for 
    an aggregated total of more than 60 months.
        (ii) To determine an employee's fitness for using a respirator, the 
    employer shall provide the limited medical examination specified in 
    paragraph (l)(6) of this section.
        (iii) The employer shall assure that all medical examinations and 
    procedures required by this standard are performed by or under the 
    supervision of a licensed physician, who has read and is familiar with 
    the health effects section of appendix A to this section, the 
    regulatory text of this section, the protocol for sample handling and 
    laboratory selection in appendix F to this section, and the 
    questionnaire of appendix D to this section. These examinations and 
    procedures shall be provided without cost to the employee and at a time 
    and place that is reasonable and convenient to employees.
        (iv) The employer shall assure that the collecting and handling of 
    biological samples of cadmium in urine (CdU), cadmium in blood (CdB), 
    and beta-2 microglobulin in urine (2-M) taken from 
    employees under this section is done in a manner that assures their 
    reliability and that analysis of biological samples of cadmium in urine 
    (CdU), cadmium in blood (CdB), and beta-2 microglobulin in urine 
    (2-M) taken from employees under this section is 
    performed in laboratories with demonstrated proficiency for that 
    particular analyte. (See appendix F to this section.)
        (2) Initial examination. (i) The employer shall provide an initial 
    (preplacement) examination to all employees covered by the medical 
    surveillance program required in paragraph (l)(1)(i) of this section. 
    The examination shall be provided to those employees within 30 days 
    after initial assignment to a job with exposure to cadmium or no later 
    than 90 days after the effective date of this section, whichever date 
    is later.
        (ii) The initial (preplacement) medical examination shall include:
        (A) A detailed medical and work history, with emphasis on: Past, 
    present, and anticipated future exposure to cadmium; any history of 
    renal, cardiovascular, respiratory, hematopoietic, reproductive, and/or 
    musculo-skeletal system dysfunction; current usage of medication with 
    potential nephrotoxic side-effects; and smoking history and current 
    status; and
        (B) Biological monitoring that includes the following tests:
        (1) Cadmium in urine (CdU), standardized to grams of creatinine (g/
    Cr);
        (2) Beta-2 microglobulin in urine (2-M), standardized 
    to grams of creatinine (g/Cr), with pH specified, as described in 
    appendix F to this section; and
        (3) Cadmium in blood (CdB), standardized to liters of whole blood 
    (lwb).
        (iii) Recent Examination: An initial examination is not required to 
    be provided if adequate records show that the employee has been 
    examined in accordance with the requirements of paragraph (l)(2)(ii) of 
    this section within the past 12 months. In that case, such records 
    shall be maintained as part of the employee's medical record and the 
    prior exam shall be treated as if it were an initial examination for 
    the purposes of paragraphs (l)(3) and (4) of this section.
        (3) Actions triggered by initial biological monitoring. (i) If the 
    results of the initial biological monitoring tests show the employee's 
    CdU level to be at or below 3 g/g Cr, 2-M level 
    to be at or below 300 g/g Cr and CdB level to be at or below 5 
    g/lwb, then:
        (A) For currently exposed employees, who are subject to medical 
    surveillance under paragraph (l)(1)(i)(A) of this section, the employer 
    shall provide the minimum level of periodic medical surveillance in 
    accordance with the requirements in paragraph (l)(4)(i) of this 
    section; and
        (B) For previously exposed employees, who are subject to medical 
    surveillance under paragraph (l)(1)(i)(B) of this section, the employer 
    shall provide biological monitoring for CdU, 2-M, and CdB 
    one year after the initial biological monitoring and then the employer 
    shall comply with the requirements of paragraph (l)(4)(v) of this 
    section.
        (ii) For all employees who are subject to medical surveillance 
    under paragraph (l)(1)(i) of this section, if the results of the 
    initial biological monitoring tests show the level of CdU to exceed 3 
    g/g Cr, the level of 2-M to exceed 300 
    g/g Cr, or the level of CdB to exceed 5 g/lwb, the 
    employer shall:
        (A) Within two weeks after receipt of biological monitoring 
    results, reassess the employee's occupational exposure to cadmium as 
    follows:
        (1) Reassess the employee's work practices and personal hygiene;
        (2) Reevaluate the employee's respirator use, if any, and the 
    respirator program;
        (3) Review the hygiene facilities;
        (4) Reevaluate the maintenance and effectiveness of the relevant 
    engineering controls;
        (5) Assess the employee's smoking history and status;
        (B) Within 30 days after the exposure reassessment, specified in 
    paragraph (l)(3)(ii)(A) of this section, take reasonable steps to 
    correct any deficiencies found in the reassessment that may be 
    responsible for the employee's excess exposure to cadmium; and,
        (C) Within 90 days after receipt of biological monitoring results, 
    provide a full medical examination to the employee in accordance with 
    the requirements of paragraph (l)(4)(ii) of this section. After 
    completing the medical examination, the examining physician shall 
    determine in a written medical opinion whether to medically remove the 
    employee. If the physician determines that medical removal is not 
    necessary, then until the employee's CdU level falls to or below 3 
    g/g Cr, 2-M level falls to or below 300 
    g/g Cr and CdB level falls to or below 5 g/lwb, the 
    employer shall:
        (1) Provide biological monitoring in accordance with paragraph 
    (l)(2)(ii)(B) of this section on a semiannual basis; and
        (2) Provide annual medical examinations in accordance with 
    paragraph (l)(4)(ii) of this section.
        (iii) For all employees who are subject to medical surveillance 
    under paragraph (l)(1)(i) of this section, if the results of the 
    initial biological monitoring tests show the level of CdU to be in 
    excess of 15 g/g Cr, or the level of CdB to be in excess of 15 
    g/lwb, or the level of 2-M to be in excess of 
    1,500 g/g Cr, the employer shall comply with the requirements 
    of paragraphs (l)(3)(ii)(A)-(B) of this section. Within 90 days after 
    receipt of biological monitoring results, the employer shall provide a 
    full medical examination to the employee in accordance with the 
    requirements of paragraph (l)(4)(ii) of this section. After completing 
    the medical examination, the examining physician shall determine in a 
    written medical opinion whether to medically remove the employee. 
    However, if the initial biological monitoring results and the 
    biological monitoring results obtained during the medical examination 
    both show that: CdU exceeds 15 g/g Cr; or CdB exceeds 15 
    g/lwb; or 2-M exceeds 1500 g/g Cr, and 
    in addition CdU exceeds 3 g/g Cr or CdB exceeds 5 g/
    liter of whole blood, then the physician shall medically remove the 
    employee from exposure to cadmium at or above the action level. If the 
    second set of biological monitoring results obtained during the medical 
    examination does not show that a mandatory removal trigger level has 
    been exceeded, then the employee is not required to be removed by the 
    mandatory provisions of this paragraph. If the employee is not required 
    to be removed by the mandatory provisions of this paragraph or by the 
    physician's determination, then until the employee's CdU level falls to 
    or below 3 g/g Cr, 2-M level falls to or below 
    300 g/g Cr and CdB level falls to or below 5 g/lwb, 
    the employer shall:
        (A) Periodically reassess the employee's occupational exposure to 
    cadmium;
        (B) Provide biological monitoring in accordance with paragraph 
    (l)(2)(ii)(B) of this section on a quarterly basis; and
        (C) Provide semiannual medical examinations in accordance with 
    paragraph (l)(4)(ii) of this section.
        (iv) For all employees to whom medical surveillance is provided, 
    beginning on January 1, 1999, and in lieu of paragraphs (l)(3)(i)-(iii) 
    of this section:
        (A) If the results of the initial biological monitoring tests show 
    the employee's CdU level to be at or below 3 g/g Cr, 
    2-M level to be at or below 300 g/g Cr and CdB 
    level to be at or below 5 g/lwb, then for currently exposed 
    employees, the employer shall comply with the requirements of paragraph 
    (l)(3)(i)(A) of this section, and for previously exposed employees, the 
    employer shall comply with the requirements of paragraph (l)(3)(i)(B) 
    of this section;
        (B) If the results of the initial biological monitoring tests show 
    the level of CdU to exceed 3 g/g Cr, the level of 
    2-M to exceed 300 g/g Cr, or the level of CdB to 
    exceed 5 g/lwb, the employer shall comply with the 
    requirements of paragraphs (l)(3)(ii)(A)-(C) of this section; and,
        (C) If the results of the initial biological monitoring tests show 
    the level of CdU to be in excess of 7 g/g Cr, or the level of 
    CdB to be in excess of 10 g/lwb, or the level of 
    2-M to be in excess of 750 g/g Cr, the employer 
    shall: Comply with the requirements of paragraphs (l)(3)(ii)(A)-(B) of 
    this section; and, within 90 days after receipt of biological 
    monitoring results, provide a full medical examination to the employee 
    in accordance with the requirements of paragraph (l)(4)(ii) of this 
    section. After completing the medical examination, the examining 
    physician shall determine in a written medical opinion whether to 
    medically remove the employee. However, if the initial biological 
    monitoring results and the biological monitoring results obtained 
    during the medical examination both show that: CdU exceeds 7 
    g/g Cr; or CdB exceeds 10 g/lwb; or 2-M 
    exceeds 750 g/g Cr, and in addition CdU exceeds 3 g/g 
    Cr or CdB exceeds 5 g/liter of whole blood, then the physician 
    shall medically remove the employee from exposure to cadmium at or 
    above the action level. If the second set of biological monitoring 
    results obtained during the medical examination does not show that a 
    mandatory removal trigger level has been exceeded, then the employee is 
    not required to be removed by the mandatory provisions of this 
    paragraph. If the employee is not required to be removed by the 
    mandatory provisions of this paragraph or by the physician's 
    determination, then until the employee's CdU level falls to or below 3 
    g/g Cr, 2-M level falls to or below 300 
    g/g Cr and CdB level falls to or below 5 g/lwb, the 
    employer shall: periodically reassess the employee's occupational 
    exposure to cadmium; provide biological monitoring in accordance with 
    paragraph (l)(2)(ii)(B) of this section on a quarterly basis; and 
    provide semiannual medical examinations in accordance with paragraph 
    (l)(4)(ii) of this section.
        (4) Periodic medical surveillance. (i) For each employee who is 
    covered under paragraph (l)(1)(i)(A) of this section, the employer 
    shall provide at least the minimum level of periodic medical 
    surveillance, which consists of periodic medical examinations and 
    periodic biological monitoring. A periodic medical examination shall be 
    provided within one year after the initial examination required by 
    paragraph (l)(2) of this section and thereafter at least biennially. 
    Biological sampling shall be provided at least annually, either as part 
    of a periodic medical examination or separately as periodic biological 
    monitoring.
        (ii) The periodic medical examination shall include:
        (A) A detailed medical and work history, or update thereof, with 
    emphasis on: Past, present and anticipated future exposure to cadmium; 
    smoking history and current status; reproductive history; current use 
    of medications with potential nephrotoxic side-effects; any history of 
    renal, cardiovascular, respiratory, hematopoietic, and/or musculo-
    skeletal system dysfunction; and as part of the medical and work 
    history, for employees who wear respirators, questions 3-11 and 25-32 
    in Appendix D to this section;
        (B) A complete physical examination with emphasis on: Blood 
    pressure, the respiratory system, and the urinary system;
        (C) A 14 inch by 17 inch, or a reasonably standard sized posterior-
    anterior chest X-ray (after the initial X-ray, the frequency of chest 
    X-rays is to be determined by the examining physician);
        (D) Pulmonary function tests, including forced vital capacity (FVC) 
    and forced expiratory volume at 1 second (FEV1);
        (E) Biological monitoring, as required in paragraph (l)(2)(ii)(B) 
    of this section;
        (F) Blood analysis, in addition to the analysis required under 
    paragraph (l)(2)(ii)(B) of this section, including blood urea nitrogen, 
    complete blood count, and serum creatinine;
        (G) Urinalysis, in addition to the analysis required under 
    paragraph (l)(2)(ii)(B) of this section, including the determination of 
    albumin, glucose, and total and low molecular weight proteins;
        (H) For males over 40 years old, prostate palpation, or other at 
    least as effective diagnostic test(s); and
        (I) Any additional tests deemed appropriate by the examining 
    physician.
        (iii) Periodic biological monitoring shall be provided in 
    accordance with paragraph (l)(2)(ii)(B) of this section.
        (iv) If the results of periodic biological monitoring or the 
    results of biological monitoring performed as part of the periodic 
    medical examination show the level of the employee's CdU, 
    2-M, or CdB to be in excess of the levels specified in 
    paragraphs (l)(3) (ii) or (iii); or, beginning on January 1, 1999, in 
    excess of the levels specified in paragraphs (l)(3) (ii) or (iv) of 
    this section, the employer shall take the appropriate actions specified 
    in paragraphs (l)(3)(ii)-(iv) of this section.
        (v) For previously exposed employees under paragraph (l)(1)(i)(B) 
    of this section:
        (A) If the employee's levels of CdU did not exceed 3 g/g 
    Cr, CdB did not exceed 5 g/lwb, and 2-M did not 
    exceed 300 g/g Cr in the initial biological monitoring tests, 
    and if the results of the followup biological monitoring required by 
    paragraph (l)(3)(i)(B) of this section one year after the initial 
    examination confirm the previous results, the employer may discontinue 
    all periodic medical surveillance for that employee.
        (B) If the initial biological monitoring results for CdU, CdB, or 
    2-M were in excess of the levels specified in paragraph 
    (l)(3)(i) of this section, but subsequent biological monitoring results 
    required by paragraph (l)(3)(ii)-(iv) of this section show that the 
    employee's CdU levels no longer exceed 3 g/g Cr, CdB levels no 
    longer exceed 5 g/lwb, and 2-M levels no longer 
    exceed 300 g/g Cr, the employer shall provide biological 
    monitoring for CdU, CdB, and 2-M one year after these 
    most recent biological monitoring results. If the results of the 
    followup biological monitoring, specified in this paragraph, confirm 
    the previous results, the employer may discontinue all periodic medical 
    surveillance for that employee.
        (C) However, if the results of the follow-up tests specified in 
    paragraph (l)(4)(v)(A) or (B) of this section indicate that the level 
    of the employee's CdU, 2-M, or CdB exceeds these same 
    levels, the employer is required to provide annual medical examinations 
    in accordance with the provisions of paragraph (l)(4)(ii) of this 
    section until the results of biological monitoring are consistently 
    below these levels or the examining physician determines in a written 
    medical opinion that further medical surveillance is not required to 
    protect the employee's health.
        (vi) A routine, biennial medical examination is not required to be 
    provided in accordance with paragraphs (l)(3)(i) and (l)(4) of this 
    section if adequate medical records show that the employee has been 
    examined in accordance with the requirements of paragraph (l)(4)(ii) of 
    this section within the past 12 months. In that case, such records 
    shall be maintained by the employer as part of the employee's medical 
    record, and the next routine, periodic medical examination shall be 
    made available to the employee within two years of the previous 
    examination.
        (5) Actions triggered by medical examinations. (i) If the results 
    of a medical examination carried out in accordance with this section 
    indicate any laboratory or clinical finding consistent with cadmium 
    toxicity that does not require employer action under paragraph (l)(2), 
    (3) or (4) of this section, the employer, within 30 days, shall 
    reassess the employee's occupational exposure to cadmium and take the 
    following corrective action until the physician determines they are no 
    longer necessary:
        (A) Periodically reassess: The employee's work practices and 
    personal hygiene; the employee's respirator use, if any; the employee's 
    smoking history and status; the respiratory protection program; the 
    hygiene facilities; and the maintenance and effectiveness of the 
    relevant engineering controls;
        (B) Within 30 days after the reassessment, take all reasonable 
    steps to correct the deficiencies found in the reassessment that may be 
    responsible for the employee's excess exposure to cadmium;
        (C) Provide semiannual medical reexaminations to evaluate the 
    abnormal clinical sign(s) of cadmium toxicity until the results are 
    normal or the employee is medically removed; and
        (D) Where the results of tests for total proteins in urine are 
    abnormal, provide a more detailed medical evaluation of the toxic 
    effects of cadmium on the employee's renal system.
        (6) Examination for respirator use. (i) To determine an employee's 
    fitness for respirator use, the employer shall provide a medical 
    examination that includes the elements specified in paragraph (l)(6)(i) 
    (A)-(D) of this section. This examination shall be provided prior to 
    the employee's being assigned to a job that requires the use of a 
    respirator or no later than 90 days after this section goes into 
    effect, whichever date is later, to any employee without a medical 
    examination within the preceding 12 months that satisfies the 
    requirements of this paragraph.
        (A) A detailed medical and work history, or update thereof, with 
    emphasis on: Past exposure to cadmium; smoking history and current 
    status; any history of renal, cardiovascular, respiratory, 
    hematopoietic, and/or musculoskeletal system dysfunction; a description 
    of the job for which the respirator is required; and questions 3-11 and 
    25-32 in appendix D to this section;
        (B) A blood pressure test;
        (C) Biological monitoring of the employee's levels of CdU, CdB and 
    2-M in accordance with the requirements of paragraph 
    (l)(2)(ii)(B) of this section, unless such results already have been 
    obtained within the previous 12 months; and
        (D) Any other test or procedure that the examining physician deems 
    appropriate.
        (ii) After reviewing all the information obtained from the medical 
    examination required in paragraph (l)(6)(i) of this section, the 
    physician shall determine whether the employee is fit to wear a 
    respirator.
        (iii) Whenever an employee has exhibited difficulty in breathing 
    during a respirator fit test or during use of a respirator, the 
    employer, as soon as possible, shall provide the employee with a 
    periodic medical examination in accordance with paragraph (l)(4)(ii) of 
    this section to determine the employee's fitness to wear a respirator.
        (iv) Where the results of the examination required under paragraph 
    (l)(6)(i), (ii), or (iii) of this section are abnormal, medical 
    limitation or prohibition of respirator use shall be considered. If the 
    employee is allowed to wear a respirator, the employee's ability to 
    continue to do so shall be periodically evaluated by a physician.
        (7) Emergency examinations. (i) In addition to the medical 
    surveillance required in paragraphs (l)(2)-(6) of this section, the 
    employer shall provide a medical examination as soon as possible to any 
    employee who may have been acutely exposed to cadmium because of an 
    emergency.
        (ii) The examination shall include the requirements of paragraph 
    (l)(4)(ii) of this section, with emphasis on the respiratory system, 
    other organ systems considered appropriate by the examining physician, 
    and symptoms of acute overexposure, as identified in paragraphs II 
    (B)(1)-(2) and IV of appendix A to this section.
        (8) Termination of employment examination. (i) At termination of 
    employment, the employer shall provide a medical examination in 
    accordance with paragraph (l)(4)(ii) of this section, including a chest 
    X-ray, to any employee to whom at any prior time the employer was 
    required to provide medical surveillance under paragraphs (l)(1)(i) or 
    (l)(7) of this section. However, if the last examination satisfied the 
    requirements of paragraph (l)(4)(ii) of this section and was less than 
    six months prior to the date of termination, no further examination is 
    required unless otherwise specified in paragraphs (l)(3) or (l)(5) of 
    this section;
        (ii) However, for employees covered by paragraph (l)(1)(i)(B) of 
    this section, if the employer has discontinued all periodic medical 
    surveillance under paragraph (l)(4)(v) of this section, no termination 
    of employment medical examination is required.
        (9) Information provided to the physician. The employer shall 
    provide the following information to the examining physician:
        (i) A copy of this standard and appendices;
        (ii) A description of the affected employee's former, current, and 
    anticipated duties as they relate to the employee's occupational 
    exposure to cadmium;
        (iii) The employee's former, current, and anticipated future levels 
    of occupational exposure to cadmium;
        (iv) A description of any personal protective equipment, including 
    respirators, used or to be used by the employee, including when and for 
    how long the employee has used that equipment; and
        (v) relevant results of previous biological monitoring and medical 
    examinations.
        (10) Physician's written medical opinion. (i) The employer shall 
    promptly obtain a written, signed medical opinion from the examining 
    physician for each medical examination performed on each employee. This 
    written opinion shall contain:
        (A) The physician's diagnosis for the employee;
        (B) The physician's opinion as to whether the employee has any 
    detected medical condition(s) that would place the employee at 
    increased risk of material impairment to health from further exposure 
    to cadmium, including any indications of potential cadmium toxicity;
        (C) The results of any biological or other testing or related 
    evaluations that directly assess the employee's absorption of cadmium;
        (D) Any recommended removal from, or limitation on the activities 
    or duties of the employee or on the employee's use of personal 
    protective equipment, such as respirators;
        (E) A statement that the physician has clearly and carefully 
    explained to the employee the results of the medical examination, 
    including all biological monitoring results and any medical conditions 
    related to cadmium exposure that require further evaluation or 
    treatment, and any limitation on the employee's diet or use of 
    medications.
        (ii) The employer promptly shall obtain a copy of the results of 
    any biological monitoring provided by an employer to an employee 
    independently of a medical examination under paragraphs (l)(2) and 
    (l)(4) of this section, and, in lieu of a written medical opinion, an 
    explanation sheet explaining those results.
        (iii) The employer shall instruct the physician not to reveal 
    orally or in the written medical opinion given to the employer specific 
    findings or diagnoses unrelated to occupational exposure to cadmium.
        (11) Medical Removal Protection (MRP)--(i) General. (A) The 
    employer shall temporarily remove an employee from work where there is 
    excess exposure to cadmium on each occasion that medical removal is 
    required under paragraph (l)(3), (l)(4), or (l)(6) of this section and 
    on each occasion that a physician determines in a written medical 
    opinion that the employee should be removed from such exposure. The 
    physician's determination may be based on biological monitoring 
    results, inability to wear a respirator, evidence of illness, other 
    signs or symptoms of cadmium-related dysfunction or disease, or any 
    other reason deemed medically sufficient by the physician.
        (B) The employer shall medically remove an employee in accordance 
    with paragraph (l)(11) of this section regardless of whether at the 
    time of removal a job is available into which the removed employee may 
    be transferred.
        (C) Whenever an employee is medically removed under paragraph 
    (l)(11) of this section, the employer shall transfer the removed 
    employee to a job where the exposure to cadmium is within the 
    permissible levels specified in that paragraph as soon as one becomes 
    available.
        (D) For any employee who is medically removed under the provisions 
    of paragraph (l)(11)(i) of this section, the employer shall provide 
    follow-up biological monitoring in accordance with (l)(2)(ii)(B) of 
    this section at least every three months and follow-up medical 
    examinations semi-annually at least every six months until in a written 
    medical opinion the examining physician determines that either the 
    employee may be returned to his/her former job status as specified 
    under paragraph (l)(11)(iv)-(v) of this section or the employee must be 
    permanently removed from excess cadmium exposure.
        (E) The employer may not return an employee who has been medically 
    removed for any reason to his/her former job status until a physician 
    determines in a written medical opinion that continued medical removal 
    is no longer necessary to protect the employee's health.
        (ii) Where an employee is found unfit to wear a respirator under 
    paragraph (l)(6)(ii) of this section, the employer shall remove the 
    employee from work where exposure to cadmium is above the PEL.
        (iii) Where removal is based on any reason other than the 
    employee's inability to wear a respirator, the employer shall remove 
    the employee from work where exposure to cadmium is at or above the 
    action level.
        (iv) Except as specified in paragraph (l)(11)(v) of this section, 
    no employee who was removed because his/her level of CdU, CdB and/or 
    2-M exceeded the medical removal trigger levels in 
    paragraph (l)(3) or (l)(4) of this section may be returned to work with 
    exposure to cadmium at or above the action level until the employee's 
    levels of CdU fall to or below 3 g/g Cr, CdB falls to or below 
    5 g/lwb, and 2-M falls to or below 300 
    g/g Cr.
        (v) However, when in the examining physician's opinion continued 
    exposure to cadmium will not pose an increased risk to the employee's 
    health and there are special circumstances that make continued medical 
    removal an inappropriate remedy, the physician shall fully discuss 
    these matters with the employee, and then in a written determination 
    may return a worker to his/her former job status despite what would 
    otherwise be unacceptably high biological monitoring results. 
    Thereafter, the returned employee shall continue to be provided with 
    medical surveillance as if he/she were still on medical removal until 
    the employee's levels of CdU fall to or below 3 g/g Cr, CdB 
    falls to or below 5 g/lwb, and 2-M falls to or 
    below 300 g/g Cr.
        (vi) Where an employer, although not required by paragraph 
    (l)(11)(i)-(iii) of this section to do so, removes an employee from 
    exposure to cadmium or otherwise places limitations on an employee due 
    to the effects of cadmium exposure on the employee's medical condition, 
    the employer shall provide the same medical removal protection benefits 
    to that employee under paragraph (l)(12) of this section as would have 
    been provided had the removal been required under paragraph (l)(11)(i)-
    (iii) of this section.
        (12) Medical Removal Protection Benefits (MRPB). (i) The employer 
    shall provide MRPB for up to a maximum of 18 months to an employee each 
    time and while the employee is temporarily medically removed under 
    paragraph (l)(11) of this section.
        (ii) For purposes of this section, the requirement that the 
    employer provide MRPB means that the employer shall maintain the total 
    normal earnings, seniority, and all other employee rights and benefits 
    of the removed employee, including the employee's right to his/her 
    former job status, as if the employee had not been removed from the 
    employee's job or otherwise medically limited.
        (iii) Where, after 18 months on medical removal because of elevated 
    biological monitoring results, the employee's monitoring results have 
    not declined to a low enough level to permit the employee to be 
    returned to his/her former job status:
        (A) The employer shall make available to the employee a medical 
    examination pursuant to this section in order to obtain a final medical 
    determination as to whether the employee may be returned to his/her 
    former job status or must be permanently removed from excess cadmium 
    exposure; and
        (B) The employer shall assure that the final medical determination 
    indicates whether the employee may be returned to his/her former job 
    status and what steps, if any, should be taken to protect the 
    employee's health.
        (iv) The employer may condition the provision of MRPB upon the 
    employee's participation in medical surveillance provided in accordance 
    with this section.
        (13) Multiple physician review. (i) If the employer selects the 
    initial physician to conduct any medical examination or consultation 
    provided to an employee under this section, the employee may designate 
    a second physician to:
        (A) Review any findings, determinations, or recommendations of the 
    initial physician; and
        (B) Conduct such examinations, consultations, and laboratory tests 
    as the second physician deems necessary to facilitate this review.
        (ii) The employer shall promptly notify an employee of the right to 
    seek a second medical opinion after each occasion that an initial 
    physician provided by the employer conducts a medical examination or 
    consultation pursuant to this section. The employer may condition its 
    participation in, and payment for, multiple physician review upon the 
    employee doing the following within fifteen (15) days after receipt of 
    this notice, or receipt of the initial physician's written opinion, 
    whichever is later:
        (A) Informing the employer that he or she intends to seek a medical 
    opinion; and
        (B) Initiating steps to make an appointment with a second 
    physician.
        (iii) If the findings, determinations, or recommendations of the 
    second physician differ from those of the initial physician, then the 
    employer and the employee shall assure that efforts are made for the 
    two physicians to resolve any disagreement.
        (iv) If the two physicians have been unable to quickly resolve 
    their disagreement, then the employer and the employee, through their 
    respective physicians, shall designate a third physician to:
        (A) Review any findings, determinations, or recommendations of the 
    other two physicians; and
        (B) Conduct such examinations, consultations, laboratory tests, and 
    discussions with the other two physicians as the third physician deems 
    necessary to resolve the disagreement among them.
        (v) The employer shall act consistently with the findings, 
    determinations, and recommendations of the third physician, unless the 
    employer and the employee reach an agreement that is consistent with 
    the recommendations of at least one of the other two physicians.
        (14) Alternate physician determination. The employer and an 
    employee or designated employee representative may agree upon the use 
    of any alternate form of physician determination in lieu of the 
    multiple physician review provided by paragraph (l)(13) of this 
    section, so long as the alternative is expeditious and at least as 
    protective of the employee.
        (15) Information the employer must provide the employee. (i) The 
    employer shall provide a copy of the physician's written medical 
    opinion to the examined employee within two weeks after receipt 
    thereof.
        (ii) The employer shall provide the employee with a copy of the 
    employee's biological monitoring results and an explanation sheet 
    explaining the results within two weeks after receipt thereof.
        (iii) Within 30 days after a request by an employee, the employer 
    shall provide the employee with the information the employer is 
    required to provide the examining physician under paragraph (l)(9) of 
    this section.
        (16) Reporting. In addition to other medical events that are 
    required to be reported on the OSHA Form No. 200, the employer shall 
    report any abnormal condition or disorder caused by occupational 
    exposure to cadmium associated with employment as specified in Chapter 
    (V)(E) of the Reporting Guidelines for Occupational Injuries and 
    Illnesses.
        (m) Communication of cadmium hazards to employees--(1) General. In 
    communications concerning cadmium hazards, employers shall comply with 
    the requirements of OSHA's Hazard Communication Standard, 29 CFR 
    1910.1200, including but not limited to the requirements concerning 
    warning signs and labels, material safety data sheets (MSDS), and 
    employee information and training. In addition, employers shall comply 
    with the following requirements:
        (2) Warning signs. (i) Warning signs shall be provided and 
    displayed in regulated areas. In addition, warning signs shall be 
    posted at all approaches to regulated areas so that an employee may 
    read the signs and take necessary protective steps before entering the 
    area.
        (ii) Warning signs required by paragraph (m)(2)(i) of this section 
    shall bear the following information:
    
    DANGER
    CADMIUM
    CANCER HAZARD
    CAN CAUSE LUNG AND KIDNEY DISEASE
    AUTHORIZED PERSONNEL ONLY
    RESPIRATORS REQUIRED IN THIS AREA
    
        (iii) The employer shall assure that signs required by this 
    paragraph are illuminated, cleaned, and maintained as necessary so that 
    the legend is readily visible.
        (3) Warning labels. (i) Shipping and storage containers containing 
    cadmium, cadmium compounds, or cadmium contaminated clothing, 
    equipment, waste, scrap, or debris shall bear appropriate warning 
    labels, as specified in paragraph (m)(3)(ii) of this section.
        (ii) The warning labels shall include at least the following 
    information:
    
    DANGER
    CONTAINS CADMIUM
    CANCER HAZARD
    AVOID CREATING DUST
    CAN CAUSE LUNG AND KIDNEY DISEASE
    
        (iii) Where feasible, installed cadmium products shall have a 
    visible label or other indication that cadmium is present.
        (4) Employee information and training. (i) The employer shall 
    institute a training program for all employees who are potentially 
    exposed to cadmium, assure employee participation in the program, and 
    maintain a record of the contents of such program.
        (ii) Training shall be provided prior to or at the time of initial 
    assignment to a job involving potential exposure to cadmium and at 
    least annually thereafter.
        (iii) The employer shall make the training program understandable 
    to the employee and shall assure that each employee is informed of the 
    following:
        (A) The health hazards associated with cadmium exposure, with 
    special attention to the information incorporated in appendix A to this 
    section;
        (B) The quantity, location, manner of use, release, and storage of 
    cadmium in the workplace and the specific nature of operations that 
    could result in exposure to cadmium, especially exposures above the 
    PEL;
        (C) The engineering controls and work practices associated with the 
    employee's job assignment;
        (D) The measures employees can take to protect themselves from 
    exposure to cadmium, including modification of such habits as smoking 
    and personal hygiene, and specific procedures the employer has 
    implemented to protect employees from exposure to cadmium such as 
    appropriate work practices, emergency procedures, and the provision of 
    personal protective equipment;
        (E) The purpose, proper selection, fitting, proper use, and 
    limitations of respirators and protective clothing;
        (F) The purpose and a description of the medical surveillance 
    program required by paragraph (l) of this section;
        (G) The contents of this section and its appendices; and
        (H) The employee's rights of access to records under Sec. 1915.1120 
    (e) and (g).
        (iv) Additional access to information and training program and 
    materials.
        (A) The employer shall make a copy of this section and its 
    appendices readily available without cost to all affected employees and 
    shall provide a copy if requested.
        (B) The employer shall provide to the Assistant Secretary or the 
    Director, upon request, all materials relating to the employee 
    information and the training program.
        (n) Recordkeeping--(1) Exposure monitoring. (i) The employer shall 
    establish and keep an accurate record of all air monitoring for cadmium 
    in the workplace.
        (ii) This record shall include at least the following information:
        (A) The monitoring date, duration, and results in terms of an 8-
    hour TWA of each sample taken;
        (B) The name, social security number, and job classification of the 
    employees monitored and of all other employees whose exposures the 
    monitoring is intended to represent;
        (C) A description of the sampling and analytical methods used and 
    evidence of their accuracy;
        (D) The type of respiratory protective device, if any, worn by the 
    monitored employee;
        (E) A notation of any other conditions that might have affected the 
    monitoring results.
        (iii) The employer shall maintain this record for at least thirty 
    (30) years, in accordance with Sec. 1915.1120 of this part.
        (2) Objective data for exemption from requirement for initial 
    monitoring. (i) For purposes of this section, objective data are 
    information demonstrating that a particular product or material 
    containing cadmium or a specific process, operation, or activity 
    involving cadmium cannot release dust or fumes in concentrations at or 
    above the action level even under the worst-case release conditions. 
    Objective data can be obtained from an industry-wide study or from 
    laboratory product test results from manufacturers of cadmium-
    containing products or materials. The data the employer uses from an 
    industry-wide survey must be obtained under workplace conditions 
    closely resembling the processes, types of material, control methods, 
    work practices and environmental conditions in the employer's current 
    operations.
        (ii) The employer shall establish and maintain a record of the 
    objective data for at least 30 years.
        (3) Medical surveillance. (i) The employer shall establish and 
    maintain an accurate record for each employee covered by medical 
    surveillance under paragraph (l)(1)(i) of this section.
        (ii) The record shall include at least the following information 
    about the employee:
        (A) Name, social security number, and description of the duties;
        (B) A copy of the physician's written opinions and an explanation 
    sheet for biological monitoring results;
        (C) A copy of the medical history, and the results of any physical 
    examination and all test results that are required to be provided by 
    this section, including biological tests, X-rays, pulmonary function 
    tests, etc., or that have been obtained to further evaluate any 
    condition that might be related to cadmium exposure;
        (D) The employee's medical symptoms that might be related to 
    exposure to cadmium; and
        (E) A copy of the information provided to the physician as required 
    by paragraph (l)(9)(ii)-(v) of this section.
        (iii) The employer shall assure that this record is maintained for 
    the duration of employment plus thirty (30) years, in accordance with 
    Sec. 1915.1120 of this part.
        (4) Training. The employer shall certify that employees have been 
    trained by preparing a certification record which includes the identity 
    of the person trained, the signature of the employer or the person who 
    conducted the training, and the date the training was completed. The 
    certification records shall be prepared at the completion of training 
    and shall be maintained on file for one (1) year beyond the date of 
    training of that employee.
        (5) Availability. (i) Except as otherwise provided for in this 
    section, access to all records required to be maintained by paragraphs 
    (n)(1)-(4) of this section shall be in accordance with the provisions 
    of Sec. 1915.1120 of this part.
        (ii) Within 15 days after a request, the employer shall make an 
    employee's medical records required to be kept by paragraph (n)(3) of 
    this section available for examination and copying to the subject 
    employee, to designated representatives, to anyone having the specific 
    written consent of the subject employee, and after the employee's death 
    or incapacitation, to the employee's family members.
        (6) Transfer of records. Whenever an employer ceases to do business 
    and there is no successor employer to receive and retain records for 
    the prescribed period or the employer intends to dispose of any records 
    required to be preserved for at least 30 years, the employer shall 
    comply with the requirements concerning transfer of records set forth 
    in Sec. 1915.1120(h) of this part.
        (o) Observation of monitoring--(1) Employee observation. The 
    employer shall provide affected employees or their designated 
    representatives an opportunity to observe any monitoring of employee 
    exposure to cadmium.
        (2) Observation procedures. When observation of monitoring requires 
    entry into an area where the use of protective clothing or equipment is 
    required, the employer shall provide the observer with that clothing 
    and equipment and shall assure that the observer uses such clothing and 
    equipment and complies with all other applicable safety and health 
    procedures.
        (p) Dates--(1) Effective date. This section shall become effective 
    December 14, 1992.
        (2) Start-up dates. All obligations of this section commence on the 
    effective date except as follows:
        (i) Exposure monitoring. Except for small businesses (nineteen (19) 
    or fewer employees), initial monitoring required by paragraph (d)(2) of 
    this section shall be completed as soon as possible and in any event no 
    later than February 12, 1993. For small businesses, initial monitoring 
    required by paragraph (d)(2) of this section shall be completed as soon 
    as possible and in any event no later than April 14, 1993.
        (ii) Regulated areas. Except for small business, defined under 
    paragraph (p)(2)(i) of this section, regulated areas required to be 
    established by paragraph (e) of this section shall be set up as soon as 
    possible after the results of exposure monitoring are known and in any 
    event no later than March 15, 1993. For small businesses, regulated 
    areas required to be established by paragraph (e) of this section shall 
    be set up as soon as possible after the results of exposure monitoring 
    are known and in any event no later than May 14, 1993.
        (iii) Respiratory protection. Except for small businesses, defined 
    under paragraph (p)(2)(i) of this section, respiratory protection 
    required by paragraph (g) of this section shall be provided as soon as 
    possible and in any event no later than 90 days after the effective 
    date of this section. For small businesses, respiratory protection 
    required by paragraph (g) of this section shall be provided as soon as 
    possible and in any event no later than March 15, 1993.
        (iv) Compliance program. Written compliance programs required by 
    paragraph (f)(2) of this section shall be completed and available for 
    inspection and copying as soon as possible and in any event no later 
    than December 14, 1993.
        (v) Methods of compliance. The engineering controls required by 
    paragraph (f)(1) of this section shall be implemented as soon as 
    possible and in any event no later than December 14, 1994. Work 
    practice controls shall be implemented as soon as possible. Work 
    practice controls that are directly related to engineering controls to 
    be implemented in accordance with the compliance plan shall be 
    implemented as soon as possible after such engineering controls are 
    implemented.
        (vi) Hygiene and lunchroom facilities. (A) Handwashing facilities, 
    permanent or temporary, shall be provided in accordance with 29 CFR 
    1910.141 (d)(1) and (2) as soon as possible and in any event no later 
    than February 12, 1993.
        (B) Change rooms, showers, and lunchroom facilities shall be 
    completed as soon as possible and in any event no later than December 
    14, 1993.
        (vii) Employee information and training. Except for small 
    businesses, defined under paragraph (p)(2)(i) of this section, employee 
    information and training required by paragraph (m)(4) of this section 
    shall be provided as soon as possible and in any event no later than 
    March 15, 1993. For small businesses, employee information and training 
    required by paragraph (m)(4) of this standard shall be provided as soon 
    as possible and in any event no later than June 14, 1993.
        (viii) Medical surveillance. Except for small businesses, defined 
    under paragraph (p)(2)(i) of this section, initial medical examinations 
    required by paragraph (l) of this section shall be provided as soon as 
    possible and in any event no later than March 15, 1993. For small 
    businesses, initial medical examinations required by paragraph (l) of 
    this section shall be provided as soon as possible and in any event no 
    later than June 14, 1993.
        (q) Appendices. (1) Appendix C to this section is incorporated as 
    part of this section, and compliance with its contents is mandatory.
        (2) Except where portions of appendices A, B, D, E, and F to this 
    section are expressly incorporated in requirements of this section, 
    these appendices are purely informational and are not intended to 
    create any additional obligations not otherwise imposed or to detract 
    from any existing obligations.
    
    Appendix A to Sec. 1915.1027--Substance Safety Data Sheet
    
    Cadmium
    
    I. Substance Identification
    
        A. Substance: Cadmium.
        B. 8-Hour, Time-weighted-average, Permissible Exposure Limit 
    (TWA PEL):
        1. TWA PEL: Five micrograms of cadmium per cubic meter of air 5 
    g/m3, time-weighted average (TWA) for an 8-hour 
    workday.
        C. Appearance: Cadmium metal--soft, blue-white, malleable, 
    lustrous metal or grayish-white powder. Some cadmium compounds may 
    also appear as a brown, yellow, or red powdery substance.
    
    II. Health Hazard Data
    
        A. Routes of Exposure. Cadmium can cause local skin or eye 
    irritation. Cadmium can affect your health if you inhale it or if 
    you swallow it.
        B. Effects of Overexposure.
        1. Short-term (acute) exposure: Cadmium is much more dangerous 
    by inhalation than by ingestion. High exposures to cadmium that may 
    be immediately dangerous to life or health occur in jobs where 
    workers handle large quantities of cadmium dust or fume; heat 
    cadmium-containing compounds or cadmium-coated surfaces; weld with 
    cadmium solders or cut cadmium-containing materials such as bolts.
        2. Severe exposure may occur before symptoms appear. Early 
    symptoms may include mild irritation of the upper respiratory tract, 
    a sensation of constriction of the throat, a metallic taste and/or a 
    cough. A period of 1-10 hours may precede the onset of rapidly 
    progressing shortness of breath, chest pain, and flu-like symptoms 
    with weakness, fever, headache, chills, sweating and muscular pain. 
    Acute pulmonary edema usually develops within 24 hours and reaches a 
    maximum by three days. If death from asphyxia does not occur, 
    symptoms may resolve within a week.
        3. Long-term (chronic) exposure. Repeated or long-term exposure 
    to cadmium, even at relatively low concentrations, may result in 
    kidney damage and an increased risk of cancer of the lung and of the 
    prostate.
        C. Emergency First Aid Procedures.
        1. Eye exposure: Direct contact may cause redness or pain. Wash 
    eyes immediately with large amounts of water, lifting the upper and 
    lower eyelids. Get medical attention immediately.
        2. Skin exposure: Direct contact may result in irritation. 
    Remove contaminated clothing and shoes immediately. Wash affected 
    area with soap or mild detergent and large amounts of water. Get 
    medical attention immediately.
        3. Ingestion: Ingestion may result in vomiting, abdominal pain, 
    nausea, diarrhea, headache and sore throat. Treatment for symptoms 
    must be administered by medical personnel. Under no circumstances 
    should the employer allow any person whom he retains, employs, 
    supervises or controls to engage in therapeutic chelation. Such 
    treatment is likely to translocate cadmium from pulmonary or other 
    tissue to renal tissue. Get medical attention immediately.
        4. Inhalation: If large amounts of cadmium are inhaled, the 
    exposed person must be moved to fresh air at once. If breathing has 
    stopped, perform cardiopulmonary resuscitation. Administer oxygen if 
    available. Keep the affected person warm and at rest. Get medical 
    attention immediately.
        5. Rescue: Move the affected person from the hazardous exposure. 
    If the exposed person has been overcome, attempt rescue only after 
    notifying at least one other person of the emergency and putting 
    into effect established emergency procedures. Do not become a 
    casualty yourself. Understand your emergency rescue procedures and 
    know the location of the emergency equipment before the need arises.
    
    III. Employee Information
    
        A. Protective Clothing and Equipment.
        1. Respirators: You may be required to wear a respirator for 
    non-routine activities; in emergencies; while your employer is in 
    the process of reducing cadmium exposures through engineering 
    controls; and where engineering controls are not feasible. If 
    respirators are worn in the future, they must have a joint Mine 
    Safety and Health Administration (MSHA) and National Institute for 
    Occupational Safety and Health (NIOSH) label of approval. Cadmium 
    does not have a detectable odor except at levels well above the 
    permissible exposure limits. If you can smell cadmium while wearing 
    a respirator, proceed immediately to fresh air. If you experience 
    difficulty breathing while wearing a respirator, tell your employer.
        2. Protective Clothing: You may be required to wear impermeable 
    clothing, gloves, foot gear, a face shield, or other appropriate 
    protective clothing to prevent skin contact with cadmium. Where 
    protective clothing is required, your employer must provide clean 
    garments to you as necessary to assure that the clothing protects 
    you adequately. The employer must replace or repair protective 
    clothing that has become torn or otherwise damaged.
        3. Eye Protection: You may be required to wear splash-proof or 
    dust resistant goggles to prevent eye contact with cadmium.
        B. Employer Requirements.
        1. Medical: If you are exposed to cadmium at or above the action 
    level, your employer is required to provide a medical examination, 
    laboratory tests and a medical history according to the medical 
    surveillance provisions under paragraph (1) of this standard. (See 
    summary chart and tables in this appendix A.) These tests shall be 
    provided without cost to you. In addition, if you are accidentally 
    exposed to cadmium under conditions known or suspected to constitute 
    toxic exposure to cadmium, your employer is required to make special 
    tests available to you.
        2. Access to Records: All medical records are kept strictly 
    confidential. You or your representative are entitled to see the 
    records of measurements of your exposure to cadmium. Your medical 
    examination records can be furnished to your personal physician or 
    designated representative upon request by you to your employer.
        3. Observation of Monitoring: Your employer is required to 
    perform measurements that are representative of your exposure to 
    cadmium and you or your designated representative are entitled to 
    observe the monitoring procedure. You are entitled to observe the 
    steps taken in the measurement procedure, and to record the results 
    obtained. When the monitoring procedure is taking place in an area 
    where respirators or personal protective clothing and equipment are 
    required to be worn, you or your representative must also be 
    provided with, and must wear the protective clothing and equipment.
        C. Employee Requirements.--You will not be able to smoke, eat, 
    drink, chew gum or tobacco, or apply cosmetics while working with 
    cadmium in regulated areas. You will also not be able to carry or 
    store tobacco products, gum, food, drinks or cosmetics in regulated 
    areas because these products easily become contaminated with cadmium 
    from the workplace and can therefore create another source of 
    unnecessary cadmium exposure.
        Some workers will have to change out of work clothes and shower 
    at the end of the day, as part of their workday, in order to wash 
    cadmium from skin and hair. Handwashing and cadmium-free eating 
    facilities shall be provided by the employer and proper hygiene 
    should always be performed before eating. It is also recommended 
    that you do not smoke or use tobacco products, because among other 
    things, they naturally contain cadmium. For further information, 
    read the labeling on such products.
    
    IV. Physician Information
    
        A. Introduction.--The medical surveillance provisions of 
    paragraph (1) generally are aimed at accomplishing three main 
    interrelated purposes: First, identifying employees at higher risk 
    of adverse health effects from excess, chronic exposure to cadmium; 
    second, preventing cadmium-induced disease; and third, detecting and 
    minimizing existing cadmium-induced disease. The core of medical 
    surveillance in this standard is the early and periodic monitoring 
    of the employee's biological indicators of: (a) Recent exposure to 
    cadmium; (b) cadmium body burden; and (c) potential and actual 
    kidney damage associated with exposure to cadmium.
        The main adverse health effects associated with cadmium 
    overexposure are lung cancer and kidney dysfunction. It is not yet 
    known how to adequately biologically monitor human beings to 
    specifically prevent cadmium-induced lung cancer. By contrast, the 
    kidney can be monitored to provide prevention and early detection of 
    cadmium-induced kidney damage. Since, for non-carcinogenic effects, 
    the kidney is considered the primary target organ of chronic 
    exposure to cadmium, the medical surveillance provisions of this 
    standard effectively focus on cadmium-induced kidney disease. Within 
    that focus, the aim, where possible, is to prevent the onset of such 
    disease and, where necessary, to minimize such disease as may 
    already exist. The by-products of successful prevention of kidney 
    disease are anticipated to be the reduction and prevention of other 
    cadmium-induced diseases.
        B. Health Effects.--The major health effects associated with 
    cadmium overexposure are described below.
        1. Kidney: The most prevalent non-malignant disease observed 
    among workers chronically exposed to cadmium is kidney dysfunction. 
    Initially, such dysfunction is manifested as proteinuria. The 
    proteinuria associated with cadmium exposure is most commonly 
    characterized by excretion of low-molecular weight proteins (15,000 
    to 40,000 MW) accompanied by loss of electrolytes, uric acid, 
    calcium, amino acids, and phosphate. The compounds commonly excreted 
    include: beta-2-microglobulin (2-M), retinol binding 
    protein (RBP), immunoglobulin light chains, and lysozyme. Excretion 
    of low molecular weight proteins are characteristic of damage to the 
    proximal tubules of the kidney (Iwao et al., 1980).
        It has also been observed that exposure to cadmium may lead to 
    urinary excretion of high-molecular weight proteins such as albumin, 
    immunoglobulin G, and glycoproteins (Ex. 29). Excretion of high-
    molecular weight proteins is typically indicative of damage to the 
    glomeruli of the kidney. Bernard et al., (1979) suggest that damage 
    to the glomeruli and damage to the proximal tubules of the kidney 
    may both be linked to cadmium exposure but they may occur 
    independently of each other.
        Several studies indicate that the onset of low-molecular weight 
    proteinuria is a sign of irreversible kidney damage (Friberg et al., 
    1974; Roels et al., 1982; Piscator 1984; Elinder et al., 1985; Smith 
    et al., 1986). Above specific levels of 2-M associated 
    with cadmium exposure it is unlikely that 2-M levels 
    return to normal even when cadmium exposure is eliminated by removal 
    of the individual from the cadmium work environment (Friberg, Ex. 
    29, 1990).
        Some studies indicate that such proteinuria may be progressive; 
    levels of 2-M observed in the urine increase with time 
    even after cadmium exposure has ceased. See, for example, Elinder et 
    al., 1985. Such observations, however, are not universal, and it has 
    been suggested that studies in which proteinuria has not been 
    observed to progress may not have tracked patients for a 
    sufficiently long time interval (Jarup, Ex. 8-661).
        When cadmium exposure continues after the onset of proteinuria, 
    chronic nephrotoxicity may occur (Friberg, Ex. 29). Uremia results 
    from the inability of the glomerulus to adequately filter blood. 
    This leads to severe disturbance of electrolyte concentrations and 
    may lead to various clinical complications including kidney stones 
    (L-140-50).
        After prolonged exposure to cadmium, glomerular proteinuria, 
    glucosuria, aminoaciduria, phosphaturia, and hypercalciuria may 
    develop (Exs. 8-86, 4-28, 14-18). Phosphate, calcium, glucose, and 
    amino acids are essential to life, and under normal conditions, 
    their excretion should be regulated by the kidney. Once low 
    molecular weight proteinuria has developed, these elements dissipate 
    from the human body. Loss of glomerular function may also occur, 
    manifested by decreased glomerular filtration rate and increased 
    serum creatinine. Severe cadmium-induced renal damage may eventually 
    develop into chronic renal failure and uremia (Ex. 55).
        Studies in which animals are chronically exposed to cadmium 
    confirm the renal effects observed in humans (Friberg et al., 1986). 
    Animal studies also confirm problems with calcium metabolism and 
    related skeletal effects which have been observed among humans 
    exposed to cadmium in addition to the renal effects. Other effects 
    commonly reported in chronic animal studies include anemia, changes 
    in liver morphology, immunosuppression and hypertension. Some of 
    these effects may be associated with co-factors. Hypertension, for 
    example, appears to be associated with diet as well as cadmium 
    exposure. Animals injected with cadmium have also shown testicular 
    necrosis (Ex. 8-86B).
    
