99-13670. Secondary Direct Food Additives Permitted in Food for Human Consumption; Boiler Water Additives  

  • [Federal Register Volume 64, Number 104 (Tuesday, June 1, 1999)]
    [Rules and Regulations]
    [Pages 29224-29227]
    From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
    [FR Doc No: 99-13670]
    
    
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    DEPARTMENT OF HEALTH AND HUMAN SERVICES
    
    Food and Drug Administration
    
    21 CFR Part 173
    
    [Docket No. 97F-0450]
    
    
    Secondary Direct Food Additives Permitted in Food for Human 
    Consumption; Boiler Water Additives
    
    AGENCY: Food and Drug Administration, HHS.
    
    ACTION: Final rule.
    
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    SUMMARY: The Food and Drug Administration (FDA) is amending the food 
    additive regulations to provide for the safe use of sorbitol anhydride 
    esters, an emulsifier blend of sorbitan monostearate, polyoxyethylene 
    (20) sorbitan monostearate (polysorbate 60), and polyoxyethylene (20) 
    sorbitan monolaurate (polysorbate 20) as an anticorrosive agent in 
    boilers where steam may contact food. This action is in response to a 
    petition filed by Nalco Chemical Co.
    
    DATES: This regulation is effective June 1, 1999; written objections 
    and requests for a hearing by July 1, 1999. The Director of the Office 
    of the Federal Register approves the incorporation by reference in 
    accordance with 5 U.S.C. 552(a) and 1 CFR part 51 of a certain 
    publication in Sec. 173.310 (21 CFR 173.310), effective June 1, 1999.
    
    ADDRESSES: Submit written objections to the Dockets Management Branch 
    (HFA-305), Food and Drug Administration,
    
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    5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
    
    FOR FURTHER INFORMATION CONTACT: Martha D. Peiperl, Center for Food 
    Safety and Applied Nutrition (HFS-215), Food and Drug Administration, 
    200 C St. SW., Washington, DC 20204, 202-418-3077.
    
    SUPPLEMENTARY INFORMATION:
    
    I. Background
    
        In a notice published in the Federal Register of November 13, 1997 
    (62 FR 60903), FDA announced that a food additive petition (FAP 7A4540) 
    had been filed by Nalco Chemical Co., One Nalco Center, Naperville, IL 
    60568-1198. The petition proposed to amend the food additive 
    regulations in Sec. 173.310 Boiler water additives to provide for the 
    safe use of an emulsifier blend containing sorbitan monostearate, 
    polyoxyethylene (20) sorbitan monostearate, and polyoxyethylene (20) 
    sorbitan monolaurate as an anticorrosive agent in boilers where steam 
    may contact food. The emulsifier blend is a simple mixture of these 
    three substances, each of which is an ester of sorbitol anhydride. For 
    convenience of listing of the mixture, the agency chooses to use the 
    name sorbitol anhydride esters (SAHE) for this additive.
        Sorbitan monostearate is currently approved in Sec. 73.1001 (21 CFR 
    73.1001) as a diluent in color additive mixtures for drug use exempt 
    from certification; in Sec. 172.515 (21 CFR 172.515) as a synthetic 
    flavoring substance and adjuvant; in 21 CFR 172.842 as an emulsifier; 
    and in Sec. 173.340 (21 CFR 173.340) as a defoaming agent. 
    Polyoxyethylene (20) sorbitan monostearate (polysorbate 60) is 
    currently approved in Sec. 73.1001 as a diluent in color additive 
    mixtures for drug use exempt from certification; in Sec. 172.515 as a 
    synthetic flavoring substance and adjuvant; in 21 CFR 172.836 as an 
    emulsifier, foaming agent, dough conditioner, dispersing agent, and 
    surfactant and wetting agent; and in Sec. 173.340 as a defoaming agent. 
    Polyoxyethylene (20) sorbitan monolaurate (polysorbate 20) is currently 
    approved in Sec. 172.515 as a synthetic flavoring substance and 
    adjuvant.
        In its evaluation of the safety of SAHE, FDA has reviewed the 
    safety of the three esters and the chemical impurities that may be 
    present in them resulting from their manufacturing process. Because 
    these three esters have similar chemical structures, which do not react 
    with each other, FDA has determined that its safety review for each of 
    the three esters would be the same as that for the SAHE mixture. 
    Therefore, FDA refers to each ester, rather than the additive as a 
    whole, in its evaluation of the safety of SAHE in this final rule.
        Although none of the esters have been shown to cause cancer, two of 
    them (polysorbate 20 and polysorbate 60) may contain minute amounts of 
    unreacted 1,4-dioxane (DX) and ethylene oxide (EO), which are 
    carcinogenic impurities resulting from their manufacture. Residual 
    amounts of impurities are commonly found in chemical products, 
    including food additives.
    
