Investigating the mixture effects of polycyclic aromatic hydrocarbons through in vitro toxicity assessments using clone-9 liver cells.
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Gaskill, Stacey Joanne, 1989-
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The Environmental Protection Agency is reevaluating current methods for assessing the toxicity of polycyclic aromatic hydrocarbons (PAHs), including the assumption of toxic additivity in mixtures. This study was aimed at testing mixture interactions using select PAH congeners through in vitro cell culture experimentation, and modeling the toxicity using quantitative structure-activity relationships (QSAR). Clone-9 rat liver cells were used to analyze cellular proliferation, viability, and genotoxicity of 15 PAHs in single doses and in binary mixtures. Tests revealed that many mixtures have non-additive toxicity, but display varying mixture effects depending on the mixture composition. QSARs were developed using viability data to predict toxic activity both in single PAH congeners and in binary mixtures. Effective concentrations inhibiting 50% of the cell populations were successfully modelled, with r^2= 0.90, 0.99 and 0.84, respectively. Our findings suggest that PAH mixtures have complex interactions, and continued mixture research will strengthen toxicological assessments of PAHs.