Modeling toxic endpoints for improving human health risk assessment

摘要

Risk assessment procedures for mixtures of polycyclic aromatic hydrocarbons(PAHs) present a problem due to the lack of available potency and toxicity data onmixtures and individual compounds. This study examines the toxicity of parentcompound PAHs and binary mixtures of PAHs in order to bridge the gap betweencomponent assessment and mixture assessment. Seven pure parent compound PAHs andfour binary mixtures of PAHs were examined in the Salmonella/MicrosomeMutagenicity Assay, a Gap Junction Intercellular Communication (GJIC) assay and the7-ethoxyresorufin-O-deethylase assay (EROD). These assays were chosen for theirability to measure specific toxic endpoints related to the carcinogenic process (i.e.initiation, promotion, progression). Data from these assays was used in further studies tobuild Quantitative Structure-Activity Relationships (QSARs) to estimate toxic endpointsand to test the additive assumption in PAH mixtures. These QSAR models will allowfor the development of bioassay based potential potencies (PPB) or toxic equivalencyfactors (TEFs) that are derived not only from bioassay data, but also from structure,activity, and physical/chemical properties. These models can be extended to anyenvironmental media to evaluate risk to human health from exposures to PAHs.