    II. Determination of Safety
    
        Under the general safety standard section of the Federal Food, 
    Drug, and Cosmetic Act (the act) (21 U.S.C. 348(c)(3)(A)), a food 
    additive cannot be approved for a particular use unless a fair 
    evaluation of the data available to FDA establishes that the additive 
    is safe for that use. FDA's food additive regulations (21 CFR 170.3(i)) 
    define safe as ``a reasonable certainty in the minds of competent 
    scientists that the substance is not harmful under the intended 
    conditions of use.''
        The food additives anticancer, or Delaney, clause of the act (21 
    U.S.C. 348(c)(3)(A)) provides that no food additive shall be deemed 
    safe if it is found to induce cancer when ingested by man or animal. 
    Importantly, however, the Delaney clause applies to the additive itself 
    and not to impurities in the additive. That is, where an additive 
    itself has not been shown to cause cancer, but contains a carcinogenic 
    impurity, the additive is properly evaluated under the general safety 
    standard using risk assessment procedures to determine whether there is 
    a reasonable certainty that no harm will result from the intended use 
    of the additive. (Scott v. FDA, 728 F.2d 322 (6th Cir. 1984)).
    
    III. Safety of Petitioned Use of the Additive
    
        FDA estimates that the petitioned use of SAHE will result in a 
    maximum daily dietary exposure to each ester of approximately 0.8 part 
    per million. This corresponds to an estimated daily intake (EDI) of 2.5 
    milligrams per person per day (/p/d) of each ester (Ref. 1).
        The agency has reviewed the available toxicological data on the 
    three sorbitol anhydride esters. Based on the available toxicology data 
    for sorbitan monostearate and polysorbate 60 and the fact that their 
    additional dietary exposure from the proposed use would be small 
    compared to that from their currently regulated uses, the agency 
    concludes that the estimated dietary exposure resulting from the 
    petitioned use of these two esters is safe. The agency also finds that 
    polysorbate 60 and polysorbate 20 would hydrolyze to similar breakdown 
    products under the proposed conditions of use, the only difference 
    being the chain length of the fatty acid residue (C12 for 
    polysorbate 20 and C16 or C18 for polysorbate 
    60). Based on the chemical similarities between polysorbate 60 and 
    polysorbate 20, the agency concludes that the toxicology data for 
    polysorbate 60 can be used to support the safety of polysorbate 20 
    under their limited exposure anticipated from the petitioned use of 
    SAHE. Moreover, based on the agency's review of the estimated dietary 
    exposure from all three esters in SAHE, the agency concludes that the 
    estimated small dietary exposure resulting from the proposed use of 
    this additive is safe.
        Under the proposed conditions of use, any residual EO will 
    quantitatively react with the boiler water to form ethylene glycol 
    (Ref. 1). Thus, no EO will be present in the steam that contacts food. 
    Consequently, the exposure to EO from the petitioned use of SAHE will 
    be zero. Therefore, FDA has evaluated the safety of this additive under 
    the general safety standard, considering all available data and using 
    risk assessment procedures to estimate the upper-bound limit of 
    lifetime human risk presented by DX, a carcinogenic chemical that may 
    be present as an impurity in two of the components of the additive 
    (polysorbate 20 and polysorbate 60). This risk evaluation of DX has two 
    aspects: (1) Assessment of the exposure to the impurity from the 
    petitioned use of the additive, and (2) extrapolation of the risk 
    observed in the animal bioassay to the conditions of exposure to 
    humans.
    
