Modeling toxic endpoints for improving human health risk assessment of polycyclic aromatic hydrocarbons parent compounds and simple mixtures
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abstract
Risk assessments for mixtures of polycyclic aromatic hydrocarbons (PAH) are problematic due to the lack of available potency and toxicity data on individual compounds and mixtures. This article examines the toxicity of parent compounds and designed mixtures of PAH in order to bridge the gap between component assessment and mixture assessment for this class of ubiquitous compounds. The objective for this study was to test seven parent PAH compounds and four PAH mixtures in a set of three bioassays to evaluate the toxicity of parent compound PAH and binary mixtures of PAH. PAH and mixtures were examined in the Salmonella/microsome mutagenicity assay, a Gap Junction Intercellular Communication assay, and the 7-ethoxyresorufin-O-deethylase assay. These assays were chosen for their ability to measure specific toxic endpoints related to the carcinogenic process (i.e. initiation, promotion, and progression). Two compounds similar in structure, benzo(a) pyrene (BAP) and benzanthracene, consistently produced positive results in all three bioassays. Conversely, a linear PAH, anthracene, produced negative results in all three bioassays. An antagonistic response was observed for the mixtures in all three bioassays. Chemical structure was important in explaining the observed responses. Using chemical structure-activity relationships with the steps of the carcinogenic process may be used to improve estimates of toxicity for compounds and mixtures for human health risk assessments. 2009 Taylor & Francis.
