National Toxicology Program: Carcinogens Report, Twelfth Edition— Agents, substances, mixtures, and exposure circumstances for listing or delisting,

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Federal Register: October 25, 2004 (Volume 69, Number 205)NoticesPage 62276-62279From the Federal Register Online via GPO Access [wais.access.gpo.gov]

DOCID:fr25oc04-62

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service

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

Background

The National Toxicology Program (NTP) initially announced its intent to review additional agents, substances, mixtures and exposure circumstances for possible listing or changing the current listing in the Report on Carcinogens (RoC), Twelfth Edition in a May 19, 2004 Federal Register notice (69 FR 28940 (May 19, 2004)). Based on some of the comments received in response to this notice, the NTP is concerned that there might have been confusion about the procedures that will be used for review of nominations to the 12th RoC. A detailed description of the current review procedures, including the steps in the formal review process, is available on the Web at http://ntp-server.niehs.nih.gov (select on 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, PO Box 12233, Research Triangle Park, NC 27709; phone: (919) 541-4096, fax: (919) 541-0144, e-mail: jameson@niehs.nih.gov.

Public Comment Requested

Because of the possibility of confusion over the review procedures for the 12th RoC nominations, additional comments concerning the nominations for listing or changing the current listing in the 12th RoC will be accepted by the NTP for a period of 30 days from the publication date of this announcement in the Federal Register. The following table identifies the 21 nominations the NTP may consider for review in 2004 or 2005, as either a new listing in or changing the current listing in the 12th RoC. These nominations are provided with their Chemical Abstracts Services (CAS) Registry numbers (where available) and pending review action. Additional nominations for the 12th RoC 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.

Individuals who submitted comments in response to the May 19, 2004 Federal Register (69 FR 28940 (May 19, 2004)) that initially announced the 12th RoC nominations need not re-submit their comments as they are already part of the public record. Individuals submitting new or additional 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 email). Nominations should be sent to Dr. Jameson's attention at the address given above.

Dated: October 15, 2004. Samuel Wilson, Deputy Director, National Institute of Environmental Health Sciences.

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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 number

Primary uses or exposures Nominated by

Basis for nomination

Aristolochia-Related Herbal

Several Aristolochia

NIEHS \1\............ Herbal remedies Remedies.

species (notably A.

containing the plant contorta, A. debilis, A.

genus Aristolochia: IARC fangchi and A.

\2\ finding evidence of manshuriensis) have been

carcinogenicity in used in traditional

humans (Vol. 83, 2002). Chinese medicine as anti- rheumatics, as diruretics, in the treatment of edema and for other conditions such as hemorrhoids, coughs and asthma. Aristolochic Acid................. Aristolochic acid, the NIEHS \1\............ Naturally occurring principle extract from

mixtures of aristolochic Aristolochia, is a

acids: IARC \2\ finding mixture of

of sufficient evidence nitrophenanthrene

of carcinogenicity in carboxylic acids.

animals and limited evidence in humans (Vol. 83, 2002). Asphalt fumes..................... Asphalt is a petroleum John Schelp of NAACP- Human epidemiological product used in paving Durham Chapter.

studies have reported an and roofing operations.

increased risk in lung Asphalt fumes are a cloud

cancer among workers of small particles

exposed to asphalt fumes generated from the

and asphalt fumes caused gaseous state after

skin tumors in volatilization of asphalt

experimental animals. aggregates.

Additionally, known human carcinogens (PAHs) have been found in asphalt fumes. Atrazine (192-24-9)............... Atrazine is an herbicide NIEHS \1\............ IARC \2\ finding of used to control grass and

sufficient evidence of broad-leaved weeks.

carcinogenicity in Atrazine has been

animals (Vol. 73, 1999). detected at levels that exceeded or approached the MCL for atrazine in 200 community surface drinking water systems. Benzofuran (271-89-6)............. Benzofuran is produced by NIEHS \1\............ Results of a NTP bioassay isolation from coal-tar

(TR 370, 1989), which oils. Benzofuran is used

reported clear evidence in the manufacture of

of carinogenicity in coumarone-indene resins,

male and female mice and which harden when heated

some evidence of and are used to make

carcinogenicity in floor titles and other

female rats. products. Captafol (2425-06-01)............. Captafol is a fungicide NIEHS \1\............ IARC \2\ finding of that has been widely used

sufficient evidence of since 1961 for the

carcinogenicity in control of fungal

animals (Vol. 53, 1991). diseases in fruits,

IARC also noted that vegetables and some other

captafol is positive in plants. Use of captafol

many genetic assays, in the United States was

including the in-vivo banned in 1999.

assay for dominant lethal mutation. Cobalt/Tungsten-Carbide Hard Metal Hard-metals are

NIEHS \1\............ Recent human cancer Manufacturing.

manufactured by a process

studies on the hard of powder metallurgy from

metal manufacturing tungsten and carbon

industry showing an (tungsten carbide), and

association between small amounts of other

exposure to hard metals metallic compounds using

(cobalt tungsten- cobalt as a binder. Hard

carbide) and lung metals are used to make

cancer. cutting and grinding tools, dies, and wear products for a broad spectrum of industries including oil and gas drilling, and mining. Di (2-Ethylhexyl) phthalate (DEHP) DEHP is mainly used as a Jun Ki-Chul,

Currently listed in the (117-81-7).

plasticizer in polyvinyl President of Aekyung RoC as reasonably chloride (PVC) resins for Petrochemical Co., anticipated to be a fabricating flexible

LTD of Seoul, Korea human carcinogen. vinyl products. PVC

(for delisting). IARC reclassification as resins have been used to

not classifiable as to manufacture toys, dolls,

its carcinogenicity to vinyl upholstery,

humans (Group 3) (Vol. tablecloths and many

73, 2000). IARC stated other products.

