[Federal Register Volume 65, Number 42 (Thursday, March 2, 2000)]
[Notices]
[Pages 11329-11331]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-4964]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service


National Institute of Environmental Health Sciences, National 
Toxicology Program; 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 (ICCEC); Solicitation of 
Information on Nominated Substances

Summary

    The National Toxicology Program (NTP) routinely solicits, accepts 
and reviews for consideration nominations for toxicological studies to 
be undertaken by the Program on substances of potential human health 
concern. Nominations are received from Federal agencies, industry, the 
public, and other interested parties and undergo several levels of 
review before 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 
December 13, 1999 meeting of the ICCEC, 12 new nominations were 
reviewed and testing recommendations made. As part of an effort to 
inform the public and to obtain input about the selection of chemicals 
for evaluation, the NTP routinely seeks public comment on (1) 
substances nominated to the Program for toxicological studies and (2) 
the testing recommendations made by the ICCEC. This announcement 
outlines briefly the process for nomination and selection of substances 
for NTP study, presents the testing recommendations made by the ICCEC 
at the December 13, 1999 meeting, requests comment on those nominations 
and recommendations, and solicits the submission of additional 
information for consideration by the NTP in its subsequent evaluation 
of the nominations.

Background

1. Nomination and Selection of Substances for NTP Studies

    The nomination and selection for study of chemicals and agents with 
the highest potential for adversely impacting public health are 
essential to the success of the NTP's testing program. The nomination 
process is open and nominations are solicited from academia, Federal 
and State regulatory and health agencies, industry, and labor unions, 
as well as from environmental groups and the general public. Particular 
assistance is sought for the nomination of studies to be undertaken by 
the NTP 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 chemicals or 
classes of chemicals. Substances selected for study generally fall into 
two broad overlapping categories: (1) Those substances of greatest 
concern for public or occupational health and (2) chemicals for which 
toxicological data is needed to reduce uncertainty in risk assessment 
by aiding species-to-species extrapolation and understanding dose-
response relationships. Substances may be studied for a variety of 
health-related effects, including but not limited to, reproductive and 
developmental toxicity, genotoxicity, immunotoxicity, metabolism and 
disposition, as well as carcinogenicity. The possible public health 
consequences of exposure remain the over-riding factor in the decision 
to study a particular chemical or agent. Selections for government 
testing are based on the principle that responsible manufacturers will 
evaluate their own chemicals or agents for health and environmental 
effects as mandated by Congress under legislative authorities. 
Increased efforts continue to be focused on: (1) Improving the quality 
of the nominations of chemicals, environmental agents, or issues for 
study so that public health and regulatory needs are addressed; (2) 
broadening the base and diversity of nominating organizations and 
individuals; and (3) increasing nominations for studying toxicological 
endpoints in addition to carcinogenesis.

II. Review Process for Substances Nominated for NTP Studies

    Nominations are first reviewed by a multi-disciplinary NIEHS 
committee to determine whether the nominated agent has undergone 
adequate toxicological testing or has been previously considered by the 
NTP. For nominations not eliminated from consideration or deferred at 
this stage, the available literature is examined in detail to prepare 
Toxicological Summaries that describe and summarize relevant 
information for each nominated substance. Included in each 
Toxicological Summary are information on chemical and physical 
properties, production levels, use, human exposure, regulatory status, 
toxicological effects, and rationale for the nomination. The 
Toxicological Summaries are distributed to the NTP Interagency 
Committee for Chemical Evaluation and Coordination (ICCEC), which 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, 
Occupational Safety and Health Administration, National Cancer 
Institute, National Institute of Environmental Health Sciences, 
National Institute for Occupational Safety and Health, and the National 
Library of Medicine. ICCEC members are assigned as reviewers for each 
substance after consideration of the nature of its uses and exposure so 
that, to the extent possible, appropriate regulatory concerns will be 
addressed. Members are requested to identify their agency's interests, 
if any, in the chemical and to provide any relevant information from 
their respective agencies regarding the nominated chemicals or 
structurally related substances. During the evaluation process, the NTP 
works actively with regulatory agencies and interested parties to 
supplement the information about nominated substances and to ensure 
that the nomination and selection process meets regulatory and public 
health needs.
    At its meeting to consider the nominated substances, the ICCEC 
makes testing recommendations including testing priorities and also may 
make recommendations for studies in addition to those requested by the 
nominator. Summaries of the ICCEC recommendations and any public 
comments received on these nominations are then presented to the NTP 
Board of Scientific Counselors (the Program's external scientific 
advisory committee) for review and comment in an open public session. 
The ICCEC's recommendations, NTP Board of Scientific Counselors' 
recommendations, and public comments are incorporated into 
recommendations that are then submitted to the NTP Executive Committee, 
the Federal interagency policy oversight body. For each substance 
nominated for the various types of studies, the NTP Executive Committee 
reviews and approves action to move forward to test, defer testing, or 
remove from testing consideration, and recommends testing priorities. 
The selection of a substance by the Executive Committee does not 
automatically commit the NTP to its evaluation. The priority of the 
nominations and the proposed studies are assessed during the nomination 
and

