Using Quantitative Structure–Activity Relationships (QSAR) to Predict Toxic Endpoints for Polycyclic Aromatic Hydrocarbons (PAH)

Abstract

Quantitative structure–activity relationships (QSAR) offer a reliable, cost-effective alternative to the time, money, and animal lives necessary to determine chemical toxicity by traditional methods. Additionally, humans are exposed to tens of thousands of chemicals in their lifetimes, necessitating the determination of chemical toxicity and screening for those posing the greatest risk to human health. This study developed models to predict toxic endpoints for three bioassays specific to several stages of carcinogenesis. The ethoxyresorufin O-deethylase assay (EROD), the Salmonella/microsome assay, and a gap junction intercellular communication (GJIC) assay were chosen for their ability to measure toxic endpoints specific to activation-, induction-, and promotion-related effects of polycyclic aromatic hydrocarbons (PAH). Shape-electronic, spatial, information content, and topological descriptors proved to be important descriptors in predicting the toxicity of PAH in these bioassays. Bioassay-based toxic equivalency factors (TEF_B) were developed for several PAH using the quantitative structure–toxicity relationships (QSTR) developed. Predicting toxicity for a specific PAH compound, such as a bioassay-based potential potency (PP_B) or a TEF_B, is possible by combining the predicted behavior from the QSTR models. These toxicity estimates may then be incorporated into a risk assessment for compounds that lack toxicity data. Accurate toxicity predictions are made by examining each type of endpoint important to the process of carcinogenicity, and a clearer understanding between composition and toxicity can be obtained.

We thank the National Institute of Environmental Health Sciences (NIEHS) and the U.S. Environmental Protection Agency (U.S. EPA), which supported this work through the Superfund Basic Research Program (SBRP) of Texas A&M University (grant ESO4917).

Notes

Accelrys Software, Inc. San Diego, CA. 2005. Cerius², Release 4.10.