[Federal Register Volume 64, Number 129 (Wednesday, July 7, 1999)]
[Notices]
[Pages 36704-36707]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-17119]
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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 Chemicals Nominated to the
National Toxicology Program (NTP) for Toxicological Studies--
Recommendations by the Interagency Committee for Chemical Evaluation
and Coordination (ICCEC) for Study, No Studies, or Deferral To Obtain
Additional Information
Summary
The National Toxicology Program (NTP) routinely solicits, accepts
and reviews for consideration nominations from Federal agencies,
industry, the public, and other interested parties for toxicological
studies to be undertaken by the Program. Nominations undergo several
levels of review before toxicological studies are designed and
implemented. The Interagency Committee for Chemical Evaluation and
Coordination (ICCEC) serves as the first level of review for NTP
nominations. At the June 1, 1999 meeting of the ICCEC, 13 nominations
were reviewed. As part of an effort to earlier inform the public and
obtain input into the selection of chemicals for evaluation, the NTP
routinely seeks public input on (1) chemicals nominated to the Program
for toxicological studies, and (2) testing recommendations made by the
ICCEC. This announcement outlines the process for nomination and
selection of agents for NTP study, presents the recommendations of the
ICCEC from the June 1, 1999 meeting, and requests comment on these
recommendations or the submission of additional information to be
considered in the evaluation of these nominations.
Background
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. From its inception, the NTP has
had an open nomination process. Nominations are solicited from a
variety of sources in academia, Federal and State regulatory and health
agencies, industry, and unions, as well as from environmental groups
and the general public. Particular assistance is sought with the
selection of studies that permit testing of hypotheses to enhance the
predictive ability of NTP studies, address mechanisms of toxicity, or
identify significant gaps in knowledge of the toxicity of chemicals or
classes of chemicals. Chemicals are selected for study based upon two
broad criteria: (1) those chemicals of greatest concern for public or
occupational health and (2) chemicals for which toxicological data is
needed to fill major knowledge gaps, address mechanisms of toxicity,
and reduce uncertainty in risk assessment by aiding species-to-species
extrapolation and understanding dose-response relationships. Chemicals
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 industries 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,
[[Page 36705]]
environmental agents, or issues for study; (2) broadening the base and
diversity of nominating organizations and individuals; and (3)
increasing nominations for endpoints of toxicity other than
carcinogenesis.
Nominated chemicals 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 chemicals not eliminated from consideration or deferred at
this stage, the available literature is examined in detail to prepare
Toxicological Summaries which evaluate and summarize the relevant data
for each chemical. Included in each Toxicological Summary are chemical
and physical information, production levels, use and exposure
categories and levels, regulatory status, toxicological effects, and
rationale for the nomination. The Toxicological Summaries are
distributed to the Interagency Committee for Chemical Evaluation and
Coordination (ICCEC), 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
chemical 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 search databases unique to their
agencies for further information on the nominated chemicals and
structurally related substances. During the evaluation process, the NTP
works actively with regulatory agencies and interest groups to
supplement the information about chemicals nominated and to ensure that
the chemical selection process meets regulatory agency needs.
At its meeting to consider the nominated chemicals, the ICCEC
assigns testing priorities, and also may make recommendations for study
in addition to those requested by the nominator. Summaries of the ICCEC
recommendations and any public comments received on these chemicals 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 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 chemical
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 chemical or agent by the Executive Committee does
not automatically commit the NTP to its evaluation. The priority of the
chemicals and the proposed studies are assessed during the nomination
process and reassessed during the study design process. During any of
these stages, a chemical or study may be withdrawn if applicable
research data is identified, higher priority studies are identified, or
if a study proves impractical. A broad range of regulatory and
toxicological concerns are 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 industry,
labor, and public interest, sit on the NTP Board of Scientific
Counselors, and thus have input into chemical selection decisions.
