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National Toxicology Program; Call for Public Comments on 21 Substances, Mixtures and Exposure Circumstances Proposed for Listing in the Report on Carcinogens, Twelfth Edition

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Background

The National Toxicology Program (NTP) announces its intent to review additional agents, substances, mixtures and exposure circumstances for possible listing in the Report on Carcinogens (RoC), Twelfth Edition that is scheduled for publication in 2006. This Report (previously known as the Annual Report on Carcinogens) is a Congressionally mandated listing of known human carcinogens and reasonably anticipated human carcinogens and its preparation is delegated to the NTP by the Secretary, Department of Health and Human Services (DHHS). Section 301(b)(4) of the Public Health Service Act, as amended, provides that the Secretary, DHHS shall publish a report, which contains a list of all substances (1) which either are known to be human carcinogens or may reasonably be anticipated to be human carcinogens, and (2) to which a significant number of persons residing in the United States (US) are exposed. The law also states that the reports should provide available information on the nature of exposures, the estimated number of persons exposed and the extent to which the implementation of Federal regulations decreases the risk to public health from exposure to these chemicals.

A nomination recommended for review in the RoC is evaluated initially by the NIEHS/NTP RoC nomination review committee, composed of scientists from the NIEHS/NTP staff, to determine if the information available for a nomination indicates the criteria for listing can be applied and warrants formal consideration by the NTP. The scientific review of a nomination involves three separate scientific reviews: two Federal review groups and one non-government peer review body (a subcommittee of the NTP Board of Scientific Counselors) that meets in an open, public forum. Throughout the review process, multiple opportunities are provided for public input including comment at the public meeting of the NTP Board RoC Subcommittee. In reviewing nominations for the RoC, all available data and public comments are considered in the application of the criteria for inclusion or removal of candidate agents, substances, mixtures Start Printed Page 28941or exposure circumstances or for a change in a candidate's classification.

The criteria used in the review process and a detailed description of the review procedures, including the steps in the current formal review process, can be obtained from the NTP Web site at http://ntp-server.niehs.nih.gov (see Report on Carcinogens) or can be obtained by contacting: 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: (919) 541-4096, fax: (919) 541-0144, e-mail: jameson@niehs.nih.gov.

Public Comment Requested

The following table identifies the 21 nominations that the NTP may consider for review in 2004 or 2005, as either a new listing in or changing the current listing in the Twelfth Report. These nominations are provided with their Chemical Abstracts Services (CAS) Registry numbers (where available) and pending review action. Additional nominations for the Twelfth Report or modifications to the nominations in the attached table may be identified and would be announced in future Federal Register notices. The NTP solicits public input on these 21 nominations and asks for relevant information concerning their carcinogenesis, as well as current production data, use patterns, or human exposure information. 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. Comments concerning these nominations for listing in or changing the current listing in the Twelfth Report on Carcinogens will be accepted for a period of 60 days from the publication date of this announcement in the Federal Register. Individuals submitting public comments are asked to include relevant contact information (name, affiliation (if any), address, telephone, fax, and e-mail). Comments or questions should be directed to Dr. C. W. Jameson at the address listed above.

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 the Twelfth and future RoCs. Nominations should contain a rationale for review. Appropriate background information and relevant data (e.g., journal articles, NTP Technical Reports, IARC listings, exposure surveys, release inventories, etc.), which 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). Nominations should be sent to Dr. Jameson's attention at the address given above.

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Dated: May 10, 2004.

Kenneth Olden,

Director, National Toxicology Program.

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Summary for Agents, Substances, Mixtures or Exposure Circumstances To Be Reviewed in 2004-2005 for Possible Listing the Report on Carcinogens, Twelfth Edition

