Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage

Pros, cons & Future potential

While it is not considered valid as a stand-alone replacement for the in vivo rabbit eye test, the BCOP test method is recommended as an initial step within a testing strategy such as the Top-Down approach to identify chemicals inducing serious eye damage, i.e. chemicals to be classified as UN GHS Category 1, without further testing. The BCOP 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 (UN GHS No Category) within a testing strategy such as the Bottom-Up approach. However, a chemical that is not predicted as causing serious eye damage or as not classified for eye irritation/serious eye damage with the BCOP test method would require additional testing (in vitro and/or in vivo) to establish a definitive classification. The choice of the most appropriate test method and the use of this Test Guideline should be seen in the context of the OECD Guidance Document on an Integrated Approaches on Testing and Assessment for Serious Eye Damage and Eye irritation.

For more information see OECD TG nr. 437

• - The potential shortcomings of the BCOP test method when used to identify chemicals inducing serious eye damage (UN GHS Category 1) are based on the high false positive rates for alcohols and ketones and the high false negative rate for solids. However, since not all alcohols and ketones are over-predicted by the BCOP test method and some are correctly predicted as UN GHS Category 1, these two organic functional groups are not considered to be out of the applicability domain of the test method.
• - The BCOP test method is not recommended for the identification of test chemicals that should be classified as irritating to eyes (UN GHS Category 2 or Category 2A) or test chemicals that should be classified as mildly irritating to eyes (UN GHS Category 2B).
• - A chemical that is not predicted as causing serious eye damage or as not classified for eye irritation/serious eye damage with the BCOP test method would require additional testing (in vitro and/or in vivo) to establish a definitive classification.
• - The time interval between collection of the eyes and use of corneas in the BCOP test method should be minimized (typically collected and used on the same day) and should be demonstrated to not compromise the assay results.
• - The BCOP test method does not consider conjunctival and iridial injuries, it addresses corneal effects.
• - The reversibility of corneal lesions cannot be evaluated per se in the BCOP test method.
• - The BCOP test method does not allow for an assessment of the potential for systemic toxicity associated with ocular exposure.

For more information see OECD TG nr. 437

- Eyes from cattle less than 12 months of age have not traditionally been used since the eyes are still developing and the corneal thickness and corneal diameter are considerably smaller than that reported for eyes from adult cattle. However, the use of corneas from young animals (i.e., 6 to 12 months old) is permissible since there are some advantages, such as increased availability, a narrow age range, and decreased hazards related to potential worker exposure to Bovine Spongiform Encephalopathy. As further evaluation of the effect of corneal size or thickness on responsiveness to corrosive and irritant substances would be useful, users are encouraged to report the estimated age and/or weight of the animals providing the corneas used in a study.

For more information see OECD TG nr. 437

• - Further scientific knowledge is required to understand how irreversible effects not linked with initial high level injury occur.
• - Histopathology may be potentially useful when a more complete characterization of corneal damage is needed. Users are encouraged to preserve corneas and prepare histopathology specimens that can be used to develop a database and decision criteria that may further improve the accuracy of this test method.
• - Further evaluation of the effect of corneal size or thickness on responsiveness to corrosive and irritant substances would be useful, users are encouraged to report the estimated age and/or weight of the animals providing the corneas used in a study.

For more information see OECD TG nr. 437