Modeling toxic endpoints for improving human health risk assessment

Abstract

Risk assessment procedures for mixtures of polycyclic aromatic hydrocarbons (PAHs) present a problem due to the lack of available potency and toxicity data on mixtures and individual compounds. This study examines the toxicity of parent compound PAHs and binary mixtures of PAHs in order to bridge the gap between component assessment and mixture assessment. Seven pure parent compound PAHs and four binary mixtures of PAHs were examined in the Salmonella/Microsome Mutagenicity Assay, a Gap Junction Intercellular Communication (GJIC) assay and the 7-ethoxyresorufin-O-deethylase assay (EROD). These assays were chosen for their ability to measure specific toxic endpoints related to the carcinogenic process (i.e. initiation, promotion, progression). Data from these assays was used in further studies to build Quantitative Structure-Activity Relationships (QSARs) to estimate toxic endpoints and to test the additive assumption in PAH mixtures. These QSAR models will allow for the development of bioassay based potential potencies (PPB) or toxic equivalency factors (TEFs) that are derived not only from bioassay data, but also from structure, activity, and physical/chemical properties. These models can be extended to any environmental media to evaluate risk to human health from exposures to PAHs.