    2. Biological Markers
    
        It is universally recognized that the best measures of cadmium 
    exposures and its effects are measurements of cadmium in biological 
    fluids, especially urine and blood. Of the two, CdU is 
    conventionally used to determine body burden of cadmium in workers 
    without kidney disease. CdB is conventionally used to monitor for 
    recent exposure to cadmium. In addition, levels of CdU and CdB 
    historically have been used to predict the percent of the population 
    likely to develop kidney disease (Thun et al., Ex. L-140-50; WHO, 
    Ex. 8-674; ACGIH, Exs. 8-667, 140-50).
        The third biological parameter upon which OSHA relies for 
    medical surveillance is Beta-2-microglobulin in urine 
    (2-M), a low molecular weight protein. Excess 
    2-M has been widely accepted by physicians and 
    scientists as a reliable indicator of functional damage to the 
    proximal tubule of the kidney (Exs. 8-447, 144-3-C, 4-47, L-140-45, 
    19-43-A).
        Excess 2-M is found when the proximal tubules can 
    no longer reabsorb this protein in a normal manner. This failure of 
    the proximal tubules is an early stage of a kind of kidney disease 
    that commonly occurs among workers with excessive cadmium exposure. 
    Used in conjunction with biological test results indicating abnormal 
    levels of CdU and CdB, the finding of excess 2-M can 
    establish for an examining physician that any existing kidney 
    disease is probably cadmium-related (Trs. 6/6/90, pp. 82-86, 122, 
    134). The upper limits of normal levels for cadmium in urine and 
    cadmium in blood are 3 g Cd/gram creatinine in urine and 5 
    gCd/liter whole blood, respectively. These levels were 
    derived from broad-based population studies.
        Three issues confront the physicians in the use of 
    2-M as a marker of kidney dysfunction and material 
    impairment. First, there are a few other causes of elevated levels 
    of 2-M not related to cadmium exposures, some of which 
    may be rather common diseases and some of which are serious diseases 
    (e.g., myeloma or transient flu, Exs. 29 and 8-086). These can be 
    medically evaluated as alternative causes (Friberg, Ex. 29). Also, 
    there are other factors that can cause 2-M to degrade 
    so that low levels would result in workers with tubular dysfunction. 
    For example, regarding the degradation of 2-M, workers 
    with acidic urine (pH<6) might="" have="">2-M levels that 
    are within the ``normal'' range when in fact kidney dysfunction has 
    occurred (Ex. L-140-1) and the low molecular weight proteins are 
    degraded in acid urine. Thus, it is very important that the pH of 
    urine be measured, that urine samples be buffered as necessary (See 
    appendix F.), and that urine samples be handled correctly, i.e., 
    measure the pH of freshly voided urine samples, then if necessary, 
    buffer to pH>6 (or above for shipping purposes), measure pH again 
    and then, perhaps, freeze the sample for storage and shipping. (See 
    also appendix F.) Second, there is debate over the pathological 
    significance of proteinuria, however, most world experts believe 
    that 2-M levels greater than 300 g/g Cr are 
    abnormal (Elinder, Ex. 55, Friberg, Ex. 29). Such levels signify 
    kidney dysfunction that constitutes material impairment of health. 
    Finally, detection of 2-M at low levels has often been 
    considered difficult, however, many laboratories have the capability 
    of detecting excess 2-M using simple kits, such as the 
    Phadebas Delphia test, that are accurate to levels of 100 g 
    2-M/g Cr U (Ex. L-140-1).
        Specific recommendations for ways to measure 2-M 
    and proper handling of urine samples to prevent degradation of 
    2-M have been addressed by OSHA in appendix F, in the 
    section on laboratory standardization. All biological samples must 
    be analyzed in a laboratory that is proficient in the analysis of 
    that particular analyte, under paragraph (l)(1)(iv). (See appendix 
    F). Specifically, under paragraph (l)(1)(iv), the employer is to 
    assure that the collecting and handling of biological samples of 
    cadmium in urine (CdU), cadmium in blood (CdB), and beta-2 
    microglobulin in urine (2-M) taken from employees is 
    collected in a manner that assures reliability. The employer must 
    also assure that analysis of biological samples of cadmium in urine 
    (CdU), cadmium in blood (CdB), and beta-2 microglobulin in urine 
    (2-M) taken from employees is performed in 
    laboratories with demonstrated proficiency for that particular 
    analyte. (See appendix F.)
    
    3. Lung and Prostate Cancer
    
        The primary sites for cadmium-associated cancer appear to be the 
    lung and the prostate (L-140-50). Evidence for an association 
    between cancer and cadmium exposure derives from both 
    epidemiological studies and animal experiments. Mortality from 
    prostate cancer associated with cadmium is slightly elevated in 
    several industrial cohorts, but the number of cases is small and 
    there is not clear dose-response relationship. More substantive 
    evidence exists for lung cancer.
        The major epidemiological study of lung cancer was conducted by 
    Thun et al., (Ex. 4-68). Adequate data on cadmium exposures were 
    available to allow evaluation of dose-response relationships between 
    cadmium exposure and lung cancer. A statistically significant excess 
    of lung cancer attributed to cadmium exposure was observed in this 
    study even when confounding variables such as co-exposure to arsenic 
    and smoking habits were taken into consideration (Ex. L-140-50).
        The primary evidence for quantifying a link between lung cancer 
    and cadmium exposure from animal studies derives from two rat 
    bioassay studies; one by Takenaka et al., (1983), which is a study 
    of cadmium chloride and a second study by Oldiges and Glaser (1990) 
    of four cadmium compounds.
        Based on the above cited studies, the U.S. Environmental 
    Protection Agency (EPA) classified cadmium as ``B1'', a probable 
    human carcinogen, in 1985 (Ex. 4-4). The International Agency for 
    Research on Cancer (IARC) in 1987 also recommended that cadmium be 
    listed as ``2A'', a probable human carcinogen (Ex. 4-15). The 
    American Conference of Governmental Industrial Hygienists (ACGIH) 
    has recently recommended that cadmium be labeled as a carcinogen. 
    Since 1984, NIOSH has concluded that cadmium is possibly a human 
    carcinogen and has recommended that exposures be controlled to the 
    lowest level feasible.
    
    4. Non-carcinogenic Effects
    
        Acute pneumonitis occurs 10 to 24 hours after initial acute 
    inhalation of high levels of cadmium fumes with symptoms such as 
    fever and chest pain (Exs. 30, 8-86B). In extreme exposure cases 
    pulmonary edema may develop and cause death several days after 
    exposure. Little actual exposure measurement data is available on 
    the level of airborne cadmium exposure that causes such immediate 
    adverse lung effects, nonetheless, it is reasonable to believe a 
    cadmium concentration of approximately 1 mg/m3 over an eight 
    hour period is ``immediately dangerous'' (55 FR 4052, ANSI; Ex. 8-
    86B).
        In addition to acute lung effects and chronic renal effects, 
    long term exposure to cadmium may cause other severe effects on the 
    respiratory system. Reduced pulmonary function and chronic lung 
    disease indicative of emphysema have been observed in workers who 
    have had prolonged exposure to cadmium dust or fumes (Exs. 4-29, 4-
    22, 4-42, 4-50, 4-63). In a study of workers conducted by Kazantzis 
    et al., a statistically significant excess of worker deaths due to 
    chronic bronchitis was found, which in his opinion was directly 
    related to high cadmium exposures of 1 mg/m3 or more (Tr. 6/8/
    90, pp. 156-157).
        Cadmium need not be respirable to constitute a hazard. 
    Inspirable cadmium particles that are too large to be respirable but 
    small enough to enter the tracheobronchial region of the lung can 
    lead to bronchoconstriction, chronic pulmonary disease, and cancer 
    of that portion of the lung. All of these diseases have been 
    associated with occupational exposure to cadmium (Ex. 8-86B). 
    Particles that are constrained by their size to the extra-thoracic 
    regions of the respiratory system such as the nose and maxillary 
    sinuses can be swallowed through mucocillary clearance and be 
    absorbed into the body (ACGIH, Ex. 8-692). The impaction of these 
    particles in the upper airways can lead to anosmia, or loss of sense 
    of smell, which is an early indication of overexposure among workers 
    exposed to heavy metals. This condition is commonly reported among 
    cadmium-exposed workers (Ex. 8-86-B).
    
    C. Medical Surveillance
    
        In general, the main provisions of the medical surveillance 
    section of the standard, under paragraphs (l)(1)-(17) of the 
    regulatory text, are as follows:
        1. Workers exposed above the action level are covered;
        2. Workers with intermittent exposures are not covered;
        3. Past workers who are covered receive biological monitoring 
    for at least one year;
        4. Initial examinations include a medical questionnaire and 
    biological monitoring of cadmium in blood (CdB), cadmium in urine 
    (CdU), and Beta-2-microglobulin in urine (2-M);
        5. Biological monitoring of these three analytes is performed at 
    least annually; full medical examinations are performed biennially;
        6. Until five years from the effective date of the standard, 
    medical removal is required when CdU is greater than 15 g/
    gram creatinine (g Cr), or CdB is greater than 15 g/liter 
    whole blood (lwb), or 2-M is greater than 1500 
    g/g Cr, and CdB is greater than 5 g/lwb or CdU is 
    greater than 3 g/g Cr;
        7. Beginning five years after the standard is in effect, medical 
    removal triggers will be reduced;
        8. Medical removal protection benefits are to be provided for up 
    to 18 months;
        9. Limited initial medical examinations are required for 
    respirator usage;
        10. Major provisions are fully described under section (l) of 
    the regulatory text; they are outlined here as follows:
        A. Eligibility
        B. Biological monitoring
        C. Actions triggered by levels of CdU, CdB, and 2-
    M (See Summary Charts and Tables in Attachment-1.)
        D. Periodic medical surveillance
        E. Actions triggered by periodic medical surveillance (See 
    appendix A Summary Chart and Tables in Attachment-1.)
        F. Respirator usage
        G. Emergency medical examinations
        H. Termination examination
        I. Information to physician
        J. Physician's medical opinion
        K. Medical removal protection
        L. Medical removal protection benefits
        M. Multiple physician review
        N. Alternate physician review
        O. Information employer gives to employee
        P. Recordkeeping
        Q. Reporting on OSHA form 200
        11. The above mentioned summary of the medical surveillance 
    provisions, the summary chart, and tables for the actions triggered 
    at different levels of CdU, CdB and 2-M (in appendix A 
    Attachment-1) are included only for the purpose of facilitating 
    understanding of the provisions of paragraphs (l)(3) of the final 
    cadmium standard. The summary of the provisions, the summary chart, 
    and the tables do not add to or reduce the requirements in paragraph 
    (l)(3).
    
    D. Recommendations to Physicians
    
        1. It is strongly recommended that patients with tubular 
    proteinuria are counseled on: The hazards of smoking; avoidance of 
    nephrotoxins and certain prescriptions and over-the-counter 
    medications that may exacerbate kidney symptoms; how to control 
    diabetes and/or blood pressure; proper hydration, diet, and exercise 
    (Ex. 19-2). A list of prominent or common nephrotoxins is attached. 
    (See appendix A Attachment-2.)
        2. DO NOT CHELATE; KNOW WHICH DRUGS ARE NEPHROTOXINS OR ARE 
    ASSOCIATED WITH NEPHRITIS.
        3. The gravity of cadmium-induced renal damage is compounded by 
    the fact there is no medical treatment to prevent or reduce the 
    accumulation of cadmium in the kidney (Ex. 8-619). Dr. Friberg, a 
    leading world expert on cadmium toxicity, indicated in 1992, that 
    there is no form of chelating agent that could be used without 
    substantial risk. He stated that tubular proteinuria has to be 
    treated in the same way as other kidney disorders (Ex. 29).
        4. After the results of a workers' biological monitoring or 
    medical examination are received the employer is required to provide 
    an information sheet to the patient, briefly explaining the 
    significance of the results. (See Attachment 3 of this appendix A.)
        5. For additional information the physician is referred to the 
    following additional resources:
        a. The physician can always obtain a copy of the preamble, with 
    its full discussion of the health effects, from OSHA's Computerized 
    Information System (OCIS).
        b. The Docket Officer maintains a record of the rulemaking. The 
    Cadmium Docket (H-057A), is located at 200 Constitution Ave. NW., 
    room N-2625, Washington, DC 20210; telephone: 202-219-7894.
        c. The following articles and exhibits in particular from that 
    docket (H-057A):
    
    ------------------------------------------------------------------------
     Exhibit No.                    Author and paper title                  
    ------------------------------------------------------------------------
    8-447.......  Lauwerys et. al., Guide for physicians, ``Health          
                   Maintenance of Workers Exposed to Cadmium,'' published by
                   the Cadmium Council.                                     
    4-67........  Takenaka, S., H. Oldiges, H. Konig, D. Hochrainer, G.     
                   Oberdorster. ``Carcinogenicity of Cadmium Chloride       
                   Aerosols in Wistar Rats''. JNCI 70:367-373, 1983. (32)   
    4-68........  Thun, M.J., T.M. Schnoor, A.B. Smith, W.E. Halperin, R.A. 
                   Lemen. ``Mortality Among a Cohort of U.S. Cadmium        
                   Production Workers--An Update.'' JNCI 74(2):325-33, 1985.
                   (8)                                                      
    4-25........  Elinder, C.G., Kjellstrom, T., Hogstedt, C., et al.,      
                   ``Cancer Mortality of Cadmium Workers.'' Brit. J. Ind.   
                   Med. 42:651-655, 1985. (14)                              
    4-26........  Ellis, K.J. et al., ``Critical Concentrations of Cadmium  
                   in Human Renal Cortex: Dose Effect Studies to Cadmium    
                   Smelter Workers.'' J. Toxicol. Environ. Health 7:691-703,
                   1981. (76)                                               
    4-27........  Ellis, K.J., S.H. Cohn and T.J. Smith. ``Cadmium          
                   Inhalation Exposure Estimates: Their Significance with   
                   Respect to Kidney and Liver Cadmium Burden.'' J. Toxicol.
                   Environ. Health 15:173-187, 1985.                        
    4-28........  Falck, F.Y., Jr., Fine, L.J., Smith, R.G., McClatchey,    
                   K.D., Annesley, T., England, B., and Schork, A.M.        
                   ``Occupational Cadmium Exposure and Renal Status.'' Am.  
                   J. Ind. Med. 4:541, 1983. (64)                           
    8-86A.......  Friberg, L., C.G. Elinder, et al., ``Cadmium and Health a 
                   Toxicological and Epidemiological Appraisal, Volume I,   
                   Exposure, Dose, and Metabolism.'' CRC Press, Inc., Boca  
                   Raton, FL, 1986. (Available from the OSHA Technical Data 
                   Center)                                                  
    8-86B.......  Friberg, L., C.G. Elinder, et al., ``Cadmium and Health: A
                   Toxicological and Epidemiological Appraisal, Volume II,  
                   Effects and Response.'' CRC Press, Inc., Boca Raton, FL, 
                   1986. (Available from the OSHA Technical Data Center)    
    L-140-45....  Elinder, C.G., ``Cancer Mortality of Cadmium Workers'',   
                   Brit. J. Ind. Med., 42, 651-655, 1985.                   
    L-140-50....  Thun, M., Elinder, C.G., Friberg, L, ``Scientific Basis   
                   for an Occupational Standard for Cadmium, Am. J. Ind.    
                   Med., 20; 629-642, 1991.                                 
    ------------------------------------------------------------------------
    
    V. Information Sheet
    
        The information sheet (appendix A Attachment-3.) or an equally 
    explanatory one should be provided to you after any biological 
    monitoring results are reviewed by the physician, or where 
    applicable, after any medical examination.
    
    Appendix A
    
    Attachment 1--Appendix A Summary Chart and Tables A and B of Actions 
    Triggered by Biological Monitoring
    
    Appendix A Summary Chart: Section (1)(3) Medical Surveillance
    
    Categorizing Biological Monitoring Results
    
        (A) Biological monitoring results categories are set forth in 
    Appendix A Table A for the periods ending December 31, 1998 and for 
    the period beginning January 1, 1999.
        (B) The results of the biological monitoring for the initial 
    medical exam and the subsequent exams shall determine an employee's 
    biological monitoring result category.
    
    Actions Triggered by Biological Monitoring
    
        (A)
        (i) The actions triggered by biological monitoring for an 
    employee are set forth in Appendix A Table B.
        (ii) The biological monitoring results for each employee under 
    section (1)(3) shall determine the actions required for that 
    employee. That is, for any employee in biological monitoring 
    category C, the employer will perform all of the actions for which 
    there is an X in column C of Appendix A Table B.
        (iii) An employee is assigned the alphabetical category (``A'' 
    being the lowest) depending upon the test results of the three 
    biological markers.
        (iv) An employee is assigned category A if monitoring results 
    for all three biological markers fall at or below the levels 
    indicated in the table listed for category A.
        (v) An employee is assigned category B if any monitoring result 
    for any of the three biological markers fall within the range of 
    levels indicated in the table listed for category B, providing no 
    result exceeds the levels listed for category B.
        (vi) An employee is assigned category C if any monitoring result 
    for any of the three biological markers are above the levels listed 
    for category C.
        (B) The user of Appendix A Tables A and B should know that these 
    tables are provided only to facilitate understanding of the relevant 
    provisions of paragraph (l)(3) of this section. Appendix A Tables A 
    and B are not meant to add to or subtract from the requirements of 
    those provisions.
    
    Appendix A Table A
    
    Categorization of Biological Monitoring Results 
    
                                              Applicable Through 1998 Only                                          
    ----------------------------------------------------------------------------------------------------------------
                                                                                Monitoring result categories        
                            Biological marker                         ----------------------------------------------
                                                                           A                B                  C    
    ----------------------------------------------------------------------------------------------------------------
    Cadmium in urine (CdU) (g/g creatinine).................  3 and 15        >15 
    2-microglobulin (2-M) (g/g creatinine)  300 and 1500      >1500*
    Cadmium in blood (CdB) (g/liter whole blood)............  5 and 15        >15 
    ----------------------------------------------------------------------------------------------------------------
    * If an employee's 2-M levels are above 1,500 g/g creatinine, in order for mandatory medical  
      removal to be required (See Appendix A Table B.), either the employee's CdU level must also be >3 g/g
      creatinine or CdB level must also be >5 g/liter whole blood.                                         
    
    
                                          Applicable Beginning January 1, 1999                                      
    ----------------------------------------------------------------------------------------------------------------
                                                                                Monitoring result categories        
                            Biological marker                         ----------------------------------------------
                                                                           A                B                  C    
    ----------------------------------------------------------------------------------------------------------------
    Cadmium in urine (CdU) (g/g creatinine).................  3 and 7         >7 
    2-microglobulin (2-M) (g/g creatinine)  300 and 750       >750*
    Cadmium in blood (CdB) (g/liter whole blood)............  5 and 10        >10 
    ----------------------------------------------------------------------------------------------------------------
    * If an employee's 2-M levels are above 750 g/g creatinine, in order for mandatory medical    
      removal to be required (See Appendix A Table B.), either the employee's CdU level must also be >3 g/g
      creatinine or CdB level must also be >5 g/liter whole blood.                                         
    
    Appendix A Table B--Actions Determined by Biological Monitoring
    
        This table presents the actions required based on the monitoring 
    result in Appendix A Table A. Each item is a separate requirement in 
    citing non-compliance. For example, a medical examination within 90 
    days for an employee in category B is separate from the requirement to 
    administer a periodic medical examination for category B employees on 
    an annual basis. 
    
    ------------------------------------------------------------------------
                                              Monitoring result category    
              Required actions           -----------------------------------
                                             A\1\        B\1\        C\1\   
    ------------------------------------------------------------------------
    (1) Biological monitoring:                                              
        (a) Annual......................  X           ..........  ..........
        (b) Semiannual..................  ..........  X           ..........
        (c) Quarterly...................  ..........  ..........  X         
    (2) Medical examination:                                                
        (a) Biennial....................  X           ..........  ..........
        (b) Annual......................  ..........  X           ..........
        (c) Semiannual..................  ..........  ..........  X         
        (d) Within 90 days..............  ..........  X           X         
    (3) Assess within two weeks:                                            
        (a) Excess cadmium exposure.....  ..........  X           X         
        (b) Work practices..............  ..........  X           X         
        (c) Personal hygiene............  ..........  X           X         
        (d) Respirator usage............  ..........  X           X         
        (e) Smoking history.............  ..........  X           X         
        (f) Hygiene facilities..........  ..........  X           X         
        (g) Engineering controls........  ..........  X           X         
        (h) Correct within 30 days......  ..........  X           X         
        (i) Periodically assess           ..........  ..........  X         
         exposures.                                                         
    (4) Discretionary medical removal...  ..........  X           X         
    (5) Mandatory medical removal.......  ..........  ..........  X\2\      
    ------------------------------------------------------------------------
    \1\For all employees covered by medical surveillance exclusively because
      of exposures prior to the effective date of this standard, if they are
      in Category A, the employer shall follow the requirements of          
      paragraphs (l)(3)(i)(B) and (l)(4)(v)(A). If they are in Category B or
      C, the employer shall follow the requirements of paragraphs           
      (l)(4)(v)(B)-(C).                                                     
    \2\See footnote Appendix A Table A.                                     
    
    Appendix A--Attachment-2: List of Medications
    
        A list of the more common medications that a physician, and the 
    employee, may wish to review is likely to include some of the 
    following: (1) Anticonvulsants: Paramethadione, phenytoin, 
    trimethadone; (2) antihypertensive drugs: Captopril, methyldopa; (3) 
    antimicrobials: Aminoglycosides, amphotericin B, cephalosporins, 
    ethambutol; (4) antineoplastic agents: Cisplatin, methotrexate, 
    mitomycin-C, nitrosoureas, radiation; (4) sulfonamide diuretics: 
    Acetazolamide, chlorthalidone, furosemide, thiazides; (5) 
    halogenated alkanes, hydrocarbons, and solvents that may occur in 
    some settings: Carbon tetrachloride, ethylene glycol, toluene; 
    iodinated radiographic contrast media; nonsteroidal anti-
    inflammatory drugs; and, (7) other miscellaneous compounds: 
    Acetominophen, allopurinol, amphetamines, azathioprine, cimetidine, 
    cyclosporine, lithium, methoxyflurane, methysergide, D-
    penicillamine, phenacetin, phenendione. A list of drugs associated 
    with acute interstitial nephritis includes: (1) Antimicrobial drugs: 
    Cephalosporins, chloramphenicol, colistin, erythromycin, ethambutol, 
    isoniazid, para-aminosalicylic acid, penicillins, polymyxin B, 
    rifampin, sulfonamides, tetracyclines, and vancomycin; (2) other 
    miscellaneous drugs: Allopurinol, antipyrene, azathioprine, 
    captopril, cimetidine, clofibrate, methyldopa, phenindione, 
    phenylpropanolamine, phenytoin, probenecid, sulfinpyrazone, 
    sulfonamid diuretics, triamterene; and, (3) metals: Bismuth, gold.
        This list have been derived from commonly available medical 
    textbooks (e.g., Ex. 14-18). The list has been included merely to 
    facilitate the physician's, employer's, and employee's 
    understanding. The list does not represent an official OSHA opinion 
    or policy regarding the use of these medications for particular 
    employees. The use of such medications should be under physician 
    discretion.
    
    Attachment 3--Biological Monitoring and Medical Examination Results
    
    Employee---------------------------------------------------------------
    Testing Date-----------------------------------------------------------
        Cadmium in Urine ______ g/g Cr--Normal Levels: 
    3 g/g Cr.
        Cadmium in Blood ______ g/lwb--Normal Levels: 
    5 g/lwb.
        Beta-2-microglobulin in Urine ______ g/g Cr--Normal 
    Levels: 300 g/g Cr.
        Physical Examination Results: N/A ______ Satisfactory ______ 
    Unsatisfactory ______ (see physician again).
        Physician's Review of Pulmonary Function Test: N/A ______ Normal 
    ______ Abnormal ______.
    Next biological monitoring or medical examination scheduled for--------
    
        The biological monitoring program has been designed for three 
    main purposes: 1) to identify employees at risk of adverse health 
    effects from excess, chronic exposure to cadmium; 2) to prevent 
    cadmium-induced disease(s); and 3) to detect and minimize existing 
    cadmium-induced disease(s).
        The levels of cadmium in the urine and blood provide an estimate 
    of the total amount of cadmium in the body. The amount of a specific 
    protein in the urine (beta-2-microglobulin) indicates changes in 
    kidney function. All three tests must be evaluated together. A 
    single mildly elevated result may not be important if testing at a 
    later time indicates that the results are normal and the workplace 
    has been evaluated to decrease possible sources of cadmium exposure. 
    The levels of cadmium or beta-2-microglobulin may change over a 
    period of days to months and the time needed for those changes to 
    occur is different for each worker.
        If the results for biological monitoring are above specific 
    ``high levels'' [cadmium urine greater than 10 micrograms per gram 
    of creatinine (g/g Cr), cadmium blood greater than 10 
    micrograms per liter of whole blood (g/lwb), or beta-2-
    microglobulin greater than 1000 micrograms per gram of creatinine 
    (g/g Cr)], the worker has a much greater chance of 
    developing other kidney diseases.
        One way to measure for kidney function is by measuring beta-2-
    microglobulin in the urine. Beta-2-microglobulin is a protein which 
    is normally found in the blood as it is being filtered in the 
    kidney, and the kidney reabsorbs or returns almost all of the beta-
    2-microglobulin to the blood. A very small amount (less than 300 
    g/g Cr in the urine) of beta-2-microglobulin is not 
    reabsorbed into the blood, but is released in the urine. If cadmium 
    damages the kidney, the amount of beta-2-microglobulin in the urine 
    increases because the kidney cells are unable to reabsorb the beta-
    2-microglobulin normally. An increase in the amount of beta-2-
    microglobulin in the urine is a very early sign of kidney 
    dysfunction. A small increase in beta-2-microglobulin in the urine 
    will serve as an early warning sign that the worker may be absorbing 
    cadmium from the air, cigarettes contaminated in the workplace, or 
    eating in areas that are cadmium contaminated.
        Even if cadmium causes permanent changes in the kidney's ability 
    to reabsorb beta-2-microglobulin, and the beta-2-microglobulin is 
    above the ``high levels'', the loss of kidney function may not lead 
    to any serious health problems. Also, renal function naturally 
    declines as people age. The risk for changes in kidney function for 
    workers who have biological monitoring results between the ``normal 
    values'' and the ``high levels'' is not well known. Some people are 
    more cadmium-tolerant, while others are more cadmium-susceptible.
        For anyone with even a slight increase of beta-2-microglobulin, 
    cadmium in the urine, or cadmium in the blood, it is very important 
    to protect the kidney from further damage. Kidney damage can come 
    from other sources than excess cadmium-exposure so it is also 
    recommended that if a worker's levels are ``high'' he/she should 
    receive counseling about drinking more water; avoiding cadmium-
    tainted tobacco and certain medications (nephrotoxins, 
    acetaminophen); controlling diet, vitamin intake, blood pressure and 
    diabetes; etc.
    
    Appendix B to Sec. 1915.1027--Substance Technical Guidelines for 
    Cadmium
    
    I. Cadmium Metal.
        A. Physical and Chemical Data.
        1. Substance Identification.
        Chemical name: Cadmium.
        Formula: Cd.
        Molecular Weight: 112.4.
        Chemical Abstracts Service (CAS) Registry No.: 7740-43-9.
        Other Identifiers: RETCS EU9800000; EPA D006; DOT 2570 53.
        Synonyms: Colloidal Cadmium: Kadmium (German): CI 77180.
        2. Physical data.
        Boiling point: (760 mm Hg): 765 degrees C.
        Melting point: 321 degrees C.
        Specific Gravity: (H[email protected] 20  deg.C): 8.64.
        Solubility: Insoluble in water; soluble in dilute nitric acid 
    and in sulfuric acid.
        Appearance: Soft, blue-white, malleable, lustrous metal or 
    grayish-white powder.
        B. Fire, Explosion and Reactivity Data.
        1. Fire.
        Fire and Explosion Hazards: The finely divided metal is 
    pyrophoric, that is the dust is a severe fire hazard and moderate 
    explosion hazard when exposed to heat or flame. Burning material 
    reacts violently with extinguishing agents such as water, foam, 
    carbon dioxide, and halons.
        Flash point: Flammable (dust).
        Extinguishing media: Dry sand, dry dolomite, dry graphite, or 
    sodimum chloride.
        2. Reactivity.
        Conditions contributing to instability: Stable when kept in 
    sealed containers under normal temperatures and pressure, but dust 
    may ignite upon contact with air. Metal tarnishes in moist air.
        Incompatibilities: Ammonium nitrate, fused: Reacts violently or 
    explosively with cadmium dust below 20  deg.C. Hydrozoic acid: 
    Violent explosion occurs after 30 minutes. Acids: Reacts violently, 
    forms hydrogen gas. Oxidizing agents or metals: Strong reaction with 
    cadmium dust. Nitryl fluoride at slightly elevated temperature: 
    Glowing or white incandescence occurs. Selenium: Reacts 
    exothermically. Ammonia: Corrosive reaction. Sulfur dioxide: 
    Corrosive reaction. Fire extinguishing agents (water, foam, carbon 
    dioxide, and halons): Reacts violently. Tellurium: Incandescent 
    reaction in hydrogen atmosphere.
        Hazardous decomposition products: The heated metal rapidly forms 
    highly toxic, brownish fumes of oxides of cadmium.
        C. Spill, Leak and Disposal Procedures.
        1. Steps to be taken if the materials is released or spilled. Do 
    not touch spilled material. Stop leak if you can do it without risk. 
    Do not get water inside container. For large spills, dike spill for 
    later disposal. Keep unnecessary people away. Isolate hazard area 
    and deny entry. The Superfund Amendments and Reauthorization Act of 
    1986 Section 304 requires that a release equal to or greater than 
    the reportable quantity for this substance (1 pound) must be 
    immediately reported to the local emergency planning committee, the 
    state emergency response commission, and the National Response 
    Center (800) 424-8802; in Washington, DC metropolitan area (202) 
    426-2675.
    II. Cadmium Oxide.
        A. Physical and Chemical Date.
        1. Substance identification.
        Chemical name: Cadmium Oxide.
        Formula: CdO.
        Molecular Weight: 128.4.
        CAS No.: 1306-19-0.
        Other Identifiers: RTECS EV1929500.
        Synonyms: Kadmu tlenek (Polish).
        2. Physical data.
        Boiling point (760 mm Hg): 950 degrees C decomposes.
        Melting point: 1500  deg.C.
        Specific Gravity: (H[email protected]  deg.C): 7.0.
        Solubility: Insoluble in water; soluble in acids and alkalines.
        Appearance: Red or brown crystals.
        B. Fire, Explosion and Reactivity Data.
        1. Fire.
        Fire and Explosion Hazards: Negligible fire hazard when exposed 
    to heat or flame.
        Flash point: Nonflammable.
        Extinguishing media: Dry chemical, carbon dioxide, water spray 
    or foam.
        2. Reactivity.
        Conditions contributing to instability: Stable under normal 
    temperatures and pressures.
        Incompatibilities: Magnesium may reduce CdO2 explosively on 
    heating.
        Hazardous decomposition products: Toxic fumes of cadmium.
        C. Spill Leak and Disposal Procedures.
        1. Steps to be taken if the material is released or spilled. Do 
    not touch spilled material. Stop leak if you can do it without risk. 
    For small spills, take up with sand or other absorbent material and 
    place into containers for later disposal. For small dry spills, use 
    a clean shovel to place material into clean, dry container and then 
    cover. Move containers from spill area. For larger spills, dike far 
    ahead of spill for later disposal. Keep unnecessary people away. 
    Isolate hazard area and deny entry. The Superfund Amendments and 
    Reauthorization Act of 1986 Section 304 requires that a release 
    equal to or greater than the reportable quantity for this substance 
    (1 pound) must be immediately reported to the local emergency 
    planning committee, the state emergency response commission, and the 
    National Response Center (800) 424-8802; in Washington, DC 
    metropolitan area (202) 426-2675.
    III. Cadmium Sulfide.
        A. Physical and Chemical Data.
        1. Substance Identification.
        Chemical name: Cadmium sulfide.
        Formula: CdS.
        Molecular weight: 144.5.
        CAS No. 1306-23-6.
        Other Identifiers: RTECS EV3150000.
        Synonyms: Aurora yellow; Cadmium Golden 366; Cadmium Lemon 
    Yellow 527; Cadmium Orange; Cadmium Primrose 819; Cadmium Sulphide; 
    Cadmium Yellow; Cadmium Yellow 000; Cadmium Yellow Conc. Deep; 
    Cadmium Yellow Conc. Golden; Cadmium Yellow Conc. Lemon; Cadmium 
    Yellow Conc. Primrose; Cadmium Yellow Oz. Dark; Cadmium Yellow 
    Primrose 47-1400; Cadmium Yellow 10G Conc.; Cadmium Yellow 892; 
    Cadmopur Golden Yellow N; Cadmopur Yellow: Capsebon; C.I. 77199; 
    C.I. Pigment Orange 20; CI Pigment Yellow 37; Ferro Lemon Yellow; 
    Ferro Orange Yellow; Ferro Yellow; Greenockite; NCI-C02711.
        2. Physical data.
        Boiling point (760 mm. Hg): sublines in N2 at 980  deg.C.
        Melting point: 1750 degrees C (100 atm).
        Specific Gravity: (H[email protected] 20  deg.C): 4.82.
        Solubility: Slightly soluble in water; soluble in acid.
        Appearance: Light yellow or yellow-orange crystals.
        B. Fire, Explosion and Reactivity Data.
        1. Fire.
        Fire and Explosion Hazards: Neglible fire hazard when exposed to 
    heat or flame.
        Flash point: Nonflammable.
        Extinguishing media: Dry chemical, carbon dioxide, water spray 
    or foam.
        2. Reactivity.
        Conditions contributing to instability: Generally non-reactive 
    under normal conditions. Reacts with acids to form toxic hydrogen 
    sulfide gas.
        Incompatibilities: Reacts vigorously with iodinemonochloride.
        Hazardous decomposition products: Toxic fumes of cadmium and 
    sulfur oxides.
        C. Spill Leak and Disposal Procedures.
        1. Steps to be taken if the material is released or spilled. Do 
    not touch spilled material. Stop leak if you can do it without risk. 
    For small, dry spills, with a clean shovel place material into 
    clean, dry container and cover. Move containers from spill area. For 
    larger spills, dike far ahead of spill for later disposal. Keep 
    unnecessary people away. Isolate hazard and deny entry.
    IV. Cadmium Chloride.
        A. Physical and Chemical Data.
        1. Substance Identification.
        Chemical name: Cadmium chloride.
        Formula: CdCl2.
        Molecular weight: 183.3.
        CAS No. 10108-64-2.
        Other Identifiers: RTECS EY0175000.
        Synonyms: Caddy; Cadmium dichloride; NA 2570 (DOT); UI-CAD; 
    dichlorocadmium.
        2. Physical data.
        Boiling point (760 mm Hg): 960 degrees C.
        Melting point: 568 degrees C.
        Specific Gravity: (H2O=1 @ 20  deg.C): 4.05.
        Solubility: Soluble in water (140 g/100 cc); soluble in acetone.
        Appearance: Small, white crystals.
        B. Fire, Explosion and Reactivity Data.
        1. Fire.
        Fire and Explosion Hazards: Negligible fire and negligible 
    explosion hazard in dust form when exposed to heat or flame.
        Flash point: Nonflamable.
        Extinguishing media: Dry chemical, carbon dioxide, water spray 
    or foam.
        2. Reactivity.
        Conditions contributing to instability: Generally stable under 
    normal temperatures and pressures.
        Incompatibilities: Bromine triflouride rapidly attacks cadmium 
    chloride. A mixture of potassium and cadmium chloride may produce a 
    strong explosion on impact.
        Hazardous decomposition products: Thermal ecompostion may 
    release toxic fumes of hydrogen chloride, chloride, chlorine or 
    oxides of cadmium.
        C. Spill Leak and Disposal Procedures.
        1. Steps to be taken if the materials is released or spilled. Do 
    not touch spilled material. Stop leak if you can do it without risk. 
    For small, dry spills, with a clean shovel place material into 
    clean, dry container and cover. Move containers from spill area. For 
    larger spills, dike far ahead of spill for later disposal. Keep 
    unnecessary people away. Isolate hazard and deny entry. The 
    Superfund Amendments and Reauthorization Act of 1986 Section 304 
    requires that a release equal to or greater than the reportable 
    quantity for this substance (100 pounds) must be immediately 
    reported to the local emergency planning committee, the state 
    emergency response commission, and the National Response Center 
    (800) 424-8802; in Washington, DC Metropolitan area (202) 426-2675.
    
    Appendix C to Sec. 1915.1027--Qualitative and Quantitative Fit 
    Testing Procedures
    
    I. Fit Test Protocols
    
        A. General: The employer shall include the following provisions 
    in the fit test procedures. These provisions apply to both 
    qualitative fit testing (QLFT) and quantitative fit testing (QNFT). 
    All testing is to be conducted annually.
        1. The test subject shall be allowed to pick the most 
    comfortable respirator from a selection including respirators of 
    various sizes from different manufacturers. The selection shall 
    include at least three sizes of elastomeric facepieces of the type 
    of respirator that is to be tested, i.e., three sizes of half mask; 
    or three sizes of full facepiece. Respirators of each size must be 
    provided from at least two manufacturers.
        2. Prior to the selection process, the test subject shall be 
    shown how to put on a respirator, how it should be positioned on the 
    face, how to set strap tension and how to determine a comfortable 
    fit. A mirror shall be available to assist the subject in evaluating 
    the fit and positioning the respirator. This instruction may not 
    constitute the subject's formal training on respirator use; it is 
    only a review.
        3. The test subject shall be informed that he/she is being asked 
    to select the respirator which provides the most comfortable fit. 
    Each respirator represents a different size and shape, and if 
    fitted, maintained and used properly, will provide substantial 
    protection.
        4. The test subject shall be instructed to hold each facepiece 
    up to the face and eliminate those which obviously do not give a 
    comfortable fit.
        5. The more comfortable facepieces are noted; the most 
    comfortable mask is donned and worn at least five minutes to assess 
    comfort. Assistance in assessing comfort can be given by discussing 
    the points in item 6 below. If the test subject is not familiar with 
    using a particular respirator, the test subject shall be directed to 
    don the mask several times and to adjust the straps each time to 
    become adept at setting proper tension on the straps.
        6. Assessment of comfort shall include reviewing the following 
    points with the test subject and allowing the test subject adequate 
    time to determine the comfort of the respirator:
        (a) Position of the mask on the nose;
        (b) Room for eye protection;
        (c) Room to talk; and
        (d) Position of mask on face and cheeks.
        7. The following criteria shall be used to help determine the 
    adequacy of the respirator fit:
        (a) Chin properly placed;
        (b) Adequate strap tension, not overly tightened;
        (c) Fit across nose bridge;
        (d) Respirator of proper size to span distance from nose to 
    chin;
        (e) Tendency of respirator to slip; and
        (f) Self-observation in mirror to evaluate fit and respirator 
    position.
        8. The test subject shall conduct the negative and positive 
    pressure fit checks as described below or in ANSI Z88.2-1980. Before 
    conducting the negative or positive pressure test, the subject shall 
    be told to seat the mask on the face by moving the head from side-
    to-side and up and down slowly while taking in a few slow deep 
    breaths. Another facepiece shall be selected and retested if the 
    test subject fails the fit check tests.
        (a). Positive pressure test. Close off the exhalation valve and 
    exhale gently onto the facepiece. The face fit is considered 
    satisfactory if a slight positive pressure can be built up inside 
    the facepiece without any evidence of outward leakage of air at the 
    seal. For most respirators this method of leak testing requires the 
    wearer to first remove the exhalation valve cover before closing off 
    the exhalation valve and then carefully replacing it after the test.
        (b). Negative pressure test. Close off the inlet opening of the 
    canister or cartridge(s) by covering with the palm of the hand(s) or 
    by replacing the filter seal(s). Inhale gently so that the facepiece 
    collapses slightly, and hold the breath for ten seconds. If the 
    facepiece remains in its slightly collapsed condition and no inward 
    leakage of air is detected, the tightness of the respirator is 
    considered satisfactory.
        9. The test shall not be conducted if there is any hair growth 
    between the skin and the facepiece sealing surface, such as stubble 
    beard growth, beard, or long sideburns which cross the respirator 
    sealing surface. Any type of apparel which interferes with a 
    satisfactory fit shall be altered or removed.
        10. If a test subject exhibits difficulty in breathing during 
    the tests, she or he shall be referred to a physician trained in 
    respiratory disease or pulmonary medicine to determine, in 
    accordance with paragraph (l)(2) and (3) of this standard, whether 
    the test subject can wear a respirator while performing her or his 
    duties.
        11. The test subject shall be given the opportunity to wear the 
    successfully fitted respirator for a period of two weeks. If at any 
    time during this period the respirator becomes uncomfortable, the 
    test subject shall be given the opportunity to select a different 
    facepiece and to be retested.
        12. The employer shall maintain a record of the fit test 
    administered to an employee. The record shall contain at least the 
    following information:
        (a) Name of employee;
        (b) Type of respirator;
        (c) Brand, size of respirator;
        (d) Date of test; and
        (e) Where QNFT is used, the fit factor and strip chart recording 
    or other recording of the results of the test. The record shall be 
    maintained until the next fit test is administered.
        13. Exercise regimen. Prior to the commencement of the fit test, 
    the test subject shall be given a description of the fit test and 
    the test subject's responsibilities during the test procedure. The 
    description of the process shall include a description of the test 
    exercises that the subject will be performing. The respirator to be 
    tested shall be worn for at least 5 minutes before the start of the 
    fit test.
        14. Test Exercises. The test subject shall perform exercises, in 
    the test environment, in the manner described below:
        (a) Normal breathing. In a normal standing position, without 
    talking, the subject shall breathe normally.
        (b) Deep breathing. In a normal standing position, without 
    talking, the subject shall breathe slowly and deeply, taking care so 
    as to not hyperventilate.
        (c) Turning head side to side. Standing in place, the subject 
    shall slowly turn his/her head from side to side between the extreme 
    positions on each side. The head shall be held at each extreme 
    momentarily so the subject can inhale at each side.
        (d) Moving head up and down. Standing in place, the subject 
    shall slowly move his/her head up and down. The subject shall be 
    instructed to inhale in the up position (i.e., when looking toward 
    the ceiling).
        (e) Talking. The subject shall talk out loud slowly and loud 
    enough so as to be heard clearly by the test conductor. The subject 
    can read from a prepared text such as the Rainbow Passage, count 
    backward from 100, or recite a memorized poem or song.
        (f) Grimace. The test subject shall grimace by smiling or 
    frowning.
        (g) Bending over. The test subject shall bend at the waist as if 
    he/she were to touch his/her toes. Jogging in place shall be 
    substituted for this exercise in those test environments such as 
    shroud type QNFT units which prohibit bending at the waist.
        (h) Normal breathing. Same as exercise 1. Each test exercise 
    shall be performed for one minute except for the grimace exercise 
    which shall be performed for 15 seconds. The test subject shall be 
    questioned by the test conductor regarding the comfort of the 
    respirator upon completion of the protocol. If it has become 
    uncomfortable, another model of respirator shall be tried.
    
    B. Qualitative Fit Test (QLFT) Protocols
    
    1. General
    
        (a) The employer shall assign specific individuals who shall 
    assume full responsibility for implementing the respirator 
    qualitative fit test program.
        (b) The employer shall assure that persons administering QLFTs 
    are able to prepare test solutions, calibrate equipment and perform 
    tests properly, recognize invalid tests, and assure that test 
    equipment is in proper working order.
        (c) The employer shall assure that QLFT equipment is kept clean 
    and well maintained so as to operate within the parameters for which 
    it was designed.
    
    2. Isoamyl Acetate Protocol
    
        (a) Odor threshold screening. The odor threshold screening test, 
    performed without wearing a respirator, is intended to determine if 
    the individual tested can detect the odor of isoamyl acetate.
        (1) Three 1-liter glass jars with metal lids are required.
        (2) Odor free water (e.g. distilled or spring water) at 
    approximately 25 degrees C shall be used for the solutions.
        (3) The isoamyl acetate (IAA) (also known as isopentyl acetate) 
    stock solution is prepared by adding 1 cc of pure IAA to 800 cc of 
    odor free water in a 1 liter jar and shaking for 30 seconds. A new 
    solution shall be prepared at least weekly.
        (4) The screening test shall be conducted in a room separate 
    from the room used for actual fit testing. The two rooms shall be 
    well ventilated and shall not be connected to the same recirculating 
    ventilation system.
        (5) The odor test solution is prepared in a second jar by 
    placing 0.4 cc of the stock solution into 500 cc of odor free water 
    using a clean dropper or pipette. The solution shall be shaken for 
    30 seconds and allowed to stand for two to three minutes so that the 
    IAA concentration above the liquid may reach equilibrium. This 
    solution shall be used for only one day.
        (6) A test blank shall be prepared in a third jar by adding 500 
    cc of odor free water.
        (7) The odor test and test blank jars shall be labeled 1 and 2 
    for jar identification. Labels shall be placed on the lids so they 
    can be periodically peeled, dried off and switched to maintain the 
    integrity of the test.
        (8) The following instruction shall be typed on a card and 
    placed on the table in front of the two test jars (i.e., 1 and 2): 
    ``The purpose of this test is to determine if you can smell banana 
    oil at a low concentration. The two bottles in front of you contain 
    water. One of these bottles also contains a small amount of banana 
    oil. Be sure the covers are on tight, then shake each bottle for two 
    seconds. Unscrew the lid of each bottle, one at a time, and sniff at 
    the mouth of the bottle. Indicate to the test conductor which bottle 
    contains banana oil.''
        (9) The mixtures used in the IAA odor detection test shall be 
    prepared in an area separate from where the test is performed, in 
    order to prevent olfactory fatigue in the subject.
        (10) If the test subject is unable to correctly identify the jar 
    containing the odor test solution, the IAA qualitative fit test 
    shall not be performed.
        (11) If the test subject correctly identifies the jar containing 
    the odor test solution, the test subject may proceed to respirator 
    selection and fit testing.
        (b) Isoamyl acetate fit test--
        (1) The fit test chamber shall be similar to a clear 55-gallon 
    drum liner suspended inverted over a 2-foot diameter frame so that 
    the top of the chamber is about 6 inches above the test subject's 
    head. The inside top center of the chamber shall have a small hook 
    attached.
        (2) Each respirator used for the fitting and fit testing shall 
    be equipped with organic vapor cartridges or offer protection 
    against organic vapors. The cartridges or masks shall be changed at 
    least weekly.
        (3) After selecting, donning, and properly adjusting a 
    respirator, the test subject shall wear it to the fit testing room. 
    This room shall be separate from the room used for odor threshold 
    screening and respirator selection, and shall be well ventilated, as 
    by an exhaust fan or lab hood, to prevent general room 
    contamination.
        (4) A copy of the test exercises and any prepared text from 
    which the subject is to read shall be taped to the inside of the 
    test chamber.
        (5) Upon entering the test chamber, the test subject shall be 
    given a 6-inch by 5-inch piece of paper towel, or other porous, 
    absorbent, single-ply material, folded in half and wetted with 0.75 
    cc of pure IAA. The test subject shall hang the wet towel on the 
    hook at the top of the chamber.
        (6) Allow two minutes for the IAA test concentration to 
    stabilize before starting the fit test exercises. This would be an 
    appropriate time to talk with the test subject; to explain the fit 
    test, the importance of his/her cooperation, and the purpose for the 
    head exercises; and to demonstrate some of the exercises.
        (7) If at any time during the test, the subject detects the 
    banana like odor of IAA, the respirator fit is inadequate. The 
    subject shall quickly exit from the test chamber and leave the test 
    area to avoid olfactory fatigue.
        (8) If the respirator fit was inadequate, the subject shall 
    return to the selection room and remove the respirator, repeat the 
    odor sensitivity test, select and put on another respirator, return 
    to the test chamber and again begin the procedure described in 
    paragraph (I)(B)(2)(b) (1) through (7) of this appendix. The process 
    continues until a respirator that fits well has been found. Should 
    the odor sensitivity test be failed, the subject shall wait about 5 
    minutes before retesting. Odor sensitivity will usually have 
    returned by this time.
        (9) When a respirator is found that passes the test, its 
    efficiency shall be demonstrated for the subject by having the 
    subject break the face seal and take a breath before exiting the 
    chamber.
        (10) When the test subject leaves the chamber, the subject shall 
    remove the saturated towel and return it to the person conducting 
    the test. To keep the test area from becoming contaminated, the used 
    towels shall be kept in a self sealing bag so there is no 
    significant IAA concentration build-up in the test chamber during 
    subsequent tests.
    
