A QUANTITATIVE STRUCTURE-TOXICITY RELATIONSHIPS MODEL FOR THE DERMAL SENSITIZATION GUINEA-PIG MAXIMIZATION ASSAY

We have developed quantitative structure-toxicity relationship (QSTR) models for assessing dermal sensitization using guinea pig maximizatio n test (GPMT) results. The models are derived from 315 carefully evalu ated chemicals. There are two models, one for aromatics (excluding one -benzene-ring compounds), and the other for aliphatics and one-benzene -ring compounds. For sensitizers, the models can resolve whether they are weak/moderate or severe sensitizers. The statistical methodology, based on linear discriminant analysis, incorporates an optimum predict ion space (OPS) algorithm. This algorithm ensures that the QSTR model will be used only to make predictions on query structures which fall w ithin its domain. Calculation of the similarities between a query stru cture and the database compounds from which the applicable model was d eveloped are used to validate each skin sensitization assessment. The cross-validated specificity of the equations ranges between 81 and 91% , and the sensitivity between 85 and 95%. For an independent test set, specificity is 79%, and sensitivity 82%. (C) 1997 Elsevier Science Lt d. All rights reserved.