National Toxicology Program: Chemicals nominated for toxicological studies; testing recommendations; comment request,

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Federal Register: July 25, 2001 (Volume 66, Number 143)NoticesPage 38717-38719From the Federal Register Online via GPO Access [wais.access.gpo.gov]

DOCID:fr25jy01-119

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service

National Toxicology Program (NTP); Request for Comments on Substances Nominated to the National Toxicology Program (NTP) for Toxicological Studies and on the Testing Recommendations Made by the NTP Interagency Committee for Chemical Evaluation and Coordination

Summary: The National Toxicology Program (NTP) continuously solicits and accepts nominations for toxicological studies to be undertaken by the Program. Nominations of substances of potential human health concern are received from Federal agencies, the public, and other interested parties. These nominations undergo several levels of review before selections for testing are made and toxicological studies are designed and implemented. The NTP Interagency Committee for Chemical Evaluation and Coordination (ICCEC) serves as the first level of review for NTP nominations. At the 8 May 2001 ICCEC meeting, 13 new nominations were reviewed and testing recommendations were made. To inform the public and to obtain input for consideration when selecting chemicals for toxicological evaluation, the NTP routinely seeks public comment on the nominated substances and the ICCEC's testing recommendations. This announcement (1) provides brief background information regarding the substances nominated to NTP for study, (2) presents the ICCEC's testing recommendations from its 8 May 2001 meeting, (3) solicits public comment on the nominations and recommendations, and (4) requests the submission of additional relevant information for consideration by the NTP in its continued evaluation of these nominations.

Background

The NTP actively seeks to identify and select for study chemicals and other agents for which sufficient information is not available to adequately evaluate potential human health hazards. The NTP accomplishes this goal through a formal open chemical nomination and selection process. Substances selected for study generally fall into two broad overlapping categories: (1) Those substances of greatest concern for public or occupational health based on the extent of human exposure and/or suspicion of toxicity; and (2) substances for which toxicological data gaps exist and additional studies would aid in assessing potential human health risks, e.g. by facilitating cross- species extrapolation or evaluating dose-response relationships. Particular assistance is also sought for the nomination of studies that permit the testing of hypotheses to enhance the predictive ability of future NTP studies, address mechanisms of toxicity, or fill significant gaps in the knowledge of the toxicity of classes of chemicals. Substances may be studied for a variety of health-related effects, including but not limited to reproductive and developmental toxicity, genotoxicity, immunotoxicity, neurotoxicity, metabolism and disposition, and carcinogenicity. In evaluating and selecting nominated substances, the NTP also considers legislative mandates that require responsible private sector commercial organizations to evaluate their products for health and environmental effects. The possible human health consequences of anticipated or known human exposure, however, remain the over-riding factor in the NTP's decision to study a particular chemical or agent.

The review and selection of substances nominated for study is a multi-step process. A broad range of concerns are addressed during this process through the participation of representatives from Federal agencies, the NTP Board of Scientific Counselors--an external scientific advisory body, the NTP Executive Committee--the NTP Federal interagency policy body, and a public comment period. This process is described in further detail in a 2 March 2000 Federal Register announcement (Volume 65, Number 42, pages 11329-11331). This multi-step evaluative process provides the NTP direction and guidance to ensure that it's testing program addresses toxicological concerns relative to all areas of public health, and furthermore, that there is balance among the types of substances selected for study (e.g., industrial chemicals, consumer products, therapeutic agents, etc.). As such, it should be recognized that for any given committee review, the new testing nominations under consideration do not necessarily reflect the overall balance of substances historically or currently being evaluated by NTP in it's testing program. For further information on NTP studies (previous or in progress) visit the NTP web site at http://ntp- server.niehs.nih.gov.

Nominated Substances and Interagency Review

The ICCEC is composed of representatives from the Agency for Toxic Substances and Disease Registry, Consumer Product Safety Commission, Department of Defense, Environmental Protection Agency, Food and Drug Administration's National Center for Toxicological Research, National Cancer Institute, National Institute of Environmental Health Sciences, National Institute for Occupational Safety and Health, National Library of Medicine, and the Occupational Safety and Health Administration. The ICCEC meets once or twice annually to evaluate groups of new nominations and to make testing recommendations with respect to both specific types of studies and testing priorities. At its meeting on 8 May 2001, the ICCEC reviewed 13 new nominations for NTP studies. For eight of these nominations, one or more types of testing was recommended, and for three nominations, no testing was recommended at this time. A testing recommendation for two nominations was deferred pending receipt of (1) additional information or data from the nominator or other organizations on related studies completed, anticipated or in progress, or (2) additional information on production, human exposure, use patterns, or regulatory needs. The nominated substances with CAS numbers, nomination source, nomination rationale, specific study recommendations, and other information are given in the attached tables.

Request for Public Comment

Interested parties are invited to submit comments or supplementary information on the nominated substances and recommendations identified in the attached tables. The NTP would welcome receiving toxicology and carcinogenesis information from completed, ongoing, or planned studies, as well as information on current production levels, use patterns, human exposure, environmental occurrence, or public health concerns for any of the nominated substances. Comments or information should be sent to Dr. Scott Masten at the address given below through September 24, 2001. Persons responding to this request are asked to include their name, affiliation, mailing address, phone, fax, e-mail address and sponsoring organization (if any) with

[Page 38718]the submission. An electronic copy of this announcement as well as further information on the NTP and the NTP Chemical Nomination and Selection Process can be accessed through the NTP web site: http://ntp- server.niehs.nih.gov.

