Advances in computational methods along the exposure to toxicological response paradigm

Human health risk assessment is a function of chemical toxicity, bioavailability to reach target biological tissues, and potential environmental exposure. These factors are complicated by many physiological, biochemical, physical and lifestyle factors. Furthermore, chemical health risk assessment is challenging in view of the large, and continually increasing, number of chemicals found in the environment. These challenges highlight the need to prioritize resources for the efficient and timely assessment of those environmental chemicals that pose greatest health risks. Computational methods, either predictive or investigative, are designed to assist in this prioritization in view of the lack of cost prohibitive in vivo experimental data. Computational methods provide specific and focused toxicity information using in vitro high throughput screening (HTS) assays. Information from the HTS assays can be converted to in vivo estimates of chemical levels in blood or target tissue, which in turn are converted to in vivo dose estimates that can be compared to exposure levels of the screened chemicals. This manuscript provides a review for the landscape of computational methods developed and used at the U.S. Environmental Protection Agency (EPA) highlighting their potentials and challenges.