[Federal Register Volume 77, Number 141 (Monday, July 23, 2012)]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-17787]
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Evaluation of an Up-and-Down Procedure for Acute Dermal Systemic
Toxicity Testing: Request for Nominations for an Independent Expert
Panel and Submission of Relevant Data
AGENCY: Division of the National Toxicology Program (DNTP), National
Institute of Environmental Health Sciences (NIEHS), National Institutes
of Health (NIH), HHS.
ACTION: Request for Data; Request for Nominations of Scientific
SUMMARY: The NTP Interagency Center for the Evaluation of Alternative
Toxicological Methods (NICEATM), in collaboration with the Interagency
Coordinating Committee on the Validation of Alternative Methods
(ICCVAM), is planning to convene an independent scientific peer review
panel (Panel) to assess the validation status of an up-and-down
procedure (UDP) for acute dermal systemic toxicity testing. NICEATM
requests nominations of scientific experts who can be considered for
the Panel and submission of data for substances tested in in vivo acute
dermal and oral systemic toxicity tests.
DATES: Nominations and test method data for the acute dermal and oral
tests should be submitted by September 6, 2012. Data submitted after
this date will be considered in the evaluation where feasible.
FOR FURTHER INFORMATION CONTACT: Dr. William S. Stokes, Director,
NICEATM, NIEHS, P.O. Box 12233, Mail Stop: K2-16, Research Triangle
Park, NC 27709, (telephone) 919-541-2384, (fax) 919-541-0947, (email)
[email protected]. Courier address: NICEATM, NIEHS, Room 2034, 530
Davis Drive, Morrisville, NC 27560.
Acute poisoning from chemicals and chemical products, including
pharmaceuticals, is a significant public health problem. In 2009, 2.5
million human poisoning cases were reported to U.S. poison control
centers (Bronstein et al., 2010). Dermal exposures were involved in
7.25% (179,832 cases) of the poisonings, which was second in frequency
only to exposures by oral ingestion (2,080,781 cases). To protect
workers and consumers from acute dermal poisoning exposures, regulatory
agencies in the U.S. (e.g., the Environmental Protection Agency [EPA],
the Consumer Products Safety Commission, Department of Transportation,
Occupational Safety and Health Administration) use the information from
acute dermal systemic toxicity tests using rabbits or rodents to
determine the potential of chemicals and chemical products to cause
life-threatening health effects or death from acute dermal exposures.
Test results are used as the basis for hazard classification and
labeling and to inform consumers and workers how to avoid acute dermal
exposures to hazardous chemicals and products during the handling,
transport, and use of chemicals and products.
In 2002, ICCVAM recommended the revised UDP for acute oral systemic
toxicity as a replacement for the conventional test. The revised oral
UDP was accepted internationally as Organisation for Economic Co-
operation and Development (OECD) Test Guideline 425 in 2001 (OECD,
2001). The oral UDP reduces animal use by up to 70% compared to the
traditional testing procedure. NICEATM is now developing a UDP
procedure for acute dermal systemic toxicity testing, which is one of
the four most commonly conducted product safety tests worldwide.
Alternative test methods for acute dermal systemic toxicity testing are
an ICCVAM priority because such testing is required by multiple
agencies, can involve large numbers of animals, and can result in
significant pain and distress to test animals (ICCVAM, 2008).
The acute dermal systemic toxicity UDP protocol is expected to
reduce the number of animals used compared with current EPA (EPA, 1998)
and OECD (OECD, 1987) test guidelines. A draft background review
document (BRD) will include a proposed dermal UDP test method protocol
and analyses comparing the results of simulated testing using the UDP
protocol with the standard acute dermal systemic toxicity reference
test described in EPA Health Effects Test Guidelines OPPTS 870.1200
(EPA, 1998) and OECD Test Guideline 402 (OECD, 1987). The draft BRD
will form the basis for the ICCVAM draft test method recommendations
for the proposed UDP method. Draft recommendations on usefulness and
limitations, standardized test method protocol, and future studies will
be provided to the Panel and made available to the public.
The Panel will meet in public session to review the validation
status of the UDP for acute dermal systemic toxicity testing. The Panel
will comment on the extent to which the BRD supports the draft ICCVAM
test method recommendations. Meeting information, including dates,
locations, and public availability of the meeting documents will be
announced in a future Federal Register notice and will also be posted
on the NICEATM-ICCVAM Web site (http://iccvam.niehs.nih.gov).