    3. Irritant Fume Protocol
    
        (a) The respirator to be tested shall be equipped with high-
    efficiency particulate air (HEPA) filters.
        (b) The test subject shall be allowed to smell a weak 
    concentration of the irritant smoke before the respirator is donned 
    to become familiar with its characteristic odor.
        (c) Break both ends of a ventilation smoke tube containing 
    stannic oxychloride, such as the MSA part No. 5645, or equivalent. 
    Attach one end of the smoke tube to a low flow air pump set to 
    deliver 200 milliliters per minute.
        (d) Advise the test subject that the smoke can be irritating to 
    the eyes and instruct the subject to keep his/her eyes closed while 
    the test is performed.
        (e) The test conductor shall direct the stream of irritant smoke 
    from the smoke tube towards the face seal area of the test subject. 
    He/she shall begin at least 12 inches from the facepiece and 
    gradually move to within one inch, moving around the whole perimeter 
    of the mask.
        (f) The exercises identified in section I. A. 14 above shall be 
    performed by the test subject while the respirator seal is being 
    challenged by the smoke.
        (g) Each test subject passing the smoke test without evidence of 
    a response shall be given a sensitivity check of the smoke from the 
    same tube once the respirator has been removed to determine whether 
    he/she reacts to the smoke. Failure to evoke a response shall void 
    the fit test.
        (h) The fit test shall be performed in a location with exhaust 
    ventilation sufficient to prevent general contamination of the 
    testing area by the test agent.
    
    4. Saccharin Solution Aerosol Protocol
    
        The entire screening and testing procedure shall be explained to 
    the test subject prior to the conduct of the screening test.
        (a) Taste threshold screening. The saccharin taste threshold 
    screening, performed without wearing a respirator, is intended to 
    determine whether the individual being tested can detect the taste 
    of saccharin.
        (1) Threshold screening as well as fit testing subjects shall 
    wear an enclosure about the head and shoulders that is approximately 
    12 inches in diameter by 14 inches tall with at least the front 
    portion clear and that allows free movements of the head when a 
    respirator is worn. An enclosure substantially similar to the 3M 
    hood assembly, parts # FT 14 and # FT 15 combined, is adequate.
        (2) The test enclosure shall have a \3/4\ inch hole in front of 
    the test subject's nose and mouth area to accommodate the nebulizer 
    nozzle.
        (3) The test subject shall don the test enclosure. Throughout 
    the threshold screening test, the test subject shall breathe through 
    his/her wide open mouth with tongue extended.
        (4) Using a DeVilbiss Model 40 Inhalation Medication Nebulizer 
    the test conductor shall spray the threshold check solution into the 
    enclosure. This nebulizer shall be clearly marked to distinguish it 
    from the fit test solution nebulizer.
        (5) The threshold check solution consists of 0.83 grams of 
    sodium saccharin USP in 1 cc of warm water. It can be prepared by 
    putting 1 cc of the fit test solution (see (b)(5) below) in 100 cc 
    of distilled water.
        (6) To produce the aerosol, the nebulizer bulb is firmly 
    squeezed so that it collapses completely, then released and allowed 
    to fully expand.
        (7) Ten squeezes are repeated rapidly and then the test subject 
    is asked whether the saccharin can be tasted.
        (8) If the first response is negative, ten more squeezes are 
    repeated rapidly and the test subject is again asked whether the 
    saccharin is tasted.
        (9) If the second response is negative, ten more squeezes are 
    repeated rapidly and the test subject is again asked whether the 
    saccharin is tasted.
        (10) The test conductor will take note of the number of squeezes 
    required to solicit a taste response.
        (11) If the saccharin is not tasted after 30 squeezes (step 10), 
    the test subject may not perform the saccharin fit test.
        (12) If a taste response is elicited, the test subject shall be 
    asked to take note of the taste for reference in the fit test.
        (13) Correct use of the nebulizer means that approximately 1 cc 
    of liquid is used at a time in the nebulizer body.
        (14) The nebulizer shall be thoroughly rinsed in water, shaken 
    dry, and refilled at least each morning and afternoon or at least 
    every four hours.
        (b) Saccharin solution aerosol fit test procedure
        (1) The test subject may not eat, drink (except plain water), or 
    chew gum for 15 minutes before the test.
        (2) The fit test uses the same enclosure described in (a) above.
        (3) The test subject shall don the enclosure while wearing the 
    respirator selected in section (a) above. The respirator shall be 
    properly adjusted and equipped with a particulate filter(s).
        (4) A second DeVilbiss Model 40 Inhalation Medication Nebulizer 
    is used to spray the fit test solution into the enclosure. This 
    nebulizer shall be clearly marked to distinguish it from the 
    screening test solution nebulizer.
        (5) The fit test solution is prepared by adding 83 grams of 
    sodium saccharin to 100 cc of warm water.
        (6) As before, the test subject shall breathe through the open 
    mouth with tongue extended.
        (7) The nebulizer is inserted into the hole in the front of the 
    enclosure and the fit test solution is sprayed into the enclosure 
    using the same number of squeezes required to elicit a taste 
    response in the screening test.
        (8) After generating the aerosol the test subject shall be 
    instructed to perform the exercises in section I.A. 14 above.
        (9) Every 30 seconds the aerosol concentration shall be 
    replenished using one half the number of squeezes as initially.
        (10) The test subject shall indicate to the test conductor if at 
    any time during the fit test the taste of saccharin is detected.
        (11) If the taste of saccharin is detected, the fit is deemed 
    unsatisfactory and a different respirator shall be tried''.
    
    C. Quantitative Fit Test (QNFT) Protocol
    
    1. General
    
        (a) The employer shall assign specific individuals who shall 
    assume full responsibility for implementing the respirator 
    quantitative fit test program.
        (b) The employer shall ensure that persons administering QNFT 
    are able to calibrate equipment and perform tests properly, 
    recognize invalid tests, calculate fit factors properly and assure 
    that test equipment is in proper working order.
        (c) The employer shall assure that QNFT equipment is kept clean 
    and well maintained so as to operate at the parameters for which it 
    was designed.
    
    2. Definitions
    
        (a) Quantitative fit test. The test is performed in a test 
    chamber. The normal air-purifying element of the respirator is 
    replaced by a high-efficiency particulate air (HEPA) filter in the 
    case of particulate QNFT aerosols or a sorbent offering contaminant 
    penetration protection equivalent to high-efficiency filters where 
    the QNFT test agent is a gas or vapor.
        (b) Challenge agent means the aerosol, gas or vapor introduced 
    into a test chamber so that its concentration inside and outside the 
    respirator may be measured.
        (c) Test subject means the person wearing the respirator for 
    quantitative fit testing.
        (d) Normal standing position means standing erect and straight 
    with arms down along the sides and looking straight ahead.
        (e) Maximum peak penetration method means the method of 
    determining test agent penetration in the respirator as determined 
    by strip chart recordings of the test. The highest peak penetration 
    for a given exercise is taken to be representative of average 
    penetration into the respirator for that exercise.
        (f) Average peak penetration method means the method of 
    determining test agent penetration into the respirator utilizing a 
    strip chart recorder, integrator, or computer. The agent penetration 
    is determined by an average of the peak heights on the graph or by 
    computer integration, for each exercise except the grimace exercise. 
    Integrators or computers which calculate the actual test agent 
    penetration into the respirator for each exercise will also be 
    considered to meet the requirements of the average peak penetration 
    method.
        (g) ``Fit Factor'' means the ration of challenge agent 
    concentration outside with respect to the inside of a respirator 
    inlet covering (facepiece or enclosure).
    
    3. Apparatus
    
        (a) Instrumentation. Aerosol generation, dilution, and 
    measurement systems using corn oil or sodium chloride as test 
    aerosols shall be used for quantitative fit testing.
        (b) Test chamber. The test chamber shall be large enough to 
    permit all test subjects to perform freely all required exercises 
    without disturbing the challenge agent concentration or the 
    measurement apparatus. The test chamber shall be equipped and 
    constructed so that the challenge agent is effectively isolated from 
    the ambient air, yet uniform in concentration throughout the 
    chamber.
        (c) When testing air-purifying respirators, the normal filter or 
    cartridge element shall be replaced with a high-efficiency 
    particulate filter supplied by the same manufacturer.
        (d) The sampling instrument shall be selected so that a strip 
    chart record may be made of the test showing the rise and fall of 
    the challenge agent concentration with each inspiration and 
    expiration at fit factors of at least 2,000. Integrators or 
    computers which integrate the amount of test agent penetration 
    leakage into the respirator for each exercise may be used provided a 
    record of the readings is made.
        (e) The combination of substitute air-purifying elements, 
    challenge agent and challenge agent concentration in the test 
    chamber shall be such that the test subject is not exposed in excess 
    of an established exposure limit for the challenge agent at any time 
    during the testing process.
        (f) The sampling port on the test specimen respirator shall be 
    placed and constructed so that no leakage occurs around the port 
    (e.g. where the respirator is probed), a free air flow is allowed 
    into the sampling line at all times and so that there is no 
    interference with the fit or performance of the respirator.
        (g) The test chamber and test set up shall permit the person 
    administering the test to observe the test subject inside the 
    chamber during the test.
        (h) The equipment generating the challenge atmosphere shall 
    maintain the concentration of challenge agent inside the test 
    chamber constant to within a 10-percent variation for the duration 
    of the test.
        (i) The time lag (interval between an event and the recording of 
    the event on the strip chart or computer or integrator) shall be 
    kept to a minimum. There shall be a clear association between the 
    occurrence of an event inside the test chamber and its being 
    recorded.
        (j) The sampling line tubing for the test chamber atmosphere and 
    for the respirator sampling port shall be of equal diameter and of 
    the same material. The length of the two lines shall be equal.
        (k) The exhaust flow from the test chamber shall pass through a 
    high-efficiency filter before release.
        (l) When sodium chloride aerosol is used, the relative humidity 
    inside the test chamber shall not exceed 50 percent.
        (m) The limitations of instrument detection shall be taken into 
    account when determining the fit factor.
        (n) Test respirators shall be maintained in proper working order 
    and inspected for deficiencies such as cracks, missing valves and 
    gaskets, etc.
    
    4. Procedural Requirements
    
        (a) When performing the initial positive or negative pressure 
    test the sampling line shall be crimped closed in order to avoid air 
    pressure leakage during either of these tests.
        (b) An abbreviated screening isoamyl acetate test or irritant 
    fume test may be utilized in order to quickly identify poor fitting 
    respirators which passed the positive and/or negative pressure test 
    and thus reduce the amount of QNFT time. When performing a screening 
    isoamyl acetate test, combination high-efficiency organic vapor 
    cartridges/canisters shall be used.
        (c) A reasonably stable challenge agent concentration shall be 
    measured in the test chamber prior to testing. For canopy or shower 
    curtain type of test units the determination of the challenge agent 
    stability may be established after the test subject has entered the 
    test environment.
        (d) Immediately after the subject enters the test chamber, the 
    challenge agent concentration inside the respirator shall be 
    measured to ensure that the peak penetration does not exceed 5 
    percent for a half mask or 1 percent for a full facepiece 
    respirator.
        (e) A stable challenge concentration shall be obtained prior to 
    the actual start of testing.
        (f) Respirator restraining straps shall not be overtightened for 
    testing. The straps shall be adjusted by the wearer without 
    assistance from other persons to give a reasonable comfortable fit 
    typical of normal use.
        (g) The test shall be terminated whenever any single peak 
    penetration exceeds 5 percent for half masks and 1 percent for full 
    facepiece respirators. The test subject shall be refitted and 
    retested. If two of the three required tests are terminated, the fit 
    shall be deemed inadequate.
        (h) In order to successfully complete a QNFT, three successful 
    fit tests are required. The results of each of the three independent 
    fit tests must exceed the minimum fit factor needed for the class of 
    respirator (e.g. half mask respirator, full facepiece respirator).
        (i) Calculation of fit factors.
        (1) The fit factor shall be determined for the quantitative fit 
    test by taking the ratio of the average chamber concentration to the 
    concentration inside the respirator.
        (2) The average test chamber concentration is the arithmetic 
    average of the test chamber concentration at the beginning and at 
    the end of the test.
        (3) The concentration of the challenge agent inside the 
    respirator shall be determined by one of the following methods:
        (i) Average peak concentration;
        (ii) Maximum peak concentration;
        (iii) Integration by calculation of the area under the 
    individual peak for each exercise. This includes computerized 
    integration.
        (j) Interpretation of test results. The fit factor established 
    by the quantitative fit testing shall be the lowest of the three fit 
    factor values calculated from the three required fit tests.
        (k) The test subject shall not be permitted to wear a half mask, 
    or full facepiece respirator unless a minimum fit factor equivalent 
    to at least 10 times the hazardous exposure level is obtained.
        (l) Filters used for quantitative fit testing shall be replaced 
    at least weekly, or whenever increased breathing resistance is 
    encountered, or when the test agent has altered the integrity of the 
    filter media. Organic vapor cartridges/canisters shall be replaced 
    daily (when used) or sooner if there is any indication of 
    breakthrough by a test agent.
    
    Appendix D to Sec. 1915.1027--Occupational Health History Interview 
    With Reference to Cadmium Exposure
    
    Directions
    
    (To be read by employee and signed prior to the interview)
    
        Please answer the questions you will be asked as completely and 
    carefully as you can. These questions are asked of everyone who works 
    with cadmium. You will also be asked to give blood and urine samples. 
    The doctor will give your employer a written opinion on whether you are 
    physically capable of working with cadmium. Legally, the doctor cannot 
    share personal information you may tell him/her with your employer. The 
    following information is considered strictly confidential. The results 
    of the tests will go to you, your doctor and your employer. You will 
    also receive an information sheet explaining the results of any 
    biological monitoring or physical examinations performed.
        If you are just being hired, the results of this interview and 
    examination will be used to:
        (1) Establish your health status and see if working with cadmium 
    might be expected to cause unusual problems,
        (2) Determine your health status today and see if there are changes 
    over time,
        (3) See if you can wear a respirator safely.
        If you are not a new hire:
        OSHA says that everyone who works with cadmium can have periodic 
    medical examinations performed by a doctor. The reasons for this are:
        (a) If there are changes in your health, either because of cadmium 
    or some other reason, to find them early,
        (b) to prevent kidney damage.
    
    Please sign below.
    
        I have read these directions and understand them:
    
    ----------------------------------------------------------------------
    Employee signature
    
    ----------------------------------------------------------------------
    Date
    
        Thank you for answering these questions. (Suggested Format)
    Name-------------------------------------------------------------------
    Age--------------------------------------------------------------------
    Social Security #------------------------------------------------------
    Company----------------------------------------------------------------
    Job--------------------------------------------------------------------
        Type of Preplacement Exam:
        [  ] Periodic
        [  ] Termination
        [  ] Initial
        [  ] Other
    Blood Pressure---------------------------------------------------------
    Pulse Rate-------------------------------------------------------------
    1. How long have you worked at the job listed above?
        [  ] Not yet hired
        [  ] Number of months
        [  ] Number of years
    2. Job Duties etc.
    
    ----------------------------------------------------------------------
    ----------------------------------------------------------------------
    ----------------------------------------------------------------------
    3. Have you ever been told by a doctor that you had bronchitis?
        [  ] Yes
        [  ] No
        If yes, how long ago?
        [  ] Number of months
        [  ] Number of years
    4. Have you ever been told by a doctor that you had emphysema?
        [  ] Yes
        [  ] No
        If yes, how long ago?
        [  ] Number of years
        [  ] Number of months
    5. Have you ever been told by a doctor that you had other lung 
    problems?
        [  ] Yes
        [  ] No
        If yes, please describe type of lung problems and when you had 
    these problems
    ----------------------------------------------------------------------
    ----------------------------------------------------------------------
    ----------------------------------------------------------------------
    6. In the past year, have you had a cough?
        [  ] Yes
        [  ] No
        If yes, did you cough up sputum?
        [  ] Yes
        [  ] No
        If yes, how long did the cough with sputum production last?
        [  ] Less than 3 months
        [   ] 3 months or longer
        If yes, for how many years have you had episodes of cough with 
    sputum production lasting this long?
        [  ] Less than one
        [  ] 1
        [  ] 2
        [  ] Longer than 2
    7. Have you ever smoked cigarettes?
        [  ] Yes
        [  ] No
    8. Do you now smoke cigarettes?
        [  ] Yes
        [  ] No
    9. If you smoke or have smoked cigarettes, for how many years have 
    you smoked, or did you smoke?
        [  ] Less than 1 year
        [  ] Number of years
        What is or was the greatest number of packs per day that you 
    have smoked?
        [  ] Number of packs
        If you quit smoking cigarettes, how many years ago did you quit?
        [  ] Less than 1 year
        [  ] Number of years
        How many packs a day do you now smoke?
        [  ] Number of packs per day
    10. Have you ever been told by a doctor that you had a kidney or 
    urinary tract disease or disorder?
        [  ] Yes
        [  ] No
    11. Have you ever had any of these disorders? 
    
                                                                            
                                                                            
                                                                            
    Kidney stones...................................  [] Yes      [] No     
    Protein in urine................................  [] Yes      [] No     
    Blood in urine..................................  [] Yes      [] No     
    Difficulty urinating............................  [] Yes      [] No     
    Other kidney/Urinary disorders..................  [] Yes      [] No     
                                                                            
    
        Please describe problems, age, treatment, and follow up for any 
    kidney or urinary problems you have had:
    ----------------------------------------------------------------------
    ----------------------------------------------------------------------
    ----------------------------------------------------------------------
    12. Have you ever been told by a doctor or other health care 
    provider who took your blood pressure that your blood pressure was 
    high?
        [  ] Yes
        [  ] No
    13. Have you ever been advised to take any blood pressure 
    medication?
        [  ] Yes
        [  ] No
    14. Are you presently taking any blood pressure medication?
        [  ] Yes
        [  ] No
    15. Are you presently taking any other medication?
        [  ] Yes
        [  ] No
    16. Please list any blood pressure or other medications and describe 
    how long you have been taking each one:
    
    Medicine:
    ----------------------------------------------------------------------
    ----------------------------------------------------------------------
    -----------------------------------------------------------------------
    
    How Long Taken
    ----------------------------------------------------------------------
    ----------------------------------------------------------------------
    ----------------------------------------------------------------------
    17. Have you ever been told by a doctor that you have diabetes? 
    (sugar in your blood or urine)
        [  ] Yes
        [  ] No
        If yes, do you presently see a doctor about your diabetes?
        [  ] Yes
        [  ] No
        If yes, how do you control your blood sugar?
        [  ] Diet alone
        [  ] Diet plus oral medicine
        [  ] Diet plus insulin (injection)
    18. Have you ever been told by a doctor that you had: 
    
                                                                            
                                                                            
                                                                            
    Anemia..........................................  [] Yes      [] No     
    A low blood count?..............................  [] Yes      [] No     
                                                                            
    
    19. Do you presently feel that you tire or run out of energy sooner 
    than normal or sooner than other people your age?
        [  ] Yes
        [  ] No
        If yes, for how long have you felt that you tire easily?
        [  ] Less than 1 year
        [  ] Number of years
    20. Have you given blood within the last year?
        [  ] Yes
        [  ] No
        If yes, how many times?
        [  ] Number of times
        How long ago was the last time you gave blood?
        [  ] Less than 1 month
        [  ] Number of months
    21. Within the last year have you had any injuries with heavy 
    bleeding?
        [  ] Yes
        [  ] No
        If yes, how long ago?
        [  ] Less than 1 month
        [  ] Number of months
    Describe:--------------------------------------------------------------
    ----------------------------------------------------------------------
    ----------------------------------------------------------------------
    ----------------------------------------------------------------------
    22. Have you recently had any surgery?
        [  ] Yes
        [  ] No
    If yes, please describe:-----------------------------------------------
    ----------------------------------------------------------------------
    ----------------------------------------------------------------------
    ----------------------------------------------------------------------
    23. Have you seen any blood lately in your stool or after a bowel 
    movement?
        [  ] Yes
        [  ] No
    24. Have you ever had a test for blood in your stool?
        [  ] Yes
        [  ] No
        If yes, did the test show any blood in the stool?
        [  ] Yes
        [  ] No
    What further evaluation and treatment were done?-----------------------
    ----------------------------------------------------------------------
    ----------------------------------------------------------------------
        The following questions pertain to the ability to wear a 
    respirator. Additional information for the physician can be found in 
    The Respiratory Protective Devices Manual.
    25. Have you ever been told by a doctor that you have asthma?
        [  ] Yes
        [  ] No
        If yes, are you presently taking any medication for asthma? Mark 
    all that apply.
        [  ] Shots
        [  ] Pills
        [  ] Inhaler
    26. Have you ever had a heart attack?
        [  ] Yes
        [  ] No
        If yes, how long ago?
        [  ] Number of years
        [  ] Number of months
    27. Have you ever had pains in your chest?
        [  ] Yes
        [  ] No
        If yes, when did it usually happen?
        [  ] While resting
        [  ] While working
        [  ] While exercising
        [  ] Activity didn't matter
    28. Have you ever had a thyroid problem?
        [  ] Yes
        [  ] No
    29. Have you ever had a seizure or fits?
        [  ] Yes
        [  ] No
    30. Have you ever had a stroke (cerebrovascular accident)?
        [  ] Yes
        [  ] No
    31. Have you ever had a ruptured eardrum or a serious hearing 
    problem?
        [  ] Yes
        [  ] No
    32. Do you now have a claustrophobia, meaning fear of crowded or 
    closed in spaces or any psychological problems that would make it 
    hard for you to wear a respirator?
        [  ] Yes
        [  ] No
        The following questions pertain to reproductive history.
    33. Have you or your partner had a problem conceiving a child?
        [  ] Yes
        [  ] No
        If yes, specify:
        [  ] Self
        [  ] Present mate
        [  ] Previous mate
    34. Have you or your partner consulted a physician for a fertility 
    or other reproductive problem?
        [  ] Yes
        [  ] No
        If yes, specify who consulted the physician:
        [  ] Self
        [  ] Spouse/partner
        [  ] Self and partner
    If yes, specify diagnosis made:----------------------------------------
    ----------------------------------------------------------------------
    ----------------------------------------------------------------------
    35. Have you or your partner ever conceived a child resulting in a 
    miscarriage, still birth or deformed offspring?
        [  ] Yes
        [  ] No
        If yes, specify:
        [  ] Miscarriage
        [  ] Still birth
        [  ] Deformed offspring
    If outcome was a deformed offspring, please specify type:--------------
    ----------------------------------------------------------------------
    ----------------------------------------------------------------------
    ----------------------------------------------------------------------
    36. Was this outcome a result of a pregnancy of:
        [  ] Yours with present partner
        [  ] Yours with a previous partner
    37. Did the timing of any abnormal pregnancy outcome coincide with 
    present employment?
        [  ] Yes
        [  ] No
    List dates of occurrences:---------------------------------------------
    ----------------------------------------------------------------------
    38. What is the occupation of your spouse or partner?
    ----------------------------------------------------------------------
    ----------------------------------------------------------------------
    
    For Women Only
    
    39. Do you have menstrual periods?
        [  ] Yes
        [  ] No
        Have you had menstrual irregularities?
        [  ] Yes
        [  ] No
    If yes, specify type:--------------------------------------------------
    ----------------------------------------------------------------------
    ----------------------------------------------------------------------
    If yes, what was the approximate date this problem began?--------------
    ----------------------------------------------------------------------
    Approximate date problem stopped?--------------------------------------
    ----------------------------------------------------------------------
    
    For Men Only
    
    40. Have you ever been diagnosed by a physician as having prostate 
    gland problem(s)?
        [  ] Yes
        [  ] No
    If yes, please describe type of problem(s) and what was done to 
    evaluate and treat the problem(s):-------------------------------------
    ----------------------------------------------------------------------
    
    Appendix E to Sec. 1915.1027--Cadmium in Workplace Atmospheres
    
    Method Number: ID-189
    Matrix: Air
    OSHA Permissible Exposure Limits: 5 g/m\3\ (TWA), 2.5 
    g/m\3\ (Action Level TWA)
    Collection Procedure: A known volume of air is drawn through a 37-mm 
    diameter filter cassette containing a 0.8-m mixed cellulose 
    ester membrane filter (MCEF).
    Recommended Air Volume: 960 L
    Recommended Sampling Rate: 2.0 L/min
    Analytical Procedure: Air filter samples are digested with nitric 
    acid. After digestion, a small amount of hydrochloric acid is added. 
    The samples are then diluted to volume with deionized water and 
    analyzed by either flame atomic absorption spectroscopy (AAS) or 
    flameless atomic absorption spectroscopy using a heated graphite 
    furnace atomizer (AAS-HGA).
    Detection Limits:
    Qualitative: 0.2 g/m\3\ for a 200 L sample by Flame AAS, 
    0.007 g/m\3\ for a 60 L sample by AAS-HGA
    Quantitative: 0.70 g/m\3\ for a 200 L sample by Flame AAS, 
    0.025 g/m\3\ for a 60 L sample by AAS-HGA
    Precision and Accuracy: (Flame AAS Analysis and AAS-HGA Analysis):
        Validation Level: 2.5 to 10 g/m\3\ for a 400 L air vol, 
    1.25 to 5.0 g/m\3\ for a 60 L air vol
        CV1 (pooled): 0.010, 0.043
    Analytical Bias: +4.0%, -5.8%
    Overall Analytical Error: 6.0%, 14.2%
    Method Classification: Validated
    Date: June, 1992
    
        Inorganic Service Branch II, OSHA Salt Lake Technical Center, 
    Salt Lake City, Utah
        Commercial manufacturers and products mentioned in this method 
    are for descriptive use only and do not constitute endorsements by 
    USDOL-OSHA. Similar products from other sources can be substituted.
    
    1. Introduction
    
    1.1. Scope
    
        This method describes the collection of airborne elemental 
    cadmium and cadmium compounds on 0.8-m mixed cellulose 
    ester membrane filters and their subsequent analysis by either flame 
    atomic absorption spectroscopy (AAS) or flameless atomic absorption 
    spectroscopy using a heated graphite furnace atomizer (AAS-HGA). It 
    is applicable for both TWA and Action Level TWA Permissible Exposure 
    Level (PEL) measurements. The two atomic absorption analytical 
    techniques included in the method do not differentiate between 
    cadmium fume and cadmium dust samples. They also do not 
    differentiate between elemental cadmium and its compounds.
    
    1.2. Principle
    
        Airborne elemental cadmium and cadmium compounds are collected 
    on a 0.8-m mixed cellulose ester membrane filter (MCEF). 
    The air filter samples are digested with concentrated nitric acid to 
    destroy the organic matrix and dissolve the cadmium analytes. After 
    digestion, a small amount of concentrated hydrochloric acid is added 
    to help dissolve other metals which may be present. The samples are 
    diluted to volume with deionized water and then aspirated into the 
    oxidizing air/acetylene flame of an atomic absorption 
    spectrophotometer for analysis of elemental cadmium.
        If the concentration of cadmium in a sample solution is too low 
    for quantitation by this flame AAS analytical technique, and the 
    sample is to be averaged with other samples for TWA calculations, 
    aliquots of the sample and a matrix modifier are later injected onto 
    a L'vov platform in a pyrolytically-coated graphite tube of a Zeeman 
    atomic absorption spectrophotometer/graphite furnace assembly for 
    analysis of elemental cadmium. The matrix modifier is added to 
    stabilize the cadmium metal and minimize sodium chloride as an 
    interference during the high temperature charring step of the 
    analysis (5.1., 5.2.).
    
    1.3. History
    
        Previously, two OSHA sampling and analytical methods for cadmium 
    were used concurrently (5.3., 5.4.). Both of these methods also 
    required 0.8-m mixed cellulose ester membrane filters for 
    the collection of air samples. These cadmium air filter samples were 
    analyzed by either flame atomic absorption spectroscopy (5.3.) or 
    inductively coupled plasma/atomic emission spectroscopy (ICP-AES) 
    (5.4.). Neither of these two analytical methods have adequate 
    sensitivity for measuring workplace exposure to airborne cadmium at 
    the new lower TWA and Action Level TWA PEL levels when consecutive 
    samples are taken on one employee and the sample results need to be 
    averaged with other samples to determine a single TWA.
        The inclusion of two atomic absorption analytical techniques in 
    the new sampling and analysis method for airborne cadmium permits 
    quantitation of sample results over a broad range of exposure levels 
    and sampling periods. The flame AAS analytical technique included in 
    this method is similar to the previous procedure given in the 
    General Metals Method ID-121 (5.3.) with some modifications. The 
    sensitivity of the AAS-HGA analytical technique included in this 
    method is adequate to measure exposure levels at 1/10 the Action 
    Level TWA, or lower, when less than full-shift samples need to be 
    averaged together.
    
    1.4. Properties (5.5.)
    
        Elemental cadmium is a silver-white, blue-tinged, lustrous metal 
    which is easily cut with a knife. It is slowly oxidized by moist air 
    to form cadmium oxide. It is insoluble in water, but reacts readily 
    with dilute nitric acid. Some of the physical properties and other 
    descriptive information of elemental cadmium are given below:
    
    CAS No.
    7440-43-9
    Atomic Number
    48
    Atomic Symbol
    Cd
    Atomic Weight
    112.41
    Melting Point
    321  deg.C
    Boiling Point
    765  deg.C
    Density
    8.65 g/mL (25  deg.C)
    
        The properties of specific cadmium compounds are described in 
    reference 5.5.
    
    1.5. Method Performance
    
        A synopsis of method performance is presented below. Further 
    information can be found in Section 4.
        1.5.1. The qualitative and quantitative detection limits for the 
    flame AAS analytical technique are 0.04 g (0.004 
    g/mL) and 0.14 g (0.014 g/mL) cadmium, 
    respectively, for a 10 mL solution volume. These correspond, 
    respectively, to 0.2 g/m\3\ and 0.70 g/m\3\ for a 
    200 L air volume.
        1.5.2. The qualitative and quantitative detection limits for the 
    AAS-HGA analytical technique are 0.44 ng (0.044 ng/mL) and 1.5 ng 
    (0.15 ng/mL) cadmium, respectively, for a 10 mL solution volume. 
    These correspond, respectively, to 0.007 g/m\3\ and 0.025 
    g/m\3\ for a 60 L air volume.
        1.5.3. The average recovery by the flame AAS analytical 
    technique of 17 spiked MCEF samples containing cadmium in the range 
    of 0.5 to 2.0 times the TWA target concentration of 5 g/
    m\3\ (assuming a 400 L air volume) was 104.0% with a pooled 
    coefficient of variation (CV1) of 0.010. The flame analytical 
    technique exhibited a positive bias of +4.0% for the validated 
    concentration range. The overall analytical error (OAE) for the 
    flame AAS analytical technique was 6.0%.
        1.5.4. The average recovery by the AAS-HGA analytical technique 
    of 18 spiked MCEF samples containing cadmium in the range of 0.5 to 
    2.0 times the Action Level TWA target concentration of 2.5 
    g/m\3\ (assuming a 60 L air volume) was 94.2% with a pooled 
    coefficient of variation (CV1) of 0.043. The AAS-HGA analytical 
    technique exhibited a negative bias of -5.8% for the validated 
    concentration range. The overall analytical error (OAE) for the AAS-
    HGA analytical technique was 14.2%.
        1.5.5. Sensitivity in flame atomic absorption is defined as the 
    characteristic concentration of an element required to produce a 
    signal of 1% absorbance (0.0044 absorbance units). Sensitivity 
    values are listed for each element by the atomic absorption 
    spectrophotometer manufacturer and have proved to be a very valuable 
    diagnostic tool to determine if instrumental parameters are 
    optimized and if the instrument is performing up to specification. 
    The sensitivity of the spectrophotometer used in the validation of 
    the flame AAS analytical technique agreed with the manufacturer 
    specifications (5.6.); the 2 g/mL cadmium standard gave an 
    absorbance reading of 0.350 abs. units.
        1.5.6. Sensitivity in graphite furnace atomic absorption is 
    defined in terms of the characteristic mass, the number of picograms 
    required to give an integrated absorbance value of 0.0044 
    absorbance-second (5.7.). Data suggests that under Stabilized 
    Temperature Platform Furnace (STPF) conditions (see Section 1.6.2.), 
    characteristic mass values are transferable between properly 
    functioning instruments to an accuracy of about 20% (5.2.). The 
    characteristic mass for STPF analysis of cadmium with Zeeman 
    background correction listed by the manufacturer of the instrument 
    used in the validation of the AAS-HGA analytical technique was 0.35 
    pg. The experimental characteristic mass value observed during the 
    determination of the working range and detection limits of the AAS-
    HGA analytical technique was 0.41 pg.
    
    1.6. Interferences
    
        1.6.1. High concentrations of silicate interfere in determining 
    cadmium by flame AAS (5.6.). However, silicates are not 
    significantly soluble in the acid matrix used to prepare the 
    samples.
        1.6.2. Interferences, such as background absorption, are reduced 
    to a minimum in the AAS-HGA analytical technique by taking full 
    advantage of the Stabilized Temperature Platform Furnace (STPF) 
    concept. STPF includes all of the following parameters (5.2.):
    
    a. Integrated Absorbance,
    b. Fast Instrument Electronics and Sampling Frequency,
    c. Background Correction,
    d. Maximum Power Heating,
    e. Atomization off the L'vov platform in a pyrolytically coated 
    graphite tube,
    f. Gas Stop during Atomization,
    g. Use of Matrix Modifiers.
    
    1.7. Toxicology (5.14.)
    
        Information listed within this section is synopsis of current 
    knowledge of the physiological effects of cadmium and is not 
    intended to be used as the basis for OSHA policy. IARC classifies 
    cadmium and certain of its compounds as Group 2A carcinogens 
    (probably carcinogenic to humans). Cadmium fume is intensely 
    irritating to the respiratory tract. Workplace exposure to cadmium 
    can cause both chronic and acute effects. Acute effects include 
    tracheobronchitis, pneumonitis, and pulmonary edema. Chronic effects 
    include anemia, rhinitis/anosmia, pulmonary emphysema, proteinuria 
    and lung cancer. The primary target organs for chronic disease are 
    the kidneys (non-carcinogenic) and the lungs (carcinogenic).
    
    2. Sampling
    
    2.1. Apparatus
    
        2.1.1. Filter cassette unit for air sampling: A 37-mm diameter 
    mixed cellulose ester membrane filter with a pore size of 0.8-
    m contained in a 37-mm polystyrene two- or three-piece 
    cassette filter holder (part no. MAWP 037 A0, Millipore Corp., 
    Bedford, MA). The filter is supported with a cellulose backup pad. 
    The cassette is sealed prior to use with a shrinkable gel band.
        2.1.2. A calibrated personal sampling pump whose flow is 
    determined to an accuracy of 5% at the recommended flow 
    rate with the filter cassette unit in line.
    
    2.2. Procedure
    
        2.2.1. Attach the prepared cassette to the calibrated sampling 
    pump (the backup pad should face the pump) using flexible tubing. 
    Place the sampling device on the employee such that air is sampled 
    from the breathing zone.
        2.2.2. Collect air samples at a flow rate of 2.0 L/min. If the 
    filter does not become overloaded, a full-shift (at least seven 
    hours) sample is strongly recommended for TWA and Action Level TWA 
    measurements with a maximum air volume of 960 L. If overloading 
    occurs, collect consecutive air samples for shorter sampling periods 
    to cover the full workshift.
        2.2.3. Replace the end plugs into the filter cassettes 
    immediately after sampling. Record the sampling conditions.
        2.2.4. Securely wrap each sample filter cassette end-to-end with 
    an OSHA Form 21 sample seal.
        2.2.5. Submit at least one blank sample with each set of air 
    samples. The blank sample should be handled the same as the other 
    samples except that no air is drawn through it.
        2.2.6. Ship the samples to the laboratory for analysis as soon 
    as possible in a suitable container designed to prevent damage in 
    transit.
    
    3. Analysis
    
    3.1. Safety Precautions
    
        3.1.1. Wear safety glasses, protective clothing and gloves at 
    all times.
        3.1.2. Handle acid solutions with care. Handle all cadmium 
    samples and solutions with extra care (see Sect. 1.7.). Avoid their 
    direct contact with work area surfaces, eyes, skin and clothes. 
    Flush acid solutions which contact the skin or eyes with copious 
    amounts of water.
        3.1.3. Perform all acid digestions and acid dilutions in an 
    exhaust hood while wearing a face shield. To avoid exposure to acid 
    vapors, do not remove beakers containing concentrated acid solutions 
    from the exhaust hood until they have returned to room temperature 
    and have been diluted or emptied.
        3.1.4. Exercise care when using laboratory glassware. Do not use 
    chipped pipets, volumetric flasks, beakers or any glassware with 
    sharp edges exposed in order to avoid the possibility of cuts or 
    abrasions.
        3.1.5. Never pipet by mouth.
        3.1.6. Refer to the instrument instruction manuals and SOPs 
    (5.8., 5.9.) for proper and safe operation of the atomic absorption 
    spectrophotometer, graphite furnace atomizer and associated 
    equipment.
        3.1.7. Because metallic elements and other toxic substances are 
    vaporized during AAS flame or graphite furnace atomizer operation, 
    it is imperative that an exhaust vent be used. Always ensure that 
    the exhaust system is operating properly during instrument use.
    
    3.2. Apparatus for Sample and Standard Preparation
    
        3.2.1. Hot plate, capable of reaching 150  deg.C, installed in 
    an exhaust hood.
        3.2.2. Phillips beakers, 125 mL.
        3.2.3. Bottles, narrow-mouth, polyethylene or glass with 
    leakproof caps: used for storage of standards and matrix modifier.
        3.2.4. Volumetric flasks, volumetric pipets, beakers and other 
    associated general laboratory glassware.
        3.2.5. Forceps and other associated general laboratory 
    equipment.
    
    3.3. Apparatus for Flame AAS Analysis
    
        3.3.1. Atomic absorption spectrophotometer consisting of a(an):
    
    Nebulizer and burner head
    Pressure regulating devices capable of maintaining constant oxidant 
    and fuel pressures
    Optical system capable of isolating the desired wavelength of 
    radiation (228.8 nm)
    Adjustable slit
    Light measuring and amplifying device
    Display, strip chart, or computer interface for indicating the 
    amount of absorbed radiation
    Cadmium hollow cathode lamp or electrodeless discharge lamp (EDL) 
    and power supply
    
        3.3.2. Oxidant: compressed air, filtered to remove water, oil 
    and other foreign substances.
        3.3.3. Fuel: standard commercially available tanks of acetylene 
    dissolved in acetone; tanks should be equipped with flash arresters.
    
        Caution: Do not use grades of acetylene containing solvents 
    other than acetone because they may damage the PVC tubing used in 
    some instruments.
    
        3.3.4. Pressure-reducing valves: two gauge, two-stage pressure 
    regulators to maintain fuel and oxidant pressures somewhat higher 
    than the controlled operating pressures of the instrument.
        3.3.5. Exhaust vent installed directly above the 
    spectrophotometer burner head.
    
    3.4. Apparatus for AAS-HGA Analysis
    
        3.4.1. Atomic absorption spectrophotometer consisting of a(an):
    
    Heated graphite furnace atomizer (HGA) with argon purge system
    Pressure-regulating devices capable of maintaining constant argon 
    purge pressure
    Optical system capable of isolating the desired wavelength of 
    radiation (228.8 nm)
    Adjustable slit
    Light measuring and amplifying device
    Display, strip chart, or computer interface for indicating the 
    amount of absorbed radiation (as integrated absorbance, peak area)
    Background corrector: Zeeman or deuterium arc. The Zeeman background 
    corrector is recommended
    Cadmium hollow cathode lamp or electrodeless discharge lamp (EDL) 
    and power supply
    Autosampler capable of accurately injecting 5 to 20 L 
    sample aliquots onto the L'vov Platform in a graphite tube
    
        3.4.2. Pyrolytically coated graphite tubes containing solid, 
    pyrolytic L'vov platforms.
        3.4.3. Polyethylene sample cups, 2.0 to 2.5 mL, for use with the 
    autosampler.
        3.4.4. Inert purge gas for graphite furnace atomizer: compressed 
    gas cylinder of purified argon.
        3.4.5. Two gauge, two-stage pressure regulator for the argon gas 
    cylinder.
        3.4.6. Cooling water supply for graphite furnace atomizer.
        3.4.7. Exhaust vent installed directly above the graphite 
    furnace atomizer.
    
    3.5. Reagents
    
        All reagents should be ACS analytical reagent grade or better.
        3.5.1. Deionized water with a specific conductance of less than 
    10 S.
        3.5.2. Concentrated nitric acid, HNO3.
        3.5.3. Concentrated hydrochloric acid, HCl.
        3.5.4. Ammonium phosphate, monobasic, NH4H2PO4.
        3.5.5. Magnesium nitrate, Mg(NO3)2  6H2O.
        3.5.6. Diluting solution (4% HNO3, 0.4% HCl): Add 40 mL 
    HNO3 and 4 mL HCl carefully to approximately 500 mL deionized 
    water and dilute to 1 L with deionized water.
        3.5.7. Cadmium standard stock solution, 1,000 g/mL: Use 
    a commercially available certified 1,000 g/mL cadmium 
    standard or, alternatively, dissolve 1.0000 g of cadmium metal in a 
    minimum volume of 1:1 HCl and dilute to 1 L with 4% HNO3. 
    Observe expiration dates of commercial standards. Properly dispose 
    of commercial standards with no expiration dates or prepared 
    standards one year after their receipt or preparation date.
        3.5.8. Matrix modifier for AAS-HGA analysis: Dissolve 1.0 g 
    NH4H2PO4 and 0.15 g Mg(NO3)2 
    6H2O in approximately 200 mL deionized water. Add 1 mL 
    HNO3 and dilute to 500 mL with deionized water.
        3.5.9  Nitric Acid, 1:1 HNO3/DI H2O mixture: Carefully 
    add a measured volume of concentrated HNO3 to an equal volume 
    of DI H2O.
        3.5.10. Nitric acid, 10% v/v: Carefully add 100 mL of 
    concentrated HNO3 to 500 mL of DI H2O and dilute to 1 L.
    
    3.6. Glassware Preparation
    
        3.6.1. Clean Phillips beakers by refluxing with 1:1 nitric acid 
    on a hot plate in a fume hood. Thoroughly rinse with deionized water 
    and invert the beakers to allow them to drain dry.
        3.6.2. Rinse volumetric flasks and all other glassware with 10% 
    nitric acid and deionized water prior to use.
    
    3.7. Standard Preparation for Flame AAS Analysis
    
        3.7.1. Dilute stock solutions: Prepare 1, 5, 10 and 100 
    g/mL cadmium standard stock solutions by making appropriate 
    serial dilutions of 1,000 g/mL cadmium standard stock 
    solution with the diluting solution described in Section 3.5.6.
        3.7.2. Working standards: Prepare cadmium working standards in 
    the range of 0.02 to 2.0 g/mL by making appropriate serial 
    dilutions of the dilute stock solutions with the same diluting 
    solution. A suggested method of preparation of the working standards 
    is given below.
    
    ------------------------------------------------------------------------
                                               Standard                     
                                               solution     Aliquot   Final 
        Working standard (g/mL)     (g/    (mL)      vol. 
                                                  mL)                  (mL) 
    ------------------------------------------------------------------------
    0.02...................................            1         10      500
    0.05...................................            5          5      500
    0.1....................................           10          5      500
    0.2....................................           10         10      500
    0.5....................................           10         25      500
    1......................................          100          5      500
    2......................................          100         10     500 
    ------------------------------------------------------------------------
    
        Store the working standards in 500-mL, narrow-mouth polyethylene 
    or glass bottles with leak proof caps. Prepare every twelve months.
    
    3.8. Standard Preparation for AAS-HGA Analysis
    
        3.8.1. Dilute stock solutions: Prepare 10, 100 and 1,000 ng/mL 
    cadmium standard stock solutions by making appropriate ten-fold 
    serial dilutions of the 1,000 g/mL cadmium standard stock 
    solution with the diluting solution described in Section 3.5.6.
        3.8.2. Working standards: Prepare cadmium working standards in 
    the range of 0.2 to 20 ng/mL by making appropriate serial dilutions 
    of the dilute stock solutions with the same diluting solution. A 
    suggested method of preparation of the working standards is given 
    below.
    
    ------------------------------------------------------------------------
                                                 Standard             Final 
             Working standard (ng/mL)            solution   Aliquot    vol. 
                                                 (ng/mL)     (mL)      (mL) 
    ------------------------------------------------------------------------
    0.2.......................................         10         2      100
    0.5.......................................         10         5      100
    1.........................................         10        10      100
    2.........................................        100         2      100
    5.........................................        100         5      100
    10........................................        100        10      100
    20........................................      1,000         2     100 
    ------------------------------------------------------------------------
    
        Store the working standards in narrow-mouth polyethylene or 
    glass bottles with leakproof caps. Prepare monthly.
    
    3.9. Sample Preparation
    
        3.9.1. Carefully transfer each sample filter with forceps from 
    its filter cassette unit to a clean, separate 125-mL Phillips beaker 
    along with any loose dust found in the cassette. Label each Phillips 
    beaker with the appropriate sample number.
        3.9.2. Digest the sample by adding 5 mL of concentrated nitric 
    acid (HNO3) to each Phillips beaker containing an air filter 
    sample. Place the Phillips beakers on a hot plate in an exhaust hood 
    and heat the samples until approximately 0.5 mL remains. The sample 
    solution in each Phillips beaker should become clear. If it is not 
    clear, digest the sample with another portion of concentrated nitric 
    acid.
        3.9.3. After completing the HNO3 digestion and cooling the 
    samples, add 40 L (2 drops) of concentrated HCl to each air 
    sample solution and then swirl the contents. Carefully add about 5 
    mL of deionized water by pouring it down the inside of each beaker.
        3.9.4. Quantitatively transfer each cooled air sample solution 
    from each Phillips beaker to a clean 10-mL volumetric flask. Dilute 
    each flask to volume with deionized water and mix well.
    
    3.10. Flame AAS Analysis
    
        Analyze all of the air samples for their cadmium content by 
    flame atomic absorption spectroscopy (AAS) according to the 
    instructions given below.
        3.10.1. Set up the atomic absorption spectrophotometer for the 
    air/acetylene flame analysis of cadmium according to the SOP (5.8.) 
    or the manufacturer's operational instructions. For the source lamp, 
    use the cadmium hollow cathode or electrodeless discharge lamp 
    operated at the manufacturer's recommended rating for continuous 
    operation. Allow the lamp to warm up 10 to 20 min or until the 
    energy output stabilizes. Optimize conditions such as lamp position, 
    burner head alignment, fuel and oxidant flow rates, etc. See the SOP 
    or specific instrument manuals for details. Instrumental parameters 
    for the Perkin-Elmer Model 603 used in the validation of this method 
    are given in Attachment 1.
        3.10.2. Aspirate and measure the absorbance of a standard 
    solution of cadmium. The standard concentration should be within the 
    linear range. For the instrumentation used in the validation of this 
    method a 2 g/mL cadmium standard gives a net absorbance 
    reading of about 0.350 abs. units (see Section 1.5.5.) when the 
    instrument and the source lamp are performing to manufacturer 
    specifications.
        3.10.3. To increase instrument response, scale expand the 
    absorbance reading of the aspirated 2 g/mL working standard 
    approximately four times. Increase the integration time to at least 
    3 seconds to reduce signal noise.
        3.10.4. Autozero the instrument while aspirating a deionized 
    water blank. Monitor the variation in the baseline absorbance 
    reading (baseline noise) for a few minutes to insure that the 
    instrument, source lamp and associated equipment are in good 
    operating condition.
        3.10.5. Aspirate the working standards and samples directly into 
    the flame and record their absorbance readings. Aspirate the 
    deionized water blank immediately after every standard or sample to 
    correct for and monitor any baseline drift and noise. Record the 
    baseline absorbance reading of each deionized water blank. Label 
    each standard and sample reading and its accompanying baseline 
    reading.
        3.10.6. It is recommended that the entire series of working 
    standards be analyzed at the beginning and end of the analysis of a 
    set of samples to establish a concentration-response curve, ensure 
    that the standard readings agree with each other and are 
    reproducible. Also, analyze a working standard after every five or 
    six samples to monitor the performance of the spectrophotometer. 
    Standard readings should agree within 10 to 15% of the 
    readings obtained at the beginning of the analysis.
        3.10.7. Bracket the sample readings with standards during the 
    analysis. If the absorbance reading of a sample is above the 
    absorbance reading of the highest working standard, dilute the 
    sample with diluting solution and reanalyze. Use the appropriate 
    dilution factor in the calculations.
        3.10.8. Repeat the analysis of approximately 10% of the samples 
    for a check of precision.
        3.10.9. If possible, analyze quality control samples from an 
    independent source as a check on analytical recovery and precision.
        3.10.10. Record the final instrument settings at the end of the 
    analysis. Date and label the output.
    
