An ICCVAM recommendation to U.S. Federal agencies allows the identification of chemical eye hazards with fewer animals. ICCVAM concluded that using a classification criterion of one or more positive animals in a three-animal test maintains hazard classification equivalent to that provided by current procedures cited in 16 CFR 1500.42 while using 50% to 83% fewer animals. ICCVAM recommended consideration of this classification criterion with ocular toxicity 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 harmonized the number of animals used for ocular toxicity testing across U.S. regulatory agencies and international test guidelines.
Test Method Evaluation Report (October 2012) containing ICCVAM recommendations
ICCVAM also recommended that in vitro test methods should always be considered before using animals for ocular toxicity testing and used where determined appropriate. When it is necessary to use animals for ocular toxicity testing, ICCVAM recommended that medications and humane endpoints should always be used to prevent or minimize pain and distress.
ICCVAM considered comments from the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM) and the public as it finalized its recommendations. These recommendations have been forwarded to Federal agencies.
Ocular toxicity testing is performed to determine if substances cause temporary or permanent eye damage. Test results are then used for hazard classification of chemicals and products using appropriate national or international hazard classification systems.
Ocular toxicity 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.
Modified guidelines using a maximum of three animals per test have been implemented by some U.S. and international agencies to reduce the number of animals used for ocular toxicity testing. 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 three animals per test. However, current testing procedures cited in 16 CFR 1500.42 do not provide criteria to classify the results from three-animal tests.
NICEATM and ICCVAM conducted an analysis (Haseman et al. 2011) to determine if classification criteria based on the results from a three-animal test would maintain eye hazard classification equivalent to current testing procedures (16 CFR 1500.42). The ICCVAM recommendations are based on this analysis.
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 ocular toxicity testing, testing should be conducted using the minimum number of animals in the most humane manner possible consistent with testing objectives.
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.