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selection process and reassessed during the study design process. 
During any of these stages, a chemical or study may be withdrawn if 
applicable research data or higher priority studies are identified, or 
if a study proves impractical. A broad range of regulatory and 
toxicological concerns is addressed during the nomination and selection 
process through the participation of representatives from Federal 
agencies concerned with public health issues. In addition, 
representatives from non-government organizations including academia, 
industry, labor, and public interest sit on the NTP Board of Scientific 
Counselors, and thus have input into chemical selection decisions.

Nominated Substances and ICCEC Review

    At its meeting on December 13, 1999, the ICCEC reviewed 12 
nominations for NTP studies. For six of these nominations, metabolism, 
toxicity, or carcinogenicity studies were recommended. No studies were 
recommended at this time for two nominations, and a testing 
recommendation for four chemicals was deferred pending receipt of (1) 
additional data from other organizations on related studies completed, 
anticipated, or in progress or (2) information on production, exposure, 
and use patterns. The nominated substances with CAS numbers, nomination 
source, types of studies recommended, study rationale, and other 
information are given in the attached tables.

Request for Comment

    Interested parties are encouraged to provide comments or 
supplementary information on the nominated substances and 
recommendations that appear in this announcement. The Program would 
welcome receiving toxicology and carcinogenesis information from 
completed, ongoing, or planned studies, as well as information on 
current production levels, human exposure, use patterns, or 
environmental occurrence for any of the substances listed in the 
attached tables. To provide comments or information, please contact Dr. 
William Eastin at the address given below within 60 days of the 
publication date of this announcement. Persons submitting comments or 
additional information are asked to include their name, affiliation, 
mailing address, phone, fax, e-mail and sponsoring organization (if 
any) with 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. The URL 
for the NTP homepage is http://ntp-server.niehs.nih.gov.
    Contact may be made by mail to Dr. William Eastin, NIEHS/NTP, P. O. 
Box 12233, Research Triangle Park, North Carolina 27709; by telephone 
at (919) 541-7941; by FAX at (919) 558-7057; or by email at 
[email protected].

    Dated: February 17, 2000.
Samuel H. Wilson,
Deputy Director, National Institute of Environmental Health Sciences.

Attachment--Substances Nominated to the NTP for Study and Testing 
Recommendations Made by the ICCEC on December 13, 1999