Nomination to be reviewed/CAS No.Primary uses or exposuresNominated byBasis for nomination
Aristolochia-Related RemediesSeveral Aristolochia Herbal species (notably A. contorta, A. debilis, A. fangchi and A. manshuriensis) have been used in traditional Chinese medicine as anti-rheumatics, as diuretics, in the treatment of edema and for other conditions such as hemorrhoids, coughs and asthmaNIEHS 1Herbal remedies containing the plant genus Aristolochia: IARC 2 finding of sufficient evidence of carcinogenicity in humans (Vol. 83, 2002).
Aristolochic AcidAristolochic acid, the principle extract from Aristolochia, is a mixture of nitrophenanthrene carboxylic acidsNIEHS 1Naturally occurring mixtures of aristolochic acids: IARC 2 finding of sufficient evidence of carcinogenicity in animals and limited evidence in humans (Vol. 83, 2002).
Asphalt fumesAsphalt is a petroleum product used in paving and roofing operations. Asphalt fumes are a cloud of small particles generated from the gaseous state after volatilization of asphalt aggregatesJohn Schelp of NAACP-Durham ChapterHuman epidemiological studies have reported an increased risk in lung cancer among workers exposed to asphalt fumes and asphalt fumes caused skin tumors in experimental animals. Additionally, known human carcinogens (PAHs) have been found in asphalt fumes.
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 MCL for atrazine in 200 community surface drinking water systemNIEHS 1IARC 2 finding of sufficient evidence of carcinogenicity in animals (Vol. 73, 1999).
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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 titles and other productsNIEHS 1Results of a NTP bioassay (TR 370, 1989) that reported clear evidence of carcinogenicity in male and female mice and some evidence of carcinogenicity in female rats.
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 1999NIEHS 1IARC 2 finding of sufficient evidence of carcinogenicity in animals (Vol. 53, 1991). IARC also noted that captafol is positive in many genetic assays, including the in-vivo assay for dominant lethal mutation.
Cobalt/Tungsten-Carbide Hard Metal ManufacturingHard-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. Hard metals are used to make cutting and grinding tools, dies, and wear products for a broad spectrum of industries including oil and gas drilling, and miningNIEHS 1Recent human cancer studies on the hard metal manufacturing industry an association between exposure to hard metals (cobalt tungsten-carbide) and lung cancer.
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 productsJun Ki-Chul, President of Aekyung Petrochemical Co., LTD of Seoul, Korea (for delisting)Currently listed in the RoC as reasonably anticipated to be a human carcinogen. IARC reclassification as not classifiable as to its carcinogenicity to humans (Group 3) (Vol. 73, 2000). IARC stated that there is sufficient evidence for the carcinogenicity in experimental animals; however, the mechanism for liver tumor involves peroxisome proliferation that is not relevant to humans.
Etoposide in combination with cisplatin and bleomycinEtoposide in combination with cisplatin and bleomycin is used to treat testicular germ cell cancersNIEHS 1IARC 2 finding of sufficient evidence of carcinogenicity in humans (Vol 76, 2000).
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 malignanciesNIEHS 1IARC 2 finding of limited evidence of carcinogenicity in humans (Vol. 76, 2000).
Glass wool (respirable size): Two nominations: (1) Insulation glass wool fibers (2) Special purposes glass fibersThe major uses of glass wool are in thermal, electrical, and acoustical insulation, weatherproofing, and filtration media. In 1980, approximately 80% of the glass wool produced for structural insulation was used in houses. Special purpose fibers are used for high-efficiency air filtration media, and acid battery separatorsNorth American Insulation Manufacturers Association nominated glass wool (respirable size) for delisting Special purpose glass wool fibers: NIEHS 1Glass 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) (Vol. 81, 2002). Special-purpose glass fibers: IARC 2 finding of sufficient evidence of carcinogenicity in animals (Vol. 81, 2002).
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Metalworking FluidsMetal 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 operationsNIEHS 1Recent human cancer studies of metal working fluid that show an association between exposure to these materials and cancer at several tissue sites.
otho-Nirotoluine (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 paperNIEHS 1Results of a NTP bioassay (TR 504, 2002), which reported clear evidence of carcinogenicity in rats and mice.
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 withdrawalNIEHS 1Results of a NTP bioassay (TR 443, 1993), which reported clear evidence of carcinogenicity in male and female mice.
Riddelliine (232476-96-0)Riddelliine is found in a class of plants growing in western United States. Cattle, horses and sheep ingest these toxic plants. Residues have been found in, milk, and honeyNIEHS 1Results of a NTP bioassay (TR 508, 2003), which reported clear evidence of carcinogenicity in male and female rats and mice.
Styrene (100-42-5)Styrene is used in the production of polystyrene, acrylonitrile-butadiene-styrene resins, styrene-butadiene rubbers and latexes, and unsaturated polystyrene resinsLorenzo TomatisIARC 2 finding of limited evidence of carcinogenicity in animals and limited evidence of carcinogenicity in humans (Vol. 82, 2002).
Talc Two nominations (1) Cosmetic talc (2) Occupational exposure to talcTalc 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 processingNIEHS 1The NTP deferred consideration of listing talc (asbestiform and non-asbestiform talc) in the 10th RoC because its 2000 review of talc found confusion in the scientific literature over the mineral nature of talc. Given the confusion over defining exposure to talc based on asbestiform fibers, the NPT has decided that the most appropriate approach would be to characterize talc exposure as cosmetic talc and occupational exposure to talc. The basis for the review of talc is as follows: Cosmetic talc: Human epidemiological studies reporting an increased risk of ovarian cancer among women using talc for personal use. Occupational exposure to talc: Human epidemiological studies reporting an increase risk of cancer among workers exposed to talc.
Teniposide (29767-20-2)Teniposide is a DNA toposiomerase II inhibitors used mainly in the treatment of adult childhood leukemiaNIEHS 1IARC 2 finding of limited evidence of carcinogenicity in humans (Vol. 76, 2000).
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Vinyl Mono-Halides as a classVinyl 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 of 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 buildingsNIEHS1Vinyl 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 known to be a human carcinogen in the Report on Carcinogens. Vinyl Mono-Halides: Structural similarities and common mechanisms of tumor formation.
1 The National Institute of Environmental Health Sciences (NIEHS).
2 International Agency for Research on Cancer (IARC).
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[FR Doc. 04-11359 Filed 5-18-04; 8:45 am]

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