Ability of in vitro (corneal injury--eye organ--and chorioallantoic membrane) tests to represent histopathological features of acute eye inflammation.

The spontaneous removal of substances from the eye in vivo and histopathological responses to mild or moderate irritants were examined to define the main features that may be reflected in a valid in vitro test for irritant potential. Solutions or fine particulate suspensions applied to the rabbit eye are quickly removed from the central corneal surface by the blink reflex, gravity and drainage. The histological changes in the first 24 hours of mild-to-moderate irritation show some thinning of, but no severe irreversible damage to, the corneal epithelium. Other changes are oedema, congestion, some leucocyte infiltration and variable degeneration and desquamation of the conjunctival epithelium. In vitro cell-culture cytotoxicity tests are a useful screen for direct cytotoxic damage to epithelial cells but there are anomalies between the results of such tests and in vivo eye responses. Test systems using inhibition of DNA synthesis in cultured fibroblasts and histamine release from mast cells have shown poor correlation between in vitro and in vivo test results. The in vitro corneal injury (eye organ) test of Burton et al. (Fd Cosmet. Toxicol. 1981, 19,471) predicts very effectively the activity of moderate-to-severe irritants, and that of mild irritants when the contact time is modified or fluorescein or histology are used. This method demonstrates the response of a specialized tissue of the eye and facilitates the examination of powders, acids and alkalies, for which cell systems are not suitable. So far the chorioallantoic membrane of the egg has not been found to predict for pure chemicals the activities demonstrated in in vivo or in vitro tests on the eye; the main change seen in the egg membrane is necrosis, with little evidence of inflammation.