05-20729. National Toxicology Program (NTP); Report on Carcinogens; Status of Nominations to the 12th Report on Carcinogens (RoC): Request for Comments and Nominations of Scientific Experts

AGENCY:

National Institute of Environmental Sciences (NIEHS), National Institutes of Health (NIH), HHS.

ACTION:

Request for Comments and Nominations of Scientific Experts.

SUMMARY:

The NTP invites public comments on an updated list of nominations proposed for review in the 12th RoC and the nomination of scientists who have expertise and/or knowledge relevant to the evaluation of carcinogenicity for these nominations (see SUPPLEMENTARY INFORMATION). Information on the nominations under consideration for the RoC can be obtained at the NTP Web site http://ntp.niehs.nih.gov (select “Report on Carcinogens”) or by contacting Dr. C.W. Jameson at the address provided below.

DATES:

Comments and nominations will be accepted until November 17, 2005.

ADDRESSES:

All correspondence should be directed to Dr. C. W. Jameson, National Toxicology Program, Report on Carcinogens, 79 Alexander Drive, Building 4401, Room 3118, P.O. Box 12233, Research Triangle Park, NC 27709; phone: [phone], fax: [phone], e-mail: [e-mail].

SUPPLEMENTARY INFORMATION:

Background

This notice provides an update on the current status of and/or additions to the list of nominations identified in earlier Federal Register notices relevant to the 12th RoC [69FR28940 (May 19, 2004) and 69FR62276 (October 25, 2004)]. All but the newly identified nomination of formaldehyde were announced in earlier Federal Register notices. Any additional nominations for the 12th RoC or modifications to the nominations in the attached table will be announced in future Federal Register notices.

Request for Comments on Nominations to the RoC

The following table identifies the nominations that the NTP has under consideration for review as either a new listing in the RoC or as a change in the current listing. These nominations are provided with their Chemical Abstracts Services (CAS) Registry numbers (where available) and pending review action. The NTP solicits public input on these nominations and asks for relevant information concerning their carcinogenicity as well as current data on production, patterns of use, or human exposure. The NTP also invites interested parties to identify any scientific issues related to the listing of a specific nomination in the RoC that they feel should be addressed during the reviews. Individuals who submitted comments in response to the May 19, 2004 Federal Register (69FR28940) and/or the October 25, 2004 Federal Register notice (69FR62276) need not re-submit their comments as they are already part of the public record. Individuals submitting public comments are asked to include relevant contact information [name, affiliation (if any), address, telephone, fax, and e-mail] and sponsoring organization, if applicable. Written submissions will be made available on the NTP Web site as they are received (http://ntp.niehs.nih.gov/​ select “Report on Carcinogens”) and added to the public record.

Request for Nominations of Scientific Experts

The NTP solicits nominations of scientists who have expertise and/or knowledge relevant to the evaluation of carcinogenicity for the selected nominations. These scientists should have expertise in various aspects of toxicology, epidemiology, carcinogenesis, or other relevant areas of science (e.g., genetic toxicity, metabolism, etc.) and/or experience with the agent being reviewed. The experts may be used to write and/or review the background documents prepared on selected nominations. Nominations of scientists should include contact information for the nominee [name, affiliation (if any), address, telephone, fax, and e-mail], the specific nominated agent(s) (listed in the table below) for which they are being recommended as an expert, and a curriculum vitae (if possible). Contact information for the nominator must also be provided.

Additional Nominations Encouraged

The NTP solicits and encourages the broadest participation from interested individuals or parties in nominating agents, substances, or mixtures for review for future RoCs. Nominations should contain a rationale for review. Appropriate background information and relevant data [e.g., journal articles, NTP Technical Reports, International Agency for Research on Cancer (IARC) listings, exposure surveys, release inventories, etc.] that support the review of a nomination should be provided or referenced when possible. Contact information for the nominator should also be included [name, affiliation (if any), address, telephone, fax, and e-mail].