    3.11. AAS-HGA Analysis
    
        Initially analyze all of the air samples for their cadmium 
    content by flame atomic absorption spectroscopy (AAS) according to 
    the instructions given in Section 3.10. If the concentration of 
    cadmium in a sample solution is less than three times the 
    quantitative detection limit [0.04 g/mL (40 ng/mL) for the 
    instrumentation used in the validation] and the sample results are 
    to be averaged with other samples for TWA calculations, proceed with 
    the AAS-HGA analysis of the sample as described below.
        3.11.1. Set up the atomic absorption spectrophotometer and HGA 
    for flameless atomic absorption analysis of cadmium according to the 
    SOP (5.9.) or the manufacturer's operational instructions and allow 
    the instrument to stabilize. The graphite furnace atomizer is 
    equipped with a pyrolytically coated graphite tube containing a 
    pyrolytic platform. For the source lamp, use a cadmium hollow 
    cathode or electrodeless discharge lamp operated at the 
    manufacturer's recommended setting for graphite furnace operation. 
    The Zeeman background corrector and EDL are recommended for use with 
    the L'vov platform. Instrumental parameters for the Perkin-Elmer 
    Model 5100 spectrophotometer and Zeeman HGA-600 graphite furnace 
    used in the validation of this method are given in Attachment 2.
        3.11.2. Optimize the energy reading of the spectrophotometer at 
    228.8 nm by adjusting the lamp position and the wavelength according 
    to the manufacturer's instructions.
        3.11.3. Set up the autosampler to inject a 5-L aliquot 
    of the working standard, sample or reagent blank solution onto the 
    L'vov platform along with a 10-L overlay of the matrix 
    modifier.
        3.11.4. Analyze the reagent blank (diluting solution, Section 
    3.5.6.) and then autozero the instrument before starting the 
    analysis of a set of samples. It is recommended that the reagent 
    blank be analyzed several times during the analysis to assure the 
    integrated absorbance (peak area) reading remains at or near zero.
        3.11.5. Analyze a working standard approximately midway in the 
    linear portion of the working standard range two or three times to 
    check for reproducibility and sensitivity (see sections 1.5.5. and 
    1.5.6.) before starting the analysis of samples. Calculate the 
    experimental characteristic mass value from the average integrated 
    absorbance reading and injection volume of the analyzed working 
    standard. Compare this value to the manufacturer's suggested value 
    as a check of proper instrument operation.
        3.11.6. Analyze the reagent blank, working standard, and sample 
    solutions. Record and label the peak area (abs-sec) readings and the 
    peak and background peak profiles on the printer/plotter.
        3.11.7. It is recommended the entire series of working standards 
    be analyzed at the beginning and end of the analysis of a set of 
    samples. Establish a concentration-response curve and ensure 
    standard readings agree with each other and are reproducible. Also, 
    analyze a working standard after every five or six samples to 
    monitor the performance of the system. Standard readings should 
    agree within 15% of the readings obtained at the 
    beginning of the analysis.
        3.11.8. Bracket the sample readings with standards during the 
    analysis. If the peak area reading of a sample is above the peak 
    area reading of the highest working standard, dilute the sample with 
    the diluting solution and reanalyze. Use the appropriate dilution 
    factor in the calculations.
        3.11.9. Repeat the analysis of approximately 10% of the samples 
    for a check of precision.
        3.11.10. If possible, analyze quality control samples from an 
    independent source as a check of analytical recovery and precision.
        3.11.11. Record the final instrument settings at the end of the 
    analysis. Date and label the output.
    
    3.12. Calculations
    
        Note: Standards used for HGA analysis are in ng/mL. Total 
    amounts of cadmium from calculations will be in ng (not g) 
    unless a prior conversion is made.
        3.12.1. Correct for baseline drift and noise in flame AAS 
    analysis by subtracting each baseline absorbance reading from its 
    corresponding working standard or sample absorbance reading to 
    obtain the net absorbance reading for each standard and sample.
        3.12.2. Use a least squares regression program to plot a 
    concentration-response curve of net absorbance reading (or peak area 
    for HGA analysis) versus concentration (g/mL or ng/mL) of 
    cadmium in each working standard.
        3.12.3. Determine the concentration (g/mL or ng/mL) of 
    cadmium in each sample from the resulting concentration-response 
    curve. If the concentration of cadmium in a sample solution is less 
    than three times the quantitative detection limit [0.04 g/
    mL (40 ng/mL) for the instrumentation used in the validation of the 
    method] and if consecutive samples were taken on one employee and 
    the sample results are to be averaged with other samples to 
    determine a single TWA, reanalyze the sample by AAS-HGA as described 
    in Section 3.11. and report the AAS-HGA analytical results.
        3.12.4. Calculate the total amount (g or ng) of cadmium 
    in each sample from the sample solution volume (mL) :
    
    W=(C)(sample vol, mL)(DF)
    
    Where:
        W=Total cadmium in sample
        C=Calculated concentration of cadmium
        DF=Dilution Factor (if applicable)
    
        3.12.5. Make a blank correction for each air sample by 
    subtracting the total amount of cadmium in the corresponding blank 
    sample from the total amount of cadmium in the sample.
        3.12.6. Calculate the concentration of cadmium in an air sample 
    (mg/m\3\ or g/m\3\) by using one of the following 
    equations:
    
    mg/m\3\=Wbc/(Air vol sampled, L)
    
    or
    
    g/m\3\=(Wbc)(1,000 ng/g)/(Air vol sampled, L)
    Where:
        Wbc=blank corrected total g cadmium in the sample. 
    (1g=1,000 ng)
    
    4. Backup Data
    
    4.1. Introduction
    
        4.1.1. The purpose of this evaluation is to determine the 
    analytical method recovery, working standard range, and qualitative 
    and quantitative detection limits of the two atomic absorption 
    analytical techniques included in this method. The evaluation 
    consisted of the following experiments:
        1. An analysis of 24 samples (six samples each at 0.1, 0.5, 1 
    and 2 times the TWA-PEL) for the analytical method recovery study of 
    the flame AAS analytical technique.
        2. An analysis of 18 samples (six samples each at 0.5, 1 and 2 
    times the Action Level TWA-PEL) for the analytical method recovery 
    study of the AAS-HGA analytical technique.
        3. Multiple analyses of the reagent blank and a series of 
    standard solutions to determine the working standard range and the 
    qualitative and quantitative detection limits for both atomic 
    absorption analytical techniques.
        4.1.2. The analytical method recovery results at all test levels 
    were calculated from concentration-response curves and statistically 
    examined for outliers at the 99% confidence level. Possible outliers 
    were determined using the Treatment of Outliers test (5.10.). In 
    addition, the sample results of the two analytical techniques, at 
    0.5, 1.0 and 2.0 times their target concentrations, were tested for 
    homogeneity of variances also at the 99% confidence level. 
    Homogeneity of the coefficients of variation was determined using 
    the Bartlett's test (5.11.). The overall analytical error (OAE) at 
    the 95% confidence level was calculated using the equation (5.12.):
    
    OAE=[|Bias|+(1.96)(CV1(pooled))(100%)]
    
        4.1.3. A derivation of the International Union of Pure and 
    Applied Chemistry (IUPAC) detection limit equation (5.13.) was used 
    to determine the qualitative and quantitative detection limits for 
    both atomic absorption analytical techniques:
    
    Cld=k(sd)/m        (Equation 1)
    
    Where:
        Cld=the smallest reliable detectable concentration an 
    analytical instrument can determine at a given confidence level.
        k=3 for the Qualitative Detection Limit at the 99.86% Confidence 
    Level
        =10 for the Quantitative Detection Limit at the 99.99% 
    Confidence Level.
        sd=standard deviation of the reagent blank (Rbl) readings.
        m=analytical sensitivity or slope as calculated by linear 
    regression.
    
        4.1.4. Collection efficiencies of metallic fume and dust 
    atmospheres on 0.8-m mixed cellulose ester membrane filters 
    are well documented and have been shown to be excellent (5.11.). 
    Since elemental cadmium and the cadmium component of cadmium 
    compounds are nonvolatile, stability studies of cadmium spiked MCEF 
    samples were not performed.
    
    4.2. Equipment
    
        4.2.1. A Perkin-Elmer (PE) Model 603 spectrophotometer equipped 
    with a manual gas control system, a stainless steel nebulizer, a 
    burner mixing chamber, a flow spoiler and a 10 cm. (one-slot) burner 
    head was used in the experimental validation of the flame AAS 
    analytical technique. A PE cadmium hollow cathode lamp, operated at 
    the manufacturer's recommended current setting for continuous 
    operation (4 mA), was used as the source lamp. Instrument parameters 
    are listed in Attachment 1.
        4.2.2. A PE Model 5100 spectrophotometer, Zeeman HGA-600 
    graphite furnace atomizer and AS-60 HGA autosampler were used in the 
    experimental validation of the AAS-HGA analytical technique. The 
    spectrophotometer was equipped with a PE Series 7700 professional 
    computer and Model PR-310 printer. A PE System 2 cadmium 
    electrodeless discharge lamp, operated at the manufacturer's 
    recommended current setting for modulated operation (170 mA), was 
    used as the source lamp. Instrument parameters are listed in 
    Attachment 2.
    
    4.3. Reagents
    
        4.3.1. J.T. Baker Chem. Co. (Analyzed grade) concentrated nitric 
    acid, 69.0-71.0%, and concentrated hydrochloric acid, 36.5-38.0%, 
    were used to prepare the samples and standards.
        4.3.2. Ammonium phosphate, monobasic, NH4H2PO4 
    and magnesium nitrate, Mg(NO3)2 6H2O, both 
    manufactured by the Mallinckrodt Chem. Co., were used to prepare the 
    matrix modifier for AAS-HGA analysis.
    
    4.4. Standard Preparation for Flame AAS Analysis
    
        4.4.1. Dilute stock solutions: Prepared 0.01, 0.1, 1, 10 and 100 
    g/mL cadmium standard stock solutions by making appropriate 
    serial dilutions of a commercially available 1,000 g/mL 
    cadmium standard stock solution (RICCA Chemical Co., Lot# A102) with 
    the diluting solution (4% HNO3, 0.4% HCl).
        4.4.2. Analyzed Standards: Prepared cadmium standards in the 
    range of 0.001 to 2.0 g/mL by pipetting 2 to 10 mL of the 
    appropriate dilute cadmium stock solution into a 100-mL volumetric 
    flask and diluting to volume with the diluting solution. (See 
    Section 3.7.2.)
    
    4.5. Standard Preparation for AAS-HGA Analysis
    
        4.5.1. Dilute stock solutions: Prepared 1, 10, 100 and 1,000 ng/
    mL cadmium standard stock solutions by making appropriate serial 
    dilutions of a commercially available 1,000 g/mL cadmium 
    standard stock solution (J.T. Baker Chemical Co., Instra-analyzed, 
    Lot# D22642) with the diluting solution (4% HNO3, 0.4% HCl).
        4.5.2. Analyzed Standards: Prepared cadmium standards in the 
    range of 0.1 to 40 ng/mL by pipetting 2 to 10 mL of the appropriate 
    dilute cadmium stock solution into a 100-mL volumetric flask and 
    diluting to volume with the diluting solution. (See Section 3.8.2.)
    
    4.6. Detection Limits and Standard Working Range for Flame AAS Analysis
    
        4.6.1. Analyzed the reagent blank solution and the entire series 
    of cadmium standards in the range of 0.001 to 2.0 g/mL 
    three to six times according to the instructions given in Section 
    3.10. The diluting solution (4% HNO3, 0.4% HCl) was used as the 
    reagent blank. The integration time on the PE 603 spectrophotometer 
    was set to 3.0 seconds and a four-fold expansion of the absorbance 
    reading of the 2.0 g/mL cadmium standard was made prior to 
    analysis. The 2.0 g/mL standard gave a net absorbance 
    reading of 0.350 abs. units prior to expansion in agreement with the 
    manufacturer's specifications (5.6.).
        4.6.2. The net absorbance readings of the reagent blank and the 
    low concentration Cd standards from 0.001 to 0.1 g/mL and 
    the statistical analysis of the results are shown in Table I. The 
    standard deviation, sd, of the six net absorbance readings of the 
    reagent blank is 1.05 abs. units. The slope, m, as calculated by a 
    linear regression plot of the net absorbance readings (shown in 
    Table II) of the 0.02 to 1.0 g/mL cadmium standards versus 
    their concentration is 772.7 abs. units/(g/mL).
        4.6.3. If these values for sd and the slope, m, are used in Eqn. 
    1 (Sect. 4.1.3.), the qualitative and quantitative detection limits 
    as determined by the IUPAC Method are:
    
    Cld=(3)(1.05 abs. units)/(772.7 abs. units/(g/mL))
        = 0.0041 g/mL for the qualitative detection limit.
    Cld=(10)(1.05 abs. units)/(772.7 abs. units/g/mL))
        =0.014 g/mL for the quantitative detection limit.
    
    The qualitative and quantitative detection limits for the flame AAS 
    analytical technique are 0.041 g and 0.14 g 
    cadmium, respectively, for a 10 mL solution volume. These 
    correspond, respectively, to 0.2 g/m3 and 0.70 
    g/m3 for a 200 L air volume.
        4.6.4. The recommended Cd standard working range for flame AAS 
    analysis is 0.02 to 2.0 g/mL. The net absorbance readings 
    of the reagent blank and the recommended working range standards and 
    the statistical analysis of the results are shown in Table II. The 
    standard of lowest concentration in the working range, 0.02 
    g/mL, is slightly greater than the calculated quantitative 
    detection limit, 0.014 g/mL. The standard of highest 
    concentration in the working range, 2.0 g/mL, is at the 
    upper end of the linear working range suggested by the manufacturer 
    (5.6.). Although the standard net absorbance readings are not 
    strictly linear at concentrations above 0.5 g/mL, the 
    deviation from linearity is only about 10% at the upper end of the 
    recommended standard working range. The deviation from linearity is 
    probably caused by the four-fold expansion of the signal suggested 
    in the method. As shown in Table II, the precision of the standard 
    net absorbance readings are excellent throughout the recommended 
    working range; the relative standard deviations of the readings 
    range from 0.009 to 0.064.
    
    4.7.  Detection Limits and Standard Working Range for AAS-HGA Analysis
    
        4.7.1. Analyzed the reagent blank solution and the entire series 
    of cadmium standards in the range of 0.1 to 40 ng/mL according to 
    the instructions given in Section 3.11. The diluting solution (4% 
    HNO3, 0.4% HCl) was used as the reagent blank. A fresh aliquot 
    of the reagent blank and of each standard was used for every 
    analysis. The experimental characteristic mass value was 0.41 pg, 
    calculated from the average peak area (abs-sec) reading of the 5 ng/
    mL standard which is approximately midway in the linear portion of 
    the working standard range. This agreed within 20% with the 
    characteristic mass value, 0.35 pg, listed by the manufacturer of 
    the instrument (5.2.).
        4.7.2. The peak area (abs-sec) readings of the reagent blank and 
    the low concentration Cd standards from 0.1 to 2.0 ng/mL and 
    statistical analysis of the results are shown in Table III. Five of 
    the reagent blank peak area readings were zero and the sixth reading 
    was 1 and was an outlier. The near lack of a blank signal does not 
    satisfy a strict interpretation of the IUPAC method for determining 
    the detection limits. Therefore, the standard deviation of the six 
    peak area readings of the 0.2 ng/mL cadmium standard, 0.75 abs-sec, 
    was used to calculate the detection limits by the IUPAC method. The 
    slope, m, as calculated by a linear regression plot of the peak area 
    (abs-sec) readings (shown in Table IV) of the 0.2 to 10 ng/mL 
    cadmium standards versus their concentration is 51.5 abs-sec/(ng/
    mL).
        4.7.3. If 0.75 abs-sec (sd) and 51.5 abs-sec/(ng/mL) (m) are 
    used in Eqn. 1 (Sect. 4.1.3.), the qualitative and quantitative 
    detection limits as determined by the IUPAC method are:
    
    Cld= (3)(0.75 abs-sec)/(51.5 abs-sec/(ng/mL)
        = 0.044 ng/mL for the qualitative detection limit.
    
    Cld= (10)(0.75 abs-sec)/(51.5 abs-sec/(ng/mL) = 0.15 ng/mL for 
    the quantitative detection limit.
    The qualitative and quantitative detection limits for the AAS-HGA 
    analytical technique are 0.44 ng and 1.5 ng cadmium, respectively, 
    for a 10 mL solution volume. These correspond, respectively, to 
    0.007 g/m3 and 0.025 g/m3 for a 60 L air 
    volume.
        4.7.4. The peak area (abs-sec) readings of the Cd standards from 
    0.2 to 40 ng/mL and the statistical analysis of the results are 
    given in Table IV. The recommended standard working range for AAS-
    HGA analysis is 0.2 to 20 ng/mL. The standard of lowest 
    concentration in the recommended working range is slightly greater 
    than the calculated quantitative detection limit, 0.15 ng/mL. The 
    deviation from linearity of the peak area readings of the 20 ng/mL 
    standard, the highest concentration standard in the recommended 
    working range, is approximately 10%. The deviations from linearity 
    of the peak area readings of the 30 and 40 ng/mL standards are 
    significantly greater than 10%. As shown in Table IV, the precision 
    of the peak area readings are satisfactory throughout the 
    recommended working range; the relative standard deviations of the 
    readings range from 0.025 to 0.083.
    
    4.8. Analytical Method Recovery for Flame AAS Analysis
    
        4.8.1. Four sets of spiked MCEF samples were prepared by 
    injecting 20 L of 10, 50, 100 and 200 g/mL dilute 
    cadmium stock solutions on 37 mm diameter filters (part no. AAWP 037 
    00, Millipore Corp., Bedford, MA) with a calibrated micropipet. The 
    dilute stock solutions were prepared by making appropriate serial 
    dilutions of a commercially available 1,000 g/mL cadmium 
    standard stock solution (RICCA Chemical Co., Lot# A102) with the 
    diluting solution (4% HNO3, 0.4% HCl). Each set contained six 
    samples and a sample blank. The amount of cadmium in the prepared 
    sets were equivalent to 0.1, 0.5, 1.0 and 2.0 times the TWA PEL 
    target concentration of 5 g/m3 for a 400 L air volume.
        4.8.2. The air-dried spiked filters were digested and analyzed 
    for their cadmium content by flame atomic absorption spectroscopy 
    (AAS) following the procedure described in Section 3. The 0.02 to 
    2.0 g/mL cadmium standards (the suggested working range) 
    were used in the analysis of the spiked filters.
        4.8.3. The results of the analysis are given in Table V. One 
    result at 0.5 times the TWA PEL target concentration was an outlier 
    and was excluded from statistical analysis. Experimental 
    justification for rejecting it is that the outlier value was 
    probably due to a spiking error. The coefficients of variation for 
    the three test levels at 0.5 to 2.0 times the TWA PEL target 
    concentration passed the Bartlett's test and were pooled.
        4.8.4. The average recovery of the six spiked filter samples at 
    0.1 times the TWA PEL target concentration was 118.2% with a 
    coefficient of variation (CV1) of 0.128. The average recovery 
    of the spiked filter samples in the range of 0.5 to 2.0 times the 
    TWA target concentration was 104.0% with a pooled coefficient of 
    variation (CV1) of 0.010. Consequently, the analytical bias 
    found in these spiked sample results over the tested concentration 
    range was +4.0% and the OAE was 6.0%.
    
    4.9. Analytical Method Recovery for AAS-HGA Analysis
    
        4.9.1. Three sets of spiked MCEF samples were prepared by 
    injecting 15 L of 5, 10 and 20 g/mL dilute cadmium 
    stock solutions on 37 mm diameter filters (part no. AAWP 037 00, 
    Millipore Corp., Bedford, MA) with a calibrated micropipet. The 
    dilute stock solutions were prepared by making appropriate serial 
    dilutions of a commercially available certified 1,000 g/mL 
    cadmium standard stock solution (Fisher Chemical Co., Lot# 913438-
    24) with the diluting solution (4% HNO3, 0.4% HCl). Each set 
    contained six samples and a sample blank. The amount of cadmium in 
    the prepared sets were equivalent to 0.5, 1 and 2 times the Action 
    Level TWA target concentration of 2.5 g/m3 for a 60 L 
    air volume.
        4.9.2. The air-dried spiked filters were digested and analyzed 
    for their cadmium content by flameless atomic absorption 
    spectroscopy using a heated graphite furnace atomizer following the 
    procedure described in Section 3. A five-fold dilution of the spiked 
    filter samples at 2 times the Action Level TWA was made prior to 
    their analysis. The 0.05 to 20 ng/mL cadmium standards were used in 
    the analysis of the spiked filters.
        4.9.3. The results of the analysis are given in Table VI. There 
    were no outliers. The coefficients of variation for the three test 
    levels at 0.5 to 2.0 times the Action Level TWA PEL passed the 
    Bartlett's test and were pooled. The average recovery of the spiked 
    filter samples was 94.2% with a pooled coefficient of variation 
    (CV1) of 0.043. Consequently, the analytical bias was -5.8% and 
    the OAE was 14.2%.
    
    4.10. Conclusions
    
        The experiments performed in this evaluation show the two atomic 
    absorption analytical techniques included in this method to be 
    precise and accurate and have sufficient sensitivity to measure 
    airborne cadmium over a broad range of exposure levels and sampling 
    periods.
    
    5. References
    
        5.1. Slavin, W. Graphite Furnace AAS--A Source Book; Perkin-
    Elmer Corp., Spectroscopy Div.: Ridgefield, CT , 1984; p. 18 and pp. 
    83-90.
        5.2. Grosser, Z., Ed.; Techniques in Graphite Furnace Atomic 
    Absorption Spectrophotometry; Perkin-Elmer Corp., Spectroscopy Div.: 
    Ridgefield, CT, 1985.
        5.3. Occupational Safety and Health Administration Salt Lake 
    Technical Center: Metal and Metalloid Particulate in Workplace 
    Atmospheres (Atomic Absorption) (USDOL/OSHA Method No. ID-121). In 
    OSHA Analytical Methods Manual 2nd ed. Cincinnati, OH: American 
    Conference of Governmental Industrial Hygienists, 1991.
        5.4. Occupational Safety and Health Administration Salt Lake 
    Technical Center: Metal and Metalloid Particulate in Workplace 
    Atmospheres (ICP) (USDOL/OSHA Method No. ID-125G). In OSHA 
    Analytical Methods Manual 2nd ed. Cincinnati, OH: American 
    Conference of Governmental Industrial Hygienists, 1991.
        5.5. Windholz, M., Ed.; The Merck Index, 10th ed.; Merck & Co.: 
    Rahway, NJ, 1983.
        5.6. Analytical Methods for Atomic Absorption Spectrophotometry, 
    The Perkin-Elmer Corporation: Norwalk, CT, 1982.
        5.7. Slavin, W., D.C. Manning, G. Carnrick, and E. Pruszkowska: 
    Properties of the Cadmium Determination with the Platform Furnace 
    and Zeeman Background Correction. Spectrochim. Acta 38B:1157-1170 
    (1983).
        5.8. Occupational Safety and Health Administration Salt Lake 
    Technical Center: Standard Operating Procedure for Atomic 
    Absorption. Salt Lake City, UT: USDOL/OSHA-SLTC, In progress.
        5.9. Occupational Safety and Health Administration Salt Lake 
    Technical Center: AAS-HGA Standard Operating Procedure. Salt Lake 
    City, UT: USDOL/OSHA-SLTC, In progress.
        5.10. Mandel, J.: Accuracy and Precision, Evaluation and 
    Interpretation of Analytical Results, The Treatment of Outliers. In 
    Treatise On Analytical Chemistry, 2nd ed., Vol.1, edited by I. M. 
    Kolthoff and P. J. Elving. New York: John Wiley and Sons, 1978. pp. 
    282-285.
        5.11. National Institute for Occupational Safety and Health: 
    Documentation of the NIOSH Validation Tests by D. Taylor, R. Kupel, 
    and J. Bryant (DHEW/NIOSH Pub. No. 77-185). Cincinnati, OH: National 
    Institute for Occupational Safety and Health, 1977.
        5.12. Occupational Safety and Health Administration Analytical 
    Laboratory: Precision and Accuracy Data Protocol for Laboratory 
    Validations. In OSHA Analytical Methods Manual 1st ed. Cincinnati, 
    OH: American Conference of Governmental Industrial Hygienists (Pub. 
    No. ISBN: 0-936712-66-X), 1985.
        5.13. Long, G.L. and J.D. Winefordner: Limit of Detection--A 
    Closer Look at the IUPAC Definition. Anal.Chem. 55:712A-724A (1983).
        5.14. American Conference of Governmental Industrial Hygienists: 
    Documentation of Threshold Limit Values and Biological Exposure 
    Indices. 5th ed. Cincinnati, OH: American Conference of Governmental 
    Industrial Hygienists, 1986. 
    
                       Table I.--Cd Detection Limit Study                   
                              [Flame AAS Analysis]                          
    ------------------------------------------------------------------------
                                    Absorbance                              
        STD (g/mL)      reading at 228.8    Statistical analysis   
                                        nm                                  
    ------------------------------------------------------------------------
    Reagent blank.............                 52  n=6.                     
                                               43  mean=3.50.               
                                               43  std dev=1.05.            
                                                   CV=0.30.                 
    0.001.....................                 66  n=6.                     
                                               24  mean=5.00.               
                                               66  std dev=1.67.            
                                                   CV=0.335.                
    0.002.....................                 57  n=6.                     
                                               73  mean=5.50.               
                                               74  std dev=1.76.            
                                                   CV=0.320.                
    0.005.....................                 77  n=6.                     
                                               88  mean=7.33.               
                                               86  std dev=0.817.           
                                                   CV=0.111.                
    0.010.....................                109  n=6.                     
                                             1013  mean=10.3.               
                                             1010  std dev=1.37.            
                                                   CV=0.133.                
    0.020.....................               2023  n=6.                     
                                             2022  mean=20.8.               
                                             2020  std dev=1.33.            
                                                   CV=0.064.                
    0.050.....................               4242  n=6.                     
                                             4242  mean=42.5.               
                                             4245  std dev=1.22.            
                                                   CV=0.029.                
    0.10......................                 84  n=3.                     
                                               80  mean=82.3.               
                                               83  std dev=2.08.            
                                                   CV=0.025.                
    ------------------------------------------------------------------------
    
    
                   Table II.--Cd Standard Working Range Study               
                              [Flame AAS Analysis]                          
    ------------------------------------------------------------------------
                                    Absorbance                              
       STD (g/mL)       reading at 228.8    Statistical analysis   
                                       nm                                   
    ------------------------------------------------------------------------
    Reagent blank.............                 52  n=6.                     
                                               43  mean=3.50.               
                                               43  std dev=1.05.            
                                                   CV=0.30.                 
    0.020.....................               2023  n=6.                     
                                             2022  mean=20.8.               
                                             2020  std dev=1.33.            
                                                   CV=0.064.                
    0.050.....................               4242  n=6.                     
                                             4242  mean=42.5.               
                                             4245  std dev=1.22.            
                                                   CV=0.029.                
    0.10......................                 84  n=3.                     
                                               80  mean=82.3.               
                                               83  std dev=2.08.            
                                                   CV=0.025.                
    0.20......................                161  n=3.                     
                                              161  mean=160.0.              
                                              158  std dev=1.73.            
                                                   CV=0.011.                
    0.50......................                391  n=3.                     
                                              389  mean=391.0.              
                                              393  std dev=2.00.            
                                                   CV=0.005.                
    1.00......................                760  n=3.                     
                                              748  mean=753.3.              
                                              752  std dev=6.11.            
                                                   CV=0.008.                
    2.00......................               1416  n=3.                     
                                             1426  mean=1414.3.             
                                             1401  std dev=12.6.            
                                                   CV=0.009.                
    ------------------------------------------------------------------------
    
    
                      Table III.--Cd Detection Limit Study                  
                               [AAS-HGA Analysis]                           
    ------------------------------------------------------------------------
                                    Peak area                               
                                   readings  x                              
            STD (ng/mL)           103 at 228.8      Statistical analysis    
                                       nm                                   
    ------------------------------------------------------------------------
    Reagent blank..............              00  n=6.                       
                                             01  mean=0.167.                
                                             00  std dev=0.41.              
                                                 CV=2.45.                   
    0.1........................              86  n=6.                       
                                             57  mean=7.7.                  
                                            137  std dev=2.8.               
                                                 CV=0.366.                  
    0.2........................            1113  n=6.                       
                                           1112  mean=11.8.                 
                                           1212  std dev=0.75.              
                                                 CV=0.064.                  
    0.5........................            2833  n=6.                       
                                           2628  mean=28.8.                 
                                           2830  std dev=2.4.               
                                                 CV=0.083.                  
    1.0........................            5255  n=6.                       
                                           5658  mean=54.8.                 
                                           5454  std dev=2.0.               
                                                 CV=0.037.                  
    2.0........................          101112  n=6.                       
                                         110110  mean=108.8.                
                                         110110  std dev=3.9.               
                                                 CV=0.036.                  
    ------------------------------------------------------------------------
    
    
                   Table IV.--Cd Standard Working Range Study               
                               [AAS-HGA Analysis]                           
    ------------------------------------------------------------------------
                                    Peak area                               
                                   readings  x                              
            STD (ng/mL)           103 at 228.8      Statistical analysis    
                                       nm                                   
    ------------------------------------------------------------------------
    0.2........................            1113  n=6.                       
                                           1112  mean=11.8.                 
                                           1212  std dev=0.75.              
                                                 CV=0.064.                  
    0.5........................            2833  n=6.                       
                                           2628  mean=28.8.                 
                                           2830  std dev=2.4.               
                                                 CV=0.083.                  
    1.0........................            5255  n=6.                       
                                           5658  mean=54.8.                 
                                           5454  std dev=2.0.               
                                                 CV=0.037.                  
    2.0........................          101112  n=6.                       
                                         110110  mean=108.8.                
                                         110110  std dev=3.9.               
                                                 CV=0.036.                  
    5.0........................          247265  n=6.                       
                                         268275  mean=265.5.                
                                         259279  std dev=11.5.              
                                                 CV=0.044.                  
    10.0.......................          495520  n=6.                       
                                         523513  mean=516.7.                
                                         516533  std dev=12.7.              
                                                 CV=0.025.                  
    20.0.......................          950953  n=6.                       
                                         951958  mean=941.8.                
                                         949890  std dev=25.6.              
                                                 CV=0.027.                  
    30.0.......................        12691291  n=6.                       
                                       13031307  mean=1293.                 
                                       12951290  std dev=13.3.              
                                                 CV=0.010.                  
    40.0.......................        15051567  n=6.                       
                                       15351567  mean=1552.                 
                                       15661572  std dev=26.6.              
                                                 CV=0.017.                  
    ------------------------------------------------------------------------
    
    
                                          Table V.--Analytical Method Recovery                                      
                                                  [Flame AAS Analysis]                                              
    ----------------------------------------------------------------------------------------------------------------
        Test level         0.5 x                              1.0 x                              2.0 x              
    --------------------------------  Percent   g ------------  Percent   g ------------  Percent 
                         g    rec.       taken     g    rec.       taken     g     rec.  
     g taken      found                              found                              found              
    ----------------------------------------------------------------------------------------------------------------
    1.00...............      1.0715      107.2        2.00      2.0688      103.4        4.00      4.1504      103.8
    1.00...............      1.0842      108.4        2.00      2.0174      100.9        4.00      4.1108      102.8
    1.00...............      1.0842      108.4        2.00      2.0431      102.2        4.00      4.0581      101.5
    1.00...............     *1.0081     *100.8        2.00      2.0431      102.2        4.00      4.0844      102.1
    1.00...............      1.0715      107.2        2.00      2.0174      100.9        4.00      4.1504      103.8
    1.00...............      1.0842      108.4        2.00      2.0045      100.2        4.00      4.1899     104.7 
    ----------------------------------------------------------------------------------------------------------------
    
    
    n=                                             5                             6                             6    
    mean=                                        107.9                         101.6                         103.1  
    std dev=                                       0.657                         1.174                         1.199
    CV1=                                           0.006                         0.011                         0.012 
                                                   CV1 (pooled)=0.010                                               
    *Rejected as an outlier--this value did not pass the outlier T-test at the 99% confidence level.                
    
    
    ------------------------------------------------------------------------
                 Test level                     0.1 x                       
    --------------------------------------------------------   Percent rec. 
              g taken            g found                  
    ------------------------------------------------------------------------
    0.200...............................             0.2509          125.5  
    0.200...............................             0.2509          125.5  
    0.200...............................             0.2761          138.1  
    0.200...............................             0.2258          112.9  
    0.200...............................             0.2258          112.9  
    0.200...............................             0.1881           94.1  
    ------------------------------------------------------------------------
    
    
    n=..................................                               6    
    mean=...............................                             118.2  
    std dev=............................                              15.1  
    CV1=................................                               0.128 
    
    
                                          Table VI.--Analytical Method Recovery                                     
                                                   [AAS-HGA analysis]                                               
    ----------------------------------------------------------------------------------------------------------------
           Test level           0.5 x                            1.0 x                            2.0 x             
    ------------------------------------  Percent    ng taken -----------  Percent    ng taken -----------  Percent 
            ng taken           ng found     rec.                ng found     rec.                ng found     rec.  
    ----------------------------------------------------------------------------------------------------------------
    75......................      71.23       95.0        150     138.00       92.0        300     258.43       86.1
    75......................      71.47       95.3        150     138.29       92.2        300     258.46       86.2
    75......................      70.02       93.4        150     136.30       90.9        300     280.55       93.5
    75......................      77.34      103.1        150     146.62       97.7        300     288.34       96.1
    75......................      78.32      104.4        150     145.17       96.8        300     261.74       87.2
    75......................      71.96       95.9        150     144.88       96.6        300     277.22       92.4
    ----------------------------------------------------------------------------------------------------------------
    
    
    n=                                             6                             6                             6    
    mean=                                         97.9                          94.4                          90.3  
    std dev=                                       4.66                          2.98                          4.30 
    CV1=                                           0.048                         0.032                         0.048
                                                    CV1(pooled)=0.043                                               
    
    Attachment 1
    
    Instrumental Parameters for Flame AAS Analysis
    
    Atomic Absorption Spectrophotometer (Perkin-Elmer Model 603)
    
    Flame: Air/Acetylene--lean, blue
    Oxidant Flow: 55
    Fuel Flow: 32
    Wavelength: 228.8 nm
    Slit: 4 (0.7 nm)
    Range: UV
    Signal: Concentration (4 exp)
    Integration Time: 3 sec
    
    Attachment 2
    
    Instrumental Parameters for HGA Analysis
    
    Atomic Absorption Spectrophotometer (Perkin-Elmer Model 5100)
    
    Signal Type: Zeeman AA
    Slitwidth: 0.7 nm
    Wavelength: 228.8 nm
    Measurement: Peak Area
    Integration Time: 6.0 sec
    BOC Time: 5 sec
        BOC=Background Offset Correction.
    
                                  Zeeman Graphite Furnace (Perkin-Elmer Model HGA-600)                              
    ----------------------------------------------------------------------------------------------------------------
                                                           Ramp time   Hold time    Temp. (   Argon flow            
                            Step                             (sec)       (sec)      deg.C)     (mL/min)   Read (sec)
    ----------------------------------------------------------------------------------------------------------------
    1) Predry...........................................           5          10          90         300  ..........
    2) Dry..............................................          30          10         140         300  ..........
    3) Char.............................................          10          20         900         300  ..........
    4) Cool Down........................................           1           8          30         300  ..........
    5) Atomize..........................................           0           5        1600           0          -1
    6) Burnout..........................................           1           8        2500         300  ..........
    ----------------------------------------------------------------------------------------------------------------
    
    Appendix F to Sec. 1915.1027--Nonmandatory Protocol for Biological 
    Monitoring
    
    1.00  Introduction
    
        Under the final OSHA cadmium rule (29 CFR part 1910), monitoring 
    of biological specimens and several periodic medical examinations 
    are required for eligible employees. These medical examinations are 
    to be conducted regularly, and medical monitoring is to include the 
    periodic analysis of cadmium in blood (CDB), cadmium in urine (CDU) 
    and beta-2-microglobulin in urine (B2MU). As CDU and B2MU are to be 
    normalized to the concentration of creatinine in urine (CRTU), then 
    CRTU must be analyzed in conjunction with CDU and B2MU analyses.
        The purpose of this protocol is to provide procedures for 
    establishing and maintaining the quality of the results obtained 
    from the analyses of CDB, CDU and B2MU by commercial laboratories. 
    Laboratories conforming to the provisions of this nonmandatory 
    protocol shall be known as ``participating laboratories.'' The 
    biological monitoring data from these laboratories will be evaluated 
    by physicians responsible for biological monitoring to determine the 
    conditions under which employees may continue to work in locations 
    exhibiting airborne-cadmium concentrations at or above defined 
    actions levels (see paragraphs (l)(3) and (l)(4) of the final rule). 
    These results also may be used to support a decision to remove 
    workers from such locations.
        Under the medical monitoring program for cadmium, blood and 
    urine samples must be collected at defined intervals from workers by 
    physicians responsible for medical monitoring; these samples are 
    sent to commerical laboratories that perform the required analyses 
    and report results of these analyses to the responsible physicians. 
    To ensure the accuracy and reliability of these laboratory analyses, 
    the laboratories to which samples are submitted should participate 
    in an ongoing and efficacious proficiency testing program. 
    Availability of proficiency testing programs may vary with the 
    analyses performed.
        To test proficiency in the analysis of CDB, CDU and B2MU, a 
    laboratory should participate either in the interlaboratory 
    comparison program operated by the Centre de Toxicologie du Quebec 
    (CTQ) or an equivalent program. (Currently, no laboratory in the 
    U.S. performs proficiency testing on CDB, CDU or B2MU.) Under this 
    program, CTQ sends participating laboratories 18 samples of each 
    analyte (CDB, CDU and/or B2MU) annually for analysis. Participating 
    laboratories must return the results of these analyses to CTQ within 
    four to five weeks after receiving the samples.
        The CTQ program pools analytical results from many participating 
    laboratories to derive consensus mean values for each of the samples 
    distributed. Results reported by each laboratory then are compared 
    against these consensus means for the analyzed samples to determine 
    the relative performance of each laboratory. The proficiency of a 
    participating laboratory is a function of the extent of agreement 
    between results submitted by the participating laboratory and the 
    consensus values for the set of samples analyzed.
        Proficiency testing for CRTU analysis (which should be performed 
    with CDU and B2MU analyses to evaluate the results properly) also is 
    recommended. In the U.S., only the College of American Pathologists 
    (CAP) currently conducts CRTU proficiency testing; participating 
    laboratories should be accredited for CRTU analysis by the CAP.
        Results of the proficiency evaluations will be forwarded to the 
    participating laboratory by the proficiency-testing laboratory, as 
    well as to physicians designated by the participating laboratory to 
    receive this information. In addition, the participating laboratory 
    should, on request, submit the results of their internal Quality 
    Assurance/Quality Control (QA/QC) program for each analytic 
    procedure (i.e., CDB, CDU and/or B2MU) to physicians designated to 
    receive the proficiency results. For participating laboratories 
    offering CDU and/or B2MU analyses, QA/QC documentation also should 
    be provided for CRTU analysis. (Laboratories should provide QA/QC 
    information regarding CRTU analysis directly to the requesting 
    physician if they perform the analysis in-house; if CRTU analysis is 
    performed by another laboratory under contract, this information 
    should be provided to the physician by the contract laboratory.)
        QA/QC information, along with the actual biological specimen 
    measurements, should be provided to the responsible physician using 
    standard formats. These physicians then may collate the QA/QC 
    information with proficiency test results to compare the relative 
    performance of laboratories, as well as to facilitate evaluation of 
    the worker monitoring data. This information supports decisions made 
    by the physician with regard to the biological monitoring program, 
    and for mandating medical removal.
        This protocol describes procedures that may be used by the 
    responsible physicians to identify laboratories most likely to be 
    proficient in the analysis of samples used in the biological 
    monitoring of cadmium; also provided are procedures for record 
    keeping and reporting by laboratories participating in proficiency 
    testing programs, and recommendations to assist these physicians in 
    interpreting analytical results determined by participating 
    laboratories. As the collection and handling of samples affects the 
    quality of the data, recommendations are made for these tasks. 
    Specifications for analytical methods to be used in the medical 
    monitoring program are included in this protocol as well.
        In conclusion, this document is intended as a supplement to 
    characterize and maintain the quality of medical monitoring data 
    collected under the final cadmium rule promulgated by OSHA (29 CFR 
    part 1910). OSHA has been granted authority under the Occupational 
    Safety and Health Act of 1970 to protect workers from the effects of 
    exposure to hazardous substances in the work place and to mandate 
    adequate monitoring of workers to determine when adverse health 
    effects may be occurring. This nonmandatory protocol is intended to 
    provide guidelines and recommendations to improve the accuracy and 
    reliability of the procedures used to analyze the biological samples 
    collected as part of the medical monitoring program for cadmium.
    
    2.0  Definitions
    
        When the terms below appear in this protocol, use the following 
    definitions.
        Accuracy: A measure of the bias of a data set. Bias is a 
    systematic error that is either inherent in a method or caused by 
    some artifact or idiosyncracy of the measurement system. Bias is 
    characterized by a consistent deviation (positive or negative) in 
    the results from an accepted reference value.
        Arithmetic Mean: The sum of measurements in a set divided by the 
    number of measurements in a set.
        Blind Samples: A quality control procedure in which the 
    concentration of analyte in the samples should be unknown to the 
    analyst at the time that the analysis is performed.
        Coefficient of Variation: The ratio of the standard deviation of 
    a set of measurements to the mean (arithmetic or geometric) of the 
    measurements.
        Compliance Samples: Samples from exposed workers sent to a 
    participating laboratory for analysis.
        Control Charts: Graphic representations of the results for 
    quality control samples being analyzed by a participating 
    laboratory.
        Control Limits: Statistical limits which define when an analytic 
    procedure exceeds acceptable parameters; control limits provide a 
    method of assessing the accuracy of analysts, laboratories, and 
    discrete analytic runs.
        Control Samples: Quality control samples.
        F/T: The measured amount of an analyte divided by the 
    theoretical value (defined below) for that analyte in the sample 
    analyzed; this ratio is a measure of the recovery for a quality 
    control sample.
        Geometric Mean: The natural antilog of the mean of a set of 
    natural log-transformed data.
        Geometric Standard Deviation: The antilog of the standard 
    deviation of a set of natural log-transformed data.
        Limit of Detection: Using a predefined level of confidence, this 
    is the lowest measured value at which some of the measured material 
    is likely to have come from the sample.
        Mean: A central tendency of a set of data; in this protocol, 
    this mean is defined as the arithmetic mean (see definition of 
    arithmetic mean above) unless stated otherwise.
        Performance: A measure of the overall quality of data reported 
    by a laboratory.
        Pools: Groups of quality-control samples to be established for 
    each target value (defined below) of an analyte. For the protocol 
    provided in attachment 3, for example, the theoretical value of the 
    quality control samples of the pool must be within a range defined 
    as plus or minus () 50% of the target value. Within each 
    analyte pool, there must be quality control samples of at least 4 
    theoretical values.
        Precision: The extent of agreement between repeated, independent 
    measurements of the same quantity of an analyte.
        Proficiency: The ability to satisfy a specified level of analyte 
    performance.
        Proficiency Samples: Specimens, the values of which are unknown 
    to anyone at a participating laboratory, and which are submitted by 
    a participating laboratory for proficiency testing.
        Quality or Data Quality: A measure of the confidence in the 
    measurement value.
        Quality Control (QC) Samples: Specimens, the value of which is 
    unknown to the analyst, but is known to the appropriate QA/QC 
    personnel of a participating laboratory; when used as part of a 
    laboratory QA/QC program, the theoretical values of these samples 
    should not be known to the analyst until the analyses are complete. 
    QC samples are to be run in sets consisting of one QC sample from 
    each pool (see definition of ``pools'' above).
        Sensitivity: For the purposes of this protocol, the limit of 
    detection.
        Standard Deviation: A measure of the distribution or spread of a 
    data set about the mean; the standard deviation is equal to the 
    positive square root of the variance, and is expressed in the same 
    units as the original measurements in the data set.
        Standards: Samples with values known by the analyst and used to 
    calibrate equipment and to check calibration throughout an analytic 
    run. In a laboratory QA/QC program, the values of the standards must 
    exceed the values obtained for compliance samples such that the 
    lowest standard value is near the limit of detection and the highest 
    standard is higher than the highest compliance sample or QC sample. 
    Standards of at least three different values are to be used for 
    calibration, and should be constructed from at least 2 different 
    sources.
        Target Value: Those values of CDB, CDU or B2MU which trigger 
    some action as prescribed in the medical surveillance section of the 
    regulatory text of the final cadmium rule. For CDB, the target 
    values are 5, 10, and 15 g/l. For CDU, the target values 
    are 3, 7, and 15 g/g CRTU. For 
    2MU, the target values are 300, 750, and 
    1500 g/g CRTU. (Note that target values may vary as a 
    function of time.)
        Theoretical Value (or Theoretical Amount): The reported 
    concentration of a quality-control sample (or calibration standard) 
    derived from prior characterizations of the sample.
        Value or Measurement Value: The numerical result of a 
    measurement.
        Variance: A measure of the distribution or spread of a data set 
    about the mean; the variance is the sum of the squares of the 
    differences between the mean and each discrete measurement divided 
    by one less than the number of measurements in the data set.
    
    3.0  Protocol
    
        This protocol provides procedures for characterizing and 
    maintaining the quality of analytic results derived for the medical 
    monitoring program mandated for workers under the final cadmium 
    rule.
    
    3.1  Overview
    
        The goal of this protocol is to assure that medical monitoring 
    data are of sufficient quality to facilitate proper interpretation. 
    The data quality objectives (DQOs) defined for the medical 
    monitoring program are summarized in Table 1. Based on available 
    information, the DQOs presented in Table 1 should be achievable by 
    the majority of laboratories offering the required analyses 
    commercially; OSHA recommends that only laboratories meeting these 
    DQOs be used for the analysis of biological samples collected for 
    monitoring cadmium exposure. 
    
             Table 1.--Recommended Data Quality Objectives (DQOs) for the Cadmium Medical Monitoring Program        
    ----------------------------------------------------------------------------------------------------------------
                                                                   Precision                                        
      Analyte/concentration pool         Limit of detection         (CV) (%)                  Accuracy              
    ----------------------------------------------------------------------------------------------------------------
    Cadmium in blood.............  0.5 g/l.............  ...........  1 g/l or 15% of 
                                                                                the mean.                           
        2 g/l  .............................           40                                       
        >2 g/l..........  .............................           20                                       
    Cadmium in urine.............  0.5 g/g creatinine..  ...........  1 g/l or 15% of 
                                                                                the mean.                           
        2 g/l  .............................           40                                       
         creatinine.                                                                                                
        >2 g/l            .............................           20                                       
         creatinine.                                                                                                
    -2-microglobulin in   100 g/g creatinine..            5  15% of the mean.         
     urine: 100 g/g                                                                                        
     creatine.                                                                                                      
    ----------------------------------------------------------------------------------------------------------------
    
        To satisfy the DQOs presented in Table 1, OSHA provides the 
    following guidelines:
        1. Procedures for the collection and handling of blood and urine 
    are specified (Section 3.4.1 of this protocol);
        2. Preferred analytic methods for the analysis of CDB, CDU and 
    B2MU are defined (and a method for the determination of CRTU also is 
    specified since CDU and B2MU results are to be normalized to the 
    level of CRTU).
        3. Procedures are described for identifying laboratories likely 
    to provide the required analyses in an accurate and reliable manner;
        4. These guidelines (Sections 3.2.1 to 3.2.3, and Section 3.3) 
    include recommendations regarding internal QA/QC programs for 
    participating laboratories, as well as levels of proficiency through 
    participation in an interlaboratory proficiency program;
        5. Procedures for QA/QC record keeping (Section 3.3.2), and for 
    reporting QC/QA results are described (Section 3.3.3); and,
        6. Procedures for interpreting medical monitoring results are 
    specified (Section 3.4.3).
        Methods recommended for the biological monitoring of eligible 
    workers are:
        1. The method of Stoeppler and Brandt (1980) for CDB 
    determinations (limit of detection: 0.5 g/l);
        2. The method of Pruszkowska et al. (1983) for CDU 
    determinations (limit of detection: 0.5 g/l of urine); and,
        3. The Pharmacia Delphia test kit (Pharmacia 1990) for the 
    determination of B2MU (limit of detection: 100 g/l urine).
        Because both CDU and B2MU should be reported in g/g 
    CRTU, an independent determination of CRTU is recommended. Thus, 
    both the OSHA Salt Lake City Technical Center (OSLTC) method (OSHA, 
    no date) and the Jaffe method (Du Pont, no date) for the 
    determination of CRTU are specified under this protocol (i.e., 
    either of these 2 methods may be used). Note that although detection 
    limits are not reported for either of these CRTU methods, the range 
    of measurements expected for CRTU (0.9-1.7 g/l) are well 
    above the likely limit of detection for either of these methods 
    (Harrison, 1987).
        Laboratories using alternate methods should submit sufficient 
    data to the responsible physicians demonstrating that the alternate 
    method is capable of satisfying the defined data quality objectives 
    of the program. Such laboratories also should submit a QA/QC plan 
    that documents the performance of the alternate method in a manner 
    entirely equivalent to the QA/QC plans proposed in Section 3.3.1.
        3.2  Duties of the Responsible Physician
        The responsible physician will evaluate biological monitoring 
    results provided by participating laboratories to determine whether 
    such laboratories are proficient and have satisfied the QA/QC 
    recommendations. In determining which laboratories to employ for 
    this purpose, these physicians should review proficiency and QA/QC 
    data submitted to them by the participating laboratories.
        Participating laboratories should demonstrate proficiency for 
    each analyte (CDU, CDB and B2MU) sampled under the biological 
    monitoring program. Participating laboratories involved in analyzing 
    CDU and B2MU also should demonstrate proficiency for CRTU analysis, 
    or provide evidence of a contract with a laboratory proficient in 
    CRTU analysis.
    
