Use of an in vitro test battery as a prescreen in the assessment of ocular irritancy

Abstract

The current OECD guideline for the assessment of eye irritation recommends, in initial considerations, the use of data from skin irritation tests as a prescreen to detect the most severely irritating materials, assuming that materials that are severely irritating to the skin are also significantly irritating to the eyes. However, analysis of data for 179 materials tested in this laboratory for both dermal and ocular irritancy, revealed that, at most, only 36% of severe eye irritants were also severe skin irritants. This resulted in a significant number of rabbits developing severe ocular effects that had not been predicted from the dermal responses. This study reports the results of an alternative approach for predicting severe eye irritants. The approach was a two-stage test battery in vitro: the first stage was a cytotoxicity assay utilizing the K562 cell line; the second was the isolated rabbit eye test. In contrast to the use of skin irritation tests, the in vitro battery was significantly more predictive (83% of severe eye irritants were detected). Although the incidence of false positive responses in each of the assays precludes their routine use as a replacement from the in vivo rabbit eye test they provide a powerful aid to reducing animal use and guiding in vivo studies to minimize the severity of effects. The need for an interlaboratory assessment to confirm and extend these findings is discussed.