Background Information on the Report on Carcinogens

The RoC is a congressionally mandated document [Section 301(b)(4) of the Public Health Services Act, 42 U.S.C. 241(b)(4)], published by the Secretary of Health and Human Services (HHS), that identifies agents, substances, mixtures, or exposure circumstances (collectively referred to as “substances”) that may pose a carcinogenic hazard to human health. The Secretary, HHS, has delegated responsibility for preparing the draft report to the NTP. Substances are listed in the RoC as either known to be a human carcinogen or reasonably anticipated to be a human carcinogen. Review of nominations (substances that are under consideration for listing or removing from the RoC) involves a multi-step scientific review process with opportunity for public comment.

Dated: October 6, 2005.

Samuel H. Wilson,

Deputy Director, National Institute of Environmental Health Sciences.

Status of Nominations To Be Reviewed for the Report on Carcinogens

Nomination/CAS No.	Primary uses or exposures	Nominator	Basis for nomination	Status
1 Herbal remedies containing aristolochic acid *Note—this nomination was previously identified as “Aristolochia-Related Herbal Remedies”	Several Aristolochia species (notably A. contorta, A. debilis, A. fangchi and A. manshuriensis) have been used in traditional Chinese medicine as antirheumatics, as diuretics, in the treatment of edema, and for other conditions such as hemorrhoids, coughs, and asthma	NIEHS	Herbal remedies containing the plant genus Aristolochia: IARC 2 finding of sufficient evidence of carcinogenicity in humans (IARC Monograph Vol. 82, 2002)	Review for possible listing in 12th RoC.
Aristolochic Acid	Aristolochic acid, the principle extract from Aristolochia, is a mixture of nitrophenanthrene carboxylic acids	NIEHS	Naturally occurring mixtures of aristolochic acids: IARC 2 finding of sufficient evidence of carcinogenicity in animals and limited evidence in humans (IARC Monograph Vol. 82, 2002)	Review for possible listing in 12th RoC.
Asphalt fumes	Asphalt is a petroleum product used in paving and roofing operations. Asphalt fumes are a cloud of small particles generated after volatilization of asphalt aggregates	Private Individual	Human epidemiological studies have reported an increased risk of lung cancer among workers exposed to asphalt fumes and asphalt fumes caused skin tumors in experimental animals. Additionally, known human carcinogens (polycyclic aromatic hydrocarbons or PAHs) have been found in asphalt fumes	Defer review of nomination until the 13th RoC.
Atrazine (192-24-9)	Atrazine is an herbicide used to control grass and broad-leaved weeds. Atrazine has been detected at levels that exceeded or approached the maximum contaminant level (MCL) for atrazine in 200 community surface drinking water systems	NIEHS	IARC 2 finding of sufficient evidence of carcinogenicity in animals (IARC Monograph Vol. 73, 1999)	Defer review of nomination until the 13th RoC.
Benzofuran (271-89-6)	Benzofuran is produced by isolation from coal-tar oils. Benzofuran is used in the manufacture of coumarone-indene resins, which harden when heated and are used to make floor tiles and other products	NIEHS	Results of a NTP bioassay (NTP Technical Report 370, 1989) 3, which reported clear evidence of carcinogenicity in male and female mice and some evidence of carcinogenicity in female rats	Defer review of nomination until the 13th RoC.
Captafol (2425-06-01)	Captafol is a fungicide that has been widely used since 1961 for the control of fungal diseases in fruits, vegetables, and some other plants. Use of captafol in the United States was banned in 1999	NIEHS	IARC 2 finding of sufficient evidence of carcinogenicity in animals (IARC Monograph Vol. 53, 1991). IARC also noted that captafol is positive in many genetic assays including the in-vivo assay for dominant lethal mutation	Review for possible listing in 12th RoC.