    A. 1,4-Dioxane
    
        FDA has estimated the exposure to DX from the petitioned use of the 
    additive as an anticorrosive agent in boilers where steam may contact 
    food to be no more than 17 parts per trillion in the daily diet (3 
    kilograms), or 50 nanograms (ng)/p/d (Ref. 1). The agency used data 
    from a carcinogenesis bioassay on DX, conducted by the National Cancer 
    Institute (Ref. 2), to estimate the upper-bound limit of lifetime human 
    risk from exposure to this chemical resulting from the petitioned use 
    of the additive. The results of the bioassay on DX demonstrated that 
    the material was carcinogenic for female rats under the conditions of 
    the study. The authors reported that the rodent bioassay showed that 
    the test material caused a significantly increased incidence of
    
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    squamous cell carcinomas and hepatocellular tumors in female rats.
        Based on the agency's estimate that exposure to DX will not exceed 
    50 ng/p/d, FDA estimates that the upper-bound limit of lifetime human 
    risk from the petitioned use of the subject additive is 1.8 x 
    10-9 or 1.8 in a billion (Ref. 3). Because of the numerous 
    conservative assumptions used in calculating the exposure estimate, the 
    actual lifetime-averaged individual exposure to DX is likely to be 
    substantially less than the estimated exposure, and therefore, the 
    probable lifetime human risk would be less than the upper-bound limit 
    of lifetime human risk. Thus, the agency concludes that there is 
    reasonable certainty that no harm from exposure to DX would result from 
    the petitioned use of the additive.
    
    B. Need for Specifications
    
        The agency has also considered whether specifications are necessary 
    to control the amount of DX present as an impurity in SAHE. The agency 
    finds that new specifications are not necessary for the following 
    reasons: (1) Because of the low levels at which DX may be expected to 
    remain as an impurity following production of SAHE, the agency would 
    not expect the impurity to become a component of food at other than 
    extremely low levels; and (2) the upper-bound limit of lifetime human 
    risk from exposure to DX is very low, 1.8 in a billion.
    
    IV. Conclusion
    
        FDA has evaluated data in the petition and other relevant material. 
    Based on this information, the agency concludes that the proposed use 
    of the additive as an anticorrosive agent in boilers where steam may 
    contact food is safe, that the additive will achieve its intended 
    technical effect, and therefore, that the regulations in Sec. 173.310 
    should be amended as set forth below in this document.
        In accordance with Sec. 171.1(h) (21 CFR 171.1(h)), the petition 
    and the documents that FDA considered and relied upon in reaching its 
    decision to approve the petition are available for inspection at the 
    Center for Food Safety and Applied Nutrition by appointment with the 
    information contact person listed previously. As provided in 
    Sec. 171.1(h), the agency will delete from the documents any materials 
    that are not available for public disclosure before making the 
    documents available for inspection.
    
    V. Environmental Impact
    
        The agency has carefully considered the potential environmental 
    effects of this action. FDA has concluded that the action will not have 
    a significant impact on the human environment, and that an 
    environmental impact statement is not required. The agency's finding of 
    no significant impact and the evidence supporting that finding, 
    contained in an environmental assessment, may be seen in the Dockets 
    Management Branch (address above) between 9 a.m. and 4 p.m., Monday 
    through Friday.
    
    VI. Paperwork Reduction Act of 1995
    
        This final rule contains no collections of information. Therefore, 
    clearance by the Office of Management and Budget under the Paperwork 
    Reduction Act of 1995 is not required.
    
    VII. Objections
    
        Any person who will be adversely affected by this regulation may at 
    any time on or before July 1, 1999, file with the Dockets Management 
    Branch (address above) written objections thereto. Each objection shall 
    be separately numbered, and each numbered objection shall specify with 
    particularity the provisions of the regulation to which objection is 
    made and the grounds for the objection. Each numbered objection on 
    which a hearing is requested shall specifically so state. Failure to 
    request a hearing for any particular objection shall constitute a 
    waiver of the right to a hearing on that objection. Each numbered 
    objection for which a hearing is requested shall include a detailed 
    description and analysis of the specific factual information intended 
    to be presented in support of the objection in the event that a hearing 
    is held. Failure to include such a description and analysis for any 
    particular objection shall constitute a waiver of the right to a 
    hearing on the objection. Three copies of all documents shall be 
    submitted and shall be identified with the docket number found in 
    brackets in the heading of this document. Any objections received in 
    response to the regulation may be seen in the Dockets Management Branch 
    between 9 a.m. and 4 p.m., Monday through Friday.
    