    3.2.1  Recommendations for Selecting Among Existing Laboratories
    
        OSHA recommends that existing laboratories providing commercial 
    analyses for CDB, CDU and/or B2MU for the medical monitoring program 
    satisfy the following criteria:
        1. Should have performed commercial analyses for the appropriate 
    analyte (CDB, CDU and/or B2MU) on a regular basis over the last 2 
    years;
        2. Should provide the responsible physician with an internal QA/
    QC plan;
        3. If performing CDU or B2MU analyses, the participating 
    laboratory should be accredited by the CAP for CRTU analysis, and 
    should be enrolled in the corresponding CAP survey (note that 
    alternate credentials may be acceptable, but acceptability is to be 
    determined by the responsible physician); and,
        4. Should have enrolled in the CTQ interlaboratory comparison 
    program for the appropriate analyte (CDB, CDU and/or B2MU).
        Participating laboratories should submit appropriate 
    documentation demonstrating compliance with the above criteria to 
    the responsible physician. To demonstrate compliance with the first 
    of the above criteria, participating laboratories should submit the 
    following documentation for each analyte they plan to analyze (note 
    that each document should cover a period of at least 8 consecutive 
    quarters, and that the period designated by the term ``regular 
    analyses'' is at least once a quarter):
        1. Copies of laboratory reports providing results from regular 
    analyses of the appropriate analyte (CDB, CDU and/or B2MU);
        2. Copies of 1 or more signed and executed contracts for the 
    provision of regular analyses of the appropriate analyte (CDB, CDU 
    and/or B2MU); or,
        3. Copies of invoices sent to 1 or more clients requesting 
    payment for the provision of regular analyses of the appropriate 
    analyte (CDB, CDU and/or B2MU). Whatever the form of documentation 
    submitted, the specific analytic procedures conducted should be 
    identified directly. The forms that are copied for submission to the 
    responsible physician also should identify the laboratory which 
    provided these analyses.
        To demonstrate compliance with the second of the above criteria, 
    a laboratory should submit to the responsible physician an internal 
    QA/QC plan detailing the standard operating procedures to be adopted 
    for satisfying the recommended QA/QC procedures for the analysis of 
    each specific analyte (CDB, CDU and/or B2MU). Procedures for 
    internal QA/QC programs are detailed in Section 3.3.1 below.
        To satisfy the third of the above criteria, laboratories 
    analyzing for CDU or B2MU also should submit a QA/QC plan for 
    creatinine analysis (CRTU); the QA/QC plan and characterization 
    analyses for CRTU must come from the laboratory performing the CRTU 
    analysis, even if the CRTU analysis is being performed by a contract 
    laboratory.
        Laboratories enrolling in the CTQ program (to satisfy the last 
    of the above criteria) must remit, with the enrollment application, 
    an initial fee of approximately $100 per analyte. (Note that this 
    fee is only an estimate, and is subject to revision without notice.) 
    Laboratories should indicate on the application that they agree to 
    have proficiency test results sent by the CTQ directly to the 
    physicians designated by participating laboratories.
        Once a laboratory's application is processed by the CTQ, the 
    laboratory will be assigned a code number which will be provided to 
    the laboratory on the initial confirmation form, along with 
    identification of the specific analytes for which the laboratory is 
    participating. Confirmation of participation will be sent by the CTQ 
    to physicians designated by the applicant laboratory.
    
    3.2.2  Recommended Review of Laboratories Selected to Perform Analyses
    
        Six months after being selected initially to perform analyte 
    determinations, the status of participating laboratories should be 
    reviewed by the responsible physicians. Such reviews should then be 
    repeated every 6 months or whenever additional proficiency or QA/QC 
    documentation is received (whichever occurs first).
        As soon as the responsible physician has received the CTQ 
    results from the first 3 rounds of proficiency testing (i.e., 3 sets 
    of 3 samples each for CDB, CDU and/or B2MU) for a participating 
    laboratory, the status of the laboratory's continued participation 
    should be reviewed. Over the same initial 6-month period, 
    participating laboratories also should provide responsible 
    physicians the results of their internal QA/QC monitoring program 
    used to assess performance for each analyte (CDB, CDU and/or B2MU) 
    for which the laboratory performs determinations. This information 
    should be submitted using appropriate forms and documentation.
        The status of each participating laboratory should be determined 
    for each analyte (i.e., whether the laboratory satisfies minimum 
    proficiency guidelines based on the proficiency samples sent by the 
    CTQ and the results of the laboratory's internal QA/QC program). To 
    maintain competency for analysis of CDB, CDU and/or B2MU during the 
    first review, the laboratory should satisfy performance requirements 
    for at least 2 of the 3 proficiency samples provided in each of the 
    3 rounds completed over the 6-month period. Proficiency should be 
    maintained for the analyte(s) for which the laboratory conducts 
    determinations.
        To continue participation for CDU and/or B2MU analyse, 
    laboratories also should either maintain accreditation for CRTU 
    analysis in the CAP program and participate in the CAP surveys, or 
    they should contract the CDU and B2MU analyses to a laboratory which 
    satisfies these requirements (or which can provide documentation of 
    accreditation/participation in an equivalent program).
        The performance requirement for CDB analysis is defined as an 
    analytical result within 1 g/l blood or 15% of 
    the consensus mean (whichever is greater). For samples exhibiting a 
    consensus mean less than 1 g/l, the performance requirement 
    is defined as a concentration between the detection limit of the 
    analysis and a maximum of 2 g/l. The purpose for redefining 
    the acceptable interval for low CDB values is to encourage proper 
    reporting of the actual values obtained during measurement; 
    laboratories, therefore, will not be penalized (in terms of a narrow 
    range of acceptability) for reporting measured concentrations 
    smaller than 1 g/l.
        The performance requirement for CDU analysis is defined as an 
    analytical result within 1 g/l urine or 15% of 
    the consensus mean (whichever is greater). For samples exhibiting a 
    consensus mean less than 1 g/l urine, the performance 
    requirement is defined as a concentration between the detection 
    limit of the analysis and a maximum of 2 g/l urine. 
    Laboratories also should demonstrate proficiency in creatinine 
    analysis as defined by the CAP. Note that reporting CDU results, 
    other than for the CTQ proficiency samples (i.e., compliance 
    samples), should be accompanied with results of analyses for CRTU, 
    and these 2 sets of results should be combined to provide a measure 
    of CDU in units of g/g CRTU.
        The performance requirement for B2MU is defined as analytical 
    results within  15% of the consensus mean. Note that 
    reporting B2MU results, other than for CTQ proficiency samples 
    (i.e., compliance samples), should be accompanied with results of 
    analyses for CRTU, and these 2 sets of results should be combined to 
    provide a measure of B2MU in units of g/g CRTU.
        There are no recommended performance checks for CRTU analyses. 
    As stated previously, laboratories performing CRTU analysis in 
    support of CDU or B2MU analyses should be accredited by the CAP, and 
    participating in the CAP's survey for CRTU.
        Following the first review, the status of each participating 
    laboratory should be reevaluated at regular intervals (i.e., 
    corresponding to receipt of results from each succeeding round of 
    proficiency testing and submission of reports from a participating 
    laboratory's internal QA/QC program).
        After a year of collecting proficiency test results, the 
    following proficiency criterion should be added to the set of 
    criteria used to determine the participating laboratory's status 
    (for analyzing CDB, CDU and/or B2MU): A participating laboratory 
    should not fail performance requirements for more than 4 samples 
    from the 6 most recent consecutive rounds used to assess proficiency 
    for CDB, CDU and/or B2MU separately (i.e., a total of 18 discrete 
    proficiency samples for each analyte). Note that this requirement 
    does not replace, but supplements, the recommendation that a 
    laboratory should satisfy the performance criteria for at least 2 of 
    the 3 samples tested for each round of the program.
    
    3.2.3  Recommendations for Selecting Among Newly-Formed Laboratories 
    (or Laboratories that Previously Failed to Meet the Protocol 
    Guidelines)
    
        OSHA recommends that laboratories that have not previously 
    provided commercial analyses of CDB, CDU and/or B2MU (or have done 
    so for a period less than 2 years), or which have provided these 
    analyses for 2 or more years but have not conformed previously with 
    these protocol guidelines, should satisfy the following provisions 
    for each analyte for which determinations are to be made prior to 
    being selected to analyze biological samples under the medical 
    monitoring program:
        1. Submit to the responsible physician an internal QA/QC plan 
    detailing the standard operating procedures to be adopted for 
    satisfying the QA/QC guidelines (guidelines for internal QA/QC 
    programs are detailed in Section 3.3.1);
        2. Submit to the responsible physician the results of the 
    initial characterization analyses for each analyte for which 
    determinations are to be made;n
        3. Submit to the responsible physician the results, for the 
    initial 6-month period, of the internal QA/QC program for each 
    analyte for which determinations are to be made (if no commercial 
    analyses have been conducted previously, a minimum of 2 mock 
    standardization trials for each analyte should be completed per 
    month for a 6-month period);
        4. Enroll in the CTQ program for the appropriate analyte for 
    which determinations are to be made, and arrange to have the CTQ 
    program submit the initial confirmation of participation and 
    proficiency test results directly to the designated physicians. Note 
    that the designated physician should receive results from 3 
    completed rounds from the CTQ program before approving a laboratory 
    for participation in the biological monitoring program;
        5. Laboratories seeking participation for CDU and/or B2MU 
    analyses should submit to the responsible physician documentation of 
    accreditation by the CAP for CRTU analyses performed in conjunction 
    with CDU and/or B2MU determinations (if CRTU analyses are conducted 
    by a contract laboratory, this laboratory should submit proof of CAP 
    accreditation to the responsible physician); and,
        6. Documentation should be submitted on an appropriate form.
        To participate in CDB, CDU and/or B2MU analyses, the laboratory 
    should satisfy the above criteria for a minimum of 2 of the 3 
    proficiency samples provided in each of the 3 rounds of the CTQ 
    program over a 6-month period; this procedure should be completed 
    for each appropriate analyte. Proficiency should be maintained for 
    each analyte to continue participation. Note that laboratories 
    seeking participation for CDU or B2MU also should address the 
    performance requirements for CRTU, which involves providing evidence 
    of accreditation by the CAP and participation in the CAP surveys (or 
    an equivalent program).
        The performance requirement for CDB analysis is defined as an 
    analytical result within 1 g/l or 15% of the 
    consensus mean (whichever is greater). For samples exhibiting a 
    consensus mean less than 1 g/l, the performance requirement 
    is defined as a concentration between the detection limit of the 
    analysis and a maximum of 2 g/l. The purpose of redefining 
    the acceptable interval for low CDB values is to encourage proper 
    reporting of the actual values obtained during measurement; 
    laboratories, therefore, will not be penalized (in terms of a narrow 
    range of acceptability) for reporting measured concentrations less 
    than 1 g/l.
        The performance requirement for CDU analysis is defined as an 
    analytical result within 1 g/l urine or 15% of 
    the consensus mean (whichever is greater). For samples exhibiting a 
    consensus mean less than 1 g/l urine, the performance 
    requirement is defined as a concentration that falls between the 
    detection limit of the analysis and a maximum of 2 g/l 
    urine. Performance requirements for the companion CRTU analysis 
    (defined by the CAP) also should be met. Note that reporting CDU 
    results, other than for CTQ proficiency testing should be 
    accompanied with results of CRTU analyses, and these 2 sets of 
    results should be combined to provide a measure of CDU in units of 
    g/g CRTU.
        The performance requirement for B2MU is defined as an analytical 
    result within 15% of the consensus mean. Note that 
    reporting B2MU results, other than for CTQ proficiency testing 
    should be accompanied with results of CRTU analysis, these 2 sets of 
    results should be combined to provide a measure of B2MU in units of 
    g/g CRTU.
        Once a new laboratory has been approved by the responsible 
    physician for conducting analyte determinations, the status of this 
    approval should be reviewed periodically by the responsible 
    physician as per the criteria presented under Section 3.2.2.
        Laboratories which have failed previously to gain approval of 
    the responsible physician for conducting determinations of 1 or more 
    analytes due to lack of compliance with the criteria defined above 
    for existing laboratories (Section 3.2.1), may obtain approval by 
    satisfying the criteria for newly-formed laboratories defined under 
    this section; for these laboratories, the second of the above 
    criteria may be satisfied by submitting a new set of 
    characterization analyses for each analyte for which determinations 
    are to be made.
        Reevaluation of these laboratories is discretionary on the part 
    of the responsible physician. Reevaluation, which normally takes 
    about 6 months, may be expedited if the laboratory can achieve 100% 
    compliance with the proficiency test criteria using the 6 samples of 
    each analyte submitted to the CTQ program during the first 2 rounds 
    of proficiency testing.
        For laboratories seeking reevaluation for CDU or B2MU analysis, 
    the guidelines for CRTU analyses also should be satisfied, including 
    accreditation for CRTU analysis by the CAP, and participation in the 
    CAP survey program (or accreditation/participation in an equivalent 
    program).
    
    3.2.4  Future Modifications to the Protocol Guidelines
    
        As participating laboratories gain experience with analyses for 
    CDB, CDU and B2MU, it is anticipated that the performance achievable 
    by the majority of laboratories should improve until it approaches 
    that reported by the research groups which developed each method. 
    OSHA, therefore, may choose to recommend stricter performance 
    guidelines in the future as the overall performance of participating 
    laboratories improves.
    
    3.3  Guidelines for Record Keeping and Reporting
    
        To comply with these guidelines, participating laboratories 
    should satisfy the above-stated performance and proficiency 
    recommendations, as well as the following internal QA/QC, record 
    keeping, and reporting provisions.
        If a participating laboratory fails to meet the provisions of 
    these guidelines, it is recommended that the responsible physician 
    disapprove further analyses of biological samples by that laboratory 
    until it demonstrates compliance with these guidelines. On 
    disapproval, biological samples should be sent to a laboratory that 
    can demonstrate compliance with these guidelines, at least until the 
    former laboratory is reevaluated by the responsible physician and 
    found to be in compliance.
        The following record keeping and reporting procedures should be 
    practiced by participating laboratories.
    
    3.3.1  Internal Quality Assurance/Quality Control Procedures
    
        Laboratories participating in the cadmium monitoring program 
    should develop and maintain an internal quality assurance/quality 
    control (QA/QC) program that incorporates procedures for 
    establishing and maintaining control for each of the analytic 
    procedures (determinations of CDB, CDU and/or B2MU) for which the 
    laboratory is seeking participation. For laboratories analyzing CDU 
    and/or B2MU, a QA/QC program for CRTU also should be established.
        Written documentation of QA/QC procedures should be described in 
    a formal QA/QC plan; this plan should contain the following 
    information: Sample acceptance and handling procedures (i.e., chain-
    of-custody); sample preparation procedures; instrument parameters; 
    calibration procedures; and, calculations. Documentation of QA/QC 
    procedures should be sufficient to identify analytical problems, 
    define criteria under which analysis of compliance samples will be 
    suspended, and describe procedures for corrective actions.
    
    3.3.1.1  QA/QC procedures for establishing control of CDB and CDU 
    analyses
    
        The QA/QC program for CDB and CDU should address, at a minimum, 
    procedures involved in calibration, establishment of control limits, 
    internal QC analyses and maintaining control, and corrective-action 
    protocols. Participating laboratory should develop and maintain 
    procedures to assure that analyses of compliance samples are within 
    control limits, and that these procedures are documented thoroughly 
    in a QA/QC plan.
        A nonmandatory QA/QC protocol is presented in Attachment 1. This 
    attachment is illustrative of the procedures that should be 
    addressed in a proper QA/QC program.
        Calibration. Before any analytic runs are conducted, the 
    analytic instrument should be calibrated. Calibration should be 
    performed at the beginning of each day on which QC and/or compliance 
    samples are run. Once calibration is established, QC or compliance 
    samples may be run. Regardless of the type of samples run, about 
    every fifth sample should serve as a standard to assure that 
    calibration is being maintained.
        Calibration is being maintained if the standard is within 
    15% of its theoretical value. If a standard is more than 
    15% of its theoretical value, the run has exceeded 
    control limits due to calibration error; the entire set of samples 
    then should be reanalyzed after recalibrating or the results should 
    be recalculated based on a statistical curve derived from that set 
    of standards.
        It is essential that the value of the highest standard analyzed 
    be higher than the highest sample analyzed; it may be necessary, 
    therefore, to run a high standard at the end of the run, which has 
    been selected based on results obtained over the course of the run 
    (i.e., higher than any standard analyzed to that point).
        Standards should be kept fresh; as samples age, they should be 
    compared with new standards and replaced if necessary.
        Internal Quality Control Analyses. Internal QC samples should be 
    determined interspersed with analyses of compliance samples. At a 
    minimum, these samples should be run at a rate of 5% of the 
    compliance samples or at least one set of QC samples per analysis of 
    compliance samples, whichever is greater. If only 2 samples are run, 
    they should contain different levels of cadmium.
        Internal QC samples may be obtained as commercially-available 
    reference materials and/or they may be internally prepared. 
    Internally-prepared samples should be well characterized and traced, 
    or compared to a reference material for which a consensus value is 
    available.
        Levels of cadmium contained in QC samples should not be known to 
    the analyst prior to reporting the results of the analysis.
        Internal QC results should be plotted or charted in a manner 
    which describes sample recovery and laboratory control limits.
        Internal Control Limits. The laboratory protocol for evaluating 
    internal QC analyses per control limits should be clearly defined. 
    Limits may be based on statistical methods (e.g., as 2s from the 
    laboratory mean recovery), or on proficiency testing limits (e.g., 
    1 g or 15% of the mean, whichever is greater). 
    Statistical limits that exceed 40% should be reevaluated 
    to determine the source error in the analysis.
        When laboratory limits are exceeded, analytic work should 
    terminate until the source of error is determined and corrected; 
    compliance samples affected by the error should be reanalyzed. In 
    addition, the laboratory protocol should address any unusual trends 
    that develop which may be biasing the results. Numerous, consecutive 
    results above or below laboratory mean recoveries, or outside 
    laboratory statistical limits, indicate that problems may have 
    developed.
        Corrective Actions. The QA/QC plan should document in detail 
    specific actions taken if control limits are exceeded or unusual 
    trends develop. Corrective actions should be noted on an appropriate 
    form, accompanied by supporting documentation.
        In addition to these actions, laboratories should include 
    whatever additional actions are necessary to assure that accurate 
    data are reported to the responsible physicians.
        Reference Materials. The following reference materials may be 
    available:
    
    Cadmium in Blood (CDB)
    
        1. Centre de Toxicologie du Quebec, Le Centre Hospitalier de 
    l'Universite Laval, 2705 boul. Laurier, Quebec, Que., Canada G1V 
    4G2. (Prepared 6 times per year at 1-15 g Cd/l.)
        2. H. Marchandise, Community Bureau of Reference-BCR, 
    Directorate General XII, Commission of the European Communities, 
    200, rue de la Loi, B-1049, Brussels, Belgium. (Prepared as Bl CBM-1 
    at 5.37 g Cd/l, and Bl CBM-2 at 12.38 g Cd/l.)
        3. Kaulson Laboratories Inc., 691 Bloomfield Ave., Caldwell, NJ 
    07006; tel: (201) 226-9494, FAX (201) 226-3244. (Prepared as #0141 
    [As, Cd, Hg, Pb] at 2 levels.)
    
    Cadmium in Urine (CDU)
    
        1. Centre de Toxicologie du Quebec, Le Centre Hospitalier de 
    l'Universite Laval, 2705 boul. Laurier, Quebec, Que., Canada G1V 
    4G2. (Prepared 6 times per year.)
        2. National Institute of Standards and Technology (NIST), Dept. 
    of Commerce, Gaithersburg, MD; tel: (301) 975-6776. (Prepared as SRM 
    2670 freeze-dried urine [metals]; set includes normal and elevated 
    levels of metals; cadmium is certified for elevated level of 88.0 
    g/l in reconstituted urine.)
        3. Kaulson Laboratories Inc., 691 Bloomfield Ave., Caldwell, NJ 
    07006; tel: (201) 226-9494, FAX (201) 226-3244. (Prepared as #0140 
    [As, Cd, Hg, Pb] at 2 levels.)
    
    3.3.1.2  QA/QC procedures for establishing control of B2MU
    
        A written, detailed QA/QC plan for B2MU analysis should be 
    developed. The QA/QC plan should contain a protocol similar to those 
    protocols developed for the CDB/CDU analyses. Differences in 
    analyses may warrant some differences in the QA/QC protocol, but 
    procedures to ensure analytical integrity should be developed and 
    followed.
        Examples of performance summaries that can be provided include 
    measurements of accuracy (i.e., the means of measured values versus 
    target values for the control samples) and precision (i.e., based on 
    duplicate analyses). It is recommended that the accuracy and 
    precision measurements be compared to those reported as achievable 
    by the Pharmacia Delphia kit (Pharmacia 1990) to determine if and 
    when unsatisfactory analyses have arisen. If the measurement error 
    of 1 or more of the control samples is more than 15%, the run 
    exceeds control limits. Similarly, this decision is warranted when 
    the average CV for duplicate samples is greater than 5%.
    
    3.3.2  Procedures for Record Keeping
    
        To satisfy reporting requirements for commercial analyses of 
    CDB, CDU and/or B2MU performed for the medical monitoring program 
    mandated under the cadmium rule, participating laboratories should 
    maintain the following documentation for each analyte:
        1. For each analytic instrument on which analyte determinations 
    are made, records relating to the most recent calibration and QC 
    sample analyses;
        2. For these instruments, a tabulated record for each analyte of 
    those determinations found to be within and outside of control 
    limits over the past 2 years;
        3. Results for the previous 2 years of the QC sample analyses 
    conducted under the internal QA/QC program (this information should 
    be: Provided for each analyte for which determinations are made and 
    for each analytic instrument used for this purpose, sufficient to 
    demonstrate that internal QA/QC programs are being executed 
    properly, and consistent with data sent to responsible physicians.
        4. Duplicate copies of monitoring results for each analyte sent 
    to clients during the previous 5 years, as well as associated 
    information; supporting material such as chain-of-custody forms also 
    should be retained; and,
        5. Proficiency test results and related materials received while 
    participating in the CTQ interlaboratory program over the past 2 
    years; results also should be tabulated to provide a serial record 
    of relative error (derived per Section 3.3.3 below).
    
    3.3.3  Reporting Procedures
    
        Participating laboratories should maintain these documents: QA/
    QC program plans; QA/QC status reports; CTQ proficiency program 
    reports; and, analytical data reports. The information that should 
    be included in these reports is summarized in Table 2; a copy of 
    each report should be sent to the responsible physician.
          
    
      Table 2.--Reporting Procedures for Laboratories Participating in the  
                       Cadmium Medical Monitoring Program                   
    ------------------------------------------------------------------------
                              Frequency (time                               
            Report                 frame)                  Contents         
    ------------------------------------------------------------------------
    1 QA/QC Program Plan.  Once (initially).....  A detailed description of 
                                                   the QA/QC protocol to be 
                                                   established by the       
                                                   laboratory to maintain   
                                                   control of analyte       
                                                   determinations.          
    2 QA/QC Status Report  Every 2 months.......  Results of the QC samples 
                                                   incorporated into regular
                                                   runs for each instrument 
                                                   (over the period since   
                                                   the last report).        
    3 Proficiency Report.  Attached to every      Results from the last full
                            data report.           year of proficiency      
                                                   samples submitted to the 
                                                   CTQ program and Results  
                                                   of the 100 most recent QC
                                                   samples incorporated into
                                                   regular runs for each    
                                                   instrument.              
    4 Analytical Data      For all reports of     Date the sample was       
     Report.                data results.          received; Date the sample
                                                   was analyzed; Appropriate
                                                   chain-of-custody         
                                                   information; Types of    
                                                   analyses performed;      
                                                   Results of the requested 
                                                   analyses and Copy of the 
                                                   most current proficiency 
                                                   report.                  
    ------------------------------------------------------------------------
    
        As noted in Section 3.3.1, a QA/QC program plan should be 
    developed that documents internal QA/QC procedures (defined under 
    Section 3.3.1) to be implemented by the participating laboratory for 
    each analyte; this plan should provide a list identifying each 
    instrument used in making analyte determinations.
        A QA/QC status report should be written bimonthly for each 
    analyte. In this report, the results of the QC program during the 
    reporting period should be reported for each analyte in the 
    following manner: The number (N) of QC samples analyzed during the 
    period; a table of the target levels defined for each sample and the 
    corresponding measured values; the mean of F/T value (as defined 
    below) for the set of QC samples run during the period; and, use of 
    X2s (as defined below) for the set of QC samples run 
    during the period as a measure of precision.
        As noted in Section 2, an F/T value for a QC sample is the ratio 
    of the measured concentration of analyte to the established (i.e., 
    reference) concentration of analyte for that QC sample. The equation 
    below describes the derivation of the mean for F/T values, X (with N 
    being analyzed the total number of samples analyzed):
    
    TR03JA94.000
    
    The standard deviation, s, for these measurements is derived using 
    the following equation (note that 2s is twice this value):
    
    TR03JA94.001
    
        The nonmandatory QA/QC protocol (see Attachment 1) indicates 
    that QC samples should be divided into several discrete pools, and a 
    separate estimate of precision for each pools then should be 
    derived. Several precision estimates should be provided for 
    concentrations which differ in average value. These precision 
    measures may be used to document improvements in performance with 
    regard to the combined pool.
        Participating laboratories should use the CTQ proficiency 
    program for each analyte. Results of the this program will be sent 
    by CTQ directly to physicians designated by the participating 
    laboratories. Proficiency results from the CTQ program are used to 
    establish the accuracy of results from each participating 
    laboratory, and should be provided to responsible physicians for use 
    in trend analysis. A proficiency report consisting of these 
    proficiency results should accompany data reports as an attachment.
        For each analyte, the proficiency report should include the 
    results from the 6 previous proficiency rounds in the following 
    format:
        1. Number (N) of samples analyzed;
        2. Mean of the target levels, (1/N)i, 
    with Ti being a consensus mean for the sample;
        3. Mean of the measurements, (1/N)i, with 
    Mi being a sample measurement;
        4. A measure of error defined by:
    
    (1/N)(Ti-Mi)\2\
    
        Analytical data reports should be submitted to responsible 
    physicians directly. For each sample, report the following 
    information: The date the sample was received; the date the sample 
    was analyzed; appropriate chain-of-custody information; the type(s) 
    of analyses performed; and, the results of the analyses. This 
    information should be reported on a form similar to the form 
    provided an appropriate form. The most recent proficiency program 
    report should accompany the analytical data reports (as an 
    attachment).
        Confidence intervals for the analytical results should be 
    reported as X2s, with X being the measured value and 2s 
    the standard deviation calculated as described above.
        For CDU or B2MU results, which are combined with CRTU 
    measurements for proper reporting, the 95% confidence limits are 
    derived from the limits for CDU or B2MU, (p), and the limits for 
    CRTU, (q), as follows:
    
    TR03JA94.002
    
    For these calculations, Xp is the measurement and 
    confidence limits for CDU or B2MU, and Yq is the 
    measurement and confidence limit for CRTU.
        Participating laboratories should notify responsible physicians 
    as soon as they receive information indicating a change in their 
    accreditation status with the CTQ or the CAP. These physicians 
    should not be expected to wait until formal notice of a status 
    change has been received from the CTQ or the CAP.
    
    3.4  Instructions to Physicians
    
        Physicians responsible for the medical monitoring of cadmium-
    exposed workers must collect the biological samples from workers; 
    they then should select laboratories to perform the required 
    analyses, and should interpret the analytic results.
    
    3.4.1  Sample Collection and Holding Procedures
    
        Blood Samples. The following procedures are recommended for the 
    collection, shipment and storage of blood samples for CDB analysis 
    to reduce analytical variablility; these recommendations were 
    obtained primarily through personal communications with J.P. Weber 
    of the CTQ (1991), and from reports by the Centers for Disease 
    Control (CDC, 1986) and Stoeppler and Brandt (1980).
        To the extent possible, blood samples should be collected from 
    workers at the same time of day. Workers should shower or thoroughly 
    wash their hands and arms before blood samples are drawn. The 
    following materials are needed for blood sample collection: Alcohol 
    wipes; sterile gauze sponges; band-aids; 20-gauge, 1.5-in. stainless 
    steel needles (sterile); preprinted labels; tourniquets; vacutainer 
    holders; 3-ml ``metal free'' vacutainer tubes (i.e., dark-blue 
    caps), with EDTA as an anti-coagulant; and, styrofoam vacutainer 
    shipping containers.
        Whole blood samples are taken by venipuncture. Each blue-capped 
    tube should be labeled or coded for the worker and company before 
    the sample is drawn. (Blue-capped tubes are recommended instead of 
    red-capped tubes because the latter may consist of red coloring 
    pigment containing cadmium, which could contaminate the samples.) 
    Immediately after sampling, the vacutainer tubes must be thoroughly 
    mixed by inverting the tubes at least 10 times manually or 
    mechanically using a Vortex device (for 15 sec). Samples should be 
    refrigerated immediately or stored on ice until they can be packed 
    for shipment to the participating laboratory for analysis.
        The CDC recommends that blood samples be shipped with a ``cool 
    pak'' to keep the samples cold during shipment. However, the CTQ 
    routinely ships and receives blood samples for cadmium analysis that 
    have not been kept cool during shipment. The CTQ has found no 
    deterioration of cadmium in biological fluids that were shipped via 
    parcel post without a cooling agent, even though these deliveries 
    often take 2 weeks to reach their destination.
        Urine Samples. The following are recommended procedures for the 
    collection, shipment and storage of urine for CDU and B2MU analyses, 
    and were obtained primarily through personal communications with 
    J.P. Weber of the CTQ (1991), and from reports by the CDC (1986) and 
    Stoeppler and Brandt (1980).
        Single ``spot'' samples are recommended. As B2M can degrade in 
    the bladder, workers should first empty their bladder and then drink 
    a large glass of water at the start of the visit. Urine samples then 
    should be collected within 1 hour. Separate samples should be 
    collected for CDU and B2MU using the following materials: Sterile 
    urine collection cups (250 ml); small sealable plastic bags; 
    preprinted labels; 15-ml polypropylene or polyethylene screw-cap 
    tubes; lab gloves (``metal free''); and, preservatives (as 
    indicated).
        The sealed collection cup should be kept in the plastic bag 
    until collection time. The workers should wash their hands with soap 
    and water before receiving the collection cup. The collection cup 
    should not be opened until just before voiding and the cup should be 
    sealed immediately after filling. It is important that the inside of 
    the container and cap are not touched by, or come into contact with, 
    the body, clothing or other surfaces.
        For CDU analyzes, the cup is swirled gently to resuspend any 
    solids, and the 15-ml tube is filled with 10-12 ml urine. The CDC 
    recommends the addition of 100 l concentrated HNO3 as 
    a preservative before sealing the tube and then freezing the sample. 
    The CTQ recommends minimal handling and does not acidify their 
    interlaboratory urine reference materials prior to shipment, nor do 
    they freeze the sample for shipment. At the CTQ, if the urine sample 
    has much sediment, the sample is acidified in the lab to free any 
    cadmium in the precipitate.
        For B2M, the urine sample should be collected directly into a 
    polyethylene bottle previously washed with dilute nitric acid. The 
    pH of the urine should be measured and adjusted to 8.0 with 0.1 N 
    NaOH immediately following collection. Samples should be frozen and 
    stored at -20 deg.C until testing is performed. The B2M in the 
    samples should be stable for 2 days when stored at 2-8 deg.C, and 
    for at least 2 months at -20 deg.C. Repeated freezing and thawing 
    should be avoided to prevent denaturing the B2M (Pharmacia 1990).
    
    3.4.2  Recommendations for Evaluating Laboratories
    
        Using standard error data and the results of proficiency testing 
    obtained from CTQ, responsible physicians can make an informed 
    choice of which laboratory to select to analyze biological samples. 
    In general, laboratories with small standard errors and little 
    disparity between target and measured values tend to make precise 
    and accurate sample determinations. Estimates of precision provided 
    to the physicians with each set of monitoring results can be 
    compared to previously-reported proficiency and precision estimates. 
    The latest precision estimates should be at least as small as the 
    standard error reported previously by the laboratory. Moreover, 
    there should be no indication that precision is deteriorating (i.e., 
    increasing values for the precision estimates). If precision is 
    deteriorating, physicians may decide to use another laboratory for 
    these analyses. QA/QC information provided by the participating 
    laboratories to physicians can, therefore, assist physicians in 
    evaluating laboratory performance.
    
    3.4.3  Use and Interpretation of Results
    
        When the responsible physician has received the CDB, CDU and/or 
    B2MU results, these results must be compared to the action levels 
    discussed in the final rule for cadmium. The comparison of the 
    sample results to action levels is straightforward. The measured 
    value reported from the laboratory can be compared directly to the 
    action levels; if the reported value exceeds an action level, the 
    required actions must be initiated.
    
    4.0  Background
    
        Cadmium is a naturally-occurring environmental contaminant to 
    which humans are continually exposed in food, water, and air. The 
    average daily intake of cadmium by the U.S. population is estimated 
    to be 10-20 g/day. Most of this intake is via ingestion, 
    for which absorption is estimated at 4-7% (Kowal et al. 1979). An 
    additional nonoccupational source of cadmium is smoking tobacco; 
    smoking a pack of cigarettes a day adds an additional 2-4 g 
    cadmium to the daily intake, assuming absorption via inhalation of 
    25-35% (Nordberg and Nordberg 1988; Friberg and Elinder 1988; Travis 
    and Haddock 1980).
        Exposure to cadmium fumes and dusts in an occupational setting 
    where air concentrations are 20-50 g/m\3\ results in an 
    additional daily intake of several hundred micrograms (Friberg and 
    Elinder 1988, p. 563). In such a setting, occupational exposure to 
    cadmium occurs primarily via inhalation, although additional 
    exposure may occur through the ingestion of material via 
    contaminated hands if workers eat or smoke without first washing. 
    Some of the particles that are inhaled initially may be ingested 
    when the material is deposited in the upper respiratory tract, where 
    it may be cleared by mucociliary transport and subsequently 
    swallowed.
        Cadmium introduced into the body through inhalation or ingestion 
    is transported by the albumin fraction of the blood plasma to the 
    liver, where it accumulates and is stored principally as a bound 
    form complexed with the protein metallothionein. Metallothionein-
    bound cadmium is the main form of cadmium subsequently transported 
    to the kidney; it is these 2 organs, the liver and kidney, in which 
    the majority of the cadmium body burden accumulates. As much as one 
    half of the total body burden of cadmium may be found in the kidneys 
    (Nordberg and Nordberg 1988).
        Once cadmium has entered the body, elimination is slow; about 
    0.02% of the body burden is excreted per day via urinary/fecal 
    elimination. The whole-body half-life of cadmium is 10-35 years, 
    decreasing slightly with increasing age (Travis and Haddock 1980).
        The continual accumulation of cadmium is the basis for its 
    chronic noncarcinogenic toxicity. This accumulation makes the kidney 
    the target organ in which cadmium toxicity usually is first observed 
    (Piscator 1964). Renal damage may occur when cadmium levels in the 
    kidney cortex approach 200 g/g wet tissue-weight (Travis 
    and Haddock 1980).
        The kinetics and internal distribution of cadmium in the body 
    are complex, and depend on whether occupational exposure to cadmium 
    is ongoing or has terminated. In general, cadmium in blood is 
    related principally to recent cadmium exposure, while cadmium in 
    urine reflects cumulative exposure (i.e., total body burden) 
    (Lauwerys et al. 1976; Friberg and Elinder 1988).
    
    4.1  Health Effects
    
        Studies of workers in a variety of industries indicate that 
    chronic exposure to cadmium may be linked to several adverse health 
    effects including kidney dysfunction, reduced pulmonary function, 
    chronic lung disease and cancer (Federal Register 1990). The primary 
    sites for cadmium-associated cancer appear to be the lung and the 
    prostate.
        Cancer. Evidence for an association between cancer and cadmium 
    exposure comes from both epidemiological studies and animal 
    experiments. Pott (1965) found a statistically significant elevation 
    in the incidence of prostate cancer among a cohort of cadmium 
    workers. Other epidemiology studies also report an elevated 
    incidence of prostate cancer; however, the increases observed in 
    these other studies were not statistically significant (Meridian 
    Research, Inc. 1989).
        One study (Thun et al. 1985) contains sufficiently quantitative 
    estimates of cadmium exposure to allow evaluation of dose-response 
    relationships between cadmium exposure and lung cancer. A 
    statistically significant excess of lung cancer attributed to 
    cadmium exposure was found in this study, even after accounting for 
    confounding variables such as coexposure to arsenic and smoking 
    habits (Meridian Research, Inc. 1989).
        Evidence for quantifying a link between lung cancer and cadmium 
    exposure comes from a single study (Takenaka et al. 1983). In this 
    study, dose-response relationships developed from animal data were 
    extrapolated to humans using a variety of models. OSHA chose the 
    multistage risk model for estimating the risk of cancer for humans 
    using these animal data. Animal injection studies also suggest an 
    association between cadmium exposure and cancer, particularly 
    observations of an increased incidence of tumors at sites remote 
    from the point of injection. The International Agency for Research 
    on Cancer (IARC) (Supplement 7, 1987) indicates that this, and 
    related, evidence is sufficient to classify cadmium as an animal 
    carcinogen. However, the results of these injection studies cannot 
    be used to quantify risks attendant to human occupational exposures 
    due to differences in routes of exposure (Meridian Research, Inc. 
    1989).
        Based on the above-cited studies, the U.S. Environmental 
    Protection Agency (EPA) classifies cadmium as ``B1,'' a probable 
    human carcinogen (USEPA 1985). IARC in 1987 recommended that cadmium 
    be listed as a probable human carcinogen.
        Kidney Dysfunction. The most prevalent nonmalignant effect 
    observed among workers chronically exposed to cadmium is kidney 
    dysfunction. Initially, such dysfunction is manifested by 
    proteinuria (Meridian Research, Inc. 1989; Roth Associates, Inc. 
    1989). Proteinuria associated with cadmium exposure is most commonly 
    characterized by excretion of low-molecular weight proteins (15,000-
    40,000 MW), accompanied by loss of electrolytes, uric acid, calcium, 
    amino acids, and phosphate. Proteins commonly excreted include 
    -2-microglobulin (B2M), retinol-binding protein (RBP), 
    immunoglobulin light chains, and lysozyme. Excretion of low 
    molecular weight proteins is characteristic of damage to the 
    proximal tubules of the kidney (Iwao et al. 1980).
        Exposure to cadmium also may lead to urinary excretion of high-
    molecular weight proteins such as albumin, immunoglobulin G, and 
    glycoproteins (Meridian Research, Inc. 1989; Roth Associates, Inc. 
    1989). Excretion of high-molecular weight proteins is indicative of 
    damage to the glomeruli of the kidney. Bernard et al. (1979) suggest 
    that cadmium-associated damage to the glomeruli and damage to the 
    proximal tubules of the kidney develop independently of each other, 
    but may occur in the same individual.
        Several studies indicate that the onset of low-molecular weight 
    proteinuria is a sign of irreversible kidney damage (Friberg et al. 
    1974; Roels et al. 1982; Piscator 1984; Elinder et al. 1985; Smith 
    et al. 1986). For many workers, once sufficiently elevated levels of 
    B2M are observed in association with cadmium exposure, such levels 
    do not appear to return to normal even when cadmium exposure is 
    eliminated by removal of the worker from the cadmium-contaminated 
    work environment (Friberg, exhibit 29, 1990).
        Some studies indicate that cadmium-induced proteinuria may be 
    progressive; levels of B2MU increase even after cadmium exposure has 
    ceased (Elinder et al. 1985). Other researchers have reached similar 
    conclusions (Frieburg testimony, OSHA docket exhibit 29, Elinder 
    testimony, OSHA docket exhibit 55, and OSHA docket exhibits 8-86B). 
    Such observations are not universal, however (Smith et al. 1986; 
    Tsuchiya 1976). Studies in which proteinuria has not been observed, 
    however, may have initiated the reassessment too early (Meridian 
    Research, Inc.1989; Roth Associates, Inc. 1989; Roels 1989).
        A quantitative assessment of the risks of developing kidney 
    dysfunction as a result of cadmium exposure was performed using the 
    data from Ellis et al. (1984) and Falck et al. (1983). Meridian 
    Research, Inc. (1989) and Roth Associates, Inc. (1989) employed 
    several mathematical models to evaluate the data from the 2 studies, 
    and the results indicate that cumulative cadmium exposure levels 
    between 5 and 100 g-years/m\3\ correspond with a one-in-a-
    thousand probability of developing kidney dysfunction.
        When cadmium exposure continues past the onset of early kidney 
    damage (manifested as proteinuria), chronic nephrotoxicity may occur 
    (Meridian Research, Inc. 1989; Roth Associates, Inc. 1989). Uremia, 
    which is the loss of the glomerulus' ability to adequately filter 
    blood, may result. This condition leads to severe disturbance of 
    electrolyte concentrations, which may result in various clinical 
    complications including atherosclerosis, hypertension, pericarditis, 
    anemia, hemorrhagic tendencies, deficient cellular immunity, bone 
    changes, and other problems. Progression of the disease may require 
    dialysis or a kidney transplant.
        Studies in which animals are chronically exposed to cadmium 
    confirm the renal effects observed in humans (Friberg et al. 1986). 
    Animal studies also confirm cadmium-related problems with calcium 
    metabolism and associated skeletal effects, which also have been 
    observed among humans. Other effects commonly reported in chronic 
    animal studies include anemia, changes in liver morphology, 
    immunosuppression and hypertension. Some of these effects may be 
    associated with cofactors; hypertension, for example, appears to be 
    associated with diet, as well as with cadmium exposure. Animals 
    injected with cadmium also have shown testicular necrosis.
    
    4.2  Objectives for Medical Monitoring
    
        In keeping with the observation that renal disease tends to be 
    the earliest clinical manifestation of cadmium toxicity, the final 
    cadmium standard mandates that eligible workers must be medically 
    monitored to prevent this condition (as well as cadmimum-induced 
    cancer). The objectives of medical-monitoring, therefore, are to: 
    Identify workers at significant risk of adverse health effects from 
    excess, chronic exposure to cadmium; prevent future cases of 
    cadmium-induced disease; detect and minimize existing cadmium-
    induced disease; and, identify workers most in need of medical 
    intervention.
        The overall goal of the medical monitoring program is to protect 
    workers who may be exposed continuously to cadmium over a 45-year 
    occupational lifespan. Consistent with this goal, the medical 
    monitoring program should assure that:
        1. Current exposure levels remain sufficiently low to prevent 
    the accumulation of cadmium body burdens sufficient to cause disease 
    in the future by monitoring CDB as an indicator of recent cadmium 
    exposure;
        2. Cumulative body burdens, especially among workers with 
    undefined historical exposures, remain below levels potentially 
    capable of leading to damage and disease by assessing CDU as an 
    indicator of cumulative exposure to cadmium; and,
        3. Health effects are not occurring among exposed workers by 
    determining B2MU as an early indicator of the onset of cadmium-
    induced kidney disease.
    
    4.3  Indicators of Cadmium Exposure and Disease
    
        Cadmium is present in whole blood bound to albumin, in 
    erythrocytes, and as a metallothionein-cadmium complex. The 
    metallothionein-cadmium complex that represents the primary 
    transport mechanism for cadmium delivery to the kidney. CDB 
    concentrations in the general, nonexposed population average 1 
    g Cd/l whole blood, with smokers exhibiting higher levels 
    (see Section 5.1.6). Data presented in Section 5.1.6 shows that 95% 
    of the general population not occupationally exposed to cadmium have 
    CDB levels less than 5 g Cd/l.
        If total body burdens of cadmium remain low, CDB concentrations 
    indicate recent exposure (i.e., daily intake). This conclusion is 
    based on data showing that cigarette smokers exhibit CDB 
    concentrations of 2-7 g/l depending on the number of 
    cigarettes smoked per day (Nordberg and Nordberg 1988), while CDB 
    levels for those who quit smoking return to general population 
    values (approximately 1 g/l) within several weeks (Lauwerys 
    et al. 1976). Based on these observations, Lauwerys et al. (1976) 
    concluded that CDB has a biological half-life of a few weeks to less 
    than 3 months. As indicated in Section 3.1.6, the upper 95th 
    percentile for CDB levels observed among those who are not 
    occupationally exposed to cadmium is 5 g/l, which suggests 
    that the absolute upper limit to the range reported for smokers by 
    Nordberg and Nordberg may have been affected by an extreme value 
    (i.e., beyond 2 above the mean).
        Among occupationally-exposed workers, the occupational history 
    of exposure to cadmium must be evaluated to interpret CDB levels. 
    New workers, or workers with low exposures to cadmium, exhibit CDB 
    levels that are representative of recent exposures, similar to the 
    general population. However, for workers with a history of chronic 
    exposure to cadmium, who have accumulated significant stores of 
    cadmium in the kidneys/liver, part of the CDB concentrations appear 
    to indicate body burden. If such workers are removed from cadmium 
    exposure, their CDB levels remain elevated, possibly for years, 
    reflecting prior long-term accumulation of cadmium in body tissues. 
    This condition tends to occur, however, only beyond some threshold 
    exposure value, and possibly indicates the capacity of body tissues 
    to accumulate cadmium which cannot be excreted readily (Friberg and 
    Elinder 1988; Nordberg and Nordberg 1988).
        CDU is widely used as an indicator of cadmium body burdens 
    (Nordberg and Nordberg 1988). CDU is the major route of elimination 
    and, when CDU is measured, it is commonly expressed either as 
    g Cd/l urine (unadjusted), g Cd/l urine (adjusted 
    for specific gravity), or g Cd/g CRTU (see Section 5.2.1). 
    The metabolic model for CDU is less complicated than CDB, since CDU 
    is dependentin large part on the body (i.e., kidney) burden of 
    cadmium. However, a small proportion of CDU still be attributed to 
    recent cadmium exposure, particularly if exposure to high airborne 
    concentrations of cadmium occurred. Note that CDU is subject to 
    larger interindividual and day-to-day variations than CDB, so 
    repeated measurements are recommended for CDU evaluations.
        CDU is bound principally to metallothionein, regardless of 
    whether the cadmium originates from metallothionein in plasma or 
    from the cadmium pool accumulated in the renal tubules. Therefore, 
    measurement of metallothionein in urine may provide information 
    similar to CDU, while avoiding the contamination problems that may 
    occur during collection and handling urine for cadmium analysis 
    (Nordberg and Nordberg 1988). However, a commercial method for the 
    determination of metallothionein at the sensitivity levels required 
    under the final cadmium rule is not currently available; therefore, 
    analysis of CDU is recommended.
        Among the general population not occupationally exposed to 
    cadmium, CDU levels average less than 1 g/l (see Section 
    5.2.7). Normalized for creatinine (CRTU), the average CDU 
    concentration of the general population is less than 1 g/g 
    CRTU. As cadmium accumulates over the lifespan, CDU increases with 
    age. Also, cigarette smokers may eventually accumulate twice the 
    cadmium body burden of nonsmokers, CDU is slightly higher in smokers 
    than in nonsmokers, even several years after smoking cessation 
    (Nordberg and Nordberg 1988). Despite variations due to age and 
    smoking habits, 95% of those not occupationally exposed to cadmium 
    exhibit levels of CDU less than 3 g/g CRTU (based on the 
    data presented in Section 5.2.7).
        About 0.02% of the cadmium body burden is excreted daily in 
    urine. When the critical cadmium concentration (about 200 ppm) in 
    the kidney is reached, or if there is sufficient cadmium-induced 
    kidney dysfunction, dramatic increases in CDU are observed (Nordberg 
    and Nordberg 1988). Above 200 ppm, therefore, CDU concentrations 
    cease to be an indicator of cadmium body burden, and are instead an 
    index of kidney failure.
        Proteinuria is an index of kidney dysfunction, and is defined by 
    OSHA to be a material impairment. Several small proteins may be 
    monitored as markers for proteinuria. Below levels indicative of 
    proteinuria, these small proteins may be early indicators of 
    increased risk of cadmium-induced renal tubular disease. Analytes 
    useful for monitoring cadmium-induced renal tubular damage include:
        1. -2-Microglobulin (B2M), currently the most widely 
    used assay for detecting kidney dysfunction, is the best 
    characterized analyte available (Iwao et al. 1980; Chia et al. 
    1989);
        2. Retinol Binding Protein (RBP) is more stable than B2M in 
    acidic urine (i.e., B2M breakdown occurs if urinary pH is less than 
    5.5; such breakdown may result in false [i.e., low] B2M values 
    [Bernard and Lauwerys, 1990]);
        3. N-Acetyl-B-Glucosaminidase (NAG) is the analyte of an assay 
    that is simple, inexpensive, reliable, and correlates with cadmium 
    levels under 10 g/g CRTU, but the assay is less sensitive 
    than RBP or B2M (Kawada et al. 1989);
        4. Metallothionein (MT) correlates with cadmium and B2M levels, 
    and may be a better predictor of cadmium exposure than CDU and B2M 
    (Kawada et al. 1989);
        5. Tamm-Horsfall Glycoprotein (THG) increases slightly with 
    elevated cadmium levels, but this elevation is small compared to 
    increases in urinary albumin, RBP, or B2M (Bernard and Lauwerys 
    1990);
        6. Albumin (ALB), determined by the biuret method, is not 
    sufficiently sensitive to serve as an early indicator of the onset 
    of renal disease (Piscator 1962);
        7. Albumin (ALB), determined by the Amido Black method, is 
    sensitive and reproducible, but involves a time-consuming procedure 
    (Piscator 1962);
        8. Glycosaminoglycan (GAG) increases among cadmium workers, but 
    the significance of this effect is unknown because no relationship 
    has been found between elevated GAG and other indices of tubular 
    damage (Bernard and Lauwerys 1990);
        9. Trehalase seems to increase earlier than B2M during cadmium 
    exposure, but the procedure for analysis is complicated and 
    unreliable (Iwata et al. 1988); and,
        10. Kallikrein is observed at lower concentrations among 
    cadmium-exposed workers than among normal controls (Roels et al. 
    1990).
        Of the above analytes, B2M appears to be the most widely used 
    and best characterized analyte to evaluate the presence/absence, as 
    well as the extent of, cadmium-induced renal tubular damage (Kawada, 
    Koyama, and Suzuki 1989; Shaikh and Smith 1984; Nogawa 1984). 
    However, it is important that samples be collected and handled so as 
    to minimize B2M degradation under acidic urine conditions.
        The threshold value of B2MU commonly used to indicate the 
    presence of kidney damage 300 g/g CRTU (Kjellstrom et al. 
    1977a; Buchet et al. 1980; and Kowal and Zirkes 1983). This value 
    represents the upper 95th or 97.5th percentile level of urinary 
    excretion observed among those without tubular dysfunction (Elinder, 
    exbt L-140-45, OSHA docket H057A). In agreement with these 
    conclusions, the data presented in Section 5.3.7 of this protocol 
    generally indicate that the level of 300 g/g CRTU appears 
    to define the boundary for kidney dysfunction. It is not clear, 
    however, that this level represents the upper 95th percentile of 
    values observed among those who fail to demonstrate proteinuria 
    effects.
        Although elevated B2MU levels appear to be a fairly specific 
    indicator of disease associated with cadmium exposure, other 
    conditions that may lead to elevated B2MU levels include high fevers 
    from influenza, extensive physical exercise, renal disease unrelated 
    to cadmium exposure, lymphomas, and AIDS (Iwao et al. 1980; Schardun 
    and van Epps 1987). Elevated B2M levels observed in association with 
    high fevers from influenza or from extensive physical exercise are 
    transient, and will return to normal levels once the fever has 
    abated or metabolic rates return to baseline values following 
    exercise. The other conditions linked to elevated B2M levels can be 
    diagnosed as part of a properly-designed medical examination. 
    Consequently, monitoring B2M, when accompanied by regular medical 
    examinations and CDB and CDU determinations (as indicators of 
    present and past cadmium exposure), may serve as a specific, early 
    indicator of cadmium-induced kidney damage.
    
