Table of Validated and Accepted Alternative Methods

Validation & Regulatory Acceptance Status of Alternative Test Methods & Testing Strategies

 ¹ All in vitro and ex vivo methods listed; in vivo methods proposed to reduce or refine animal use also listed
 ² Replaces animal use for initial dose setting, but in vivo test required to complete assessment
 ³ Screening assays to be used as part of a broader testing strategy
 ⁴ Recommended for use as initial step within a Top-Down Approach to identify ocular corrosives and severe irritants (EU R41, GHS Category 1, and EPA Category I) for water-soluble chemicals and/or as initial step within a Bottom-Up Approach to identify non-irritants (EU:NC; GHS: NC; EPA: cat IV) for water-soluble surfactants and water-soluble surfactant-containing mixtures; does NOT correctly identify moderate and mild ocular irritants (EU: R36; GHS: Cat 2A/B; EPA: Cat II/III) so can be used for only two of the three EU and GHS classification categories for ocular irritation; cannot be used for default categorization; additional limitations on equipment availability
 ⁵ Can be used as screening test to distinguish water-soluble surfactant chemicals and certain types of surfactant-containing formulations that are not labeled as irritants (i.e., EPA Category IV, EU Not Labeled, FHSA Not Labeled) from all other hazard categories (i.e., EPA Category I, II, III; EU R41, R36; FHSA Irritant) for hazard classification and labeling under EPA, EU and FHSA classification systems; high false negative rate (24%-40%) for non-surfactant substances and formulations; high false positive rate (50% to 69%) for substances not labeled as irritants. Can be used as a screening test to identify water soluble substances as ocular corrosives and severe irritants (i.e., EPA Category I, EU R41, GHS Category 1) in tiered-testing strategy as part of weight-of-evidence approach; negative results need to be tested in another test method
 ⁶ Recommended for use as initial step within a Top-Down Approach to identify ocular corrosives and severe irritants (EU R41, GSH Category 1, and EPA Category I) for water-soluble chemicals; further refinement with respect to variability and applicability domain recommended
 ⁷ Restrictions include use of existing data only
 ⁸ Retrospective LVET data can be used in a weight-of-evidence approach to identify potential ocular irritants
 ⁹ rLLNA can be used for hazard classification when dose-response information is not needed
 ¹⁰ ICCVAM recommendations on use of LLNA for skin sensitization potency categorization anticipated in 2011
 ¹¹ Subject to product-specific validation to demonstrate equivalence to the rabbit pyrogen test (RPT)
 ¹² Statement on 2 reference chemicals for in vitro skin corrosion testing
 ¹³ Recommended as screening test or as part of sequential testing strategy; only positive test results accepted in the 2007 endorsement

Supplemental Information

A. ECVAM: Summary of test methods evaluated by ECVAM and accepted by EU regulatory authorities; ESAC statements; TSAR (Tracking System for Alternative test methods Review, Validation and Approval in the Context of EU Regulations on Chemicals)

B. ICCVAM: Summary of test methods evaluated by ICCVAM and accepted by US regulatory authorities; table showing validation and acceptance status of all methods reviewed

C. JaCVAM: Summary of test methods evaluated and accepted by Japan's regulatory authorities

D. OECD Test Guidelines (TGs), Guidance Documents, Draft Test Guidelines

E. ICH test guidelines

F. VICH test guidelines

Acronyms

EMEA: European Medicines Agency
EPA: US Environmental Protection Agency
ESAC: ECVAM Scientific Advisory Committee
GD: OECD Guidance Document
GHS: Globally Harmonized System of Classification and Labelling of Chemicals
ICCVAM: US Interagency Coordinating Committee on the Validation of Alternative Methods
JaCVAM: Japanese Center for the Validation of Alternative Methods
OECD: Organisation for Economic Cooperation and Development
OPPTS: US EPA's Office of Prevention, Pesticides and Toxic Substances
TG: OECD Test Guideline