Applicability domain of BCOP and ICE extended to identifying ocular non-irritants

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In the Spotlight

Applicability domain of BCOP and ICE extended to identifying ocular non-irritants

Sherry Ward, AltTox Contributing Editor

Published: May 15, 2013

The national/regional validation centers, ICCVAM, ECVAM, and JaCVAM, previously endorsed the bovine corneal opacity and permeability (BCOP) and the isolated chicken eye (ICE) test methods for the assessment of corrosive and severely irritating materials to the ocular surface. In 2006, ICCVAM led the review  of these test methods in collaboration with ECVAM and JaCVAM, followed by the adoption of their OECD Test Guidelines (TGs) in 2009: OECD TG 437 for BCOP, and OECD TG 438 for ICE. The TGs explain, with certain limitations on chemical classes and physical properties, how the BCOP and ICE test methods can be used to identify substances as ocular corrosives or severe ocular irritants for regulatory testing purposes.

However, the BCOP and ICE test methods failed in previous assessments to be endorsed for evaluating the ocular irritation potential of materials in the non-to-moderate irritant range.

EURL ECVAM now reports, following additional validation of the BCOP and ICE test methods, that the OECD TGs have been revised to extend the applicability domain of the BCOP and ICE for the additional purpose of ocular irritation testing. The revision of these TGs “was adopted at the OECD meeting of the Working Group of National Coordinators of the Test Guideline Programme held in Paris on 9 to 11 April 2013.” EURL ECVAM led this additional assessment of the ocular test methods, in collaboration with ICCVAM and JaCVAM.

The Draft Updated TG 437 states that “the BCOP test method can also be used to identify chemicals that do not require classification for eye irritation or serious eye damage under the UN GHS classification systems…. Since the BCOP test method can only identify correctly 31% of the chemicals that do not require classification for eye irritation or serious eye damage, this test method should not be the first choice to initiate a Bottom-Up approach, if other validated and accepted in vitro methods with similar high sensitivity but higher specificity are available.”

Furthermore, “the BCOP test method is not recommended for the identification of test substances that should be classified as irritating to eyes (UN GHS Category 2 or Category 2A) or test substances that should be classified as mildly irritating to eyes (UN GHS Category 2B)….”

The Draft Updated TG 438 likewise states that “the ICE test method is also recommended to identify chemicals that do not require classification for eye irritation or serious eye damage as defined by the UN GHS (No Category, NC), and may therefore be used as an initial step within a Bottom-Up testing strategy approach…. The ICE test method is not recommended for the identification of test substances that should be classified as irritating to eyes (i.e., UN GHS Category 2 or Category 2A) or test substances that should be classified as mildly irritating to eyes (UN GHS Category 2B)….”

So, the BCOP and ICE test methods can now be used to identify some types of “ocular corrosive/severe irritants” and “ocular non-irritants,” at least for those regulatory agencies using the UN GHS for classification, but cannot be used to classify a substance as an “ocular irritant.” The ICCVAM website does not yet indicate the status of US regulatory agency acceptance of the BCOP or ICE for identifying ocular non-irritants.

The testing strategy for using the BCOP or ICE to reduce/replace animal use in ocular toxicity testing is described in the article by Scott, et al. (2010) as a “bottom-up and top-down approach.” This paper describes an expert panel assessment convened by ECVAM in 2005 to identify a testing strategy capable of identifying eye irritants. It had been understood by many ophthalmic researchers for at least the prior decade that no one in vitro method would be able to predict eye irritation potential over all product types and/or degrees of eye injury. Therefore, a testing scheme composed of different test methods was under consideration at this ECVAM meeting. The newly endorsed applicability domain of BCOP and ICE, to identify ocular non-irritants, now makes the bottom-up and top-down approach feasible for materials that fall within certain chemical and product categories. Substances not classified as either as ocular non-irritants or severe/corrosive ocular irritants with these in vitro methods will still need further testing for regulatory classification purposes, meaning the Draize rabbit eye test.

The Cytosensor® microphysiometer test method, endorsed by ICCVAM in 2010, is the only other in vitro method accepted for identifying ocular non-irritants, but can be used for only a very limited range of substances. The OECD is expected to adopt the Draft TG for the Cytosensor test method sometime in the near future.

Abbreviations:

BCOP: bovine corneal opacity and permeability (an ex vivo test method)
ECVAM: European Centre for the Validation of Alternative Methods
EURL ECVAM: European Union Reference Laboratory on Alternatives to Animal Testing
ICCVAM: Interagency Coordinating Committee on the Validation of Alternative Methods (US)
ICE: isolated chicken eye (an ex vivo test method)
JaCVAM: Japanese Center for the Validation of Alternative Methods
OECD: Organisation for Economic Cooperation and Development
TG: Test Guideline (OECD)
UN GHS: United Nations Globally Harmonized System for Classification and Labeling of Chemicals

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