    4.4  Criteria for Medical Monitoring of Cadmium Workers
    
        Medical monitoring mandated by the final cadmium rule includes a 
    combination of regular medical examinations and periodic monitoring 
    of 3 analytes: CDB, CDU and B2MU. As indicated above, CDB is 
    monitored as an indicator of current cadmium exposure, while CDU 
    serves as an indicator of the cadmium body burden; B2MU is assessed 
    as an early marker of irreversible kidney damage and disease.
        The final cadmium rule defines a series of action levels that 
    have been developed for each of the 3 analytes to be monitored. 
    These action levels serve to guide the responsible physician through 
    a decision-making process. For each action level that is exceeded, a 
    specific response is mandated. The sequence of action levels, and 
    the attendant actions, are described in detail in the final cadmium 
    rule.
        Other criteria used in the medical decision-making process 
    relate to tests performed during the medical examination (including 
    a determination of the ability of a worker to wear a respirator). 
    These criteria, however, are not affected by the results of the 
    analyte determinations addressed in the above paragraphs and, 
    consequently, will not be considered further in these guidelines.
    
    4.5  Defining to Quality and Proficiency of the Analyte Determinations
    
        As noted above in Sections 2 and 3, the quality of a measurement 
    should be defined along with its value to properly interpret the 
    results. Generally, it is necessary to know the accuracy and the 
    precision of a measurement before it can be properly evaluated. The 
    precision of the data from a specific laboratory indicates the 
    extent to which the repeated measurements of the same sample vary 
    within that laboratory. The accuracy of the data provides an 
    indication of the extent to which these results deviate from average 
    results determined from many laboratories performing the same 
    measurement (i.e., in the absence of an independent determination of 
    the true value of a measurement). Note that terms are defined 
    operationally relative to the manner in which they will be used in 
    this protocol. Formal definitions for the terms in italics used in 
    this section can be found in the list of definitions (Section 2).
        Another data quality criterion required to properly evaluate 
    measurement results is the limit of detection of that measurement. 
    For measurements to be useful, the range of the measurement which is 
    of interest for biological monitoring purposes must lie entirely 
    above the limit of detection defined for that measurement.
        The overall quality of a laboratory's results is termed the 
    performance of that laboratory. The degree to which a laboratory 
    satisfies a minimum performance level is referred to as the 
    proficiency of the laboratory. A successful medical monitoring 
    program, therefore, should include procedures developed for 
    monitoring and recording laboratory performance; these procedures 
    can be used to identify the most proficient laboratories.
    
    5.0  Overview of Medical Monitoring Tests for CDB, CDU, B2MU and CRTU
    
        To evaluate whether available methods for assessing CDB, CDU, 
    B2MU and CRTU are adequate for determining the parameters defined by 
    the proposed action levels, it is necessary to review procedures 
    available for sample collection, preparation and analysis. A variety 
    of techniques for these purposes have been used historically for the 
    determination of cadmium in biological matrices (including CDB and 
    CDU), and for the determination of specific proteins in biological 
    matrices (including B2MU). However, only the most recent techniques 
    are capable of satisfying the required accuracy, precision and 
    sensitivity (i.e., limit of detection) for monitoring at the levels 
    mandated in the final cadmium rule, while still facilitating 
    automated analysis and rapid processing.
    
    5.1  Measuring Cadmium in Blood (CDB)
    
        Analysis of biological samples for cadmium requires strict 
    analytical discipline regarding collection and handling of samples. 
    In addition to occupational settings, where cadmium contamination 
    would be apparent, cadmium is a ubiquitous environmental 
    contaminant, and much care should be exercised to ensure that 
    samples are not contaminated during collection, preparation or 
    analysis. Many common chemical reagents are contaminated with 
    cadmium at concentrations that will interfere with cadmium analysis; 
    because of the widespread use of cadmium compounds as colored 
    pigments in plastics and coatings, the analyst should continually 
    monitor each manufacturer's chemical reagents and collection 
    containers to prevent contamination of samples.
        Guarding against cadmium contamination of biological samples is 
    particularly important when analyzing blood samples because cadmium 
    concentrations in blood samples from nonexposed populations are 
    generally less than 2 g/l (2 ng/ml), while occupationally-
    exposed workers can be at medical risk to cadmium toxicity if blood 
    concentrations exceed 5 g/l (ACGIH 1991 and 1992). This 
    narrow margin between exposed and unexposed samples requires that 
    exceptional care be used in performing analytic determinations for 
    biological monitoring for occupational cadmium exposure.
        Methods for quantifying cadmium in blood have improved over the 
    last 40 years primarily because of improvements in analytical 
    instrumentation. Also, due to improvements in analytical techniques, 
    there is less need to perform extensive multi-step sample 
    preparations prior to analysis. Complex sample preparation was 
    previously required to enhance method sensitivity (for cadmium), and 
    to reduce interference by other metals or components of the sample.
    
    5.1.1  Analytical Techniques Used to Monitor Cadmium in Biological 
    Matrices
    
          
    
    Table 3.--Comparison of Analytical Procedures/Instrumentation for Determination of Cadmium in Biological Samples
    ----------------------------------------------------------------------------------------------------------------
                                Limit of                                                                            
      Analytical procedure   detection [ng/    Specified biological          Reference               Comments       
                               (g or ml)]             matrix                                                        
    ----------------------------------------------------------------------------------------------------------------
    Flame Atomic Absorption  1.0  Any matrix.............  Perkin-Elmer (1982)...  Not sensitive enough  
     Spectroscopy (FAAS).                                                                      for biomonitoring    
                                                                                               without extensive    
                                                                                               sample digestion,    
                                                                                               metal chelation and  
                                                                                               organic solvent      
                                                                                               extraction.          
    Graphite Furnace Atomic            0.04  Urine..................  Pruszkowska et al.      Methods of choice for 
     Absorption                                                        (1983).                 routine cadmium      
     Spectroscopy (GFAAS).                                                                     analysis.            
                             0.2  Blood..................  Stoeppler and Brandt                          
                                       0                               (1980).                                      
    Inductively-Coupled                2.0   Any matrix.............  NIOSH (1984A).........  Requires extensive    
     Argon-Plasma Atomic                                                                       sample preparation   
     Emission Spectroscopy                                                                     and concentration of 
     (ICAP AES).                                                                               metal with chelating 
                                                                                               resin. Advantage is  
                                                                                               simultaneous analyses
                                                                                               for as many as 10    
                                                                                               metals from 1 sample.
    Neutron Activation                 1.5   In vivo (liver)........  Ellis et al. (1983)...  Only available in vivo
     Gamma Spectroscopy                                                                        method for direct    
     (NA).                                                                                     determination of     
                                                                                               cadmium body tissue  
                                                                                               burdens; expensive;  
                                                                                               absolute             
                                                                                               determination of     
                                                                                               cadmium in reference 
                                                                                               materials.           
    Isotope Dilution Mass             <1.0 any="" matrix.............="" michiels="" and="" debievre="" suitable="" for="" absolute="" spectroscopy="" (idms).="" (1986).="" determination="" of="" cadmium="" in="" reference="" materials;="" expensive.="" differential="" pulse=""><1.0 any="" matrix.............="" stoeppler="" and="" brandt="" suitable="" for="" absolute="" anodic="" stripping="" (1980).="" determination="" of="" voltammetry="" (dpasv).="" cadmium="" in="" reference="" materials;="" efficient="" method="" to="" check="" accuracy="" of="" analytical="" method.="" ----------------------------------------------------------------------------------------------------------------="" a="" number="" of="" analytical="" techniques="" have="" been="" used="" for="" determining="" cadmium="" concentrations="" in="" biological="" materials.="" a="" summary="" of="" the="" characteristics="" of="" the="" most="" widely="" employed="" techniques="" is="" presented="" in="" table="" 3.="" the="" technique="" most="" suitable="" for="" medical="" monitoring="" for="" cadmium="" is="" atomic="" absorption="" spectroscopy="" (aas).="" to="" obtain="" a="" measurement="" using="" aas,="" a="" light="" source="" (i.e.,="" hollow="" cathode="" or="" lectrode-free="" discharge="" lamp)="" containing="" the="" element="" of="" interest="" as="" the="" cathode,="" is="" energized="" and="" the="" lamp="" emits="" a="" spectrum="" that="" is="" unique="" for="" that="" element.="" this="" light="" source="" is="" focused="" through="" a="" sample="" cell,="" and="" a="" selected="" wavelength="" is="" monitored="" by="" a="" monochrometer="" and="" photodetector="" cell.="" any="" ground="" state="" atoms="" in="" the="" sample="" that="" match="" those="" of="" the="" lamp="" element="" and="" are="" in="" the="" path="" of="" the="" emitted="" light="" may="" absorb="" some="" of="" the="" light="" and="" decrease="" the="" amount="" of="" light="" that="" reaches="" the="" photodetector="" cell.="" the="" amount="" of="" light="" absorbed="" at="" each="" characteristic="" wavelength="" is="" proportional="" to="" the="" number="" of="" ground="" state="" atoms="" of="" the="" corresponding="" element="" that="" are="" in="" the="" pathway="" of="" the="" light="" between="" the="" source="" and="" detector.="" to="" determine="" the="" amount="" of="" a="" specific="" metallic="" element="" in="" a="" sample="" using="" aas,="" the="" sample="" is="" dissolved="" in="" a="" solvent="" and="" aspirated="" into="" a="" high-temperature="" flame="" as="" an="" aerosol.="" at="" high="" temperatures,="" the="" solvent="" is="" rapidly="" evaporated="" or="" decomposed="" and="" the="" solute="" is="" initially="" solidified;="" the="" majority="" of="" the="" sample="" elements="" then="" are="" transformed="" into="" an="" atomic="" vapor.="" next,="" a="" light="" beam="" is="" focused="" above="" the="" flame="" and="" the="" amount="" of="" metal="" in="" the="" sample="" can="" be="" determined="" by="" measuring="" the="" degree="" of="" absorbance="" of="" the="" atoms="" of="" the="" target="" element="" released="" by="" the="" flame="" at="" a="" characteristic="" wavelength.="" a="" more="" refined="" atomic="" absorption="" technique,="" flameless="" aas,="" substitutes="" an="" electrothermal,="" graphite="" furnace="" for="" the="" flame.="" an="" aliquot="" (10-100="">l) of the sample is pipetted into the cold 
    furnace, which is then heated rapidly to generate an atomic vapor of 
    the element.
        AAS is a sensitive and specific method for the elemental 
    analysis of metals; its main drawback is nonspecific background 
    absorbtion and scattering of the light beam by particles of the 
    sample as it decomposes at high temperatures; nonspecific absorbance 
    reduces the sensitivity of the analytical method. The problem of 
    nonspecific absorbance and scattering can be reduced by extensive 
    sample pretreatment, such as ashing and/or acid digestion of the 
    sample to reduce its organic content.
        Current AAS instruments employ background correction devices to 
    adjust electronically for background absorbtion and scattering. A 
    common method to correct for background effects is to use a 
    deuterium arc lamp as a second light source. A continuum light 
    source, such as the deuterium lamp, emits a broad spectrum of 
    wavelengths instead of specific wavelengths characteristic of a 
    particular element, as with the hollow cathode tube. With this 
    system, light from the primary source and the continuum source are 
    passed alternately through the sample cell. The target element 
    effectively absorbs light only from the primary source (which is 
    much brighter than the continuum source at the characteristic 
    wavelengths), while the background matrix absorbs and scatters light 
    from both sources equally. Therefore, when the ratio of the two 
    beams is measured electronically, the effect of nonspecific 
    background absorption and scattering is eliminated. A less common, 
    but more sophisticated, backgrond correction system is based on the 
    Zeeman effect, which uses a magnetically-activated light polarizer 
    to compensate electronically for nonspecific absorbtion and 
    scattering.
        Atomic emission spectroscopy with inductively-coupled argon 
    plasma (AES-ICAP) is widely used to analyze for metals. With this 
    instrument, the sample is aspirated into an extremely hot argon 
    plasma flame, which excites the metal atoms; emission spectra 
    specific for the sample element then are generated. The quanta of 
    emitted light passing through a monochrometer are amplified by 
    photomultiplier tubes and measured by a photodetector to determine 
    the amount of metal in the sample. An advantage of AES-ICAP over AAS 
    is that multi-elemental analyses of a sample can be performed by 
    simultaneously measuring specific elemental emission energies. 
    However, AES-ICAP lacks the sensitivity of AAS, exhibiting a limit 
    of detection which is higher than the limit of detection for 
    graphite-furnace AAS (Table 3).
        Neutron activation (NA) analysis and isotope dilution mass 
    spectrometry (IDMS) are 2 additional, but highly specialized, 
    methods that have been used for cadmium determinations. These 
    methods are expensive because they require elaborate and 
    sophisticated instrumentation.
        NA analysis has the distinct advantage over other analytical 
    methods of being able to determine cadmium body burdens in specific 
    organs (e.g., liver, kidney) in vivo (Ellis et al. 1983). Neutron 
    bombardment of the target transforms cadmium-113 to cadmium-114, 
    which promptly decays (<>-14 sec) to its ground state, 
    emitting gamma rays that are measured using large gamma detectors; 
    appropriate shielding and instrumentation are required when using 
    this method.
        IDMS analysis, a definitive but laborious method, is based on 
    the change in the ratio of 2 isotopes of cadmium (cadmium 111 and 
    112) that occurs when a known amount of the element (with an 
    artificially altered ratio of the same isotopes [i.e., a cadmium 111 
    ``spike''] is added to a weighed aliquot of the sample (Michiels and 
    De Bievre 1986).
    
    5.1.2  Methods Developed for CDB Determinations
    
        A variety of methods have been used for preparing and analyzing 
    CDB samples; most of these methods rely on one of the analytical 
    techniques described above. Among the earliest reports, Princi 
    (1947) and Smith et al. (1955) employed a colorimetric procedure to 
    analyze for CDB and CDU. Samples were dried and digested through 
    several cycles with concentrated mineral acids (HNO3 and 
    H2SO4) and hydrogen peroxide (H2O2). The digest 
    was neutralized, and the cadmium was complexed with 
    diphenylthiocarbazone and extracted with chloroform. The dithizone-
    cadmium complex then was quantified using a spectrometer.
        Colorimetric procedures for cadmium analyses were replaced by 
    methods based on atomic absorption spectroscopy (AAS) in the early 
    1960s, but many of the complex sample preparation procedures were 
    retained. Kjellstrom (1979) reports that in Japanese, American and 
    Swedish laboratories during the early 1970s, blood samples were wet 
    ashed with mineral acids or ashed at high temperature and wetted 
    with nitric acid. The cadmium in the digest was complexed with metal 
    chelators including diethyl dithiocarbamate (DDTC), ammonium 
    pyrrolidine dithiocarbamate (APDC) or diphenylthiocarbazone 
    (dithizone) in ammonia-citrate buffer and extracted with methyl 
    isobutyl ketone (MIBK). The resulting solution then was analyzed by 
    flame AAS or graphite-furnace AAS forcadmium determinations using 
    deuterium-lamp background correction.
        In the late 1970s, researchers began developing simpler 
    preparation procedures. Roels et al. (1978) and Roberts and Clark 
    (1986) developed simplified digestion procedures. Using the Roberts 
    and Clark method, a 0.5 ml aliquot of blood is collected and 
    transferred to a digestion tube containing 1 ml concentrated 
    HNO3. The blood is then digested at 110  deg.C for 4 hours. The 
    sample is reduced in volume by continued heating, and 0.5 ml 30% 
    H2O2 is added as the sample dries. The residue is 
    dissolved in 5 ml dilute (1%) HNO3, and 20 l of sample 
    is then analyzed by graphite-furnace AAS with deuterium-background 
    correction.
        The current trend in the preparation of blood samples is to 
    dilute the sample and add matrix modifiers to reduce background 
    interference, rather than digesting the sample to reduce organic 
    content. The method of Stoeppler and Brandt (1980), and the 
    abbreviated procedure published in the American Public Health 
    Association's (APHA) Methods for Biological Monitoring (1988), are 
    straightforward and are nearly identical. For the APHA method, a 
    small aliquot (50-300 l) of whole blood that has been 
    stabilized with ethylenediaminetetraacetate (EDTA) is added to 1.0 
    ml 1MHNO3, vigorously shaken and centrifuged. Aliquots (10-25 
    l) of the supernatant then are then analyzed by graphite-
    furnace AAS with appropriate background correction.
        Using the method of Stoeppler and Brandt (1980), aliquots (50-
    200 l) of whole blood that have been stabilized with EDTA 
    are pipetted into clean polystyrene tubes and mixed with 150-600 
    l of 1 M HNO3. After vigorous shaking, the solution is 
    centrifuged and a 10-25 l aliquot of the supernatant then 
    is analyzed by graphite-furnace AAS with appropriate background 
    correction.
        Claeys-Thoreau (1982) and DeBenzo et al. (1990) diluted blood 
    samples at a ratio of 1:10 with a matrix modifier (0.2% Triton X-
    100, a wetting agent) for direct determinations of CDB. DeBenzo et 
    al. also demonstrated that aqueous standards of cadmium, instead of 
    spiked, whole-blood samples, could be used to establish calibration 
    curves if standards and samples are treated with additional small 
    volumes of matrix modifiers (i.e., 1% HNO3, 0.2% ammonium 
    hydrogenphosphate and 1 mg/ml magnesium salts).
        These direct dilution procedures for CDB analysis are simple and 
    rapid. Laboratories can process more than 100 samples a day using a 
    dedicated graphite-furnace AAS, an auto-sampler, and either a 
    Zeeman- or a deuterium-background correction system. Several authors 
    emphasize using optimum settings for graphite-furnace temperatures 
    during the drying, charring, and atomization processes associated 
    with the flameless AAS method, and the need to run frequent QC 
    samples when performing automated analysis.
    
    5.1.3  Sample Collection and Handling
    
        Sample collection procedures are addressed primarily to identify 
    ways to minimize the degree of variability that may be introduced by 
    sample collection during medical monitoring. It is unclear at this 
    point the extent to which collection procedures contribute to 
    variability among CDB samples. Sources of variation that may result 
    from sampling procedures include time-of-day effects and 
    introduction of external contamination during the collection 
    process. To minimize these sources, strict adherence to a sample 
    collection protocol is recommended. Such a protocol must include 
    provisions for thorough cleaning of the site from which blood will 
    be extracted; also, every effort should be made to collect samples 
    near the same time of day. It is also important to recognize that 
    under the recent OSHA blood-borne pathogens standard (29 CFR 
    1910.1030), blood samples and certain body fluids must be handled 
    and treated as if they are infectious.
    
    5.1.4  Best Achievable Performance
    
        The best achievable performance using a particular method for 
    CDB determinations is assumed to be equivalent to the performance 
    reported by research laboratories in which the method was developed.
        For their method, Roberts and Clark (1986) demonstrated a limit 
    of detection of 0.4 g Cd/l in whole blood, with a linear 
    response curve from 0.4 to 16.0 g Cd/l. They report a 
    coefficient of variation (CV) of 6.7% at 8.0 g/l.
        The APHA (1988) reports a range of 1.0-25 g/l, with a 
    CV of 7.3% (concentration not stated). Insufficient documentation 
    was available to critique this method.
        Stoeppler and Brandt (1980) achieved a detection limit of 0.2 
    g Cd/l whole blood, with a linear range of 0.4-12.0 
    g Cd/l, and a CV of 15-30%, for samples at <1.0>g/
    l. Improved precision (CV of 3.8%) was reported for CDB 
    concentrations at 9.3 g/l.
    
    5.1.5  General Method Performance
    
        For any particular method, the performance expected from 
    commercial laboratories may be somewhat lower than that reported by 
    the research laboratory in which the method was developed. With 
    participation in appropriate proficiency programs and use of a 
    proper in-house QA/QC program incorporating provisions for regular 
    corrective actions, the performance of commercial laboratories is 
    expected to approach that reported by research laboratories. Also, 
    the results reported for existing proficiency programs serve as a 
    gauge of the likely level of performance that currently can be 
    expected from commercial laboratories offering these analyses.
        Weber (1988) reports on the results of the proficiency program 
    run by the Centre de Toxicologie du Quebec (CTQ). As indicated 
    previously, participants in that program receive 18 blood samples 
    per year having cadmium concentrations ranging from 0.2-20 
    g/l. Currently, 76 laboratories are participating in this 
    program. The program is established for several analytes in addition 
    to cadmium, and not all of these laboratories participate in the 
    cadmium proficiency-testing program.
        Under the CTQ program, cadmium results from individual 
    laboratories are compared against the consensus mean derived for 
    each sample. Results indicate that after receiving 60 samples (i.e., 
    after participation for approximately three years), 60% of the 
    laboratories in the program are able to report results that fall 
    within 1 g/l or 15% of the mean, whichever is 
    greater. (For this procedure, the 15% criterion was applied to 
    concentrations exceeding 7 g/l.) On any single sample of 
    the last 20 samples, the percentage of laboratories falling within 
    the specified range is between 55 and 80%.
        The CTQ also evaluates the performance of participating 
    laboratories against a less severe standard: 2 
    g/l or 15% of the mean, whichever is greater (Weber 1988); 
    90% of participating laboratories are able to satisfy this standard 
    after approximately 3 years in the program. (The 15% criterion is 
    used for concentrations in excess of 13 g/l.) On any single 
    sample of the last 15 samples, the percentage of laboratories 
    falling within the specified range is between 80 and 95% (except for 
    a single test for which only 60% of the laboratories achieved the 
    desired performance).
        Based on the data presented in Weber (1988), the CV for analysis 
    of CDB is nearly constant at 20% for cadmium concentrations 
    exceeding 5 g/l, and increases for cadmium concentrations 
    below 5 g/l. At 2 g/l, the reported CV rises to 
    approximately 40%. At 1 g/l, the reported CV is 
    approximately 60%.
        Participating laboratories also tend to overestimate 
    concentrations for samples exhibiting concentrations less than 2 
    g/l (see Figure 11 of Weber 1988). This problem is due in 
    part to the proficiency evaluation criterion that allows reporting a 
    minimum 2.0 g/l for evaluated CDB samples. 
    There is currently little economic or regulatory incentive for 
    laboratories participating in the CTQ program to achieve greater 
    accuracy for CDB samples containing cadmium at concentrations less 
    than 2.0 g/l, even if the laboratory has the experience and 
    competency to distinguish among lower concentrations in the samples 
    obtained from the CTQ.
        The collective experience of international agencies and 
    investigators demonstrate the need for a vigorous QC program to 
    ensure that CDB values reported by participating laboratories are 
    indeed reasonably accurate. As Friberg (1988) stated:
    
    ``Information about the quality of published data has often been 
    lacking. This is of concern as assessment of metals in trace 
    concentrations in biological media are fraught with difficulties 
    from the collection, handling, and storage of samples to the 
    chemical analyses. This has been proven over and over again from the 
    results of interlaboratory testing and quality control exercises. 
    Large variations in results were reported even from `experienced' 
    laboratories.''
    
        The UNEP/WHO global study of cadmium biological monitoring set a 
    limit for CDB accuracy using the maximum allowable deviation method 
    at Y=X(0.1X+1) for a targeted concentration of 10 
    g Cd/l (Friberg and Vahter 1983). The performance of 
    participating laboratories over a concentration range of 1.5-12 
    g/l was reported by Lind et al. (1987). Of the 3 QC runs 
    conducted during 1982 and 1983, 1 or 2 of the 6 laboratories failed 
    each run. For the years 1983 and 1985, between zero and 2 
    laboratories failed each of the consecutive QC runs.
        In another study (Vahter and Friberg 1988), QC samples 
    consisting of both external (unknown) and internal (stated) 
    concentrations were distributed to laboratories participating in the 
    epidemiology research. In this study, the maximum acceptable 
    deviation between the regression analysis of reported results and 
    reference values was set at Y=X(0.05X+0.2) for a 
    concentration range of 0.3-5.0 g Cd/l. It is reported that 
    only 2 of 5 laboratories had acceptable data after the first QC set, 
    and only 1 of 5 laboratories had acceptable data after the second QC 
    set. By the fourth QC set, however, all 5 laboratories were judged 
    proficient.
        The need for high quality CDB monitoring is apparent when the 
    toxicological and biological characteristics of this metal are 
    considered; an increase in CDB from 2 to 4 g/l could cause 
    a doubling of the cadmium accumulation in the kidney, a critical 
    target tissue for selective cadmium accumulation (Nordberg and 
    Nordberg 1988).
        Historically, the CDC's internal QC program for CDB cadmium 
    monitoring program has found achievable accuracy to be 
    10% of the true value at CDB concentrations 
    5.0 g/l (Paschal 1990). Data on the performance 
    of laboratories participating in this program currently are not 
    available.
    
    5.1.6  'Observed CDB Concentrations
    
        As stated in Section 4.3, CDB concentrations are representative 
    of ongoing levels of exposure to cadmium. Among those who have been 
    exposed chronically to cadmium for extended periods, however, CDB 
    may contain a component attributable to the general cadmium body 
    burden.
    
    5.1.6.1  CDB Concentrations Among Unexposed Samples
    
        Numerous studies have been conducted examining CDB 
    concentrations in the general population, and in control groups used 
    for comparison with cadmium-exposed workers. A number of reports 
    have been published that present erroneously high values of CDB 
    (Nordberg and Nordberg 1988). This problem was due to contamination 
    of samples during sampling and analysis, and to errors in analysis. 
    Early AAS methods were not sufficiently sensitive to accurately 
    estimate CDB concentrations.
        Table 4 presents results of recent studies reporting CDB levels 
    for the general U.S. population not exposed occupationally to 
    cadmium. Other surveys of tissue cadmium using U.S. samples and 
    conducted as part of a cooperative effort among Japan, Sweden and 
    the U.S., did not collect CDB data because standard analytical 
    methodologies were unavailable, and because of analytic problems 
    (Kjellstrom 1979; SWRI 1978).
    
                                                    Table 4.--Blood Cadmium Concentrations of U.S. Population Not Occupationally Exposed to Cadmiuma                                                
    ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                              Lower 95th     Upper 95th                             
                                               No. in                           Smoking       Arithmetic mean      Absolute     Geometric   percentile of  percentile of                            
                    Study No.                   study     Sex       Age         habitsb     (S.D.)c    range or   mean (GSD)e   distributionf  distributionf          Reference         
                                                 (n)                                                              (95% CI)d                                                                         
    ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
    1.......................................        80  M       4 to 69      NS,S                      1.13        0.35-3.3   0.982.1     (0.5-5.0)                         g(0)         g(5.8)  Ellis et al. (1983).      
    3.......................................        24  M       Adults       NS                                               0.62.1     (0.5-7.3)                         g(0)         g(5.6)  Mueller et al. (1989).    
    ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
    aConcentrations reported in g Cd/l blood unless otherwise stated.                                                                                                                      
    bNS--never smoked; S--current cigarette smoker.                                                                                                                                                 
    cA.S.D.--Arithmetic Standard Deviation.                                                                                                                                                         
    dC.I.--Confidence Interval.                                                                                                                                                                     
    eG.S.D.--Geometric Standard Deviation.                                                                                                                                                          
    f Based on assumed lognormal distribution.                                                                                                                                                      
    g Based on assumed normal distribution.                                                                                                                                                         
    
        Arithmetic and/or geometric means and standard deviations are 
    provided in Table 4 for measurements among the populations defined 
    in each study listed. The range of reported measurements and/or the 
    95% upper and lower confidence intervals for the means are presented 
    when this information was reported in a study. For studies reporting 
    either an arithmetic or geometric standard deviation along with a 
    mean, the lower and upper 95th percentile for the distribution also 
    were derived and reported in the table.
        The data provided in Table 4 from Kowal et al. (1979) are from 
    studies conducted between 1974 and 1976 evaluating CDB levels for 
    the general population in Chicago, and are considered to be 
    representative of the U.S. population. These studies indicate that 
    the average CDB concentration among those not occupationally exposed 
    to cadmium is approximately 1 g/l.
        In several other studies presented in Table 4, measurements are 
    reported separately for males and females, and for smokers and 
    nonsmokers. The data in this table indicate that similar CDB levels 
    are observed among males and females in the general population, but 
    that smokers tend to exhibit higher CDB levels than nonsmokers. 
    Based on the Kowal et al. (1979) study, smokers not occupationally 
    exposed to cadmium exhibit an average CDB level of 1.4 g/l.
        In general, nonsmokers tend to exhibit levels ranging to 2 
    g/l, while levels observed among smokers range to 5 
    g/l. Based on the data presented in Table 4, 95% of those 
    not occupationally exposed to cadmium exhibit CDB levels less than 5 
    g/l.
    
    5.1.6.2  CDB Concentrations Among Exposed Workers
    
        Table 5 is a summary of results from studies reporting CDB 
    levels among workers exposed to cadmium in the work place. As in 
    Table 4, arithmetic and/or geometric means and standard deviations 
    are provided if reported in the listed studies. The absolute range, 
    or the 95% confidence interval around the mean, of the data in each 
    study are provided when reported. In addition, the lower and upper 
    95th percentile of the distribution are presented for each study in 
    which a mean and corresponding standard deviation were reported. 
    Table 5 also provides estimates of the duration, and level, of 
    exposure to cadmium in the work place if these data were reported in 
    the listed studies. The data presented in Table 5 suggest that CDB 
    levels are dose related. Sukuri et al. (1983) show that higher CDB 
    levels are observed among workers experiencing higher work place 
    exposure. This trend appears to be true of every one of the studies 
    listed in the table.
        CDB levels reported in Table 5 are higher among those showing 
    signs of cadmium-related kidney damage than those showing no such 
    damage. Lauwerys et al. (1976) report CDB levels among workers with 
    kidney lesions that generally are above the levels reported for 
    workers without kidney lesions. Ellis et al. (1983) report a similar 
    observation comparing workers with and without renal dysfunction, 
    although they found more overlap between the 2 groups than Lauwerys 
    et al.
    
                                                                  Table 5--Blood Cadmium in Workers Exposed to Cadmium in the Workplace                                                             
    ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    Concentrations of Cadmium in blooda                             
                                                                                            Mean      ----------------------------------------------------------------------------------------------
      Study         Work environment (worker population        Number    Employment    concentration                         Absolute                                                               
      number                     monitored)                   in study    in years     of cadmium in     Arithmetic mean     range or    Geometric    Lower 95th      Upper 95th                    
                                                                           (mean)     air (g/ (S.D.)b     (95%        mean      percentile of   percentile of      Reference   
                                                                                            m3)                               C.I.)c      (GSD)d      rangee ()f      rangee ()f                    
    ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
    1........  Ni-Cd battery plant and Cd production plant:                     3-40    90                                                                               Lauwerys et al. 
                                                                                                                                                                                     1976.          
               (Workers without kidney lesions).............        96  ............  ...............  21.41.9  ..........  ..........            (18)            (25)                  
               (Workers with kidney lesions)................        25  ............  ...............  38.83.8  ..........  ..........            (32)            (45)                  
    2........  Ni-Cd battery plant:                                                                                                                                                 Adamsson et al. 
                                                                                                                                                                                     (1979).        
               (Smokers)....................................         7           (5)             10.1             22.7        7.3-67.2                                                              
               (Nonsmokers).................................         8           (9)              7.0              7.0        4.9-10.5                                                              
    3........  Cadmium alloy plant:                                                                                                                                                 Sukuri et al.   
                                                                                                                                                                                     1982.          
               (High exposure group)........................         7        (10.6)    [1,000-5 yrs;  20.87.1  ..........  ..........           (7.3)            (34)                  
               (Low exposure group).........................         9         (7.3)        40-5 yrs]  7.11.1   ..........  ..........           (5.1)           (9.1)                  
    4........  Retrospective study of workers with renal            19         15-41                                                                                ..............  Roels et al.    
                problems:                                                                                                                                                            1982.          
               (Before removal).............................  ........        (27.2)  ...............  39.93.7      11-179  ..........            (34)            (46)                  
               (After removal)..............................  ........        (4.2)g  ...............  14.15.6    5.7-27.4  ..........           (4.4)            (24)                  
    5........  Cadmium production plant:                                                                                                                                            Ellis et al.    
                                                                                                                                                                                     1983.          
               (Workers without renal dysfunction)..........        33          1-34  ...............  155.7          7-31  ..........           (5.4)            (25)                  
               (Workers with renal dysfunction).............        18         10-34  ...............  248.5         10-34  ..........           (9.3)            (39)                  
    6........  Cd-Cu alloy plant............................        75      Up to 39  ...............  ...................  ..........  8.85.3    2.2-18.8  ..........           (1.3)            (19)  Mueller et al.  
                                                                                                                                                                                     1989.          
    ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
    aConcentrations reported in g Cd/l blood unless otherwise stated.                                                                                                                      
    bS.D.--Standard Deviation.                                                                                                                                                                      
    cC.I.--Confidence Interval.                                                                                                                                                                     
    dG.S.D.--Geometric Standard Deviation.                                                                                                                                                          
    e Based on assumed lognormal distribution.                                                                                                                                                      
    f Based on assumed normal distribution.                                                                                                                                                         
    g Years following removal.                                                                                                                                                                      
    
        The data in Table 5 also indicate that CDB levels are higher 
    among those experiencing current occupational exposure than those 
    who have been removed from such exposure. Roels et al. (1982) 
    indicate that CDB levels observed among workers experiencing ongoing 
    exposure in the work place are almost entirely above levels observed 
    among workers removed from such exposure. This finding suggests that 
    CDB levels decrease once cadmium exposure has ceased.
        A comparison of the data presented in Tables 4 and 5 indicates 
    that CDB levels observed among cadmium-exposed workers is 
    significantly higher than levels observed among the unexposed 
    groups. With the exception of 2 studies presented in Table 5 (1 of 
    which includes former workers in the sample group tested), the lower 
    95th percentile for CDB levels among exposed workers are greater 
    than 5 g/l, which is the value of the upper 95th percentile 
    for CDB levels observed among those who are not occupationally 
    exposed. Therefore, a CDB level of 5 g/l represents a 
    threshold above which significant work place exposure to cadmium may 
    be occurring.
    
    5.1.7  Conclusions and Recommendations for CDB
    
        Based on the above evaluation, the following recommendations are 
    made for a CDB proficiency program.
    
    5.1.7.1  Recommended Method
    
        The method of Stoeppler and Brandt (1980) should be adopted for 
    analyzing CDB. This method was selected over other methods for its 
    straightforward sample-preparation procedures, and because 
    limitations of the method were described adequately. It also is the 
    method used by a plurality of laboratories currently participating 
    in the CTQ proficiency program. In a recent CTQ interlaboratory 
    comparison report (CTQ 1991), analysis of the methods used by 
    laboratories to measure CDB indicates that 46% (11 of 24) of the 
    participating laboratories used the Stoeppler and Brandt methodology 
    (HNO3 deproteinization of blood followed by analysis of the 
    supernatant by GF-AAS). Other CDB methods employed by participating 
    laboratories identified in the CTQ report include dilution of blood 
    (29%), acid digestion (12%) and miscellaneous methods (12%).
        Laboratories may adopt alternate methods, but it is the 
    responsibility of the laboratory to demonstrate that the alternate 
    methods meet the data quality objectives defined for the Stoeppler 
    and Brandt method (see section 5.1.7.2 below).
    
    5.1.7.2  Data Quality Objectives
    
        Based on the above evaluation, the following data quality 
    objectives (DQOs) should facilitate interpretation of analytical 
    results.
        Limit of Detection. 0.5 g/l should be achievable using 
    the Stoeppler and Brandt method. Stoeppler and Brandt (1980) report 
    a limit of detection equivalent to 0.2 g/l in 
    whole blood using 25 l aliquots of deproteinized, diluted 
    blood samples.
        Accuracy. Initially, some of the laboratories performing CDB 
    measurements may be expected to satisfy criteria similar to the less 
    severe criteria specified by the CTQ program, i.e., measurements 
    within 2 g/l or 15% (whichever is greater) of the target 
    value. About 60% of the laboratories enrolled in the CTQ program 
    could meet this criterion on the first proficiencey test (Weber 
    1988).
        Currently, approximately 12 laboratories in the CTQ program are 
    achieving an accuracy for CDB analysis within the more severe 
    constraints of 1 g/l or 15% (whichever is 
    greater). Later, as laboratories gain experience, they should 
    achieve the level of accuracy exhibited by these 12 laboratories. 
    The experience in the CTQ program has shown that, even without 
    incentives, laboratories benefit from the feedback of the program; 
    after they have analyzed 40-50 control samples from the program, 
    performance improves to the point where about 60% of the 
    laboratories can meet the stricter criterion of 1 
    g/l or 15% (Weber 1988). Thus, this stricter target 
    accuracy is a reasonable DQO.
        Precision. Although Stoeppler and Brandt (1980) suggest that a 
    coefficient of variation (CV) near 1.3% (for a 10 g/l 
    concentration) is achievable for within-run reproducibility, it is 
    recognized that other factors affecting within- and between-run 
    comparability will increase the achievable CV. Stoeppler and Brandt 
    (1980) observed CVs that were as high as 30% for low concentrations 
    (0.4 g/l), and CVs of less than 5% for higher 
    concentrations.
        For internal QC samples (see section 3.3.1), laboratories should 
    to attain an overall precision near 25%. For CDB samples with 
    concentrations less than 2 g/l, a target precision of 40% 
    is reasonable, while precisions of 20% should be achievable for 
    concentrations greater than 2 g/l. Although these values 
    are more strict than values observed in the CTQ interlaboratory 
    program reported by Webber (1988), they are within the achievable 
    limits reported by Stoeppler and Brandt (1980).
    
    5.1.7.3  Quality Assurance/Quality Control
    
        Commercial laboratories providing measurement of CDB should 
    adopt an internal QA/QC program that incorporates the following 
    components: Strict adherence to the selected method, including all 
    calibration requirements; regular incorporation of QC samples during 
    actual runs; a protocol for corrective actions, and documentation of 
    these actions; and, participation in an interlaboratory proficiency 
    program. Note that the nonmandatory QA/QC program presented in 
    Attachment 1 is based on the Stoeppler and Brandt method for CDB 
    analysis. Should an alternate method be adopted, the laboratory 
    should develop a QA/QC program satisfying the provisions of Section 
    3.3.1.
    
    5.2  Measuring Cadmium in Urine (CDU)
    
        As in the case of CDB measurement, proper determination of CDU 
    requires strict analytical discipline regarding collection and 
    handling of samples. Because cadmium is both ubiquitous in the 
    environment and employed widely in coloring agents for industrial 
    products that may be used during sample collection, preparation and 
    analysis, care should be exercised to ensure that samples are not 
    contaminated during the sampling procedure.
        Methods for CDU determination share many of the same features as 
    those employed for the determination of CDB. Thus, changes and 
    improvements to methods for measuring CDU over the past 40 years 
    parallel those used to monitor CDB. The direction of development has 
    largely been toward the simplification of sample preparation 
    techniques made possible because of improvements in analytic 
    techniques.
    
    5.2.1  Units of CDU Measurement
    
        Procedures adopted for reporting CDU concentrations are not 
    uniform. In fact, the situation for reporting CDU is more 
    complicated than for CDB, where concentrations are normalized 
    against a unit volume of whole blood.
        Concentrations of solutes in urine vary with several biological 
    factors (including the time since last voiding and the volume of 
    liquid consumed over the last few hours); as a result, solute 
    concentrations should be normalized against another characteristic 
    of urine that represents changes in solute concentrations. The 2 
    most common techniques are either to standardize solute 
    concentrations against the concentration of creatinine, or to 
    standardize solute concentrations against the specific gravity of 
    the urine. Thus, CDU concentrations have been reported in the 
    literature as ``uncorrected'' concentrations of cadmium per volume 
    of urine (i.e., g Cd/l urine), ``corrected'' concentrations 
    of cadmium per volume of urine at a standard specific gravity (i.e., 
    g Cd/l urine at a specific gravity of 1.020), or 
    ``corrected'' mass concentration per unit mass of creatinine (i.e., 
    g Cd/g creatinine). (CDU concentrations [whether 
    uncorrected or corrected for specific gravity, or normalized to 
    creatinine] occasionally are reported in nanomoles [i.e., nmoles] of 
    cadmium per unit mass or volume. In this protocol, these values are 
    converted to g of cadmium per unit mass or volume using 89 
    nmoles of cadmium=10 g.)
        While it is agreed generally that urine values of analytes 
    should be normalized for reporting purposes, some debate exists over 
    what correction method should be used. The medical community has 
    long favored normalization based on creatinine concentration, a 
    common urinary constituent. Creatinine is a normal product of tissue 
    catabolism, is excreted at a uniform rate, and the total amount 
    excreted per day is constant on a day-to-day basis (NIOSH 1984b). 
    While this correction method is accepted widely in Europe, and 
    within some occupational health circles, Kowals (1983) argues that 
    the use of specific gravity (i.e., total solids per unit volume) is 
    more straightforward and practical (than creatinine) in adjusting 
    CDU values for populations that vary by age or gender.
        Kowals (1983) found that urinary creatinine (CRTU) is lower in 
    females than males, and also varies with age. Creatinine excretion 
    is highest in younger males (20-30 years old), decreases at middle 
    age (50-60 years), and may rise slightly in later years. Thus, 
    cadmium concentrations may be underestimated for some workers with 
    high CRTU levels.
        Within a single void urine collection, urine concentration of 
    any analyte will be affected by recent consumption of large volumes 
    of liquids, and by heavy physical labor in hot environments. The 
    absolute amount of analyte excreted may be identical, but 
    concentrations will vary widely so that urine must be corrected for 
    specific gravity (i.e., to normalize concentrations to the quantity 
    of total solute) using a fixed value (e.g., 1.020 or 1.024). 
    However, since heavy-metal exposure may increase urinary protein 
    excretion, there is a tendency to underestimate cadmium 
    concentrations in samples with high specific gravities when 
    specific-gravity corrections are applied.
        Despite some shortcomings, reporting solute concentrations as a 
    function of creatinine concentration is accepted generally; OSHA 
    therefore recommends that CDU levels be reported as the mass of 
    cadmium per unit mass of creatinine (g/g CTRU).
        Reporting CDU as g/g CRTU requires an additional 
    analytical process beyond the analysis of cadmium: Samples must be 
    analyzed independently for creatinine so that results may be 
    reported as the ratio of cadmium to creatinine concentrations found 
    in the urine sample. Consequently, the overall quality of the 
    analysis depends on the combined performance by a laboratory on 
    these 2 determinations. The analysis used for CDU determinations is 
    addressed below in terms of g Cd/l, with analysis of 
    creatinine addressed separately. Techniques for assessing creatinine 
    are discussed in Section 5.4.
        Techniques for deriving cadmium as a ratio of CRTU, and the 
    confidence limits for independent measurements of cadmium and CRTU, 
    are provided in Section 3.3.3.
    
    5.2.2  Analytical Techniques Used to Monitor CDU
    
        Analytical techniques used for CDU determinations are similar to 
    those employed for CDB determinations; these techniques are 
    summarized in Table 3. As with CDB monitoring, the technique most 
    suitable for CDU determinations is atomic absorption spectroscopy 
    (AAS). AAS methods used for CDU determinations typically employ a 
    graphite furnace, with background correction made using either the 
    deuterium-lamp or Zeeman techniques; Section 5.1.1 provides a 
    detailed description of AAS methods.
    
    5.2.3  Methods Developed for CDU Determinations
    
        Princi (1947), Smith et al. (1955), Smith and Kench (1957), and 
    Tsuchiya (1967) used colorimetric procedures similar to those 
    described in the CDB section above to estimate CDU concentrations. 
    In these methods, urine (50 ml) is reduced to dryness by heating in 
    a sand bath and digested (wet ashed) with mineral acids. Cadmium 
    then is complexed with dithiazone, extracted with chloroform and 
    quantified by spectrophotometry. These early studies typically 
    report reagent blank values equivalent to 0.3 g Cd/l, and 
    CDU concentrations among nonexposed control groups at maximum levels 
    of 10 g Cd/l--erroneously high values when compared to more 
    recent surveys of cadmium concentrations in the general population.
        By the mid-1970s, most analytical procedures for CDU analysis 
    used either wet ashing (mineral acid) or high temperatures (>400 
    deg.C) to digest the organic matrix of urine, followed by cadmium 
    chelation with APDC or DDTC solutions and extraction with MIBK. The 
    resulting aliquots were analyzed by flame or graphite-furnace AAS 
    (Kjellstrom 1979).
        Improvements in control over temperature parameters with 
    electrothermal heating devices used in conjunction with flameless 
    AAS techniques, and optimization of temperature programs for 
    controlling the drying, charring, and atomization processes in 
    sample analyses, led to improved analytical detection of diluted 
    urine samples without the need for sample digestion or ashing. Roels 
    et al. (1978) successfully used a simple sample preparation, 
    dilution of 1.0 ml aliquots of urine with 0.1 N HNO3, to 
    achieve accurate low-level determinations of CDU.
        In the method described by Pruszkowska et al. (1983), which has 
    become the preferred method for CDU analysis, urine samples were 
    diluted at a ratio of 1:5 with water; diammonium hydrogenphosphate 
    in dilute HNO3 was used as a matrix modifier. The matrix 
    modifier allows for a higher charring temperature without loss of 
    cadmium through volatilization during pre-atomization. This 
    procedure also employs a stabilized temperature platform in a 
    graphite furnace, while nonspecific background absorbtion is 
    corrected using the Zeeman technique. This method allows for an 
    absolute detection limit of approximately 0.04 g Cd/l 
    urine.
    
