[Federal Register Volume 77, Number 141 (Monday, July 23, 2012)]
[Notices]
[Pages 43089-43090]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-17787]


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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 
Experts.

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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.

SUPPLEMENTARY INFORMATION:

Background

    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), 
curriculum

[[Page 43090]]

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).

References

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. 
Available: www.oecd.org/dataoecd/17/51/1948378.pdf.

    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