[Federal Register Volume 71, Number 69 (Tuesday, April 11, 2006)]
[Notices]
[Pages 18341-18344]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-5217]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES


National Toxicology Program (Ntp); Office of Chemical Nomination 
and Selection; Announcement of and Request for Public Comment on 
Toxicological Study Nominations to the NTP

AGENCY: National Institute of Environmental Health Sciences (NIEHS), 
National Institutes of Health.

ACTION: Notice; request for comments and additional information.

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SUMMARY: The 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 
are subject to several levels of review before selections for testing 
are made and toxicological studies are designed and implemented. This 
notice (1) provides brief background information

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and study recommendations regarding 10 nominations for study by the NTP 
(Table 1), (2) solicits public comment on the nominations and study 
recommendations, and (3) requests the submission of additional relevant 
information for consideration by the NTP in its continued review of 
these nominations. An electronic copy of this announcement, supporting 
documents for each nomination, and further information on the NTP and 
the NTP Study Nomination and Review Process can be accessed through the 
NTP Web site (http://ntp.niehs.nih.gov/; select ``Nominations to the 
Testing Program'').

DATES: Comments or information should be submitted by May 10, 2006.

ADDRESSES: Correspondence should be addressed to Dr. Scott A. Masten, 
Director, Office of Chemical Nomination and Selection, NIEHS/NTP, 111 
T.W. Alexander Drive, P. O. Box 12233, Research Triangle Park, North 
Carolina 27709; telephone: 919-541-5710; FAX: 919-541-3647; e-mail: 
[email protected].

SUPPLEMENTARY INFORMATION:

Background Information

    The NTP actively seeks to identify and select for study chemicals 
and other substances for which sufficient information is not available 
to adequately evaluate potential human health hazards. The NTP 
accomplishes this goal through a formal open nomination and selection 
process. Nominations can be submitted to the NTP at http://ntp.niehs.nih.gov/ select ``Nominations to the Testing Program'' or by 
contacting Dr. Scott Masten (see ADDRESSES above). Substances 
considered appropriate for study generally fall into two broad yet 
overlapping categories: (1) Substances judged to have high concern as 
possible public health hazards 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 
for evaluating dose-response relationships. Nominations are also 
solicited for 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 chemical, biological, or physical agents.
    Study nominations may entail the evaluation of a variety of health-
related effects including, but not limited to, reproductive and 
developmental toxicity, genetic toxicity, immunotoxicity, 
neurotoxicity, metabolism and disposition, and carcinogenicity in 
appropriate experimental models. In reviewing and selecting nominations 
for study, the NTP also considers legislative mandates that require 
responsible private sector 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 
substance.
    Nominations undergo a multi-step, formal process of review. 
Briefly, during the entire nomination review and selection process, the 
NTP works with staff at other federal agencies and interested parties 
to supplement information about nominated substances and to ensure that 
regulatory and public health needs are addressed. The nomination review 
and selection process is accomplished through the participation of 
representatives from the NIEHS, other federal agencies represented on 
the Interagency Committee for Chemical Evaluation and Coordination 
(ICCEC), the NTP Board of Scientific Counselors (BSC)--an external 
scientific advisory body, the NTP Executive Committee--the NTP federal 
interagency policy body, and the public. Preliminary study 
recommendations for each nomination are developed and refined by the 
nominator, NTP staff, and the ICCEC. Preliminary study recommendation 
for the nominations may be refined as the formal review process 
continues. NTP also considers recommendations from the BSC and the NTP 
Executive Committee, public comments received on the nominations, and 
other available information in selecting candidate substances for 
study. The NTP initiates appropriate toxicology and carcinogenicity 
studies as time and resources permit.
    The nomination review and selection process is described in further 
detail on the NTP Web site (http://ntp.niehs.nih.gov/; select 
``Nominations to the Testing Program'').

Request for Comments and Additional Information

    The NTP invites interested parties to submit written comments or 
supplementary information on the nominated substances and study 
recommendations that appear in Table 1. The NTP welcomes toxicology and 
carcinogenesis study information from completed, ongoing, or 
anticipated studies, as well as information on current U.S. production 
levels, use or consumption patterns, human exposure, environmental 
occurrence, or public health concerns for any of the nominated 
substances. The NTP is interested in identifying appropriate animal and 
non-animal experimental models for mechanistic-based research, 
including genetically modified rodents and higher-throughput in vitro 
test methods, and as such, solicits comments regarding the use of 
specific in vivo and in vitro experimental approaches to address 
questions relevant to the nominated substances and issues under 
consideration. The BSC will discuss the nominations listed in Table 1 
at a public meeting on June 13, 2006. A separate Federal Register 
notice will be published in the future about this meeting. Comments or 
additional information may be submitted at any time; however, to ensure 
adequate time for consideration prior to the June 13, 2006 BSC meeting, 
comments should be submitted by May 10, 2006. The NTP will not respond 
to submitted comments; however, all information received will be become 
part of the official record that the NTP considers in its ongoing 
review of these nominations. Persons submitting comments should include 
their name, affiliation, mailing address, phone, fax, e-mail address, 
and sponsoring organization (if any) with the submission. Written 
submissions will be made publicly available electronically on the NTP 
website as they are received (http://ntp.niehs.nih.gov/ select 
``Nominations to the Testing Program'').