1 Cobalt-tungsten carbide powders and hard metals *Note—This nomination was previously identified as “Cobalt/Tungsten-Carbide Hard Metal Manufacturing”	Cobalt-tungsten carbide hard-metals are manufactured by a process of powder metallurgy from tungsten and carbon (tungsten carbide), and small amounts of other metallic compounds using cobalt as a binder. They are used to make cutting and grinding tools, dies, and wear products for a broad spectrum of industries including oil and gas drilling, and mining	NIEHS	Recent human cancer studies on the hard metal manufacturing industry showing an association between exposure to hard metals (cobalt tungsten-carbide) and lung cancer	Review for possible listing in 12th RoC.
Di (2-ethylhexyl) phthalate (DEHP) (117-81-7)	DEHP is mainly used as a plasticizer in polyvinyl chloride (PVC) resins for fabricating flexible vinyl products. PVC resins have been used to manufacture toys, dolls, vinyl upholstery, tablecloths, and many other products	Private Individual	Currently listed in the RoC as reasonably anticipated to be a human carcinogen IARC 2 reclassification as not classifiable as to its carcinogenicity to humans (Group 3) (IARC Monograph Vol. 77, 2000). IARC stated that there was sufficient evidence for the carcinogenicity in experimental animals; however, the mechanism for liver tumor involves peroxisome proliferation that is not relevant to humans	Review for possible removal of listing in 12th RoC.
Etoposide in combination with cisplatin and bleomycin	Etoposide in combination with cisplatin and bleomycin is used to treat testicular germ cell cancers	NIEHS	IARC 2 finding of sufficient evidence of carcinogenicity in humans (IARC Monograph Vol. 76, 2000)	Review for possible listing in 12th RoC.
Etoposide (33419-42-0)	Etoposide is a DNA topoisomerase II inhibitor used in chemotherapy for non-Hodgkin's lymphoma, small-cell lung cancer, testicular cancer, lymphomas, and a variety of childhood malignancies	NIEHS	IARC 2 finding of limited evidence of carcinogenicity in humans (IARC Monograph Vol. 76, 2000)	Review for possible listing in 12th RoC.
Formaldehyde (50-00-0)	Formaldehyde is primarily used in the production of resins that are used in the production of many different products including plastics, adhesives and binders for wood products, pulp and paper, synthetic fibers, and in textile finishing. It is also used as a disinfectant and preservative and as an intermediate for many industrial chemicals	NIEHS	Formaldehyde (gas) is currently listed in the RoC as reasonably anticipated to be a human carcinogen. Nominated for reconsideration based on the 2004 IACR 2 review, which concluded that there was sufficient evidence for the carcinogenicity of formaldehyde in humans (IARC Monograph Vol. 88, 2004)	Review for possible reclassification of listing status in 12th RoC.
1 Certain Glass Wool Fibers *Note—This nomination was previously identified as “Glass wool (respirable size): Two nominations: (1) Insulation glass wool fibers, and (2) Special purpose glass fibers”	Glass wool fibers, which are a type of synthetic vitreous fibers, are an inorganic fibrous material manufactured primarily from glass and processed inorganic oxides. The composition of these fibers may vary substantially because of differences in end-use, manufacturing requirements, and biopersistence considerations. The major uses of glass wool are in thermal, electrical, and acoustical insulation, weatherproofing, and filtration media. Some glass wool fibers (special purpose fibers) are used for high-efficiency air filtration media, and acid battery separators	North American Insulation Manufacturers Association nominated glass wool (respirable size) for delisting NIEHS recommended that the nomination be defined as “certain glass wool fibers” because of the considerable differences in the composition of glass wool fibers	Glass wool (respirable size) is currently listed in the RoC as reasonably anticipated to be a human carcinogen Insulation glass wool: IARC 2 finding of limited evidence of carcinogenicity in animals and evaluation as not classifiable as to its carcinogenicity to humans (Group 3) (IARC Monograph Vol. 81, 2002) Special-purpose glass fibers: IARC 2 finding of sufficient evidence of carcinogenicity in animals (IARC Monograph Vol. 81, 2002)	Review for possible listing in 12th RoC.