Following Executive Committee action, each selected chemical is
assigned to an NIEHS, FDA, or NIOSH staff scientist (project leader)
who assesses the data compiled during the chemical evaluation process
and other information obtained from detailed searches of the published
literature and public comments. The project leader also consults with
industrial or commercial sources on such issues as mode of production,
uses, worker exposure, planned or ongoing testing, and availability of
the chemical for study. The project leader together with a study design
team develops a study plan to address the research needs. The study
plan is reviewed and modified as necessary before being carried out via
the most appropriate mechanisms. Results of toxicological studies of
selected chemicals are routinely peer-reviewed. The results are
published as NTP Technical Reports and/or in the open scientific
literature. Test results are also available from the NTP subsequent to
peer-review but prior to publication.
Request for Comment
At their meeting on June 1, 1999, the ICCEC reviewed 13 agents
nominated for NTP study. For 9 of these agents, metabolism, toxicity,
or carcinogenicity studies were recommended, no additional study was
recommended for 2 chemicals, and studies of 2 other chemicals were
deferred pending receipt of additional data from other organizations or
from related studies anticipated or in progress by the NTP, or
information on production, exposure, and use patterns. Additionally,
the ICCEC reviewed 7 chemicals recommended for study in previous ICCEC
meetings. Following review of initial NTP studies and additional data
received from the public or elsewhere, these 7 chemicals were withdrawn
as priority candidates for study.
Chemicals with CAS numbers, nomination source, types of studies
under consideration, and rationale and other information are given in
the attached tables. Interested parties are encouraged to provide
comments or supplementary information on the chemicals 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 chemicals listed in this
announcement. To provide comments or information, please contact Dr.
William Eastin at the address given below by September 7, 1999.
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) 541-3687; or by email at
[email protected]. The URL for the NTP homepage is http://ntp-
server.niehs.nih.gov.
Dated: June 24, 1999.
Samuel H. Wilson,
Deputy Director, NIEHS.
[[Page 36706]]
Attachment--Chemicals Nominated to the NTP for Study, and Testing
Recommendations made by the ICCEC on June 1, 1999
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Study rationale;
Chemical [CAS Nominated by ICCEC other
Number] recommendations information
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Chemicals Recommended for Testing
------------------------------------------------------------------------
Aloe vera gel NCI --Cell --Widespread use
[8001-97-6] transformation as a dietary
[94349-62-9] assay supplement and
--Phototoxicity cosmetic.
--Tumor --Inadequate
promotion in toxicity
Tg.AC mice information.
Ammonium NCI --In vitro --Representative
molybdate chromosome soluble
[12027-67-7] aberration molybdenum
[12054-85-2] assay compound.
[13106-76-8] --In vitro --Potential for
micronucleus worker and
assay general
--Subchronic population
toxicity exposure.
(inhalation --Inadequate
studies) toxicity
information.
5,6-Benzoflavone NCI --Toxicological --Potential use
[6051-87-2] characterizatio as
n chemopreventive
--Reproductive agent.
toxicity --Lack of
--Carcinogenicit industry
y sponsorship.
--Testing
dependent on
confirmation
from nominator
that
recommended
studies are
needed for
further
development as
therapeutic
agent.
1,3-Dichloro-2- NIEHS --Toxicological --High
butene characterizatio production
[926-57-8] n industrial
--Metabolism chemical with
studies potential for
--Carcinogenicit worker
y (inhalation exposure.
studies) --Structural
similarity to
known
carcinogen.
--Inadequate
toxicity
information.
Ginseng and NCI --Genotoxicity --Widespread use
ginsenosides --Reproductive as a dietary
[50647-08-0] toxicity supplement.
--Neurotoxicity --Inadequate
--Carcinogenicit toxicity
y information.
--Subchronic
testing will
determine if
ginseng or a
specific
ginsenoside
will be subject
to
carcinogenicity
testing.
