Federal Register: July 25, 2001 (Volume 66, Number 143)
DOCID: FR Doc 01-18458
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
NOTICE: NOTICES
ACTION: National Toxicology Program:
SUBJECT CATEGORY:
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
DOCUMENT SUMMARY:
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 doseresponse 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 healthrelated 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 overriding factor in the NTP's decision to study a particular chemical or agent.
The review and selection of substances nominated for study is a multistep process. A broad range of concerns are addressed during this process through the participation of representatives from Federal agencies, the NTP Board of Scientific Counselorsan external scientific advisory body, the NTP Executive Committeethe 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 1132911331). This multistep 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, email 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) 5415710; by FAX at (919) 5587067; 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
[68917511]......................... Institute. exposure through use characterization
[84696139]......................... 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 [14345908]...... 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.
Epigallocatechin3gallate [989515] 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.
2Ethylhexylpdimethylaminobenzoic Private Individual..... High production volume Subchronic toxicity
acid [21245023]. 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, shortterm
Occupational Safety large number of in vivo and subchronic
and Health. occupationallyexposed 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 [96479]..... National Cancer Increasing use in Genotoxicity testing
Institute. alternative fuels; Shortterm 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
[32534819]. Environmental widespread human neurotoxicity and
Octabromodiphenyl ether (technical) Protection Agency. exposure chronic toxicity
[32536520]. occupationally and as testing of selected
2,2',4,4'Tetrabromodiphenyl ether environmental individual congeners
[5436431]. contaminants; No testing of
2,2',4,4',5Pentabromodiphenyl ether persistent and technical mixtures.
[60348609]. bioaccumulative;
2,2',4,4',5,5'Hexabromodiphenyl evidence for toxicity
ether [68631492]. but significant
knowledge gaps remain. [[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 [520365]............. 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 [132649]......... 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 [126001]...... 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 nButyl bromide [109659]...... 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 [67784809]...... 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. 0118458 Filed 72401; 8:45 am] BILLING CODE 414001P
SUMMARY:
Chemicals nominated for toxicological studies; testing recommendations; comment request,
DOCUMENT BODY 2:
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 doseresponse 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 healthrelated 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 overriding factor in the NTP's decision to study a particular chemical or agent.
The review and selection of substances nominated for study is a multistep process. A broad range of concerns are addressed during this process through the participation of representatives from Federal agencies, the NTP Board of Scientific Counselorsan external scientific advisory body, the NTP Executive Committeethe 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 1132911331). This multistep 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, email 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) 5415710; by FAX at (919) 5587067; 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
[68917511]......................... Institute. exposure through use characterization
[84696139]......................... 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 [14345908]...... 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.
Epigallocatechin3gallate [989515] 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.
2Ethylhexylpdimethylaminobenzoic Private Individual..... High production volume Subchronic toxicity
acid [21245023]. 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, shortterm
Occupational Safety large number of in vivo and subchronic
and Health. occupationallyexposed 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 [96479]..... National Cancer Increasing use in Genotoxicity testing
Institute. alternative fuels; Shortterm 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
[32534819]. Environmental widespread human neurotoxicity and
Octabromodiphenyl ether (technical) Protection Agency. exposure chronic toxicity
[32536520]. occupationally and as testing of selected
2,2',4,4'Tetrabromodiphenyl ether environmental individual congeners
[5436431]. contaminants; No testing of
2,2',4,4',5Pentabromodiphenyl ether persistent and technical mixtures.
[60348609]. bioaccumulative;
2,2',4,4',5,5'Hexabromodiphenyl evidence for toxicity
ether [68631492]. but significant
knowledge gaps remain. [[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 [520365]............. 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 [132649]......... 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 [126001]...... 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 nButyl bromide [109659]...... 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 [67784809]...... 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. 0118458 Filed 72401; 8:45 am] BILLING CODE 414001P