Background Information on the NTP Office of Chemical Nomination and 
Selection

    The NTP Office of Chemical Nomination and Selection (OCNS) manages 
the solicitation, receipt, and review of NTP toxicology study 
nominations. The OCNS conducts an initial review of each study 
nomination received to determine whether the substance or issue has 
been adequately studied or has been previously considered by the NTP. 
For nominations not eliminated from consideration or deferred at this 
stage, the OCNS initiates a formal review process, as described above. 
The OCNS also ensures adequate background information is available to 
support the review for each nomination and corresponds with interested 
parties regarding the status of NTP study nominations. For further 
information on the OCNS visit the NTP Web site (http://ntp.niehs.nih.gov select ``Nominations to the Testing Program'') or 
contact Dr. Masten (see ADDRESSES above).

    Dated: March 28, 2006.
Samuel H. Wilson,
Deputy Director, National Institute of Environmental Health Sciences 
and National Toxicology Program.

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          Table 1.--Study Recommendations for Substances Nominated to the NTP for Toxicological Studies
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                                                                                          Study Recommendations
         Substance [CAS No.]               Nominated by \1\       Nomination Rationale             \2\
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Arbutin 497-76-7]....................  NIEHS..................  Consumer exposure        --In vitro and in vivo
                                                                 through food,            metabolism and
                                                                 cosmetics, and dietary   disposition studies.
                                                                 supplements; lack of    --In vitro and in vivo
                                                                 adequate toxicological   genotoxicity studies.
                                                                 data; suspicion of      --Emphasis on
                                                                 toxicity based on        understanding
                                                                 chemical structure.      gastrointestinal
                                                                                          metabolism and
                                                                                          disposition,
                                                                                          identifying
                                                                                          experimental animal
                                                                                          model representative
                                                                                          of humans, and
                                                                                          development of
                                                                                          appropriate
                                                                                          biomarkers.
tert-Butylacrylamide [107-58-4]......  NCI....................  High production volume   --Metabolism and
                                                                 (HPV); potential         disposition studies.
                                                                 worker and consumer     --Subchronic toxicity
                                                                 exposures; lack of       studies.
                                                                 adequate toxicological  --Mammalian
                                                                 data; suspicion of       genotoxicity studies.
                                                                 toxicity based on       --Coordinate studies
                                                                 chemical structure.      with voluntary data
                                                                                          development activities
                                                                                          of the Extended HPV
                                                                                          (EHPV) Program.
Ceric oxide [1306-38-3]..............  NIEHS..................  Widespread industrial
                                                                 use and potential for
                                                                 increasing exposure;
                                                                 demonstrated pulmonary
                                                                 toxicity; lack of
                                                                 toxicity data for
                                                                 nanoscale form.
                                                                --Toxicological
                                                                 characterization
                                                                 including chemical
                                                                 disposition and
                                                                 toxicokinetics.
                                                                --Comparative
                                                                 inhalation toxicity
                                                                 studies of microscale
                                                                 and nanoscale forms.
                                                                --Dermal penetration
                                                                 studies.
Diazonaphthoquinone derivatives        NIEHS..................  Moderate production      --In vitro toxicity
 Sodium 1,2-naphthoquinone-2-diazide-                            volume; potential        studies evaluating
 5-sulfonate [2657-00-3] 2,3,4-                                  worker exposures from    genotoxicity,
 Trihydroxybenzophenone tris(1,2-                                production and use of    immunotoxicity and
 naphthoquinonediazide-5-sulfonate)                              photoresists; lack of    phototoxicity.
 [5610-94-6] 2,3,4-                                              adequate toxicological  --Dermal penetration
 Trihydroxybenzophenone 1,2-                                     data.                    studies.
 naphthoquinonediazide-5-sulfonate
 [68510-93-0].
3-Dimethylaminopropyl methacrylamide   NCI....................  High production volume   --Metabolism and
 [5205-93-6].                                                    (HPV); potential         disposition studies.
                                                                 worker and consumer     --Genotoxicity studies.
                                                                 exposures; lack of      --Subchronic toxicity
                                                                 adequate toxicological   studies.
                                                                 data; demonstrated      --Coordinate studies
                                                                 toxicity in short-term   with voluntary data
                                                                 studies.                 development activities
                                                                                          of the Extended HPV
                                                                                          (EHPV) Program.
Flame retardants.....................  Consumer Product Safety  Anticipated increased    See specific chemicals
Antimony trioxide [1309-64-4]........   Commission Staff.        use in upholstered       below:
Decabromodiphenyl oxide [1163-19-5]..                            furniture and bedding   --Chronic toxicity
                                                                 and potential consumer   studies (oral route).
                                                                 exposures from these    --Consider studies of
                                                                 uses; insufficient       nanoscale form if used
                                                                 toxicity data to         in or released during
                                                                 assess potential         flame retardant
                                                                 health risks.            applications.
                                                                                         --Developmental
                                                                                          neurotoxicity studies.
                                                                                         --Studies only to be
                                                                                          performed if adequate
                                                                                          private sector study
                                                                                          not identified or
                                                                                          planned.
Tris (chloropropyl) phosphate,         .......................  .......................     --Subchronic and
 mixture of four isomers [13674-84-5;                                                        chronic toxicity
 76025-08-6; 76649-15-5; 6145-73-9].                                                         studies (oral
                                                                                             route).
                                                                                         --Studies to focus on
                                                                                          commercial mixture or
                                                                                          major isomers present
                                                                                          in commercially used
                                                                                          mixtures.
Phosphonic acid, (3-((hydroxymethyl)   .......................  .......................     --Subchronic and
 amino)-3-oxopropyl)-, dimethyl ester                                                        chronic toxicity
 [20120-33-6].                                                                               studies (oral
                                                                                             route).
                                                                                         --Dermal absorption
                                                                                          studies.

