Practical applications of QSAR to in vitro toxicology illustrated by consideration of eye irritation.

Mechanistically based quantitative structure-activity relationships (QSARs) have been developed for some well defined toxic endpoints. Principal components analysis has proved to be a useful technique in visualizing the QSARs and allows ready construction of hypotheses to test. The preferred way of testing the hypotheses is to use in vitro methods: thus integrating the use of QSAR and in vitro methods. Principal components analysis affords a basis for more rational selection of test chemicals to examine the utility of an in vitro method and more specifically the selection of test chemicals to be used in the validation of an in vitro method. This is particularly important in the absence of a large number of chemicals which have been tested in animals. In addition, elucidation of the putative mechanism of action of chemicals allows re-evaluation of the appropriateness of an in vitro method for the precise detection of the toxicity of specific classes of substances and more rational design of in vitro methods with improved powers of prediction.