[Federal Register Volume 66, Number 143 (Wednesday, July 25, 2001)]
[Notices]
[Pages 38717-38719]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-18458]


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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 [email protected].

    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
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                                                                                          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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[[Page 38719]]


                      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.
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[FR Doc. 01-18458 Filed 7-24-01; 8:45 am]
BILLING CODE 4140-01-P