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Tris (hydroxymethyl) phosphine oxide   .......................  .......................     --Subchronic and
 [1067-12-5].                                                                                chronic toxicity
                                                                                             studies (oral
                                                                                             route).
                                                                                         --Dermal absorption
                                                                                          studies.
Aromatic phosphates tert-Butylphenyl   .......................  .......................  For one or more
 diphenyl phosphate [56803-37-3] 2-                                                       representative
 Ethylhexyl diphenyl phosphate [1241-                                                     aromatic phosphates:
 94-7] Isodecyl diphenyl phosphate                                                       --Subchronic and
 [29761-21-5] Phenol, isopropylated,                                                      chronic toxicity
 phosphate (3:1) [68937-41-7]                                                             studies (oral route).
 Tricresyl phosphate [1330-78-5]                                                         --Neurotoxicity and/or
 Triphenyl phosphate [115-86-6].                                                          developmental
                                                                                          neurotoxicity studies.
                                                                                         --Coordinate with the
                                                                                          U.S. Environmental
                                                                                          Protection Agency to
                                                                                          pursue additional
                                                                                          testing by
                                                                                          manufacturers.
Gypsum, natural and synthetic forms    Mount Sinai-Irving J.    Widespread worker           --Short-term
 [13397-24-5].                          Selikoff Center for      exposures in numerous       pulmonary toxicity
                                        Occupational and         occupations and to the      studies.
                                        Environmental Medicine   general population      --Comparative studies
                                        Operative Plasterers'    after destruction of     of intratracheal
                                        and Cement Masons'       the World Trade          versus inhalation
                                        International            Centers in 2001;         routes of
                                        Association of the       limited toxicity data    administration.
                                        United States and        to assess potential     --Studies are of
                                        Canada.                  health risks.            relatively low
                                                                                          priority given low
                                                                                          suspicion of toxicity.
N-methyl-3-oxobutanamide [20306-75-6]  NCI....................  High production volume;  --In vitro and in vivo
                                                                 potential worker and     genotoxicity studies.
                                                                 environmental           --Include structurally-
                                                                 exposures; lack of       related diketene
                                                                 adequate toxicological   compounds and N-phenyl
                                                                 data.                    derivatives.
Phenoxyethyl acrylate [48145-04-6]...  NCI....................  High production volume;  --Defer pending review
                                                                 potential worker and     of voluntary data
                                                                 consumer exposures;      submission through the
                                                                 lack of adequate         Extended HPV (EHPV)
                                                                 toxicological data.      Program.
Trifluoromethylbenzene [98-08-8].....  NCI....................  High production volume   Defer pending review of
                                                                 and potential for        1) production data
                                                                 increased use;           through the 2006 Toxic
                                                                 potential worker         Substances Control Act
                                                                 exposures; lack of       (TSCA) Inventory
                                                                 adequate toxicological   Update Rule, and 2)
                                                                 data; demonstrated       Organization for
                                                                 toxicity in short-term   Economic Cooperation
                                                                 studies.                 and Development (OECD)
                                                                                          Screening Information
                                                                                          Data Set (SIDS)
                                                                                          program output.
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\1\ National Institute of Environmental Health Sciences (NIEHS); National Cancer Institute (NCI)
\2\ The term ``toxicological characterization'' in this table includes studies for genotoxicity, subchronic
  toxicity, and chronic toxicity/carcinogenicity as determined to be appropriate during the conceptualization
  and design of a research program to address toxicological data needs. Other types of studies (e.g., metabolism
  and disposition, immunotoxicity, and reproductive and developmental toxicity) may be conducted as part of a
  complete toxicological characterization; however, these types of studies are not listed unless they are
  specifically recommended.

 [FR Doc. E6-5217 Filed 4-10-06; 8:45 am]
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