[Federal Register Volume 76, Number 156 (Friday, August 12, 2011)]
[Pages 50220-50221]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-20537]



Availability of Draft ICCVAM Recommendations on Using Fewer 
Animals to Identify Chemical Eye Hazards: Revised Criteria Necessary to 
Maintain Equivalent Hazard Classification; Request for Comments

AGENCY: Division of the National Toxicology Program (DNTP), National 
Institute of Environmental Health Sciences (NIEHS), National Institutes 
of Health, HHS.

ACTION: Availability of Recommendations; Request for Comments.


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), conducted an analysis to determine classification criteria 
using results from 3-animal tests that would provide eye hazard 
classification equivalent to testing conducted in accordance with 
current U.S. Federal Hazardous Substances Act (FHSA) regulations, which 
require the use of 6 to 18 animals. The results showed that using a 
classification criterion of at least 1 positive animal in a 3-animal 
test to identify eye hazards will provide the same or greater level of 
eye hazard classification as current FHSA requirements, while using 50% 
to 83% fewer animals. ICCVAM developed draft recommendations based on 
the results of this analysis. NICEATM invites public comments on these 
draft ICCVAM recommendations.

DATES: Written comments on the draft recommendations should be received 
by September 26, 2011.

ADDRESSES: NICEATM prefers that comments be submitted electronically 
via the NICEATM-ICCVAM Web site (http://iccvam.niehs.nih.gov/contact/FR_pubcomment.htm) or via e-mail to [email protected]. Written 
comments may also be sent by mail or fax to Dr. William S. Stokes, 
Director, NICEATM, NIEHS, P.O. Box 12233, Mail Stop: K2-16, Research 
Triangle Park, NC 27709; (fax) 919-541-0947. Courier address: NICEATM, 
NIEHS, Room 2034, 530 Davis Drive, Morrisville, NC 27560.

FOR FURTHER INFORMATION CONTACT: Dr. William S. Stokes: (telephone) 
919-541-2384, (fax) 919-541-0947, or (e-mail) [email protected].



    Testing requirements necessary to determine the eye hazard 
potential for substances regulated under the FHSA (FHSA, 2008) are 
provided in 16 CFR 1500.42 (U.S. Consumer Product Safety Commission 
[CPSC], 2010). Current FHSA regulations provide procedures to determine 
the eye hazard classification and labeling requirements for chemicals 
and products to which consumers may be exposed. The current procedure 
requires a minimum of 6 animals per test and may require up to 3 
sequential tests for each substance, thus requiring 6, 12, or 18 
animals to reach a hazard classification decision. The requirement for 
second and third sequential tests is based on the number of positive 
responses in the previous test.
    In 2002, the Organisation for Economic Co-operation and Development 
(OECD) Test Guidelines Program adopted U.S. proposed revisions to Test 
Guideline 405: Acute Eye Irritation/Corrosion (OECD, 2002) that reduce 
the maximum number of required animals per test from 6 to 3. The Animal 
Welfare Act (7 U.S.C. 2131 et seq) and the Public Health Service (PHS) 
Policy (PHS, 2002) similarly require that only the minimum number of 
animals necessary to obtain scientifically valid results should be used 
and that a rationale for the appropriateness of the number of animals 
used be provided to and approved by the Institutional Animal Care and 
Use Committee. In light of this policy and regulations, most in vivo 
ocular safety testing is expected to adhere to the 3-animal procedure 
described in OECD Test Guideline 405 (OECD, 2002) and in a test 
guideline issued by the U.S. Environmental Protection Agency (EPA, 
1998). However, current FHSA regulations do not provide criteria to 
classify results from a 3-animal test. Therefore, an analysis was 
conducted to determine classification criteria based on results from a 
3-animal test that would provide eye hazard classification equivalent 
to procedures in current FHSA regulations (Haseman et al., 2011). The 
results showed that using a classification criterion of at least 1 
positive in a 3-animal test to identify eye hazards will provide the 
same or greater level of eye hazard classification as current FHSA 
requirements, while using 50% to 83% fewer animals. Based on these 
results, ICCVAM developed draft recommendations to use this 
classification criterion for ocular safety testing procedures that use 
only a maximum of 3 animals per test substance.