Contact may be made by mail to Dr. Scott Masten, Office of Chemical Nomination and Selection, NIEHS/NTP, P.O. Box 12233, Research Triangle Park, North Carolina 27709; by telephone at (919) 541-5710; by FAX at (919) 558-7067; or by email to masten@niehs.nih.gov.

Dated: June 14, 2001. Samuel H. Wilson, Deputy Director, National Institute of Environmental Health Sciences.

Substances Nominated to the NTP for Toxicological Studies and Testing Recommendations Made by the ICCEC on 8 May 2001

Table 1.--Substances Recommended for Testing

ICCEC recommendations Substance [CAS No.]

Nominated by

Nomination rationale; for toxicological other information

studies

Bladderwrack......................... National Cancer

Significant human

--Chemical

[68917-51-1] ......................... Institute.

exposure through use characterization

[84696-13-9] .........................

as a dietary

(iodine content). supplement; safety --Subchronic toxicity concern due to

testing with potential thyroid

evaluation of stimulation; limited reproductive available toxicity parameters. information. Cylindrospermopsin [14345-90-8]...... National Institute of Cyanobacterial toxin --Complete Environmental Health with potential for toxicological Sciences.

widespread human

characterization exposure through

including chronic drinking water; high toxicity and acute toxicity;

carcinogenicity limited available

testing. toxicity information. Epigallocatechin-3-gallate [989-51-5] National Cancer

Major polyphenol in --Genotoxicity testing. Institute.

green tea and green --Subchronic toxicity tea extract dietary testing. supplements; potential --Consider testing chemopreventive agent; green tea extract. limited available toxicity information. 2-Ethylhexyl-p-dimethylaminobenzoic Private Individual..... High production volume --Subchronic toxicity acid [21245-02-3].

chemical with

and developmental and industrial and

reproductive toxicity consumer (sunscreen) testing by the dermal uses; evidence for route of exposure. phototoxicity and --Phototoxicity and testicular toxicity; photocarcinogenicity limited available

testing. toxicity information. Grape seed and pine bark extracts.... National Cancer

Significant human

--Genotoxicity testing. Institute.

exposure through use --Subchronic toxicity as a dietary

testing. supplement; limited --Developmental and available toxicity reproductive toxicity information.

testing. --Select a standardized commercial pine bark extract for study. Metalworking fluids.................. National Institute for High production volume; --In vitro, short-term Occupational Safety large number of

in vivo and subchronic and Health.

occupationally-exposed toxicity studies aimed workers; lack of

at evaluating toxicity carcinogenicity and and carcinogenicity chronic toxicity data. potential of multiple commercial formulations. --The ICCEC will make recommendations regarding further testing after reviewing the results of NTP preliminary studies. Methyl tetrahydrofuran [96-47-9]..... National Cancer

Increasing use in

--Genotoxicity testing Institute.

alternative fuels; --Short-term toxicity suspicion of toxicity testing. and carcinogenicity --Consider dermal and based on structure; inhalation routes of limited available

exposure. toxicity information. Polybrominated diphenyl ethers....... Private Individuals, High production volume --Subchronic toxicity, Pentabromodiphenyl ether (technical) California

flame retardants;

developmental [32534-81-9].

Environmental

widespread human

neurotoxicity and Octabromodiphenyl ether (technical) Protection Agency. exposure

chronic toxicity [32536-52-0].

occupationally and as testing of selected 2,2',4,4'-Tetrabromodiphenyl ether

environmental

individual congeners [5436-43-1].

contaminants;

--No testing of 2,2',4,4',5-Pentabromodiphenyl ether

persistent and

technical mixtures. [60348-60-9].

bioaccumulative; 2,2',4,4',5,5'-Hexabromodiphenyl

evidence for toxicity ether [68631-49-2].

but significant knowledge gaps remain.

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Table 2.--Substances for Which No Testing Is Recommended at This Time

ICCEC rationale Nomination

for not Substance [CAS No.]

Nominated by

Nominated for rationale; other recommending information

toxicological studies

Apigenin [520-36-5]............. National Cancer --Genotoxicity Naturally

Insufficient Institute.

testing.

occurring

toxicity and --Developmental flavonoid with exposure toxicity testing. potential oxidant potential. and estrogenic activity; lack of toxicity information. Dibenzofuran [132-64-9]......... National Cancer --Genotoxicity Widespread human Low commercial Institute.

testing.

exposure as an production --Carcinogenicity environmental volume; low testing..

contaminant;

potential for potential for human exposure. carcinogenicity; lack of toxicity information. Diphenolic acid [126-00-1]...... National Cancer --Genotoxicity Industrial

Low commercial Institute.

testing.

chemical

production --Subchronic

potential for volume; low toxicity testing. increasing use; potential for structurally

human exposure. related bisphenol A; lack of toxicity information.

Table 3.--Substances for Which a Testing Recommendation Is Deferred Pending Receipt and Consideration of Additional Information

Nomination Substance [CAS No.]

Nominated by

Nominated for rationale; other Additional Information information needed

n-Butyl bromide [109-65-9]...... National Cancer --Subchronic

Industrial

Manufacturers' Institute.

toxicity testing. chemical with voluntary testing --Reproductive significant

plans. toxicity testing. production volume and human exposure potential; mutagenic; potential for carcinogenicity; lack of toxicity information. Methyl soyate [67784-80-9]...... National Cancer --Genotoxicity Increasing

Toxicity data Institute.

testing.

production volume development plans --Subchronic

as an alternative through existing toxicity testing fuel (biodiesel); or future by the dermal lack of toxicity regulatory route of exposure. information.

programs.

FR Doc. 01-18458Filed7-24-01; 8:45 amBILLING CODE 4140-01-P

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