    5.2.4  Sample Collection and Handling
    
        Sample collection procedures for CDU may contribute to 
    variability observed among CDU measurements. Sources of variation 
    attendant to sampling include time-of-day, the interval since 
    ingestion of liquids, and the introduction of external contamination 
    during the collection process. Therefore, to minimize contributions 
    from these variables, strict adherence to a sample-collection 
    protocol is recommended. This a protocol should include provisions 
    for normalizing the conditions under which urine is collected. Every 
    effort also should be made to collect samples during the same time 
    of day.
        Collection of urine samples from an industrial work force for 
    biological monitoring purposes usually is performed using ``spot'' 
    (i.e., single-void) urine with the pH of the sample determined 
    immediately. Logistic and sample-integrity problems arise when 
    efforts are made to collect urine over long periods (e.g., 24 hrs). 
    Unless single-void urines are used, there are numerous opportunities 
    for measurement error because of poor control over sample 
    collection, storage and environmental contamination.
        To minimize the interval during which sample urine resides in 
    the bladder, the following adaption to the ``spot'' collection 
    procedure is recommended: The bladder should first be emptied, and 
    then a large glass of water should be consumed; the sample may be 
    collected within an hour after the water is consumed.
    
    5.2.5  Best Achievable Performance
    
        Performance using a particular method for CDU determinations is 
    assumed to be equivalent to the performance reported by the research 
    laboratories in which the method was developed. Pruszkowska et al. 
    (1983) report a detection limit of 0.04 g/l CDU, with a CV 
    of <4% between="" 0-5="">g/l. The CDC reports a minimum CDU 
    detection limit of 0.07 g/l using a modified method based 
    on Pruszkowska et al. (1983). No CV is stated in this protocol; the 
    protocol contains only rejection criteria for internal QC parameters 
    used during accuracy determinations with known standards (Attachment 
    8 of exhibit 106 of OSHA docket H057A). Stoeppler and Brandt (1980) 
    report a CDU detection limit of 0.2 g/l for their 
    methodology.
    
    5.2.6  General Method Performance
    
        For any particular method, the expected initial performance from 
    commercial laboratories may be somewhat lower than that reported by 
    the research laboratory in which the method was developed. With 
    participation in appropriate proficiency programs, and use of a 
    proper in-house QA/QC program incorporating provisions for regular 
    corrective actions, the performance of commercial laboratories may 
    be expected to improve and approach that reported by a research 
    laboratories. The results reported for existing proficiency programs 
    serve to specify the initial level of performance that likely can be 
    expected from commercial laboratories offering analysis using a 
    particular method.
        Weber (1988) reports on the results of the CTQ proficiency 
    program, which includes CDU results for laboratories participating 
    in the program. Results indicate that after receiving 60 samples 
    (i.e., after participating in the program for approximately 3 
    years), approximately 80% of the participating laboratories report 
    CDU results ranging between 2 g/l or 15% of the 
    consensus mean, whichever is greater. On any single sample of the 
    last 15 samples, the proportion of laboratories falling within the 
    specified range is between 75 and 95%, except for a single test for 
    which only 60% of the laboratories reported acceptable results. For 
    each of the last 15 samples, approximately 60% of the laboratories 
    reported results within 1 g or 15% of the mean, 
    whichever is greater. The range of concentrations included in this 
    set of samples was not reported.
        Another report from the CTQ (1991) summarizes preliminary CDU 
    results from their 1991 interlaboratory program. According to the 
    report, for 3 CDU samples with values of 9.0, 16.8, 31.5 g/
    l, acceptable results (target 2 g/l or 15% of 
    the consensus mean, whichever is greater) were achieved by only 44-
    52% of the 34 laboratories participating in the CDU program. The 
    overall CVs for these 3 CDU samples among the 34 participating 
    laboratories were 31%, 25%, and 49%, respectively. The reason for 
    this poor performance has not been determined.
        A more recent report from the CTQ (Weber, private communication) 
    indicates that 36% of the laboratories in the program have been able 
    to achieve the target of 1 g/l or 15% for more 
    than 75% of the samples analyzed over the last 5 years, while 45% of 
    participating laboratories achieved a target of 2 
    g/l or 15% for more than 75% of the samples analyzed over 
    the same period.
        Note that results reported in the interlaboratory programs are 
    in terms of g Cd/l of urine, unadjusted for creatinine. The 
    performance indicated, therefore, is a measure of the performance of 
    the cadmium portion of the analyses, and does not include variation 
    that may be introduced during the analysis of CRTU.
    
    5.2.7  Observed CDU Concentrations
    
        Prior to the onset of renal dysfunction, CDU concentrations 
    provide a general indication of the exposure history (i.e., body 
    burden)(see Section 4.3). Once renal dysfunction occurs, CDU levels 
    appear to increase and are no longer indicative solely of cadmium 
    body burden (Friberg and Elinder 1988).
    
    5.2.7.1  Range of CDU Concentrations Observed Among Unexposed Samples 
    
        Surveys of CDU concentrations in the general population were 
    first reported from cooperative studies among industrial countries 
    (i.e., Japan, U.S. and Sweden) conducted in the mid-1970s. In 
    summarizing these data, Kjellstrom (1979) reported that CDU 
    concentrations among Dallas, Texas men (age range: <9-59 years;="" smokers="" and="" nonsmokers)="" varied="" from="" 0.11-1.12="">g/l 
    (uncorrected for creatinine or specific gravity). These CDU 
    concentrations are intermediate between population values found in 
    Sweden (range: 0.11-0.80 g/l) and Japan (range: 0.14-2.32 
    g/l).
        Kowal and Zirkes (1983) reported CDU concentrations for almost 
    1,000 samples collected during 1978-79 from the general U.S. adult 
    population (i.e., nine states; both genders; ages 20-74 years). They 
    report that CDU concentrations are lognormally distributed; low 
    levels predominated, but a small proportion of the population 
    exhibited high levels. These investigators transformed the CDU 
    concentrations values, and reported the same data 3 different ways: 
    g/l urine (unadjusted), g/l (specific gravity 
    adjusted to 1.020), and g/g CRTU. These data are summarized 
    in Tables 6 and 7.
        Based on further statistical examination of these data, 
    including the lifestyle characteristics of this group, Kowal (1988) 
    suggested increased cadmium absorption (i.e., body burden) was 
    correlated with low dietary intakes of calcium and iron, as well as 
    cigarette smoking.
        CDU levels presented in Table 6 are adjusted for age and gender. 
    Results suggest that CDU levels may be slightly different among men 
    and women (i.e., higher among men when values are unadjusted, but 
    lower among men when the values are adjusted, for specific gravity 
    or CRTU). Mean differences among men and women are small compared to 
    the standard deviations, and therefore may not be significant. 
    Levels of CDU also appear to increase with age. The data in Table 6 
    suggest as well that reporting CDU levels adjusted for specific 
    gravity or as a function of CRTU results in reduced variability.
    
       Table 6--Urine Cadmium Concentrations in the U.S. Adult Population:  
            Normal and Concentration-Adjusted Values By Age and Sex1        
    ------------------------------------------------------------------------
                                  Geometric means (and geometric standard   
                                                deviations)                 
                             -----------------------------------------------
                                               SG-adjusted2      Creatine-  
                                Unadjusted     (g/l     adjusted   
                              (g/l)     at 1.020)    (g/g)
    ------------------------------------------------------------------------
    Sex:                                                                    
        Male (n=484)........      0.55 (2.9)      0.73 (2.6)      0.55 (2.7)
        Female (n=498)......      0.49 (3.0)      0.86 (2.7)      0.78 (2.7)
    Age:                                                                    
        20-29 (n=222).......      0.32 (3.0)      0.43 (2.7)      0.32 (2.7)
        30-39 (n=141).......      0.46 (3.2)      0.70 (2.8)      0.54 (2.7)
        40-49 (n=142).......      0.50 (3.0)      0.81 (2.6)      0.70 (2.7)
        50-59 (n=117).......      0.61 (2.9)      0.99 (2.4)      0.90 (2.3)
        60-69 (n=272).......      0.76 (2.6)      1.16 (2.3)      1.03 (2.3)
    ------------------------------------------------------------------------
    1From Kowal and Zirkes 1983.                                            
    2SC-adjusted is adjusted for specific gravity.                          
    
    
       Table 7--Urine Cadmium Concentrations in the U.S. Adult Population:  
          Cumulative Frequency Distribution of Urinary Cadmium (N=982)1     
                                 [In percentage]                            
    ------------------------------------------------------------------------
                                                SG-adjusted      Creatine-  
     Range of concentrations    Unadjusted     (g/l     adjusted   
                              (g/l)     at 1.020)    (g/g)
    ------------------------------------------------------------------------
    <0.5.................... 43.9="" 28.0="" 35.8="" 0.6-1.0.................="" 71.7="" 56.4="" 65.6="" 1.1-1.5.................="" 84.4="" 74.9="" 81.4="" 1.6-2.0.................="" 91.3="" 84.7="" 88.9="" 2.1-3.0.................="" 97.3="" 94.4="" 95.8="" 3.1-4.0.................="" 98.8="" 97.4="" 97.2="" 4.1-5.0.................="" 99.4="" 98.2="" 97.9="" 5.1-10.0................="" 99.6="" 99.4="" 99.3="" 10.0-20.0...............="" 99.8="" 99.6="" 99.6="" ------------------------------------------------------------------------="">1Source: Kowal and Zirkes (1983).                                       
    
        The data in the Table 6 indicate the geometric mean of CDU 
    levels observed among the general population is 0.52 g Cd/l 
    urine (unadjusted), with a geometric standard deviation of 3.0. 
    Normalized for creatinine, the geometric mean for the population is 
    0.66 g/g CRTU, with a geometric standard deviation of 2.7. 
    Table 7 provides the distributions of CDU concentrations for the 
    general population studied by Kowal and Zirkes. The data in this 
    table indicate that 95% of the CDU levels observed among those not 
    occupationally exposed to cadmium are below 3 g/g CRTU.
    
    5.2.7.2  Range of CDU Concentrations Observed Among Exposed Workers
    
        Table 8 is a summary of results from available studies of CDU 
    concentrations observed among cadmium-exposed workers. In this 
    table, arithmetic and/or geometric means and standard deviations are 
    provided if reported in these studies. The absolute range for the 
    data in each study, or the 95% confidence interval around the mean 
    of each study, also are provided when reported. The lower and upper 
    95th percentile of the distribution are presented for each study in 
    which a mean and corresponding standard deviation were reported. 
    Table 8 also provides estimates of the years of exposure, and the 
    levels of exposure, to cadmium in the work place if reported in 
    these studies. Concentrations reported in this table are in 
    g/g CRTU, unless otherwise stated. 
    
                                                          Table 8--Urine Cadmium Concentrations in Workers Exposed to Cadmium in the Workplace                                                      
    ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                 Concentration of cadmium in Urinea                                 
                                                                                     Mean      -----------------------------------------------------------------------------------------------------
      Study      Work environment (worker population    Number    Employment    Concentration                         Absolute                                                                      
      number                 monitored)                in Study    in years     of cadmium in     Arithmetic mean     range or    Geometric    Lower 95th      Upper 95th                           
                                                          (n)       (mean)     air (g/ (S.D.)b     (95%        mean      percentile of   percentile of         Reference       
                                                                                     m3)                               C.I.)c      (GSD)d      rangee ()f      rangee ()f                           
    ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
    1........  Ni-Cd battery plant and Cd production   ........          3-40    90  ...................  ..........  ..........  ..............  ..............  Lauwerys et al. 1976.  
                plant.                                                                                                                                                                              
               (Workers without kidney lesions)......        96  ............  ...............  16.316.  ..........  ..........             (0)            (44)  .......................
                                                                                                              7                                                                                     
               (Workers with kidney lesions).........        25  ............  ...............  48.242.  ..........  ..........             (0)           (120)  .......................
                                                                                                              6                                                                                     
    2........  Ni-Cd battery plant...................  ........  ............  ...............  ...................  ..........  ..........  ..............  ..............  Adamsson et al. (1979).
               (Smokers).............................         7           (5)             10.1              5.5        1.0-14.7  ..........  ..............  ..............  .......................
               (Nonsmokers)..........................         8           (9)              7.0              3.6         0.5-9.3  ..........  ..............  ..............  .......................
    3........  Cadmium salts production facility.....       148        (15.4)  ...............             15.8           2-150  ..........  ..............  ..............  Butchet et al. 1980.   
    4........  Retrospective study of workers with           19         15-41  ...............  ...................  ..........  ..........  ..............  ..............  Roels et al. 1982.     
                renal problems.                                                                                                                                                                     
               (Before removal)......................  ........        (27.2)  ...............  39.428.    10.8-117  ..........             (0)            (88)  .......................
                                                                                                              1                                                                                     
               (After removal).......................  ........        (4.2)g  ...............  16.49.0     80-42.3  ..........           (1.0)            (32)  .......................
    5........  Cadmium production plant..............  ........  ............  ...............  ...................  ..........  ..........  ..............  ..............  Ellis et al. 1983.     
               (Workers without renal dysfunction)...        33          1-34  ...............  9.46.9         2-27  ..........             (0)            (21)  .......................
               (Workers with renal dysfunction)......        18         10-34  ...............  22.812.        8-55  ..........             (1)            (45)  .......................
                                                                                                              7                                                                                     
    6........  Cd-Cu alloy plant.....................        75      Up to 39           Note h  6.99.4   ..........  ..........             (0)            (23)  Mason et al. 1988.     
    7........  Cadmium recovery operation............        45          (19)               87  9.36.9   ..........  ..........             (0)            (21)  Thun et al. 1989.      
    8........  Pigment manufacturing plant...........        29        (12.8)         0.18-3.0  ...................     0.2-9.5         1.1  ..............  ..............  Mueller et al. 1989.   
    9........  Pigment manufacturing plant...........        26        (12.1)   3.0  ...................  ..........  1.25aConcentrations are reported in g/g Cr.                                                                                                                                                
    bS.D.--Standard Deviation.                                                                                                                                                                      
    cC.I.--Confidence Interval.                                                                                                                                                                     
    dG.S.D.--Geometric Standard Deviation.                                                                                                                                                          
    e Based on assumed lognormal distribution.                                                                                                                                                      
    f Based on assumed normal distribution.                                                                                                                                                         
    g Years following removal.                                                                                                                                                                      
    h Equivalent to 50 for 20-22 yrs.                                                                                                                                                               
    
        Data in Table 8 from Lauwerys et al. (1976) and Ellis et al. 
    (1983) indicate that CDU concentrations are higher among those 
    exhibiting kidney lesions or dysfunction than among those lacking 
    these symptoms. Data from the study by Roels et al. (1982) indicate 
    that CDU levels decrease among workers removed from occupational 
    exposure to cadmium in comparison to workers experiencing ongoing 
    exposure. In both cases, however, the distinction between the 2 
    groups is not as clear as with CDB; there is more overlap in CDU 
    levels observed among each of the paired populations than is true 
    for corresponding CDB levels. As with CDB levels, the data in Table 
    8 suggest increased CDU concentrations among workers who experienced 
    increased overall exposure.
        Although a few occupationally-exposed workers in the studies 
    presented in Table 8 exhibit CDU levels below 3 g/g CRTU, 
    most of those workers exposed to cadmium levels in excess of the PEL 
    defined in the final cadmium rule exhibit CDU levels above 3 
    g/g CRTU; this level represents the upper 95th percentile 
    of the CDU distribution observed among those who are not 
    occupationally exposed to cadmium (Table 7).
        The mean CDU levels reported in Table 8 among occupationally-
    exposed groups studied (except 2) exceed 3 g/g CRTU. 
    Correspondingly, the level of exposure reported in these studies 
    (with 1 exception) are significantly higher than what workers will 
    experience under the final cadmium rule. The 2 exceptions are from 
    the studies by Mueller et al. (1989) and Kawada et al. (1990); these 
    studies indicate that workers exposed to cadmium during pigment 
    manufacture do not exhibit CDU levels as high as those levels 
    observed among workers exposed to cadmium in other occupations. 
    Exposure levels, however, were lower in the pigment manufacturing 
    plants studied. Significantly, workers removed from occupational 
    cadmium exposure for an average of 4 years still exhibited CDU 
    levels in excess of 3 g/g CRTU (Roels et al. 1982). In the 
    single-exception study with a reported level of cadmium exposure 
    lower than levels proposed in the final rule (i.e., the study of a 
    pigment manufacturing plant by Kawada et al. 1990), most of the 
    workers exhibited CDU levels less than 3 g/g CRTU (i.e., 
    the mean value was only 1.3 g/g CRTU). CDU levels among 
    workers with such limited cadmium exposure are expected to be 
    significantly lower than levels of other studies reported on Table 
    8.
        Based on the above data, a CDU level of 3 g/g CRTU 
    appear to represent a threshold above which significant work place 
    exposure to cadmium occurs over the work span of those being 
    monitored. Note that this threshold is not as distinct as the 
    corresponding threshold described for CDB. In general, the 
    variability associated with CDU measurements among exposed workers 
    appears to be higher than the variability associated with CDB 
    measurements among similar workers.
    
    5.2.8  Conclusions and Recommendations for CDU
    
        The above evaluation supports the following recommendations for 
    a CDU proficiency program. These recommendations address only 
    sampling and analysis procedures for CDU determinations 
    specifically, which are to be reported as an unadjusted g 
    Cd/l urine. Normalizing this result to creatinine requires a second 
    analysis for CRTU so that the ratio of the 2 measurements can be 
    obtained. Creatinine analysis is addressed in Section 5.4. Formal 
    procedures for combining the 2 measurements to derive a value and a 
    confidence limit for CDU in g/g CRTU are provided in 
    Section 3.3.3.
    
    5.2.8.1  Recommended Method
    
        The method of Pruszkowska et al. (1983) should be adopted for 
    CDU analysis. This method is recommended because it is simple, 
    straightforward and reliable (i.e., small variations in experimental 
    conditions do not affect the analytical results).
        A synopsis of the methods used by laboratories to determine CDU 
    under the interlaboratory program administered by the CTQ (1991) 
    indicates that more than 78% (24 of 31) of the participating 
    laboratories use a dilution method to prepare urine samples for CDU 
    analysis. Laboratories may adopt alternate methods, but it is the 
    responsibility of the laboratory to demonstrate that the alternate 
    methods provide results of comparable quality to the Pruszkowska 
    method.
    
    5.2.8.2  Data Quality Objectives
    
        The following data quality objectives should facilitate 
    interpretation of analytical results, and are achievable based on 
    the above evaluation.
        Limit of Detection. A level of 0.5 g/l (i.e., 
    corresponding to a detection limit of 0.5 g/g CRTU, 
    assuming 1 g CRT/l urine) should be achievable. Pruszkowska et al. 
    (1983) achieved a limit of detection of 0.04 g/l for CDU 
    based on the slope the the curve for their working standards (0.35 
    pg Cd/0.0044, A signal=1% absorbance using GF-AAS).
        The CDC reports a minimum detection limit for CDU of 0.07 
    g/l using a modified Pruszkowska method. This limit of 
    detection was defined as 3 times the standard deviation calculated 
    from 10 repeated measurements of a ``low level'' CDU test sample 
    (Attachment 8 of exhibit 106 of OSHA docket H057A).
        Stoeppler and Brandt (1980) report a limit of detection for CDU 
    of 0.2 g/l using an aqueous dilution (1:2) of the urine 
    samples.
        Accuracy. A recent report from the CTQ (Weber, private 
    communication) indicates that 36% of the laboratories in the program 
    achieve the target of 1 g/l or 15% for more 
    than 75% of the samples analyzed over the last 5 years, while 45% of 
    participating laboratories achieve a target of 2 
    g/l or 15% for more than 75% of the samples analyzed over 
    the same period. With time and a strong incentive for improvement, 
    it is expected that the proportion of laboratories successfully 
    achieving the stricter level of accuracy should increase. It should 
    be noted, however, these indices of performance do not include 
    variations resulting from the ancillary measurement of CRTU (which 
    is recommended for the proper recording of results). The low cadmium 
    levels expected to be measured indicate that the analysis of 
    creatinine will contribute relatively little to the overall 
    variability observed among creatinine-normalized CDU levels (see 
    Section 5.4). The initial target value for reporting CDU under this 
    program, therefore, is set at 1 g/g CRTU or 15% 
    (whichever is greater).
        Precision. For internal QC samples (which are recommended as 
    part of an internal QA/QC program, Section 3.3.1), laboratories 
    should attain an overall precision of 25%. For CDB samples with 
    concentrations less than 2 g/l, a target precision of 40% 
    is acceptable, while precisions of 20% should be achievable for CDU 
    concentrations greater than 2 g/l. Although these values 
    are more stringent than those observed in the CTQ interlaboratory 
    program reported by Webber (1988), they are well within limits 
    expected to be achievable for the method as reported by Stoeppler 
    and Brandt (1980).
    
    5.2.8.3  Quality Assurance/Quality Control
    
        Commercial laboratories providing CDU determinations should 
    adopt an internal QA/QC program that incorporates the following 
    components: Strict adherence to the selected method, including 
    calibration requirements; regular incorporation of QC samples during 
    actual runs; a protocol for corrective actions, and documentation of 
    such actions; and, participation in an interlaboratory proficiency 
    program. Note that the nonmandatory program presented in Attachment 
    1 as an example of an acceptable QA/QC program, is based on using 
    the Pruszkowska method for CDU analysis. Should an alternate method 
    be adopted by a laboratory, the laboratory should develop a QA/QC 
    program equivalent to the nonmandatory program, and which satisfies 
    the provisions of Section 3.3.1.
    
    5.3  Monitoring -2-Microglobulin in Urine (B2MU).
    
        As indicated in Section 4.3, B2MU appears to be the best of 
    several small proteins that may be monitored as early indicators of 
    cadmium-induced renal damage. Several analytic techniques are 
    available for measuring B2M.
    
    5.3.1  Units of B2MU Measurement
    
        Procedures adopted for reporting B2MU levels are not uniform. In 
    these guidelines, OSHA recommends that B2MU levels be reported as 
    g/g CRTU, similar to reporting CDU concentrations. 
    Reporting B2MU normalized to the concentration of CRTU requires an 
    additional analytical process beyond the analysis of B2M: 
    Independent analysis for creatinine so that results may be reported 
    as a ratio of the B2M and creatinine concentrations found in the 
    urine sample. Consequently, the overall quality of the analysis 
    depends on the combined performance on these 2 analyses. The 
    analysis used for B2MU determinations is described in terms of 
    g B2M/l urine, with analysis of creatinine addressed 
    separately. Techniques used to measure creatinine are provided in 
    Section 5.4. Note that Section 3.3.3 provides techniques for 
    deriving the value of B2M as function of CRTU, and the confidence 
    limits for independent measurements of B2M and CRTU.
    
    5.3.2  Analytical Techniques Used to Monitor B2MU
    
        One of the earliest tests used to measure B2MU was the radial 
    immunodiffusion technique. This technique is a simple and specific 
    method for identification and quantitation of a number of proteins 
    found in human serum and other body fluids when the protein is not 
    readily differentiated by standard electrophoretic procedures. A 
    quantitative relationship exists between the concentration of a 
    protein deposited in a well that is cut into a thin agarose layer 
    containing the corresponding monospecific antiserum, and the 
    distance that the resultant complex diffuses. The wells are filled 
    with an unknown serum and the standard (or control), and incubated 
    in a moist environment at room temperature. After the optimal point 
    of diffusion has been reached, the diameters of the resulting 
    precipition rings are measured. The diameter of a ring is related to 
    the concentration of the constituent substance. For B2MU 
    determinations required in the medical monitoring program, this 
    method requires a process that may be insufficient to concentrate 
    the protein to levels that are required for detection.
        Radioimmunoassay (RIA) techniques are used widely in immunologic 
    assays to measure the concentration of antigen or antibody in body-
    fluid samples. RIA procedures are based on competitive-binding 
    techniques. If antigen concentration is being measured, the 
    principle underlying the procedure is that radioactive-labeled 
    antigen competes with the sample's unlabeled antigen for binding 
    sites on a known amount of immobile antibody. When these 3 
    components are present in the system, an equilibrium exists. This 
    equilibrium is followed by a separation of the free and bound forms 
    of the antigen. Either free or bound radioactive-labeled antigen can 
    be assessed to determine the amount of antigen in the sample. The 
    analysis is performed by measuring the level of radiation emitted 
    either by the bound complex following removal of the solution 
    containing the free antigen, or by the isolated solution containing 
    the residual-free antigen. The main advantage of the RIA method is 
    the extreme sensitivity of detection for emitted radiation and the 
    corresponding ability to detect trace amounts of antigen. 
    Additionally, large numbers of tests can be performed rapidly.
        The enzyme-linked immunosorbent assay (ELISA) techniques are 
    similar to RIA techniques except that nonradioactive labels are 
    employed. This technique is safe, specific and rapid, and is nearly 
    as sensitive as RIA techniques. An enzyme-labeled antigen is used in 
    the immunologic assay; the labeled antigen detects the presence and 
    quantity of unlabeled antigen in the sample. In a representative 
    ELISA test, a plastic plate is coated with antibody (e.g., antibody 
    to B2M). The antibody reacts with antigen (B2M) in the urine and 
    forms an antigen-antibody complex on the plate. A second anti-B2M 
    antibody (i.e., labeled with an enzyme) is added to the mixture and 
    forms an antibody-antigen-antibody complex. Enzyme activity is 
    measured spectrophotometrically after the addition of a specific 
    chromogenic substrate which is activated by the bound enzyme. The 
    results of a typical test are calculated by comparing the 
    spectrophotometric reading of a serum sample to that of a control or 
    reference serum. In general, these procedures are faster and require 
    less laboratory work than other methods.
        In a fluorescent ELISA technique (such as the one employed in 
    the Pharmacia Delphia test for B2M), the labeled enzyme is bound to 
    a strong fluorescent dye. In the Pharmacia Delphia test, an antigen 
    bound to a fluorescent dye competes with unlabeled antigen in the 
    sample for a predetermined amount of specific, immobile antibody. 
    Once equilibrium is reached, the immobile phase is removed from the 
    labeled antigen in the sample solution and washed; an enhancement 
    solution then is added that liberates the fluorescent dye from the 
    bound antigen-antibody complex. The enhancement solution also 
    contains a chelate that complexes with the fluorescent dye in 
    solution; this complex increases the fluorescent properties of the 
    dye so that it is easier to detect.
        To determine the quantity of B2M in a sample using the Pharmacia 
    Delphia test, the intensity of the fluorescence of the enhancement 
    solution is measured. This intensity is proportional to the 
    concentration of labeled antigen that bound to the immobile antibody 
    phase during the initial competition with unlabeled antigen from the 
    sample. Consequently, the intensity of the fluorescence is an 
    inverse function of the concentration of antigen (B2M) in the 
    original sample. The relationship between the fluorescence level and 
    the B2M concentration in the sample is determined using a series of 
    graded standards, and extrapolating these standards to find the 
    concentration of the unknown sample.
    
    5.3.3  Methods Developed for B2MU Determinations
    
        B2MU usually is measured by radioimmunoassay (RIA) or enzyme-
    linked immunosorbent assay (ELISA); however, other methods 
    (including gel electrophoresis, radial immunodiffusion, and 
    nephelometric assays) also have been described (Schardun and van 
    Epps 1987). RIA and ELISA methods are preferred because they are 
    sensitive at concentrations as low as micrograms per liter, require 
    no concentration processes, are highly reliable and use only a small 
    sample volume.
        Based on a survey of the literature, the ELISA technique is 
    recommended for monitoring B2MU. While RIAs provide greater 
    sensitivity (typically about 1 g/l, Evrin et al. 1971), 
    they depend on the use of radioisotopes; use of radioisotopes 
    requires adherence to rules and regulations established by the 
    Atomic Energy Commission, and necessitates an expensive 
    radioactivity counter for testing. Radioisotopes also have a 
    relatively short half-life, which corresponds to a reduced shelf 
    life, thereby increasing the cost and complexity of testing. In 
    contrast, ELISA testing can be performed on routine laboratory 
    spectrophotometers, do not necessitate adherence to additional rules 
    and regulations governing the handling of radioactive substances, 
    and the test kits have long shelf lives. Further, the range of 
    sensitivity commonly achieved by the recommended ELISA test (i.e., 
    the Pharmacia Delphia test) is approximately 100 g/l 
    (Pharmacia 1990), which is sufficient for monitoring B2MU levels 
    resulting from cadmium exposure. Based on the studies listed in 
    Table 9 (Section 5.3.7), the average range of B2M concentrations 
    among the general, nonexposed population falls between 60 and 300 
    g/g CRTU. The upper 95th percentile of distributions, 
    derived from studies in Table 9 which reported standard deviations, 
    range between 180 and 1,140 g/g CRTU. Also, the Pharmacia 
    Delphia test currently is the most widely used test for assessing 
    B2MU.
    
    5.3.4  Sample Collection and Handling
    
        As with CDB or CDU, sample collection procedures are addressed 
    primarily to identify ways to minimize the degree of variability 
    introduced by sample collection during medical monitoring. It is 
    unclear the extent to which sample collection contributes to B2MU 
    variability. Sources of variation include time-of-day effects, the 
    interval since consuming liquids and the quantity of liquids 
    consumed, and the introduction of external contamination during the 
    collection process. A special problem unique to B2M sampling is the 
    sensitivity of this protein to degradation under acid conditions 
    commonly found in the bladder. To minimize this problem, strict 
    adherence to a sampling protocol is recommended. The protocol should 
    include provisions for normalizing the conditions under which the 
    urine is collected. Clearly, it is important to minimize the 
    interval urine spends in the bladder. It also is recommended that 
    every effort be made to collect samples during the same time of day.
        Collection of urine samples for biological monitoring usually is 
    performed using ``spot'' (i.e., single-void) urine. Logistics and 
    sample integrity become problems when efforts are made to collect 
    urine over extended periods (e.g., 24 hrs). Unless single-void 
    urines are used, numerous opportunities exist for measurement error 
    because of poor control over sample collection, storage and 
    environmental contamination.
        To minimize the interval that sample urine resides in the 
    bladder, the following adaption to the ``spot'' collection procedure 
    is recommended: The bladder should be emptied and then a large glass 
    of water should be consumed; the sample then should be collected 
    within an hour after the water is consumed.
    
    5.3.5  Best Achievable Performance
    
        The best achievable performance is assumed to be equivalent to 
    the performance reported by the manufacturers of the Pharmacia 
    Delphia test kits (Pharmacia 1990). According to the insert that 
    comes with these kits, QC results should be within 2 SDs 
    of the mean for each control sample tested; a CV of less than or 
    equal to 5.2% should be maintained. The total CV reported for test 
    kits is less than or equal to 7.2%.
    
    5.3.6  General Method Performance
    
        Unlike analyses for CDB and CDU, the Pharmacia Delphia test is 
    standardized in a commercial kit that controls for many sources of 
    variation. In the absence of data to the contrary, it is assumed 
    that the achievable performance reported by the manufacturer of this 
    test kit will serve as an achievable performance objective. The CTQ 
    proficiency testing program for B2MU analysis is expected to use the 
    performance parameters defined by the test kit manufacturer as the 
    basis of the B2MU proficiency testing program.
        Note that results reported for the test kit are expressed in 
    terms of g B2M/l of urine, and have not been adjusted for 
    creatinine. The indicated performance, therefore, is a measure of 
    the performance of the B2M portion of the analyses only, and does 
    not include variation that may have been introduced during the 
    analysis of creatinine.
    
    5.3.7  Observed B2MU Concentrations
    
        As indicated in Section 4.3, the concentration of B2MU may serve 
    as an early indicator of the onset of kidney damage associated with 
    cadmium exposure.
    
    5.3.7.1  Range of B2MU Concentrations Among Unexposed Samples
    
        Most of the studies listed in Table 9 report B2MU levels for 
    those who were not occupationally exposed to cadmium. Studies noted 
    in the second column of this table (which contain the footnote 
    ``d'') reported B2MU concentrations among cadmium-exposed workers 
    who, nonetheless, showed no signs of proteinuria. These latter 
    studies are included in this table because, as indicated in Section 
    4.3, monitoring B2MU is intended to provide advanced warning of the 
    onset of kidney dysfunction associated with cadmium exposure, rather 
    than to distinguish relative exposure. This table, therefore, 
    indicates the range of B2MU levels observed among those who had no 
    symptoms of renal dysfunction (including cadmium-exposed workers 
    with none of these symptoms). 
    
                          Table 9--B-2-Microglobulin Concentrations Observed in Urine Among Those Not Occupationally Exposed to Cadmium                     
    --------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                           Lower 95th            Upper 95th                                 
      Study No.         No. in study         Geometric mean      Geometric standard       percentile of         percentile of              Reference        
                                                                      deviation           distributiona         distributiona                               
    --------------------------------------------------------------------------------------------------------------------------------------------------------
    1............  133 mb...............  115 g/gc...  4.03................  12..................  1,140 g/gc.  Ishizaki et al. 1989.     
    2............  161 fb...............  146 g/gc...  3.11................  23..................  940 g/gc...  Ishizaki et al. 1989.     
    3............  10...................  84 g/g.....  ....................  ....................  ....................  Ellis et al. 1983.        
    4............  203..................  76 g/l.....  ....................  ....................  ....................  Stewart and Hughes 1981.  
    5............  9....................  103 g/g....  ....................  ....................  ....................  Chia et al. 1989.         
    6............  47d..................  86 g/L.....  1.9.................  30 g/l.....  250 g/L....  Kjellstrom et al. 1977.   
    7............  1,000e...............  68.1 g/gr    3.1 m & f...........  <10>g/gr     320 g/gr     Kowal 1983.               
                                           Crf.                                        Crh.                  Crh.                                           
    8............  87...................  71 g/gi....  ....................  7h..................  200h................  Buchet et al. 1980.       
    9............  10...................  0.073 mg/24h........  ....................  ....................  ....................  Evrin et al. 1971.        
    10...........  59...................  156 g/g....  1.1j................  130.................  180.................  Mason et al. 1988.        
    11...........  8....................  118 g/g....  ....................  ....................  ....................  Iwao et al. 1980.         
    12...........  34...................  79 g/g.....  ....................  ....................  ....................  Wibowo et al. 1982.       
    13...........  41 m.................  ....................  ....................  ....................  400 g/gr     Falck et al. 1983.        
                                                                                                             Crk.                                           
    14...........  35n..................  67..................  ....................  ....................  ....................  Roels et al. 1991.        
    15...........  31d..................  63..................  ....................  ....................  ....................  Roels et al. 1991.        
    16...........  36d..................  77i.................  ....................  ....................  ....................  Miksche et al. 1981.      
    17...........  18n..................  130.................  ....................  ....................  ....................  Kawada et al. 1989.       
    18...........  32p..................  122.................  ....................  ....................  ....................  Kawada et al. 1989.       
    19...........  18d..................  295.................  1.4.................  170.................  510.................  Thun et al. 1989.         
    --------------------------------------------------------------------------------------------------------------------------------------------------------
    a--Based on an assumed lognormal distribution                                                                                                           
    b--m = males, f = females                                                                                                                               
    c--Aged general population from non-polluted area; 47.9% population aged 50-69; 52.1%  70 years of age; values reported in study             
    d--Exposed workers without proteinuria                                                                                                                  
    e--492 females, 484 males                                                                                                                               
    f--Creatinine-adjusted; males = 68.1 g/g Cr, females = 64.3 g/g Cr                                                                    
    h--Reported in the study                                                                                                                                
    i--Arithmetic mean                                                                                                                                      
    j--Geometric standard error                                                                                                                             
    k--Upper 95% tolerance limits: for Falck this is based on the 24 hour urine sample                                                                      
    n--Controls                                                                                                                                             
    p--Exposed synthetic resin and pigment workers without proteinuria; Cadmium in urine levels up to 10 g/g Cr                                    
    
        To the extent possible, the studies listed in Table 9 provide 
    geometric means and geometric standard deviations for measurements 
    among the groups defined in each study. For studies reporting a 
    geometric standard deviation along with a mean, the lower and upper 
    95th percentile for these distributions were derived and reported in 
    the table.
        The data provided from 15 of the 19 studies listed in Table 9 
    indicate that the geometric mean concentration of B2M observed among 
    those who were not occupationally exposed to cadmium is 70-170 
    g/g CRTU. Data from the 4 remaining studies indicate that 
    exposed workers who exhibit no signs of proteinuria show mean B2MU 
    levels of 60-300 g/g CRTU. B2MU values in the study by Thun 
    et al. (1989), however, appear high in comparison to the other 3 
    studies. If this study is removed, B2MU levels for those who are not 
    occupationally exposed to cadmium are similar to B2MU levels found 
    among cadmium-exposed workers who exhibit no signs of kidney 
    dysfunction. Although the mean is high in the study by Thun et al., 
    the range of measurements reported in this study is within the 
    ranges reported for the other studies.
        Determining a reasonable upper limit from the range of B2M 
    concentrations observed among those who do not exhibit signs of 
    proteinuria is problematic. Elevated B2MU levels are among the signs 
    used to define the onset of kidney dysfunction. Without access to 
    the raw data from the studies listed in Table 9, it is necessary to 
    rely on reported standard deviations to estimate an upper limit for 
    normal B2MU concentrations (i.e., the upper 95th percentile for the 
    distributions measured). For the 8 studies reporting a geometric 
    standard deviation, the upper 95th percentiles for the distributions 
    are 180-1140 g/g CRTU. These values are in general 
    agreement with the upper 95th percentile for the distribution (i.e., 
    631 g/g CRTU) reported by Buchet et al. (1980). These upper 
    limits also appear to be in general agreement with B2MU values 
    (i.e., 100-690 g/g CRTU) reported as the normal upper limit 
    by Iwao et al. (1980), Kawada et al. (1989), Wibowo et al. (1982), 
    and Schardun and van Epps (1987). These values must be compared to 
    levels reported among those exhibiting kidney dysfunction to define 
    a threshold level for kidney dysfunction related to cadmium 
    exposure.
    
    5.3.7.2  Range of B2MU Concentrations Among Exposed Workers
    
        Table 10 presents results from studies reporting B2MU 
    determinations among those occupationally exposed to cadmium in the 
    work place; in some of these studies, kidney dysfunction was 
    observed among exposed workers, while other studies did not make an 
    effort to distinguish among exposed workers based on kidney 
    dysfunction. As with Table 9, this table provides geometric means 
    and geometric standard deviations for the groups defined in each 
    study if available. For studies reporting a geometric standard 
    deviation along with a mean, the lower and upper 95th percentiles 
    for the distributions are derived and reported in the table.
    
       Table 10.--2-Microglobulin Concentrations Observed in Urine Among Occupationally-Exposed Workers    
    ----------------------------------------------------------------------------------------------------------------
                                           Concentration of 2-microglobulin in                             
                                                              urine                                                 
                                        -------------------------------------------------                           
           Study number            N     Geometric mean    Geom.                                   Reference        
                                          (g/   Std. Dev.   L 95% of   U 95% of                            
                                              g)a                    rangeb     rangeb                              
    ----------------------------------------------------------------------------------------------------------------
    1..........................   1,424             160       6.19        8.1      3,300  Ishizaki et al. 1989.     
    2..........................   1,754             260       6.50         12      5,600  Ishizaki et al. 1989.     
    3..........................      33             210  .........  .........  .........  Ellis et al. 1983.        
    4..........................      65             210  .........  .........  .........  Chia et al. 1989.         
    5..........................     c44           5,700       6.49       d300    d98,000  Kjellstrom et al. 1977.   
    6..........................     148            e180  .........       f110       f280  Buchet et al. 1980.       
    7..........................      37             160       3.90         17      1,500  Kenzaburo et al. 1979.    
    8..........................     c45           3,300       8.70       d310    d89,000  Mason et al. 1988.        
    9..........................     c10           6,100       5.99       f650    f57,000  Falck et al. 1983.        
    10.........................     c11           3,900       2.96       d710    d15,000  Elinder et al. 1985.      
    11.........................     c12             300  .........  .........  .........  Roels et al. 1991.        
    12.........................      g8           7,400  .........  .........  .........  Roels et al. 1991.        
    13.........................     c23          h1,800  .........  .........  .........  Roels et al. 1989.        
    14.........................      10             690  .........  .........  .........  Iwao et al. 1980.         
    15.........................      34              71  .........  .........  .........  Wibowo et al. 1982.       
    16.........................     c15           4,700       6.49       d590    d93,000  Thun et al. 1989.         
    ----------------------------------------------------------------------------------------------------------------
    aUnless otherwise stated.                                                                                       
    bBased on an assumed lognormal distribution.                                                                    
    cAmong workers diagnosed as having renal dysfunction; for Elinder this means 2 levels greater than 300 
      micrograms per gram creatinine (g/gr Cr); for Roels, 1991, range=31-35, 170 g2/gr  
      Cr and geometric mean=63 among healthy workers; for Mason 2>300 g/gr Cr.                    
    dBased on a detailed review of the data by OSHA.                                                                
    eArithmetic mean.                                                                                               
    fReported in the study.                                                                                         
    gRetired workers.                                                                                               
    h1,800 g2/gr Cr for first survey; second survey=1,600; third survey=2,600; fourth             
      survey=2,600; fifth survey=2,600.                                                                             
    
        The data provided in Table 10 indicate that the mean B2MU 
    concentration observed among workers experiencing occupational 
    exposure to cadmium (but with undefined levels of proteinuria) is 
    160-7400 g/g CRTU. One of these studies reports geometric 
    means lower than this range (i.e., as low as 71 g/g CRTU); 
    an explanation for this wide spread in average concentrations is not 
    available.
        Seven of the studies listed in Table 10 report a range of B2MU 
    levels among those diagnosed as having renal dysfunction. As 
    indicated in this table, renal dysfunction (proteinuria) is defined 
    in several of these studies by B2MU levels in excess of 300 
    g/g CRTU (see footnote ``c'' of Table 10); therefore, the 
    range of B2MU levels observed in these studies is a function of the 
    operational definition used to identify those with renal 
    dysfunction. Nevertheless, a B2MU level of 300 g/g CRTU 
    appears to be a meaningful threshold for identifying those having 
    early signs of kidney damage. While levels much higher than 300 
    g/g CRTU have been observed among those with renal 
    dysfunction, the vast majority of those not occupationally exposed 
    to cadmium exhibit much lower B2MU concentrations (see Table 9). 
    Similarly, the vast majority of workers not exhibiting renal 
    dysfunction are found to have levels below 300 g/g CRTU 
    (Table 9).
        The 300 g/g CRTU level for B2MU proposed in the above 
    paragraph has support among researchers as the threshold level that 
    distinguishes between cadmium-exposed workers with and without 
    kidney dysfunction. For example, in the guide for physicians who 
    must evaluate cadmium-exposed workers written for the Cadmium 
    Council by Dr. Lauwerys, levels of B2M greater than 200-300 
    g/g CRTU are considered to require additional medical 
    evaluation for kidney dysfunction (exhibit 8-447, OSHA docket 
    H057A). The most widely used test for measuring B2M (i.e., the 
    Pharmacia Delphia test) defines B2MU levels above 300 g/l 
    as abnormal (exhibit L-140-1, OSHA docket H057A).
        Dr. Elinder, chairman of the Department of Nephrology at the 
    Karolinska Institute, testified at the hearings on the proposed 
    cadmium rule. According to Dr. Elinder (exhibit L-140-45, OSHA 
    docket H057A), the normal concentration of B2MU has been well 
    documented (Evrin and Wibell 1972; Kjellstrom et al. 1977a; Elinder 
    et al. 1978, 1983; Buchet et al. 1980; Jawaid et al. 1983; Kowal and 
    Zirkes, 1983). Elinder stated that the upper 95 or 97.5 percentiles 
    for B2MU among those without tubular dysfunction is below 300 
    g/g CRTU (Kjellstrom et al. 1977a; Buchet et al. 1980; 
    Kowal and Zirkes, 1983). Elinder defined levels of B2M above 300 
    g/g CRTU as ``slight'' proteinuria.
    
    5.3.8  Conclusions and Recommendations for B2MU
    
        Based on the above evaluation, the following recommendations are 
    made for a B2MU proficiency testing program. Note that the following 
    discussion addresses only sampling and analysis for B2MU 
    determinations (i.e., to be reported as an unadjusted g 
    B2M/l urine). Normalizing this result to creatinine requires a 
    second analysis for CRTU (see section 5.4) so that the ratio of the 
    2 measurements can be obtained.
    
    5.3.8.1  Recommended Method
    
        The Pharmacia Delphia method (Pharmacia 1990) should be adopted 
    as the standard method for B2MU determinations. Laboratories may 
    adopt alternate methods, but it is the responsibility of the 
    laboratory to demonstrate that alternate methods provide results of 
    comparable quality to the Pharmacia Delphia method.
    
    5.3.8.2  Data Quality Objectives
    
        The following data quality objectives should facilitate 
    interpretation of analytical results, and should be achievable based 
    on the above evaluation.
        Limit of Detection. A limit of 100 g/l urine should be 
    achievable, although the insert to the test kit (Pharmacia 1990) 
    cites a detection limit of 150 g/l; private conversations 
    with representatives of Pharmacia, however, indicate that the lower 
    limit of 100 g/l should be achievable provided an 
    additional standard of 100 g/l B2M is run with the other 
    standards to derive the calibration curve (section 3.3.1.1). The 
    lower detection limit is desirable due to the proximity of this 
    detection limit to B2MU values defined for the cadmium medical 
    monitoring program.
        Accuracy. Because results from an interlaboratory proficiency 
    testing program are not available currently, it is difficult to 
    define an achievable level of accuracy. Given the general 
    performance parameters defined by the insert to the test kits, 
    however, an accuracy of 15% of the target value appears 
    achievable.
        Due to the low levels of B2MU to be measured generally, it is 
    anticipated that the analysis of creatinine will contribute 
    relatively little to the overall variability observed among 
    creatinine-normalized B2MU levels (see section 5.4). The initial 
    level of accuracy for reporting B2MU levels under this program 
    should be set at 15%.
        Precision. Based on precision data reported by Pharmacia (1990), 
    a precision value (i.e., CV) of 5% should be achievable over the 
    defined range of the analyte. For internal QC samples (i.e., 
    recommended as part of an internal QA/QC program, section 3.3.1), 
    laboratories should attain precision near 5% over the range of 
    concentrations measured.
    
    5.3.8.3  Quality Assurance/Quality Control
    
        Commercial laboratories providing measurement of B2MU should 
    adopt an internal QA/QC program that incorporates the following 
    components: Strict adherence to the Pharmacia Delphia method, 
    including calibration requirements; regular use of QC samples during 
    routine runs; a protocol for corrective actions, and documentation 
    of these actions; and, participation in an interlaboratory 
    proficiency program. Procedures that may be used to address internal 
    QC requirements are presented in Attachment 1. Due to differences 
    between analyses for B2MU and CDB/CDU, specific values presented in 
    Attachment 1 may have to be modified. Other components of the 
    program (including characterization runs), however, can be adapted 
    to a program for B2MU.
    
    5.4  Monitoring Creatinine in Urine (CRTU)
    
        Because CDU and B2MU should be reported relative to 
    concentrations of CRTU, these concentrations should be determined in 
    addition CDU and B2MU determinations.
    
    5.4.1  Units of CRTU Measurement
    
        CDU should be reported as g Cd/g CRTU, while B2MU 
    should be reported as g B2M/g CRTU. To derive the ratio of 
    cadmium or B2M to creatinine, CRTU should be reported in units of g 
    crtn/l of urine. Depending on the analytical method, it may be 
    necessary to convert results of creatinine determinations 
    accordingly.
    
    5.4.2  Analytical Techniques Used To Monitor CRTU
    
        Of the techniques available for CRTU determinations, an 
    absorbance spectrophotometric technique and a high-performance 
    liquid chromatography (HPLC) technique are identified as acceptable 
    in this protocol.
    
    5.4.3  Methods Developed for CRTU Determinations
    
        CRTU analysis performed in support of either CDU or B2MU 
    determinations should be performed using either of the following 2 
    methods:
        1. The Du Pont method (i.e., Jaffe method), in which creatinine 
    in a sample reacts with picrate under alkaline conditions, and the 
    resulting red chromophore is monitored (at 510 nm) for a fixed 
    interval to determine the rate of the reaction; this reaction rate 
    is proportional to the concentration of creatinine present in the 
    sample (a copy of this method is provided in Attachment 2 of this 
    protocol); or
        2. The OSHA SLC Technical Center (OSLTC) method, in which 
    creatinine in an aliquot of sample is separated using an HPLC column 
    equipped with a UV detector; the resulting peak is quantified using 
    an electrical integrator (a copy of this method is provided in 
    Attachment 3 of this protocol).
    
    5.4.4  Sample Collection and Handling
    
        CRTU samples should be segregated from samples collected for CDU 
    or B2MU analysis. Sample-collection techniques have been described 
    under section 5.2.4. Samples should be preserved either to stabilize 
    CDU (with HNO3) or B2MU (with NaOH). Neither of these 
    procedures should adversely affect CRTU analysis (see Attachment 3).
    
    5.4.5  General Method Performance
    
        Data from the OSLTC indicate that a CV of 5% should be 
    achievable using the OSLTC method (Septon, L private communication). 
    The achievable accuracy of this method has not been determined.
        Results reported in surveys conducted by the CAP (CAP 1991a, 
    1991b and 1992) indicate that a CV of 5% is achievable. The accuracy 
    achievable for CRTU determinations has not been reported.
        Laboratories performing creatinine analysis under this protocol 
    should be CAP accredited and should be active participants in the 
    CAP surveys.
    
    5.4.6  Observed CRTU Concentrations
    
        Published data suggest the range of CRTU concentrations is 1.0-
    1.6 g in 24-hour urine samples (Harrison 1987). These values are 
    equivalent to about 1 g/l urine.
    
