National Toxicology Program

National Toxicology Program
http://ntp.niehs.nih.gov/go/40165

Identifying Chemical Eye Hazards with Fewer Animals

ICCVAM has made recommendations to U.S. Federal agencies that will provide for identifying chemical eye hazards with fewer animals. ICCVAM concludes that using a classification criterion of one or more positive animals in a three-animal test to identify chemicals and products that are eye hazards will maintain hazard classification equivalent to that provided by current testing procedures (16 CFR 1500.42), while using up to 50% to 83% fewer animals. ICCVAM therefore recommends consideration of the use of this classification criterion together with eye safety testing procedures that use a maximum of three animals per test substance. Consistent with ICCVAM’s duty to foster interagency and international harmonization (42 U.S.C. 285l-3), this recommendation harmonizes the number of animals used for eye safety testing across U.S. regulatory agencies and international test guidelines.

Test Method Evaluation Report (October 2012) containing ICCVAM recommendations

ICCVAM also recommends that in vitro test methods should always be considered before using animals for eye safety testing, and these should be used where determined appropriate. When it is necessary to use animals for eye safety testing, ICCVAM recommends that medications and humane endpoints should always be used to avoid or minimize pain and distress.

ICCVAM considered comments from the public and from the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM) as it finalized its recommendations. These recommendations have been forwarded to Federal agencies, with agency responses expected in 2013.

Background

Eye safety testing is performed to determine if substances may cause temporary or permanent eye damage. Test results are then used for hazard classification of chemicals and chemical products using appropriate national and/or international hazard classification systems.

Eye safety testing procedures vary among U.S. agencies. Current testing procedures specified in the U.S. Code of Federal Regulations (16 CFR 1500.42) require 6 animals per test and may require up to three sequential tests for each substance, thereby requiring 6, 12, or 18 animals to reach a hazard decision. The requirement for second and third sequential tests is based on the number of positive responses in the previous test.

Based on previous initiatives in the United States to reduce the number of animals used for eye safety testing, some U.S. and international test guidelines for eye irritation and corrosion testing have been modified, with a maximum of 3 animals typically used. U.S. agencies will accept data generated in accordance with test guidelines by the Organisation for Economic Co-operation and Development (OECD) that require only 3 animals per test. However, current testing procedures (16 CFR 1500.42) do not provide criteria to classify results from 3-animal tests.

NICEATM and ICCVAM conducted an analysis (Haseman et al. 2011; link to reference on PubMed ) to determine classification criteria based on results from a 3-animal test that would maintain eye hazard classification equivalent to current testing procedures (16 CFR 1500.42). The ICCVAM recommendations are based on this analysis.

ICCVAM concluded that using a classification criterion of one or more positive animals in a three-animal test to identify chemicals and products that are eye hazards will maintain hazard classification equivalent to that provided by current testing procedures (16 CFR 1500.42). ICCVAM recommends that alternative in vitro test methods should always be considered and used where appropriate for eye safety testing. While currently approved in vitro test methods can identify some eye hazards, they are not sufficiently validated and accepted to completely replace all animal testing. When it is determined necessary to use animals for eye safety testing, testing should be conducted using the minimum number of animals in the most humane manner possible consistent with testing objectives. Consistent with ICCVAM’s duty to foster interagency and international harmonization as stated in the ICCVAM Authorization Act (42 U.S.C. 285l-3), this recommendation harmonizes the number of animals used for eye safety testing across U.S. regulatory agencies and international test guidelines.

These ICCVAM recommendations were communicated to Federal agencies in letters from Dr. Linda Birnbaum, Director, NIEHS. These letters and responses received from Federal agencies are available below.

The NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.