    VIII. References
    
        The following references have been placed on display in the Dockets 
    Management Branch (address above) and may be seen by interested persons 
    between 9 a.m. and 4 p.m., Monday through Friday.
         1. Memorandum, dated April 20, 1998, from the Division of 
    Product Manufacture and Use (HFS-246) to the Division of Petition 
    Control (HFS-215).
         2. ``Bioassay of 1,4-Dioxane for Possible Carcinogenicity,'' 
    National Cancer Institute, NCI-CG-TR-80, 1978.
         3. Memorandum, dated June 19, 1998, from the Division of 
    Petition Control (HFS-215) to Executive Secretary, Quantitative Risk 
    Assessment Committee (QRAC) (HFS-308).
    
    List of Subjects in 21 CFR Part 173
    
        Food additives, Incorporation by reference.
        Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
    authority delegated to the Commissioner of Food and Drugs, 21 CFR part 
    173 is amended as follows:
    
    PART 173--SECONDARY DIRECT FOOD ADDITIVES PERMITTED IN FOOD FOR 
    HUMAN CONSUMPTION
    
        1. The authority citation for 21 CFR part 173 continues to read as 
    follows:
    
        Authority: 21 U.S.C. 321, 342, 348.
    
        2. Section 173.310 is amended in the table in paragraph (c) by 
    alphabetically adding an entry for ``sorbitol anhydride esters'' under 
    the headings ``Substances'' and ``Limitations'' to read as follows:
    
    
    Sec. 173.310  Boiler water additives.
    
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        (c) * * *
    
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                           Substances                                              Limitations
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    Sorbitol anhydride esters: a mixture consisting of       The mixture is used as an anticorrosive agent in steam
     sorbitan monostearate as defined in Sec.  172.842 of     boiler distribution systems, with each component not
     this chapter; polysorbate 60 ((polyoxyethylene (20)      to exceed 15 parts per million in the steam.
     sorbitan monostearate)) as defined in Sec.  172.836 of
     this chapter; and polysorbate 20 ((polyoxyethylene
     (20) sorbitan monolaurate)), meeting the
     specifications of the Food Chemicals Codex, 4th ed.
     (1996), pp. 306-307, which is incorporated by
     reference in accordance with 5 U.S.C. 552(a) and 1 CFR
     part 51. Copies are available from the National
     Academy Press, 2101 Constitution Ave. NW., Box 285,
     Washington, DC 20055 (Internet http://www.nap.edu), or
     may be examined at the Center for Food Safety and
     Applied Nutrition's Library, Food and Drug
     Administration, 200 C St. SW., rm. 3321, Washington,
     DC, or at the Office of the Federal Register, 800
     North Capitol St. NW., suite 700, Washington, DC.
     
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        Dated: May 22, 1999.
    William K. Hubbard,
    Acting Deputy Commissioner for Policy.
    [FR Doc. 99-13670 Filed 5-28-99; 8:45 am]
    BILLING CODE 4160-01-F
    
    
    

Document Information

Effective Date:
6/1/1999
Published:
06/01/1999
Department:
Food and Drug Administration
Entry Type:
Rule
Action:
Final rule.
Document Number:
99-13670
Dates:
This regulation is effective June 1, 1999; written objections and requests for a hearing by July 1, 1999. The Director of the Office of the Federal Register approves the incorporation by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51 of a certain publication in Sec. 173.310 (21 CFR 173.310), effective June 1, 1999.
Pages:
29224-29227 (4 pages)
Docket Numbers:
Docket No. 97F-0450
PDF File:
99-13670.pdf
CFR: (2)
21 CFR 171.1(h)
21 CFR 173.310