                                  Table 1.--Substances Recommended for Testing
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                                                                                          Study rationale; other
      Substance [CAS No.]           Nominated by            ICCEC recommendations               information
----------------------------------------------------------------------------------------------------------------
1-Bromopropane [106-94-5] and 2- OSHA NIOSH          1-Bromopropane                       Reported increasing
 Bromopropane [75-26-3].                             --carcinogenicity                     production and use in
                                                     --reproductive and developmental      many industrial
                                                      toxicity                             applications as an
                                                     --toxicokinetics                      alternative to ozone
                                                     --mechanistic studies                 depleting substances;
                                                     --neurotoxicity                       available data from
                                                     --genotoxicity                        limited repeat dose
                                                     --exposure studies in workers         studies indicate
                                                     2-Bromopropane                        toxicity to multiple
                                                     --subchronic toxicity                 organ systems.
                                                                                          2-Bromopropane is a
                                                                                           contaminant in
                                                                                           reagent grade 1-
                                                                                           Bromopropane with
                                                                                           known reproductive
                                                                                           toxicity.
Chitosan [9012-76-4]...........  NCI                 --mechanistic studies to evaluate    Significant human
                                                      vitamin E and mineral depletion      exposure through use
                                                                                           as a dietary
                                                                                           supplement and other
                                                                                           commercial
                                                                                           applications;
                                                                                           potential for
                                                                                           toxicity from
                                                                                           interference with
                                                                                           dietary fat
                                                                                           absorption.
DNA-based products.............  FDA                 --establish joint NIEHS/FDA program  Rapidly growing market
                                                      to evaluate long-term toxicity in    for DNA-based
                                                      anticipation of regulatory needs     therapeutic agents
                                                                                           and a lack of
                                                                                           adequate mechanisms
                                                                                           and methodologies for
                                                                                           evaluating safety.
Juglone [481-39-0].............  NCI                 --mechanistic studies                Potential human
                                                     --metabolism studies                  exposure resulting
                                                     --mouse lymphoma assay                from use of walnut-
                                                     --mammalian mutagenicity              based products as
                                                     --carcinogenicity testing pending     dietary supplements
                                                      results of preliminary studies       and natural dyes and
                                                                                           stains; suspicion of
                                                                                           carcinogenicity based
                                                                                           on quinone structure.
Potassium ferricyanide [13746-   NCI.                --genotoxicity                       Potential consumer and
 66-2].                                              --subchronic toxicity                 worker exposure
                                                                                           resulting from use in
                                                                                           photographic
                                                                                           processing; suspicion
                                                                                           of toxicity based on
                                                                                           potential for redox
                                                                                           cycling; inadequate
                                                                                           toxicity information
                                                                                           available.
Radio frequency radiation        FDA                 --establish interagency program to   Widespread consumer
 emissions of wireless                                design studies assessing cancer      and worker exposure;
 communication devices.                               and non-cancer health effects to     available data is
                                                      fulfill regulatory needs             inadequate to
                                                                                           properly assess
                                                                                           safety.
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                                          Table 2.--Substances for Which No Testing Is Recommended at this Time
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         Substance [CAS No.]                  Nominated by                       Nominated for                         Rationale for not testing
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Cafestol [469-83-0] and Kahweol [6894- Private individual         --toxicity and carcinogenicity testing.     Anti-carcinogenic effects demonstrated in
 43-5].                                                                                                        animal studies; limited data indicate low
                                                                                                               potential for toxicity; other natural
                                                                                                               products with higher potential for
                                                                                                               toxicity and human exposure exist;
                                                                                                               ongoing research efforts as opposed to
                                                                                                               new testing may provide basis for
                                                                                                               determining relevance of metabolic
                                                                                                               modulatory effects to chronic toxicity.
Plumbagin [481-42-5].................  NCI                        --mechanistic studies                       Structurally similar to Juglone which is
                                                                  --metabolism studies                         selected for study; low magnitude and/or
                                                                  --mouse lymphoma assay                       prevalence of human exposure; adequate
                                                                  --mammalian mutagenicity                     evidence of acute and reproductive
                                                                  --carcinogenicity                            toxicity.
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             Table 3.--Substances for Which a Testing Recommendation Is Deferred Pending Receipt and Consideration of Additional Information
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         Substance [CAS No.]                  Nominated by                       Nominated for                       Additional information needed
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Ethylenebis (tetra-bromophthalimide)   NIEHS                      --toxicity and carcinogenicity testing      Ongoing and planned industry testing
 [32588-76-4].                                                                                                 efforts; better characterization of uses
                                                                                                               and potential human exposures.
Terpinolene [586-62-9]...............  NIEHS                      --toxicity and carcinogenicity testing      Ongoing and planned industry testing
                                                                                                               efforts; better characterization of uses
                                                                                                               and potential human exposures; study
                                                                                                               results for structurally related
                                                                                                               compounds.
Tetrabromophthalic anhydride [632-79-  NIEHS                      --toxicity and carcinogenicity testing      Ongoing and planned industry testing
 1].                                                                                                           efforts; better characterization of uses
                                                                                                               and potential human exposures.
Texanol benzyl phthalate [16883-83-3]  NIEHS                      --toxicity and carcinogenicity testing      Ongoing and planned industry testing
 or [32333-99-6].                                                                                              efforts; better characterization of uses
                                                                                                               and potential human exposures.
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[FR Doc. 00-4964 Filed 3-1-00; 8:45 am]
BILLING CODE 4140-01-P