Toxicological evaluation of complex mixtures: fingerprinting and multivariate analysis

Abstract

The present paper describes a strategy for toxicological evaluation of complex mixtures based on chemical “fingerprinting” followed by pattern recognition (multivariate data analysis). The purpose is to correlate chemical fingerprints to measured toxicological endpoints, identify all major contributors to toxicity, and predict toxicity of additional mixtures. The strategy is illustrated with organic extracts of exhaust particles which are characterized by full scan gas chromatography-mass spectrometry (GC–MS). The complex GC–MS data are resolved into peaks and spectra for individual compounds using an automated curve resolution procedure. Projections to latent structures (PLS) is used for the regression modeling to correlate the GC–MS data to the measured responses; mutagenicity in the Ames Salmonella assay. The regression model identifies those peaks that co-vary with the observed mutagenicity. These peaks may be identified chemically from their spectra. Furthermore, the regression model can be used to predict mutagenicity from GC–MS chromatograms of additional samples.