Estimating Toxicity-related Biological Pathway Altering Doses for High-throughput Chemical Risk Assessment

We describe a framework for estimating the human dose at which a chemical significantly alters a biological pathway in vivo, making use of in vitro assay data and an in vitro-derived pharmacokinetic model, coupled with estimates of population variability and uncertainty. The quantity we calculate, the biological pathway altering dose (BPAD), is analogous to current … Continued

Immediate Consequences of Cigarette Smoking: Rapid Formation of Polycyclic Aromatic Hydrocarbon Diol Epoxides

Polycyclic aromatic hydrocarbons (PAH) are among the likely major causative agents for lung cancer in smokers. PAH require metabolic activation to exert their carcinogenic effects, and one important pathway proceeds through a three-step sequence resulting in the formation of diol epoxides, which react with DNA to produce adducts that can cause mutations and initiate the … Continued

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