Metalworking Fluids	Metal working fluids are complex mixtures that may contain mixtures of oil, emulsifiers, anti-weld agents, corrosion inhibitors, extreme pressure additives, buffers biocides, and other additives. They are used to cool and lubricate tools and working surfaces in a variety of industrial machining and grinding operations	NIEHS	Recent human cancer studies of metal working fluids that show an association between exposure to these materials and cancer at several tissue sites	Review for possible listing in 12th RoC.
ortho-Nitrotoluene (88-72-2)	ortho-Nitrotoluene is used to synthesize agricultural and rubber chemicals, azo and sulfur dyes, and dyes for cotton, wool, silk, leather, and paper	NIEHS	Results of a NTP bioassay (NTP Technical Report 504, 2002) 3, which reported clear evidence of carcinogenicity in rats and mice	Review for possible listing in 12th RoC.
Oxazepam (604-75-1)	Oxazepam is a benzodiazepine used extensively since the 1960s for the treatment of anxiety and insomnia and in the control of symptoms of alcohol withdrawal	NIEHS	Results of a NTP bioassay (NTP Technical Report 443, 1993) 3, which reported clear evidence of carcinogenicity in male and female mice	Defer review of nomination until the 13th RoC.
Riddelliine (23246-96-0)	Riddelliine is found in class of plants growing in western United States. Cattle, horses, and sheep ingest these toxic plants. Residues have been found in milk and honey	NIEHS	Results of a NTP bioassay (NTP Technical Report 508, 2003) 3, which reported clear evidence of carcinogenicity in male and female rats and mice	Review for possible listing in 12th RoC.
Styrene (100-42-5)	Styrene is used in the production of polystyrene, acrylonitrile-butadiene-styrene resins, styrene-butadiene rubbers and latexes, and unsaturated polystyrene resins	Private Individual	IARC 2 finding of limited evidence of carcinogenicity in animals and limited evidence of carcinogenicity in humans (IARC Monograph Vol. 82, 2002)	Review for possible listing in 12th RoC.
Talc (Two nominations) (1) Cosmetic talc (2) Occupational exposure to talc	Talc occurs in various geological settings around the world. Exposure to general population occurs through use of products such as cosmetics. Occupational exposure occurs during mining, milling, and processing	NIEHS	The NTP deferred consideration of listing talc (asbestiform and non-asbestiform talc) in the 10th RoC because its 2000 review of talc found that there has been considerable confusion over the mineral nature and consequences of exposure to talc, both containing asbestiform fibers and not containing asbestiform fibers. It has become evident that the literature on both forms of talc, with a few exceptions, provides an inadequate characterization of the actual materials under study to enable one to reach definitive conclusions concerning the specific substances responsible for the range of adverse health outcomes reported	Withdrawn from review.
Teniposide (29767-20-2)	Teniposide is a DNA topoisomerase II inhibitors used mainly in the treatment of adult and childhood leukemia	NIEHS	IARC 2 finding of limited evidence of carcinogenicity in humans (IARC Monograph Vol. 76, 2000)	Review for possible listing in 12th RoC.
Vinyl Mono-Halides as a class	Vinyl halides are used in the production of polymers and copolymers. Vinyl bromide is mainly used in polymers as a flame retardant and in the production of monoacrylic fibers for carpet-backing materials. Vinyl chloride is used to produce polyvinyl chloride and copolymers. Vinyl fluoride is used in the production of polyvinyl fluoride, which when laminated with aluminum, steel and other materials, is used as a protective surface for the exteriors of residential and commercial buildings	NIEHS	Vinyl fluoride and vinyl bromide are currently listed in the RoC as reasonably anticipated to be a human carcinogen and vinyl chloride is currently listed in the RoC as a known to be a human carcinogen Vinyl mono-halides: Structural similarities and common mechanisms of tumor formation	Defer review of nomination until the 13th RoC.
1 Nomination has been redefined based on public comments received from earlier Federal Register notices and/or review of the literature.
2 International Agency for Research on Cancer (IARC). IARC Monographs are available from http://monographs.iarc.fr/​.
3 NTP Technical Reports are available at http://ntp.niehs.nih.gov/​ see “NTP Study Reports.”