Suggestion of the updated IVIS cut-off values for identifying non-ocular irritants in the bovine corneal opacity and permeability (BCOP) assay

The bovine corneal opacity and permeability (BCOP) assay is an alternative to the Draize test in rabbits. Although it can be used to evaluate ocular non-irritants and severe irritants, it is not used for the assessment of mild-irritating substances. In this assay, a chemical with an in vitro irritancy score (IVIS) ≤ 3 is defined as a “non-irritant” while one with an IVIS > 55 is defined as a “corrosive” or “severe irritant.” We attempted to evaluate mild eye irritants by assessing the recovery of corneal lesions histopathologically. Our results indicated that chemicals with IVIS ≤ 6 may be defined as “non-irritants,” because the rapid recovery of lesions limited to the squamous layer was predicted by the histopathology. In cases where lesions extended to the wing and basal cell layers, when some intact basal cells remained, the lesions were also predicted to be reversible. Thus, chemicals which induce lesions in which basal cells remain intact can be considered to be mild irritants.