Availability of the Documents

    The draft ICCVAM recommendations and the supporting publication 
describing the results of the analysis are available on the NICEATM-
ICCVAM Web site (http://iccvam.niehs.nih.gov/methods/ocutox/reducenum.htm), and may also be obtained by contacting NICEATM (see FOR 

Request for Public Comments

    NICEATM invites the submission of written comments on the draft 
ICCVAM recommendations and the extent to which the NICEATM analysis 
supports the recommendations by September 26, 2011. When submitting 
written comments, please refer to this Federal Register notice and 
include appropriate contact information (name, affiliation, mailing 
address, phone, fax, e-mail, and sponsoring organization, if 
applicable). NICEATM will post all comments on the NICEATM-ICCVAM Web 
site (http://ntp-apps.niehs.nih.gov/iccvampb/searchPubCom.cfm) 
identified by the individual's name and affiliation or sponsoring 
organization (if applicable). ICCVAM will consider all public comments 
and comments made by the Scientific Advisory Committee on Alternative 
Toxicological Methods (SACATM) at the June 17-18, 2010 meeting (75 FR 
26757) when finalizing its recommendations. Final ICCVAM 
recommendations will be forwarded to relevant Federal agencies for 
their consideration. These recommendations will also be available to 
the public on the NICEATM-ICCVAM Web site (http://iccvam.niehs.nih.gov/methods/ocutox/reducenum.htm).

[[Page 50221]]

Background Information on ICCVAM, NICEATM, and SACATM

    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 with regulatory applicability and promotes the 
scientific validation and regulatory acceptance of toxicological and 
safety testing methods that more accurately assess the safety and 
hazards of chemicals and products and that reduce, refine (decrease or 
eliminate 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).
    SACATM was established in response to the ICCVAM Authorization Act 
[Section 285l-3(d)] and is composed of scientists from the public and 
private sectors. SACATM advises ICCVAM, NICEATM, and the Director of 
the NIEHS and NTP regarding statutorily mandated duties of ICCVAM and 
activities of NICEATM. SACATM provides advice on priorities and 
activities related to the development, validation, scientific review, 
regulatory acceptance, implementation, and national and international 
harmonization of new, revised, and alternative toxicological test 
methods. Additional information about SACATM, including the charter, 
roster, and records of past meetings, can be found at http://ntp.niehs.nih.gov/go/167.


AWA. 2010. Animal Welfare Act. 7 U.S.C. 2131 et seq. Public Law 89-
544. Available: http://www.aphis.usda.gov/animal_welfare/downloads/awa/awa.pdf.
CPSC. 2010. Hazardous Substances and Articles; Administration and 
Enforcement Regulations. 16 CFR part 1500. Available: http://www.gpo.gov/fdsys/pkg/CFR-2010-title16-vol2/xml/CFR-2010-title16-vol2-part1500.xml.
EPA. 1998. Health Effects Test Guideline, OPPTS 870.2400 Acute Eye 
Irritation. Washington, DC: U.S. Environmental Protection Agency. 
Available: http://iccvam.niehs.nih.gov/SuppDocs/FedDocs/EPA/EPA_870_2400.pdf.
FHSA. 2008. 15 U.S.C. 1261-1278. Public Law 86-613. Available: 
Haseman JK, Allen DG, Lipscomb EA, Truax JF, Stokes WS. 2011. Using 
fewer animals to identify chemical eye hazards: Revised criteria 
necessary to maintain equivalent hazard classification [published 
online ahead of print]. Regul Toxicol Pharmacol. Available: http://dx.doi.org/10.1016/j.yrtph.2011.06.006.
OECD. 2002. Test No. 405: Acute Eye Irritation/Corrosion. In: OECD 
Guidelines for the Testing of Chemicals, Section 4: Health Effects. 
Paris:OECD Publishing. Available: http://www.oecd-ilibrary.org/content/book/9789264070646-en.
PHS. 2002. Public Health Service Policy on Humane Care and Use of 
Laboratory Animals. Bethesda, MD: Office of Laboratory Animal 
Welfare, National Institutes of Health. Available: http://grants.nih.gov/grants/olaw/references/phspol.htm.

    Dated: August 3, 2011.
John R. Bucher,
Associate Director, National Toxicology Program.
[FR Doc. 2011-20537 Filed 8-11-11; 8:45 am]