Center for Computational Toxicology and Exposure, Office of Research and Development, U. S. Environmental Protection Agency, Research Triangle Park, NC, USA.
Center for Computational Toxicology and Exposure, Office of Research and Development, U. S. Environmental Protection Agency, Research Triangle Park, NC, USA.
Toxicol Appl Pharmacol. 2022 Sep 1;450:116141. doi: 10.1016/j.taap.2022.116141. Epub 2022 Jun 29.
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.
人类健康风险评估是化学毒性、到达目标生物组织的生物利用度和潜在环境暴露的函数。这些因素受到许多生理、生化、物理和生活方式因素的影响。此外，鉴于环境中发现的大量且不断增加的化学物质，化学健康风险评估具有挑战性。这些挑战突出表明，需要优先考虑资源，以便对那些对健康构成最大风险的环境化学物质进行高效和及时的评估。鉴于昂贵的体内实验数据缺乏，计算方法（无论是预测性的还是调查性的）旨在协助进行这种优先级排序。计算方法使用体外高通量筛选 (HTS) 测定来提供特定和有针对性的毒性信息。HTS 测定的信息可以转换为血液或靶组织中化学物质水平的体内估计值，而这些估计值又可以转换为体内剂量估计值，然后可以将其与筛选化学物质的暴露水平进行比较。本文综述了美国环境保护署 (EPA) 开发和使用的计算方法的现状，强调了它们的潜力和挑战。