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. Etoposide in combination with Etoposide in combination NIEHS \1\............ IARC \2\ finding of cisplatin and bleomycin.

with cisplating and

sufficient evidence of bleomycin is used to

carcinogenicity in treat testicular germ

humans (Vol. 76, 2000). cell cancers. Etoposide (33419-42-0)............ Etoposide is a DNA

NIEHS \1\............ IARC \2\ finding of topoisomerase II

limited evidence of inhibitor used in

carcinogenicity in chemotherapy for non-

humans (Vol. 76, 2000). Hodgkin's lyumphoma, small-cell lung cancer, testicular cancer, lymphomas and a variety of childhood malignancies.

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Glass wool (respirable size): Two The major uses of glass North American

Glass wool (respirable nominations:

wool are in thermal,

Insulation

size) is currently (1) Insulation glass wool fibers. electrical, and

Manufacturers

listed in the RoC as (2) Special purposes glass fibers. acoustical insulation, Association

reasonably anticipated weatherproofing, and

nominated glass wool to be a human filtration media. In

(respirable size) carcinogen. 1980, approximately 80% for delisting.

Insulation glass wool: of the glass wool

Special purpose glass IARC \2\ finding of produced for structural wool fibers: NIEHS limited evidence of insulation was used in \1\.

carcinogenicity in houses. Special purpose

animals and evaluation fibers are used for high-

as not classifiable as efficiency air filtration

to its carcinogenicity media, and acid battery

to humans (Group 3) separators.

(Vol. 81, 2002). Special-purpose glass fibers: IARC \2\ finding of sufficient evidence of carcinogenicity in animals (Vol. 81, 2002). Metalworking Fluids............... Metal working fluids are NIEHS \1\............ Recent human cancer complex mixtures that may

studies of metal working contain mixtures of oil,

fluid that show an emulsifiers, anti-weld

association between agents, corrosion

exposure to these inhibitors, extreme

materials and cancer at pressure additives,

several tissue sites. 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. otho-Nitrotolume (88-72-2)........ ortho-Nitrotoluene is used NIEHS \1\............ Results of a NTP bioassay to synthesize

(TR 504, 2002), which agricultural and rubber

reported clear evidence chemicals, azo and sulfur

of carcinogenicity in dyes, and dyes for

rats and mice. cotton, wool, silk, leather, and paper. Oxazepam (604-75-1)............... Oxazepam is a

NIEHS \1\............ Results of a NTP bioassay benzodiazepine used

(TR 443, 1993), which extensively since the

reported clear evidence 1960s for the treatment

of carcinogenicity in of anxiety and insomnia

male and female mice. and in the control of symptoms of alcohol withdrawal. Riddelliine (23246-96-0).......... Riddelliine is found in NIEHS \1\............ Results of a NTP bioassay class of plants growing

(TR 508, 2003), which in western US. Cattle,

reported clear evidence horses and sheep ingest

of carcinogenicity in these toxic plants.

male and female rats and Residues have been found

mice. in milk and honey. Styrene (100-42-5)................ Styrene is used in the Lorenzo Tomatis...... IARC \2\ finding of production of

limited evidence of polystyrene,

carcinogenicity in acrylonitrile-butadiene-

animals and limited styreen resins, styrene-

evidence of butadiene rubbers and

carcinogenicity in latexes, and unsaturated

humans (Vol. 82, 2002). polystyrene resins. Talc--Two nominations............. Talc occurs in various NIEHS \1\............ The NTP deferred (1) Cosmetic talc................. geological settings

consideration of listing Occupational exposure to talc..... around the world.

talc (asbestiform and Exposure to general

non-asbestiform talc) in population occurs through

the 20th RoC because its use of products such as

2000 review of talc cosmetics. Occupational

found confusion in the exposure occurs during

scientific literature mining, milling and

over the mineral nature processing.

of talc. Given the confusion over defining exposure to talc based on asbestiform fibers, the NTP 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

NIEHS \1\............ IARC \2\ finding of topoisomerase II

limited evidence of inhibitors used mainly in

carcinogenicity in the treatment of adult

humans (Vol. 76, 2000). and childhood leukemia.

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Vinyl Mono-Halides as a class..... Vinyl halides are used in NIEHS \1\............ Vinyl Fluoride and Vinyl the production of

Bromide are currently polymers and copolymers.

listed in the RoC as Vinyl bromide is mainly

reasonably anticipated used in polymers as a

to be a human carcinogen flame retardant and in

and Vinyl Chloride is the production of

currently listed in the monoacrylic fibers for

RoC as known to be a carpet-backing materials.

human carcinogen in the Vinyl Chloride is used to

Reports on Carcinogens. produced polyvinyl

Vinyl Mono-Halides: chloride and copolymers.

Structural similarities Vinyl Fluoride is used in

and common mechanisms of the production of

tumor formation. 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.

\1\ The National Institute of Environmental Health Sciences (NIEHS). \2\ International Agency for Research on Cancer (IARC).

FR Doc. 04-23788 Filed 10-22-04; 8:45 amBILLING CODE 4140-01-P

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