Indole-3-carbinol NCI --Reproductive --Widespread and
[700-06-1] toxicity rapidly
--Toxicological increasing use
characterizatio as a dietary
n supplement.
--Carcinogenicit --Potential use
y as
chemopreventive
agent.
Kava kava extract NCI --Genotoxicity --Widespread use
[9000-38-8] --Reproductive as a dietary
[84696-40-2] toxicity supplement.
--Neurotoxicity --Reported human
--Subchronic toxicity.
toxicity --Inadequate
--Carcinogenicit toxicity
y information.
Milk thistle NCI --Genotoxicity --Widespread use
extract --Metabolism as a dietary
[84604-20-6] studies supplement.
--Reproductive --Reported
toxicity hepatoprotectiv
--Subchronic e and anti-
toxicity carcinogenic
action.
--Inadequate
toxicity
information.
3-Picoline NIEHS --Subchronic --High
[108-99-6] toxicity production
--Carcinogenicit industrial
y (pending chemical with
results of potential for
subchronic worker and
studies) general
population
exposure.
--Inadequate
toxicity
information.
------------------------------------------------------------------------
Chemicals for Which No Testing is Recommended
------------------------------------------------------------------------
1-Bromo-3- NIEHS --Toxicological --Available data
chloropropane characterizatio indicate low
[109-70-6] n toxicity.
--Carcinogenicit --Low potential
y for human
exposure.
N,N- NCI --Subchronic --Available data
Diethylhydroxyla toxicity indicate low
mine toxicity.
[3710-84-7] --Low potential
for human
exposure.
------------------------------------------------------------------------
Chemicals Deferred for Additional Information
------------------------------------------------------------------------
1,3,5-Triazine- NCI --Carcinogenicit --Reconsider as
1,3,5 y part of class
(2H,4H,6H)- study of
triethanol formaldehyde-
[4719-04-4] releasing
compound.
[[Page 36707]]
s-Trioxane NIEHS --Toxicological --Reconsider as
[110-88-3] characterizatio part of class
n study of
--Carcinogenicit formaldehyde-
y releasing
compounds.
------------------------------------------------------------------------
Chemicals to be Withdrawn from Consideration
------------------------------------------------------------------------
Arsenic Trioxide NIEHS; Private --Mechanistic --Lack of an
[1327-53-3] Individual studies appropriate
--Carcinogenicit animal model
y for human
carcinogenicity
.
2,3-Butanedione NCI --Genotoxicity --Rapid and near
[431-03-8] --Metabolism complete
studies metabolism to
--Carcinogenicit carbon dioxide.
y
t-Butylcatechol NCI/FDA --Toxicological --Toxicity in
[98-29-3] characterizatio subchronic
n studies at
--Metabolism doses as high
studies as 12,500 ppm
--Carcinogenicit in the diet was
y limited to
forestomach
lesions.
Camphor NCI --Teratogenicity --Teratogenicity
[464-49-3] --Reproductive studies
[76-22-2] toxicity completed
--Carcinogenicit --Toxicity in
y subchronic
dermal studies
limited to
hyperplasia at
the site of
application.
Fluasterone NCI --Toxicological --Difficulty in
[112859-71-9] characterizatio obtaining
n sufficient
--Carcinogenicit material for
y study.
--Industry
sponsor has
responsibility
for
toxicological
evaluation of
this chemical
if pursued as a
chemotherapeuti
c agent.
Luminol Private --Toxicological --Lack of
[521-31-3] Individual characterizatio absorption from
n skin.
--Carcinogenicit --Rapid
y metabolism and
elimination of
oral doses as
nontoxic
metabolites.
Propylene Glycol NCI --Carcinogenicit --Availability
Monomethyl Ether y of industry-
[107-98-2] sponsored
reproductive
toxicity and
carcinogenicity
studies.
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[FR Doc. 99-17119 Filed 7-6-99; 8:45 am]
BILLING CODE 4140-01-P