STRATEGIES FOR TOXICOLOGICAL EVALUATION OF MIXTURES

Different strategies for the toxicological evaluation of mixtures are presented. The purpose is to determine the effects of each component ( variable) in the mixture, and possible interactions between variables. The examples presented have 3-5 predictor variables and 1-3 responses , and are based on statistical experimental design, multivariate data analysis and modelling. The following examples are presented: (1) inha lation experiments with synthetic vapour mixtures of hydrocarbons form ulated by means of mixture design at different vapour concentrations ( the experimental region covers both partial and complete evaporation o f the liquid mixtures); (2) combination of refinery streams for fuel b lending by means of mixture design with constraints, followed by engin e tests and determination of exhaust particles; (3) fractionation of o rganic extracts of diesel exhaust particles, and recombination of the extracts by means of mixture design, followed by mutagenicity testing of the recombined extracts in the Ames Salmonella assay; (4) spiking c omplex mixtures with individual compounds using factorial design, and subsequent mutagenicity testing. The data obtained from these four exa mples were analysed by means of Projections to Latent Structures (PLS) . The effects of each variable and possible interactions, were quantif ied by means of PLS regression coefficients. Furthermore, the empirica l models obtained were evaluated by means of correlation coefficients, cross validation and predictions. Copyright (C) 1997 Elsevier Science Ltd.