    5.4.7  Conclusions and Recommendations for CRTU
    
    5.4.7.1  Recommended Method
    
        Use either the Jaffe method (Attachment 2) or the OSLTC method 
    (Attachment 3). Alternate methods may be acceptable provided 
    adequate performance is demonstrated in the CAP program.
    
    5.4.7.2  Data Quality Objectives
    
        Limit of Detection. This value has not been formally defined; 
    however, a value of 0.1 g/l urine should be readily achievable.
        Accuracy. This value has not been defined formally; accuracy 
    should be sufficient to retain accreditation from the CAP.
        Precision. A CV of 5% should be achievable using the recommended 
    methods.
    
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        Ellis K, Yasumura S, Vartsky D, and Cohn S. (1983). Evaluation 
    of biological indicators of body burden of cadmium in humans. 
    Fundamentals and Applied Toxicology, 3, 169-174.
        Ellis K, Yeun K, Yasumura S, and Cohn S. (1984). Dose-response 
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        Evrin P, Peterson A, Wide I, and Berggard I. (1971). 
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        Falck F, Fine L, Smith R, Garvey J, Schork A, England B, 
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        Friberg L. and Elinder C. (1988). Cadmium toxicity in humans. In 
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        Henry J. (1991). Clinical Diagnosis and Management by Laboratory 
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        Ishizaki M., Kido T., Honda R., Tsuritani I., Yamada Y., 
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        Iwata K., Katoh T., Morikawa Y., Aoshima K., Nishijo M., 
    Teranishi H., and Kasuya M. (1988). Urinary trehalase activity as an 
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    Archives of Toxicology, 62, 435-439.
        Kawada T., Koyama H., and Suzuki S. (1989). Cadmium, NAG 
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    workers. British Journal of Industrial Medicine, 46, 52-55.
        Kawada T., Tohyama C., and Suzuki S. (1990). Significance of the 
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        Kjellstrom T. (1979). Exposure and accumulation of cadmium in 
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        Kowal N., Johnson D., Kraemer D., and Pahren H. (1979). Normal 
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        Kowal N. and Zirkes M. (1983). Urinary cadmium and B-2-
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    326, 647-655.
        Mason H, Davison A, Wright A, Guthrie C, Fayers P, Venables K, 
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    International Agency for Research on Cancer.
        Mueller P, Smith S, Steinberg K, and Thun M. (1989). Chronic 
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    52, 45-54.
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    Attachment 1--Nonmandatory Protocol for an Internal Quality Assurance/
    Quality Control Program
    
        The following is an example of the type of internal quality 
    assurance/quality control program that assures adequate control to 
    satisfy OSHA requirements under this protocol. However, other 
    approaches may also be acceptable.
        As indicated in Section 3.3.1 of the protocol, the QA/QC program 
    for CDB and CDU should address, at a minimum, the following:
         Calibration;
         Establishment of control limits;
         Internal QC analyses and maintaining control; and
         Corrective action protocols.
        This illustrative program includes both initial characterization 
    runs to establish the performance of the method and ongoing analysis 
    of quality control samples intermixed with compliance samples to 
    maintain control.
    
    Calibration
    
        Before any analytical runs are conducted, the analytic 
    instrument must be calibrated. This is to be done at the beginning 
    of each day on which quality control samples and/or compliance 
    samples are run. Once calibration is established, quality control 
    samples or compliance samples may be run. Regardless of the type of 
    samples run, every fifth sample must be a standard to assure that 
    the calibration is holding.
        Calibration is defined as holding if every standard is within 
    plus or minus () 15% of its theoretical value. If a 
    standard is more than plus or minus 15% of its theoretical value, 
    then the run is out of control due to calibration error and the 
    entire set of samples must either be reanalyzed after recalibrating 
    or results should be recalculated based on a statistical curve 
    derived from the measurement of all standards.
        It is essential that the highest standard run is higher than the 
    highest sample run. To assure that this is the case, it may be 
    necessary to run a high standard at the end of the run, which is 
    selected based on the results obtained over the course of the run.
        All standards should be kept fresh, and as they get old, they 
    should be compared with new standards and replaced if they exceed 
    the new standards by  15%.
    
    Initial Characterization Runs and Establishing Control
    
        A participating laboratory should establish four pools of 
    quality control samples for each of the analytes for which 
    determinations will be made. The concentrations of quality control 
    samples within each pool are to be centered around each of the four 
    target levels for the particular analyte identified in Section 4.4 
    of the protocol.
        Within each pool, at least 4 quality control samples need to be 
    established with varying concentrations ranging between plus or 
    minus 50% of the target value of that pool. Thus for the medium-high 
    cadmium in blood pool, the theoretical values of the quality control 
    samples may range from 5 to 15 g/l, (the target value is 10 
    g/l). At least 4 unique theoretical values must be 
    represented in this pool.
        The range of theoretical values of plus or minus 50% of the 
    target value of a pool means that there will be overlap of the 
    pools. For example, the range of values for the medium-low pool for 
    cadmium in blood is 3.5 to 10.5 g/l while the range of 
    values for the medium-high pool is 5 to 15 g/l. Therefore, 
    it is possible for a quality control sample from the medium-low pool 
    to have a higher concentration of cadmium than a quality control 
    sample from the medium-high pool.
        Quality control samples may be obtained as commercially 
    available reference materials, internally prepared, or both. 
    Internally prepared samples should be well characterized and traced 
    or compared to a reference material for which a consensus value for 
    concentration is available. Levels of analyte in the quality control 
    samples must be concealed from the analyst prior to the reporting of 
    analytical results. Potential sources of materials that may be used 
    to construct quality control samples are listed in Section 3.3.1 of 
    the protocol.
        Before any compliance samples are analyzed, control limits must 
    be established. Control limits should be calculated for every pool 
    of each analyte for which determinations will be made and control 
    charts should be kept for each pool of each analyte. A separate set 
    of control charts and control limits should be established for each 
    analytical instrument in a laboratory that will be used for analysis 
    of compliance samples.
        At the beginning of this QA/QC program, control limits should be 
    based on the results of the analysis of 20 quality control samples 
    from each pool of each analyte. For any given pool, the 20 quality 
    control samples should be run on 20 different days. Although no more 
    than one sample should be run from any single pool on a particular 
    day, a laboratory may run quality control samples from different 
    pools on the same day. This constitutes a set of initial 
    characterization runs.
        For each quality control sample analyzed, the value F/T (defined 
    in the glossary) should be calculated. To calculate the control 
    limits for a pool of an analyte, it is first necessary to calculate 
    the mean, X, of the F/T values for each quality control sample in a 
    pool and then to calculate its standard deviation, s. Thus, for the 
    control limit for a pool, X is calculated as:
    
    TR03JA94.003
    
    and s is calculated as
    
    TR03JA94.004
    
    where N is the number of quality control samples run for a pool.
        The control limit for a particular pool is then given by the 
    mean plus or minus 2 standard deviations (X 2s). The 
    control limits may be no greater than 40% of the mean F/T value. If 
    three standard deviations are greater than 40% of the mean F/T 
    value, then analysis of compliance samples may not begin.\1\ 
    Instead, an investigation into the causes of the large standard 
    deviation should begin, and the inadequacies must be remedied. Then, 
    control limits must be reestablished which will mean repeating the 
    running 20 quality control samples from each pool over 20 days.
    ---------------------------------------------------------------------------
    
        \1\Note that the value, ``40%'' may change over time as 
    experience is gained with the program.
    ---------------------------------------------------------------------------
    
    Internal Quality Control Analyses and Maintaining Control
    
        Once control limits have been established for each pool of an 
    analyte, analysis of compliance samples may begin. During any run of 
    compliance samples, quality control samples are to be interspersed 
    at a rate of no less than 5% of the compliance sample workload. When 
    quality control samples are run, however, they should be run in sets 
    consisting of one quality control sample from each pool. Therefore, 
    it may be necessary, at times, to intersperse quality control 
    samples at a rate greater than 5%.
        There should be at least one set of quality control samples run 
    with any analysis of compliance samples. At a minimum, for example, 
    4 quality control samples should be run even if only 1 compliance 
    sample is run. Generally, the number of quality control samples that 
    should be run are a multiple of four with the minimum equal to the 
    smallest multiple of four that is greater than 5% of the total 
    number of samples to be run. For example, if 300 compliance samples 
    of an analyte are run, then at least 16 quality control samples 
    should be run (16 is the smallest multiple of four that is greater 
    than 15, which is 5% of 300).
        Control charts for each pool of an analyte (and for each 
    instrument in the laboratory to be used for analysis of compliance 
    samples) should be established by plotting F/T versus date as the 
    quality control sample results are reported. On the graph there 
    should be lines representing the control limits for the pool, the 
    mean F/T limits for the pool, and the theoretical F/T of 1.000. 
    Lines representing plus or minus () 2s should also be 
    represented on the charts. A theoretical example of a control chart 
    is presented in Figure 1. 
    
                       Figure 1.--Theoretical Example of a Control Chart for a Pool of an Analyte                   
                                                                                             1.162 (Upper Control   
                                                                                              Limit)                
                                                      X                                                             
                                                                                             1.096 (Upper 2
                                                                                              Line)                 
                          X                                                                                         
                   X   .....                                                                 1.000 (Theoretical     
                                                                                              Mean)                 
                                        X      X                                             0.964 (Mean)           
                                                             X                           X                          
                                                                    X                                               
                                 X                                                           0.832 (Lower 2
                                                                                              Line)                 
                                                                           X                                        
                                                                                             0.766 (Lower Control   
                                                                                              Limit)                
    March          2      2      3      5      6      9     10     13     16     17                                 
    ----------------------------------------------------------------------------------------------------------------
    
        All quality control samples should be plotted on the chart, and 
    the charts should be checked for visual trends. If a quality control 
    sample falls above or below the control limits for its pool, then 
    corrective steps must be taken (see the section on corrective 
    actions below). Once a laboratory's program has been established, 
    control limits should be updated every 2 months.
        The updated control limits should be calculated from the results 
    of the last 100 quality control samples run for each pool. If 100 
    quality control samples from a pool have not been run at the time of 
    the update, then the limits should be based on as many as have been 
    run provided at least 20 quality control samples from each pool have 
    been run over 20 different days.
        The trends that should be looked for on the control charts are:
        1. 10 consecutive quality control samples falling above or below 
    the mean;
        2. 3 consecutive quality control samples falling more than 2s 
    from the mean (above or below the 2s lines of the chart); or
        3. the mean calculated to update the control limits falls more 
    than 10% above or below the theoretical mean of 1.000.
        If any of these trends is observed, then all analysis must be 
    stopped, and an investigation into the causes of the errors must 
    begin. Before the analysis of compliance samples may resume, the 
    inadequacies must be remedied and the control limits must be 
    reestablished for that pool of an analyte. Reestablishment of 
    control limits will entail running 20 sets of quality control 
    samples over 20 days.
        Note that alternative procedures for defining internal quality 
    control limits may also be acceptable. Limits may be based, for 
    example, on proficiency testing, such as  1 g 
    or 15% of the mean (whichever is greater). These should be clearly 
    defined.
    
    Corrective Actions
    
        Corrective action is the term used to describe the 
    identification and remediation of errors occurring within an 
    analysis. Corrective action is necessary whenever the result of the 
    analysis of any quality control sample falls outside of the 
    established control limits. The steps involved may include simple 
    things like checking calculations of basic instrument maintenance, 
    or it may involve more complicated actions like major instrument 
    repair. Whatever the source of error, it must be identified and 
    corrected (and a Corrective Action Report (CAR) must be completed. 
    CARs should be kept on file by the laboratory.
    
    Attachment 2--Creatinine in Urine (JAFFE PROCEDURE)
    
        * Note: Numbered superscripts refer to the bibliography.
        Intended use: The CREA pack is used in the Du Pont ACA 
    discrete clinical analyzer to quantitatively measure creatinine in 
    serum and urine.
        Summary: The CREA method employs a modification of the kinetic 
    Jaffe reaction reported by Larsen. This method has been reported to 
    be less susceptible than conventional methods to interference from 
    non-creatinine, Jaffe-positive compounds.\2\
    ---------------------------------------------------------------------------
    
        \2\Larsen, K, Clin Chem Acta 41, 209 (1972).
    ---------------------------------------------------------------------------
    
        A split sample comparison between the CREA method and a 
    conventional Jaffe procedure on Autoanalyzer showed a good 
    correlation. (See SPECIFIC PERFORMANCE CHARACTERISTICS).
        Autoanalyzer, is a registered trademark of Technicon 
    Corp., Tarrytown, NY.
        Principles of Procedure: In the presence of a strong base such 
    as NaOH, picrate reacts with creatinine to form a red chromophore. 
    The rate of increasing absorbance at 510 nm due to the formation of 
    this chromophore during a 17.07-second measurement period is 
    directly proportional to the creatinine concentration in the sample.
    
    TR03JA94.005
    
        Reagents: 
    
    ------------------------------------------------------------------------
       Compartmenta            Form            Ingredient        Quantityb  
    ------------------------------------------------------------------------
    No. 2, 3, & 4.....  Liquid............  Picrate..........  0.11 mmol.   
    6.................  Liquid............  NaOH (for pH                    
                                             adjustment)c .                 
    ------------------------------------------------------------------------
    a. Compartments are numbered 1-7, with compartment #7 located closest to
      pack fill position #2.                                                
    b. Nominal value at manufacture.                                        
    c. See PRECAUTIONS.                                                     
    
    
        Precautions: Compartment #6 contains 75L of 10 N NaOH; 
    avoid contact; skin irritant; rinse contacted area with water. 
    Comply with OSHA'S Bloodborne Pathogens Standard while handling 
    biological samples (29 CFR 1910.1039).
        Used packs contain human body fluids; handle with appropriate 
    care.
    
    FOR IN VITRO DIAGNOSTIC USE
    
    MIXING & DILUTING
    
        Mixing and diluting are automatically performed by the 
    ACA discrete clinical analyzer. The sample cup must 
    contain sufficient quantity to accommodate the sample volume plus 
    the ``dead volume''; precise cup filling is not required. 
    
                        Sample Cup Volumes (L)                     
    ------------------------------------------------------------------------
                                  Standard                Microsystem       
          Analyzer       ---------------------------------------------------
                             Dead         Total        Dead         Total   
    ------------------------------------------------------------------------
    II, III.............          120         3000           10          500
    IV, SX..............          120         3000           30          500
    V...................           90         3000           10          500
    ------------------------------------------------------------------------
    
    
        Storage of Unprocessed Packs: Store at 2-8 deg.C. Do not freeze. 
    Do not expose to temperatures above 35 deg.C or to direct sunlight.
        Expiration: Refer to EXPIRATION DATE on the tray label.
        Specimen Collection: Serum or urine can be collected and stored 
    by normal procedures.\3\
    ---------------------------------------------------------------------------
    
        \3\Tietz, NW, Fundamentals of Clinical Chemistry, W. B. Saunders 
    Co., Philadelphia, PA, 1976, pp 47-52, 1211.
    ---------------------------------------------------------------------------
    
    Known Interfering Substances\4\
    ---------------------------------------------------------------------------
    
        \4\Supplementary information pertaining to the effects of 
    various drugs and patient conditions on in vivo or in vitro 
    diagnostic levels can be found in ``Drug Interferences with Clinical 
    Laboratory Tests,'' Clin. Chem 21 (5) (1975), and ``Effects of 
    Disease on Clinical Laboratory Tests,'' Clin Chem, 26 (4) 1D-476D 
    (1980).
    ---------------------------------------------------------------------------
    
         Serum Protein Influence--Serum protein levels exert a 
    direct influence on the CREA assay. The following should be taken 
    into account when this method is used for urine samples and when it 
    is calibrated:
        Aqueous creatinine standards or urine specimens will give CREA 
    results depressed by approximately 0.7 mg/dL [62 mol/L] \5\ 
    and will be less precise than samples containing more than 3 g/dL 
    [30 g/L] protein.
    ---------------------------------------------------------------------------
    
        \5\ Systeme International d'unites (S.I. Units) are in brackets.
    ---------------------------------------------------------------------------
    
        All urine specimens should be diluted with an albumin solution 
    to give a final protein concentration of at least 3 g/dL [30 g/L]. 
    Du Pont Enzyme Diluent (Cat. #790035-901) may be used for this 
    purpose.
         High concentration of endrogenous bilirubin (>20 mg/dL 
    [>342 mol/L]) will give depressed CREA results (average 
    depression 0.8 mg/dL [71 mol/L]).\6\
    ---------------------------------------------------------------------------
    
        \6\Watkins, R. Fieldkamp, SC, Thibert, RJ, and Zak, B, Clin 
    Chem, 21, 1002 (1975).
    ---------------------------------------------------------------------------
    
         Grossly hemolyzed (hemoglobin >100 mg/dL [>62 
    mol/L]) or visibly lipemic specimens may cause falsely 
    elevated CREA results.7,8
    ---------------------------------------------------------------------------
    
        \7\Kawas, EE, Richards, AH, and Bigger, R, An Evaluation of a 
    Kinetic Creatinine Test for the Du Pont ACA, Du Pont Company, 
    Wilmington, DE (February 1973). (Reprints available from DuPont 
    Company, Diagnostic Systems)
        \8\Westgard, JO, Effects of Hemolysis and Lipemia on ACA 
    Creatinine Method, 0.200 L, Sample Size, Du Pont Company, 
    Wilmington, DE (October 1972).
    ---------------------------------------------------------------------------
    
         The following cephalosporin antibiotics do not 
    interfere with the CREA method when present at the concentrations 
    indicated. Systematic inaccuracies (bias) due to these substances 
    are less than or equal to 0.1 mg/dL [8.84 mol/L] at CREA 
    concentrations of approximately 1 mg/dL [88 mol/L]. 
    
    ------------------------------------------------------------------------
                                Peak serum levela,b,c    Drug concentration 
            Antibiotic         ---------------------------------------------
                                  mg/dL      [mmol/L]     mg/dL     [mmol/L]
    ------------------------------------------------------------------------
    Cephaloridine.............    1.4         0.3              25        6.0
    Cephalexin................  0.6-2.0     0.2-0.6            25        7.2
    Cephamandole..............  1.3-2.5     0.3-0.5            25        4.9
    Cephapirin................    2.0        D0.4              25        5.6
    Cephradine................  1.5-2.0     0.4-0.6            25        7.1
    Cefazolin.................  2.5-5.0     0.55-1.1           50      11.0 
    ------------------------------------------------------------------------
    aPhysicians' Desk Reference, Medical Economics Company, 33 Edition,     
      1979.                                                                 
    bHenry, JB, Clinical Diagnosis and Management by Laboratory Methods,    
      W.B. Saunders Co., Philadelphia, PA 1979, Vol. III.                   
    cKrupp, MA, Tierney, LM Jr., Jawetz, E, Roe, RI, Camargo, CA, Physicians
      Handbook, Lange Medical Publications, Los Altos, CA, 1982 pp 635-636. 
    
         The following cephalosporin antibiotics have been shown 
    to affect CREA results when present at the indicated concentrations. 
    System inaccuracies (bias) due to these substances are greater that 
    0.1 mg/dL [8.84 mol/L] at CREA concentrations of:
          
    
    ------------------------------------------------------------------------
                      Peak serum levela,b          Drug concentration       
      Antibiotic    --------------------------------------------------------
                       mg/dL      [mmol/L]     mg/dL    [mmol/L]     Effect 
    ------------------------------------------------------------------------
    Cephalothin....    1-6       0.2-1.5           100       25.2  
                                                                      20-25%
    Cephoxitin.....    2.0         0.5             5.0        1.2  
                                                                      35-40%
    ------------------------------------------------------------------------
    aHenry, JB, Clinical Diagnosis and Management by Laboratory Methods,    
      W.B. Saunders Co., Philadelphia, PA 1979, Vol. III.                   
    bSarah, AJ, Koch, TR, Drusano, GL, Celoxitin Falsely Elevates Creatinine
      Levels, JAMA 247, 205-206 (1982).                                     
    
         The single wavelength measurement used in this method 
    eliminates interference from chromophores whose 510 nm absorbance is 
    constant throughout the measurement period.
         Each laboratory should determine the acceptability of 
    its own blood collection tubes and serum separation products. 
    Variations in these products may exist between manufacturers and, at 
    times, from lot to lot.
    
        Procedure: 
    
                                 Test Materials                             
    ------------------------------------------------------------------------
                                II, III Du    IV, SX Du Pont  V Du Pont Cat.
              Item             Pont Cat. No.     Cat. No.           No.     
    ------------------------------------------------------------------------
    ACA CREA                                                      
     Analytical Test Pack...       701976901       701976901       701976901
    Sample System Kit or....       710642901       710642901       713697901
    Micro Sample System Kit                                                 
     and....................       702694901       710356901              NA
    Micro Sample System                                                     
     Holders................       702785000              NA              NA
    DYLUX                                                         
     Photosensitive.........  ..............  ..............  ..............
    Printer Paper...........       700036000              NA              NA
    Thermal Printer Paper...              NA       710639901       713645901
    Du Pont Purified Water..       704209901       710615901       710815901
    Cell Wash Solution......       701864901       710664901       710864901
    ------------------------------------------------------------------------
    
    Test Steps
    
        The operator need only load the sample kit and appropriate test 
    pack(s) into a properly prepared ACA discrete clinical 
    analyzer. It automatically advances the pack(s) through the test 
    steps and prints a result(s). See the Instrument Manual of the 
    ACA analyzer for details of mechanical travel of the test 
    pack(s).
    
    Preset Creatinine (CREA)--Test Conditions
    
     Sample Volume: 200 L
     Diluent: Purified Water
     Temperature: 37.0  0.1 deg.C
     Reaction Period: 29 seconds
     Type of Measurement: Rate
     Measurement Period: 17.07 seconds
     Wavelength: 510 nm
     Units: mg/dL [mol/L]
    
    CALIBRATION
    
        The general calibration procedure is described in the 
    Calibration/Verification chapter of the Manuals.
        The following information should be considered when calibrating 
    the CREA method.
     Assay Range: 0-20 mg/mL [0-1768 mol/L] \9\.
    ---------------------------------------------------------------------------
    
        \9\ For the results in S.I. units [mol/L] the 
    conversion factory is 88.4.
    ---------------------------------------------------------------------------
    
     Reference Material: Protein containing primary 
    standards\10\ or secondary calibrators such as Du Pont Elevated 
    Chemistry Control (Cat. #790035903) and Normal Chemistry Control 
    (Cat.\#790035905)\11\.
    ---------------------------------------------------------------------------
    
        \10\Refer to the Creatinine Standard Preparation and Calibration 
    Procedure available on request from a Du Pont Representative.
        \11\If the Du Pont Chemistry Controls are being used, prepare 
    them according to the instructions on the product insert sheets.
    ---------------------------------------------------------------------------
    
     Suggested Calibration Levels: 1,5,20, mg/mL [88, 442, 1768 
    mol/L].
     Calibration Scheme: 3 levels, 3 packs per level.
     Frequency: Each new pack lot. Every 3 months for any one 
    pack lot.
    
           
    
                    Preset Creatinine (CREA) Test Conditions                
    ------------------------------------------------------------------------
                                                              ACA 
               Item               ACA II analyzer   III, IV, SX, V
                                                                 analyzer   
    ------------------------------------------------------------------------
    Count by...................  One (1)...................  NA             
                                 [Five (5)]................                 
    Decimal point location.....  0.0 mg/dL.................  000.0 mg/dL    
                                 [000.0 mol/L]....  [000 mol/L]      
    Assigned starting point or   999.8.....................  -1.000 E1      
     offset Co                   [9823.]...................  [-8.840 E2]    
    Scale factor or assigned...  0.2000....................  2.004 E-1a     
                                 mg/dL/counta..............                 
    Linear Term C1a............  [0.3536 mol/L/     [1.772E1]      
                                  count].                                   
    ------------------------------------------------------------------------
    a The preset scale factor (linear term) was derived from the molar      
      absorptivity of the indicator and is based on an absorbance to        
      activity relationship (sensitivity) of 0.596 (mA/min)/(U/L). Due to   
      small differences in filters and electronic components between        
      instruments, the actual scale factor (linear term) may differ slightly
      from that given above.                                                
    
    Quality Control
    
        Two types of quality control procedures are recommended:
         General Instrument Check. Refer to the Filter Balance 
    Procedure and the Absorbance Test Method described in the ACA 
    Analyzerinstrument Manual. Refer also to the ABS Test Methodology 
    literature.
        Creatinine Method Check. At least once daily run a CREA test on 
    a solution of known creatinine activity such as an assayed control 
    or calibration standard other than that used to calibrate the CREA 
    method. For further details review the Quality Assurance Section of 
    the Chemistry Manual. The result obtained should fall within 
    acceptable limits defined by the day-to-day variability of the 
    system as measured in the user's laboratory. (See SPECIFIC 
    PERFORMANCE CHARACTERISTICS for guidance.) If the result falls 
    outside the laboratory's acceptable limits, follow the procedure 
    outlined in the Chemistry Troubleshooting Section of the Chemistry 
    Manual.
        A possible system malfunction is indicated when analysis of a 
    sample with five consecutive test packs gives the following results:
           
    
    ------------------------------------------------------------------------
                          Level                                  SD         
    ------------------------------------------------------------------------
    1 mg/dL..........................................  >0.15 mg/dL          
    [88 mol/L]..............................  [>13 mol/L] 
    20 mg/dL.........................................  >0.68 mg/dL          
    [1768 mol/L]............................  [>60 mol/L] 
    ------------------------------------------------------------------------
    
        Refer to the procedure outlined in the Trouble Shooting Section 
    of the Manual.
    
    Results
    
        The ACA analyzer automatically calculates and prints 
    the CREA result in mg/dL [mol/L].
    
    Limitation of Procedure
    
        Results >20 mg/dL [1768 mol/L]:
    
         Dilute with suitable protein base diluent. Reassay. 
    Correct for diluting before reporting.
        The reporting system contains error messages to warn the 
    operator of specific malfunctions. Any report slip containing a 
    letter code or word immediately following the numerical value should 
    not be reported. Refer to the Manual for the definition of error 
    codes.
    
    Reference Interval
    
    
                                                                            
                                                                            
                                                                            
    SERUM:a,b                                                               
      Males                              0.8-1.3 md/dL                      
                                         [71-115 mol/L]            
      Females                            0.6-1.0 md/dL                      
                                         [53-88 mol/L]             
    URINE:c                                                                 
      Males                              0.6-2.5 g/24 hr                    
                                         [53-221 mmol/24 hr]                
      Females                            0.6-1.5 g/24 hr                    
                                         [53-133 mmol/24 hr]                
                                                                            
    a Gadsden, RH, and Phelps, CA, A Normal Range Study of Amylase in Urine 
      and Serum on the Du Pont ACA, Du Pont Company, Wilmington, DE (March  
      1978). (Reprints available from DuPont Company, Diagnostic Systems)   
    b Reference interval data obtained from 200 apparently healthy          
      individuals (71 males, 129 females) between the ages of 19 and 72.    
    c Dicht, JJ, Reference Intervals for Serum Amylase and Urinary          
      Creatinine on the Du Pont ACA Discrete Clinical Analyzer, Du
      Pont Company, Wilmington, DE (November 1984).                         
    
        Each laboratory should establish its own reference intervals for 
    CREA as performed on the analyzer.
    
    Specific Performance Characteristics\12\
    ---------------------------------------------------------------------------
    
        \12\ All specific performance characteristics tests were run 
    after normal recommended equipment quality control checks were 
    performed (see Instrument Manual).
    ---------------------------------------------------------------------------
    
          
    
                                Reproducibilitya                            
    ------------------------------------------------------------------------
                                                      Standard deviation (% 
                                                               CV)          
                 Material                  Mean    -------------------------
                                                    Within-run   Between-day
    ------------------------------------------------------------------------
    Lyophilized......................          1.3   0.05 (3.7)   0.05 (3.7)
    Control..........................        [115]        [4.4]        [4.4]
    Lyophilized......................         20.6   0.12 (0.6)   0.37 (1.8)
    Control..........................       [1821]       [10.6]      [32.7] 
    ------------------------------------------------------------------------
    a Specimens at each level were analyzed in duplicate for twenty days.   
      The within-run and between-day standard deviations were calculated by 
      the analysis of variance method.                                      
    
    
                       Correlation--Regression Statisticsa                  
    ------------------------------------------------------------------------
                                                         Correlation        
        Comparative method        Slope      Intercept   coefficient     n  
    ------------------------------------------------------------------------
    Autoanalyzer...         1.03    0.03[2.7]        0.997     260
    ------------------------------------------------------------------------
    a Model equation for regression statistics is:                          
    
    
    Result of ACA Analyzer = Slope (Comparative method result) + 
    intercept
    
    Assay Range *
    
    0.0-20.0 mg/dl
    [0-1768 mol]
    
    
         * See REPRODUCIBILITY for method performance within the assay 
    range.Analytical Specificity
    
        See KNOWN INTERFERING SUBSTANCES section for details.
    
    Bibliography
    
        Larsen, K, Clin Chem Acta 41, 209 (1972).
        Tietz, NW, Fundamentals of Clinical Chemistry, W. B. Saunders 
    Co., Philadelphia, PA, 1976, pp 47-52, 1211.
        Supplementary information pertaining to the effects of various 
    drugs and patient conditions on in vivo or in vitro diagnostic 
    levels can be found in ``Drug Interferences with Clinical Laboratory 
    Tests,'' Clin. Chem 21 (5) (1975), and ``Effects of Disease on 
    Clinical Laboratory Tests,'' Clin Chem, 26 (4) 1D-476D (1980).
        Watkins, R. Fieldkamp, SC, Thibert, RJ, and Zak, B, Clin Chem, 
    21, 1002 (1975).
        Kawas, EE, Richards, AH, and Bigger, R, An Evaluation of a 
    Kinetic Creatinine Test for the Du Pont ACA, Du Pont Company, 
    Wilmington, DE (February 1973). (Reprints available from DuPont 
    Company, Diagnostic Systems)
        Westgard, JO, Effects of Hemolysis and Lipemia on ACA Creatinine 
    Method, 0.200 L, Sample Size, Du Pont Company, Wilmington, 
    DE (October 1972).
        Physicians' Desk Reference, Medical Economics Company, 33 
    Edition, 1979.
        Henry, JB, Clinical Diagnosis and Management by Laboratory 
    Methods, W.B. Saunders Co., Philadelphia, PA 1979, Vol. III.
        Krupp, MA, Tierney, LM Jr., Jawetz, E, Roe, RI, Camargo, CA, 
    Physicians Handbook, Lange Medical Publications, Los Altos, CA, 1982 
    pp 635-636.
        Sarah, AJ, Koch, TR, Drusano, GL, Celoxitin Falsely Elevates 
    Creatinine Levels, JAMA 247, 205-206 (1982).
        Gadsden, RH, and Phelps, CA, A Normal Range Study of Amylase in 
    Urine and Serum on the Du Pont ACA, Du Pont Company, Wilmington, DE 
    (March 1978). (Reprints available from DuPont Company, Diagnostic 
    Systems)
        Dicht, JJ, Reference Intervals for Serum Amylase and Urinary 
    Creatinine on the Du Pont ACA Discrete Clinical Analyzer, 
    Du Pont Company, Wilmington, DE (November 1984).
    
    Attachment 3--Analysis of Creatinine for the Normalization of Cadmium 
    and Beta-2-Microglobulin Concentrations in Urine (OSLTC Procedure)
    
    Matrix: Urine
    Target Concentration: 1.1 g/L (this amount is representative of 
    creatinine concentrations found in urine).
    Procedure: A 1.0 mL aliquot of urine is passed through a C18 SEP-
    PAK (Waters Associates). Approximately 30 mL of HPLC (high 
    performance liquid chromatography) grade water is then run through 
    the SEP-PAK. The resulting solution is diluted to volume in a 100-mL 
    volumetric flask and analyzed by HPLC using an ultraviolet (UV) 
    detector.
    Special Requirements: After collection, samples should be 
    appropriately stabilized for cadmium (Cd) analysis by using 10% high 
    purity (with low Cd background levels) nitric acid (exactly 1.0 mL 
    of 10% nitric acid per 10 mL of urine) or stabilized for Beta-2-
    Microglobulin (B2M) by taking to pH 7 with dilute NaOH (exactly 1.0 
    mL of 0.11 N NaOH per 10 mL of urine). If not immediately analyzed, 
    the samples should be frozen and shipped by overnight mail in an 
    insulated container.
    
        Date: January 1992.
    Chemists: David B. Armitage,
    Duane Lee,
    Organic Service Branch II, OSHA Technical Center, Salt Lake City, Utah.
    
    1. General Discussion
    
    1.1. Background
        1.1.1.  History of procedure
        Creatinine has been analyzed by several methods in the past. The 
    earliest methods were of the wet chemical type. As an example, 
    creatinine reacts with sodium picrate in basic solution to form a 
    red complex, which is then analyzed colorimetrically (Refs. 5.1. and 
    5.2.).
        Since industrial hygiene laboratories will be analyzing for Cd 
    and B2M in urine, they will be normalizing those concentrations to 
    the concentration of creatinine in urine. A literature search 
    revealed several HPLC methods (Refs. 5.3., 5.4., 5.5. and 5.6.) for 
    creatinine in urine and because many industrial hygiene laboratories 
    have HPLC equipment, it was desirable to develop an industrial 
    hygiene HPLC method for creatinine in urine. The method of Hausen, 
    Fuchs, and Wachter was chosen as the starting point for method 
    development. SEP-PAKs were used for sample clarification and cleanup 
    in this method to protect the analytical column. The urine aliquot 
    which has been passed through the SEP-PAK is then analyzed by 
    reverse-phase HPLC using ion-pair techniques.
        This method is very similar to that of Ogata and Taguchi (Ref. 
    5.6.), except they used centrifugation for sample clean-up. It is 
    also of note that they did a comparison of their HPLC results to 
    those of the Jaffe method (a picric acid method commonly used in the 
    health care industry) and found a linear relationship of close to 
    1:1. This indicates that either HPLC or colorimetric methods may be 
    used to measure creatinine concentrations in urine.
        1.1.2.  Physical properties (Ref. 5.7.)
        Molecular weight: 113.12
        Molecular formula: C4-H7-N3-O
    Chemical name: 2-amino-1,5-dihydro-1-methyl-4H-imidazol-4-one
        CAS#: 60-27-5
        Melting point: 300  deg.C (decomposes)
        Appearance: white powder
        Solubility: soluble in water; slightly soluble in alcohol; 
    practically insoluble in acetone, ether, and chloroform
        Synonyms: 1-methylglycocyamidine, 1-methylhydantoin-2-imide
        Structure: see Figure #1
    
    TR03JA94.006
    
    1.2  Advantages
        1.2.1.  This method offers a simple, straightforward, and 
    specific alternative method to the Jaffe method.
        1.2.2.  HPLC instrumentation is commonly found in many 
    industrial hygiene laboratories.
    
    2. Sample Stabilization Procedure
    
    2.1. Apparatus
        Metal-free plastic container for urine sample.
    2.2. Reagents
        2.2.1. Stabilizing Solution--1) Nitric acid (10%, high purity 
    with low Cd background levels) for stabilizing urine for Cd analysis 
    or 2) NaOH, 0.11 N, for stabilizing urine for B2M analysis.
        2.2.2. HPLC grade water
    2.3. Technique
        2.3.1. Stabilizing solution is added to the urine sample (see 
    section 2.2.1.). The stabilizing solution should be such that for 
    each 10 mL of urine, add exactly 1.0 mL of stabilizer solution. 
    (Never add water or urine to acid or base. Always add acid or base 
    to water or urine.) Exactly 1.0 mL of 0.11 N NaOH added to 10 mL of 
    urine should result in a pH of 7. Or add 1.0 mL of 10% nitric acid 
    to 10 mL of urine.
        2.3.2. After sample collection seal the plastic bottle securely 
    and wrap it with an appropriate seal. Urine samples should be frozen 
    and then shipped by overnight mail (if shipping is necessary) in an 
    insulated container. (Do not fill plastic bottle too full. This will 
    allow for expansion of contents during the freezing process.)
    2.4. The Effect of Preparation and Stabilization Techniques on 
    Creatinine Concentrations
        Three urine samples were prepared by making one sample acidic, 
    not treating a second sample, and adjusting a third sample to pH 7. 
    The samples were analyzed in duplicate by two different procedures. 
    For the first procedure a 1.0 mL aliquot of urine was put in a 100-
    mL volumetric flask, diluted to volume with HPLC grade water, and 
    then analyzed directly on an HPLC. The other procedure used SEP-
    PAKs. The SEP-PAK was rinsed with approximately 5 mL of methanol 
    followed by approximately 10 mL of HPLC grade water and both rinses 
    were discarded. Then, 1.0 mL of the urine sample was put through the 
    SEP-PAK, followed by 30 mL of HPLC grade water. The urine and water 
    were transferred to a 100-mL volumetric flask, diluted to volume 
    with HPLC grade water, and analyzed by HPLC. These three urine 
    samples were analyzed on the day they were obtained and then frozen. 
    The results show that whether the urine is acidic, untreated or 
    adjusted to pH 7, the resulting answer for creatinine is essentially 
    unchanged. The purpose of stabilizing the urine by making it acidic 
    or neutral is for the analysis of Cd or B2M respectively. 
    
             Comparison of Preparation and Stabilization Techniques         
    ------------------------------------------------------------------------
                                                 w/o SEP-PAK   with SEP- PAK
                      Sample                         (g/L           (g/L    
                                                 creatinine)    creatinine) 
    ------------------------------------------------------------------------
    Acid......................................           1.10           1.10
    Acid......................................           1.11           1.10
    Untreated.................................           1.12           1.11
    Untreated.................................           1.11           1.12
    pH7.......................................           1.08           1.02
    pH7.......................................           1.11           1.08
    ------------------------------------------------------------------------
    
    2.5. Storage
        After 4 days and 54 days of storage in a freezer, the samples 
    were thawed, brought to room temperature and analyzed using the same 
    procedures as in section 2.4. The results of several days of storage 
    show that the resulting answer for creatinine is essentially 
    unchanged. 
    
                                                      Storage Data                                                  
    ----------------------------------------------------------------------------------------------------------------
                                                                  4 days                         54 days            
                                                     ---------------------------------------------------------------
                         Sample                       W/o SEP-PAK g/  With SEP-PAK g/ W/o SEP-PAK g/  With SEP-PAK g/
                                                       L creatinine    L creatinine    L creatinine    L creatinine 
    ----------------------------------------------------------------------------------------------------------------
    Acid............................................            1.09            1.09            1.08            1.09
    Acid............................................            1.10            1.10            1.09            1.10
    Acid............................................  ..............  ..............            1.09            1.09
    Untreated.......................................            1.13            1.14            1.09            1.11
    Untreated.......................................            1.15            1.14            1.10            1.10
    Untreated.......................................  ..............  ..............            1.09            1.10
    pH 7............................................            1.14            1.13            1.12            1.12
    pH 7............................................            1.14            1.13            1.12            1.12
    pH 7............................................  ..............  ..............            1.12           1.12 
    ----------------------------------------------------------------------------------------------------------------
    
    2.6. lnterferences
        None.
    2.7. Safety precautions
        2.7.1. Make sure samples are properly sealed and frozen before 
    shipment to avoid leakage.
        2.7.2. Follow the appropriate shipping procedures.
    
        The following modified special safety precautions are based on 
    those recommended by the Centers for Disease Control (CDC)(Ref. 
    5.8.) and OSHA's Bloodborne Pathogens standard (29 CFr 1910.1039).
    
        2.7.3. Wear gloves, lab coat, and safety glasses while handling 
    all human urine products. Disposable plastic, glass, and paper 
    (pipet tips, gloves, etc.) that contact urine should be placed in a 
    biohazard autoclave bag. These bags should be kept in appropriate 
    containers until sealed and autoclaved. Wipe down all work surfaces 
    with 10% sodium hypochlorite solution when work is finished.
        2.7.4. Dispose of all biological samples and diluted specimens 
    in a biohazard autoclave bag at the end of the analytical run.
        2.7.5. Special care should be taken when handling and dispensing 
    nitric acid. Always remember to add acid to water (or urine). Nitric 
    acid is a corrosive chemical capable of severe eye and skin damage. 
    Wear metal-free gloves, a lab coat, and safety glasses. If the 
    nitric acid comes in contact with any part of the body, quickly wash 
    with copious quantities of water for at least 15 minutes.
        2.7.6. Special care should be taken when handling and dispensing 
    NaOH. Always remember to add base to water (or urine). NaOH can 
    cause severe eye and skin damage. Always wear the appropriate 
    gloves, a lab coat, and safety glasses. If the NaOH comes in contact 
    with any part of the body, quickly wash with copious quantities of 
    water for at least 15 minutes.
    
    3. Analytical Procedure
    
    3.1. Apparatus
        3.1.1. A high performance liquid chromatograph equipped with 
    pump, sample injector and UV detector.
        3.1.2. A C18 HPLC column; 25 cm  x  4.6 mm I.D.
        3.1.3. An electronic integrator, or some other suitable means of 
    determining analyte response.
        3.1.4. Stripchart recorder.
        3.1.5. C18 SEP-PAKs (Waters Associates) or equivalent.
        3.1.6. Luer-lock syringe for sample preparation (5 mL or 10 mL).
        3.1.7. Volumetric pipettes and flasks for standard and sample 
    preparation.
        3.1.8. Vacuum system to aid sample preparation (optional).
    3.2. Reagents
        3.2.1. Water, HPLC grade.
        3.2.2. Methanol, HPLC grade.
        3.2.3. PlC B-7 (Waters Associates) in small vials.
        3.2.4. Creatinine, anhydrous, Sigma Chemical Corp., purity not 
    listed.
        3.2.5. 1-Heptanesulfonic acid, sodium salt monohydrate.
        3.2.6. Phosphoric acid.
        3.2.7. Mobile phase. It can be prepared by mixing one vial of 
    PlC B-7 into a 1 L solution of 50% methanol and 50% water. The 
    mobile phase can also be made by preparing a solution that is 50% 
    methanol and 50% water with 0.005M heptanesulfonic acid and 
    adjusting the pH of the solution to 3.5 with phosphoric acid.
    3.3. Standard preparation
        3.3.1. Stock standards are prepared by weighing 10 to 15 mg of 
    creatinine. This is transferred to a 25-mL volumetric flask and 
    diluted to volume with HPLC grade water.
        3.3.2. Dilutions to a working range of 3 to 35 g/mL are 
    made in either HPLC grade water or HPLC mobile phase (standards give 
    the same detector response in either solution).
    3.4. Sample preparation
        3.4.1. The C18 SEP-PAK is connected to a Luer-lock syringe. It 
    is rinsed with 5 mL HPLC grade methanol and then 10 mL of HPLC grade 
    water. These rinses are discarded.
        3.4.2. Exactly 1.0 mL of urine is pipetted into the syringe. The 
    urine is put through the SEP-PAK into a suitable container using a 
    vacuum system.
        3.4.3. The walls of the syringe are rinsed in several stages 
    with a total of approximately 30 mL of HPLC grade water. These 
    rinses are put through the SEP-PAK into the same container. The 
    resulting solution is transferred to a 100-mL volumetric flask and 
    then brought to volume with HPLC grade water.
    3.5. Analysis (conditions and hardware are those used in this 
    evaluation.)
        3.5.1. Instrument conditions 
    
    Column..........  Zorbax ODS, 5-6 m particle size; 25
                       cm  x  4.6 mm I.D.                                   
    Mobile phase....  See Section 3.2.7.                                    
    Detector........  Dual wavelength UV; 229 nm (primary) 254 nm           
                       (secondary),                                         
    Flow rate.......  0.7 mL/minute.                                        
    Retention time..  7.2 minutes.                                          
    Sensitivity.....  0.05 AUFS.                                            
    Injection volume  20 L.                                        
                                                                            
    
        3.5.2. Chromatogram (See Figure #2).
    3.6. Interferences
        3.6.1. Any compound that has the same retention time as 
    creatinine and absorbs at 229 nm is an interference.
        3.6.2. HPLC conditions may be varied to circumvent 
    interferences. In addition, analysis at another UV wavelength (i.e. 
    254 nm) would allow a comparison of the ratio of response of a 
    standard to that of a sample. Any deviations would indicate an 
    interference.
    
    TR03JA94.007
    
    3.7. Calculations
        3.7.1. A calibration curve is constructed by plotting detector 
    response versus standard concentration (See Figure #3).
        3.7.2. The concentration of creatinine in a sample is determined 
    by finding the concentration corresponding to its detector response. 
    (See Figure #3).
        3.7.3. The g/mL creatinine from section 3.7.2. is then 
    multiplied by 100 (the dilution factor). This value is equivalent to 
    the micrograms of creatinine in the 1.0 mL stabilized urine aliquot 
    or the milligrams of creatinine per liter of urine. The desired 
    unit, g/L, is determined by the following relationship:
    
    TR03JA94.008
    
    
                                                                            
            g/        mg/L                                         
                 mL         ---------                                       
     g/L=  -------------  =                                                 
                1000           1000                                         
                                                                            
    
        3.7.4. The resulting value for creatinine is used to normalize 
    the urinary concentration of the desired analyte (A) (Cd or B2M) by 
    using the following formula. 
    
                                                                            
                               g A/L                               
       g A/g          (experimental)                               
         creatinine=     -------------------------                          
                               g/L creatinine                               
                                                                            
    
    Where A is the desired analyte. The protocol of reporting such 
    normalized results is g A/g creatinine.
    3.8. Safety precautions. See section 2.7.
    4. Conclusions
        The determination of creatinine in urine by HPLC is a good 
    alternative to the Jaffe method for industrial hygiene laboratories. 
    Sample clarification with SEP-PAKs did not change the amount of 
    creatinine found in urine samples. However, it does protect the 
    analytical column. The results of this creatinine in urine procedure 
    are unaffected by the pH of the urine sample under the conditions 
    tested by this procedure. Therefore, no special measures are 
    required for creatinine analysis whether the urine sample has been 
    stabilized with 10% nitric acid for the Cd analysis or brought to a 
    pH of 7 with 0.11 NaOH for the B2M analysis.
    5. References
        5.1. Clark, L.C.; Thompson, H.L.; Anal. Chem. 1949, 21, 1218.
        5.2. Peters, J.H.; J. Biol. Chem. 1942, 146, 176.
        5.3. Hausen, V.A.; Fuchs, D.; Wachter, H.; J. Clin. Chem. Clin. 
    Biochem. 1981, 19, 373-378.
        5.4. Clark, P.M.S.; Kricka, L.J.; Patel, A.; J. Liq. Chrom. 
    1980, 3(7), 1031-1046.
        5.5. Ballerini, R.; Chinol, M.; Cambi, A.; J. Chrom. 1979, 179, 
    365-369.
        5.6. Ogata, M.; Taguchi, T.; Industrial Health 1987, 25, 225-
    228.
        5.7. ``Merck Index'', 11th ed.; Windholz, Martha Ed.; Merck: 
    Rahway, N.J., 1989; p. 403.
        5.8. Kimberly, M.; ``Determination of Cadmium in Urine by 
    Graphite Furnace Atomic Absorption Spectrometry with Zeeman 
    Background Correction.'' Centers for Disease Control, Atlanta, 
    Georgia, unpublished, update 1990.
    
    PART 1926 -- [Amended]
    
    Subpart Z--Toxic and Hazardous Substances
    
        1. The authority citation for subpart Z of 29 CFR part 1926 
    continues to read as follows:
        Authority: Sections 6 and 8, Occupational Safety and Health Act, 
    29 U.S.C. 655, 657; Secretary of Labor's Orders Nos. 12-71 (36 FR 
    8754), 8-76 (41 FR 25059), 9-83 (48 FR 35736) or 1-90 (55 FR 9033) 
    as applicable; and 29 CFR part 1911.
        Section 1926.1102 not issued under 29 U.S.C. 655 or 29 CFR part 
    1911; also issued under 5 U.S.C. 653.
        Section 1926.1103 through 1926.1118 also issued under 29 U.S.C. 
    653.
        Section 1926.1128 also issued under 29 U.S.C. 653.
        Section 1926.1145 and 1926.1147 also issued under 29 U.S.C. 653.
        Section 1926.1148 also issued under 29 U.S.C. 653.
    
        2. In part 1926, Sec. 1926.63, Cadmium, is redesignated as 
    Sec. 1926.1127.
        3. In paragraph (m)(4)(iii)(H) of (newly redesignated) 
    Sec. 1926.1127, the reference to ``Sec. 1910.20(g)(1) and (2)'' is 
    changed to read ``Sec. 1926.33(g) (1) and (2)''; in Sec. 1926.1127(n) 
    (1)(iii), (3)(iii), and (5)(i), the reference to ``29 CFR 1910.20'' is 
    changed to read ``Sec. 1926.33 of this part''; and in 
    Sec. 1926.1127(n)(6), the reference to ``29 CFR 1910.20(h)'' is changed 
    to read ``Sec. 1926.33(h) of this part.''
    [FR Doc. 93-31820 Filed 12-30-93; 8:45 am]
    BILLING CODE 4510-26-F
    
    
    

Document Information

Published:
01/03/1994
Department:
Occupational Safety and Health Administration
Entry Type:
Rule
Action:
Final rule; miscellaneous corrections, technical amendments, and redesignation.
Document Number:
93-31820
Dates:
July 1, 1993.
Pages:
146-215 (70 pages)
Docket Numbers:
Federal Register: January 3, 1994
CFR: (4)
29 CFR 1926.1127(n)(6)
29 CFR 1915.1027
29 CFR 1915.1120
29 CFR 1926.1127