title: Toxicity characterization of complex mixtures using biological and chemical analysis in preparation for assessment of mixture similarity.
abstract: In the United States, several proposed approaches for using bioassays for the risk assessment of complex hazardous mixtures require that selected mixtures be "sufficiently similar" to each other. The goal of this research was to evaluate the utility of a protocol using in vitro bioassays and chemical analysis as a basis for assessing mixture similarity. Two wood preserving wastes (WPWs) containing polycyclic aromatic hydrocarbons and pentachlorophenol were extracted and fractionated to generate potentially similar mixtures. Chemical analysis was conducted using gas chromatography/mass spectrometry. Genotoxicity was evaluated using the Salmonella/microsome and Escherichia coli prophage induction assays. The crude extract of one WPW was also tested in the chick embryotoxicity screening test (CHEST) assay. The CHEST assay provided the most sensitive measurement of toxicity. Overall, the biological potency of the samples was not well correlated with predicted potency based on chemical analysis. Although several mixtures appeared similar based on chemical analysis, the magnitude of the response in bioassays was often dissimilar. Fractionation was required to detect the genotoxicity of mixture components in vitro. The results confirm the need for an integrated protocol, combining chemical analysis, fractionation, and biological testing to characterize the risk associated with complex mixtures.
authors.affiliation: Department of Veterinary Anatomy and Public Health, Texas A&M University, College Station, Texas 77843, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Cizmas
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: McDonald
authors.forename: Tracie D
authors.initials: TD
authors.lastname: Phillips
authors.forename: Annika M
authors.initials: AM
authors.lastname: Gillespie
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Lingenfelter
authors.forename: Leon F
authors.initials: LF
authors.lastname: Kubena
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Phillips
authors.forename: Kirby C
authors.initials: KC
authors.lastname: Donnelly
mesh_terms: D001681:Biological Assay; D004249:DNA Damage; D004347:Drug Interactions; D004785:Environmental Pollutants / Q000633:toxicity*; D004926:Escherichia coli / Q000235:genetics; D010416:Pentachlorophenol / Q000633:toxicity*; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D018570:Risk Assessment; D012475:Salmonella / Q000235:genetics; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D004785:Environmental Pollutants; D011084:Polycyclic Aromatic Hydrocarbons; D010416:Pentachlorophenol