Request for Nominations of Scientific Experts
NICEATM requests nominations of scientists with relevant knowledge
and expertise to serve on the Panel. Areas of relevant expertise
include, but are not limited to biostatistics; human and veterinary
dermatology, with an emphasis on evaluation and treatment of chemical
injuries that produce systemic effects; human and animal toxicology,
especially systemic effects due to dermal exposures; in vivo dermal and
oral toxicity testing; and test method validation. Each nomination
should include the nominee's name, affiliation, contact information
(i.e., mailing address, email address, telephone and fax numbers),
vitae, and a brief summary of relevant experience and qualifications.
Request for Data
NICEATM invites the submission of data for substances tested in
standardized in vivo acute dermal systemic toxicity tests.
Corresponding acute oral LD50 data for the same compounds
tested dermally would be particularly useful. Oral data from rat tests
and dermal data from rat and/or rabbit tests are preferred. Although
data can be accepted at any time, please submit data by September 6,
2012 to ensure consideration during the ICCVAM evaluation process.
Relevant data received after this date will be considered where
feasible. All information submitted in response to this notice will be
made publicly available and may be incorporated into future NICEATM and
ICCVAM reports and publications, as appropriate.
When submitting data, please reference this Federal Register notice
and provide appropriate contact information (name, affiliation, mailing
address, phone, fax, email, and sponsoring organization, as
applicable). NICEATM prefers that data be submitted electronically as
copies of pages from study notebooks, spreadsheets, and/or study
reports. Each submission for a substance should preferably include the
following information, as appropriate: common and trade name, Chemical
Abstracts Service Registry Number (CASRN), commercial source, in vivo
test protocols used, extent to which the data were collected in
accordance with national or international Good Laboratory Practice
guidelines, date and testing organization, physical and chemical
properties (e.g., molecular weight, pH, water solubility, log
Kow, etc.), estimated LD50, and incidence of
death and other adverse effects.
Background Information on ICCVAM and NICEATM
ICCVAM is an interagency committee composed of representatives from
15 Federal regulatory and research agencies that require, use,
generate, or disseminate toxicological and safety testing information.
ICCVAM conducts technical evaluations of new, revised, and alternative
safety testing methods and integrated testing strategies with
regulatory applicability and promotes the scientific validation and
regulatory acceptance of testing methods that more accurately assess
the safety and hazards of chemicals and products and that reduce,
refine (enhance animal well-being and lessen or avoid pain and
distress), or replace animal use. The ICCVAM Authorization Act of 2000
(42 U.S.C. 285l-3) established ICCVAM as a permanent interagency
committee of the NIEHS under NICEATM. NICEATM administers ICCVAM,
provides scientific and operational support for ICCVAM-related
activities, and conducts independent validation studies to assess the
usefulness and limitations of new, revised, and alternative test
methods and strategies. NICEATM and ICCVAM welcome the public
nomination of new, revised, and alternative test methods and strategies
for validation studies and technical evaluations. Additional
information about NICEATM and ICCVAM can be found on the NICEATM-ICCVAM
Web site (http://iccvam.niehs.nih.gov).
Bronstein AC, Spyker DA, Cantilena LR, Jr, Green JL, Rumack BH,
Giffin SL. 2010. 2009 Annual Report of the American Association of
Poison Control Centers' National Poison Data System (NPDS): 27th
Annual Report. Clinical Toxicology 48: 979-1178.
EPA. 1998. Health Effects Test Guidelines: OPPTS 870.1200--Acute
Dermal Toxicity. EPA 712-C-98-192. Washington, DC:U.S. Environmental
Protection Agency. Available: http://www.epa.gov/ocspp/pubs/frs/publications/Test_Guidelines/series870.htm.
ICCVAM. 2008. NICEATM-ICCVAM Five-Year Plan (2008-2012): A Plan to
Advance Alternative Test Methods of High Scientific Quality to
Protect and Advance the Health of People, Animals and the
Environment. Research Triangle Park, NC: National Institute of
Environmental Health Sciences. Available: http://iccvam.niehs.nih.gov/docs/5yearplan.htm.
OECD. 1987. Test No. 402. Acute Dermal Toxicity [adopted 24 February
1987]. In: OECD Guidelines for the Testing of Chemicals, Section 4:
Health Effects. Paris:OECD Publishing. Available: http://dx.doi.org/10.1787/9789264070585-en.
OECD. 2001. Test No. 425. Acute Oral Toxicity--Up-and-Down Procedure
[adopted 17 December 2001]. In: OECD Guidelines for the Testing of
Chemicals, Section 4: Health Effects. Paris:OECD Publishing.
Dated: July 12, 2012.
John R. Bucher,
Associate Director, National Toxicology Program.
[FR Doc. 2012-17787 Filed 7-20-12; 8:45 am]
BILLING CODE 4140-01-P