Utilization of biomacromolecular in vitro assay systems in the prediction of in vivo toxic responses.

Target biomacromolecular assay systems utilize as endpoints quantifiable alterations in key macromolecules elicited by various chemicals and formulations. The EYTEX Assay System, an example of a target biomacromolecular test method, has been used to predict the in vivo ocular irritancy potential of chemicals and formulations. The biomacromolecular reagent is a standardized matrix which can be produced routinely. One hundred test chemicals, representing diverse chemical classes with a wide range of toxic responses in vivo, were evaluated in the EYTEX system. In vitro results were compared to maximum 24-hour Draize scores and Draize classifications. The concordance of the in vitro and in vivo results demonstrated the relevance of the alteration of the EYTEX macromolecular matrix to the prediction of in vivo ocular irritation. The relevance of the in vitro endpoint of turbidity of the EYTEX matrix to in vivo ocular irritation has thus been demonstrated for a large number of test agents in other evaluation studies (1, 2, 3, 4, 5, 6, 7, 8). Integration of macromolecular-based test methods with in vitro cytotoxicity or cellular response methods may provide complementary information about mechanisms of target-induced toxicity. The target biomacromolecular assay systems which provide standardized, reproducible reagents are valuable components of test batteries.