IRAG WORKING GROUP-4 - CELL CYTOTOXICITY ASSAYS

Twenty-seven data sets from 12 cellular cytotoxicity assays, intended to predict ocular irritation, were submitted to the Interagency Regula tory Alternatives Group (IRAG) for review. These data consisted of pai red in vivo (Draize) and in vitro responses to individual chemicals an d formulations. In vivo data consisted of individual tissue scores so that the predictive value of the in vitro assay could be assessed for each tissue response normally measured in the standard Draize assay. D ata were compiled and evaluated according to the IRAG Guidelines Docum ent. The Pearson's linear correlation coefficient was used as the firs t step in assessing the relationship between the in vitro and in vivo responses. The majority of the data sets represented the study of surf actant-based materials. In many cases, there was good correlation betw een the in vitro scores and the in vivo tissue responses. Most pronoun ced were the particularly good correlations between the in vitro score s and conjunctival redness scores across most of the assays. Based on the data submitted, a number of the cell cytotoxicity assays show cons iderable promise as screens for ocular irritancy. None of the submitte rs recommended that their cell cytotoxicity assay be used as a sole re placement for in vivo assessment. For almost all of these assays, the materials being tested should be water-soluble/miscible. The toxicity of products with reserve acidity or alkalinity or with high reactivity may be underestimated. A given user may prefer certain assays dependi ng on the types of materials to be tested, the expected range of toxic ities Bad the resources available. The cell cytotoxicity assays can se rve as a valuable component of a tiered or battery testing program. As with any assay, a sufficient number of replicate values, concurrent p ositive and negative controls, and a strict adherence to assay accepta nce criteria are essential to produce credible data. (C) 1997 Elsevier Science Ltd.