Applications of computational toxicology methods at the Agency for Toxic Substances and Disease Registry
Applications of computational toxicology methods at the Agency for Toxic Substances and Disease Registry
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DOI：
10.1078/1438-4639-00130
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发表时间：
2002-03-01
影响因子：
6
通讯作者：
De Rosa, CT
中科院分区：
文献类型：
--
作者：
El-Masri, HA;Mumtaz, MM;De Rosa, CT
在努力向州和地方卫生部门、其他联邦机构、卫生专业人员和公众就环境污染物对健康的影响提供咨询时，有毒物质和疾病登记局依靠计算毒理学的最新进展。该机构的计算毒理学实验室不断致力于开发和应用决策支持工具的模型，如基于生理的药代动力学（PBPK）模型、基准剂量（BMD）模型和定量构效关系（QSAR）模型。PBPK模型适用于将暴露情景与生物指标（如组织剂量或终点反应）联系起来。该机构使用这些模型来确定暴露途径对生活在危险废物填埋场附近的人们产生可能污染物的组织水平的重要性。此外，PBPK模型为路线到路线的健康指导值外推提供了可靠的科学方法，这些值通常是由一组非常具体的实验确定的。此外，计算毒理学实验室的科学家们正在使用PBPK模型在联合毒性评估和儿童毒性评估等领域推进毒理学研究。利用BMD建模，所有嵌入在实验确定的剂量-反应关系中的信息都用于以最小的外推估计环境物质的人类健康指导值。在许多情况下，实验室里的科学家也依赖于QSAR模型，在这些情况下，来自该机构的咨询报告缺乏足够的实验文件的化学品。
In its efforts to provide consultations to state and local health departments, other federal agencies, health professionals, and the public on the health effects of environmental pollutants, the Agency for Toxic Substances and Disease Registry relies on the latest advances in computational toxicology. The computational toxicology laboratory at the agency is continually engaged in developing and applying models for decision-support tools such as physiologically based pharmacokinetic (PBPK) models, benchmark dose (BMD) models, and quantitative structure-activity relationship (QSAR) models. PBPK models are suitable for connecting exposure scenarios to biological indicators such as tissue dose or end point response. The models are used by the agency to identify the significance of exposure routes in producing tissue levels of possible contaminants for people living near hazardous waste sites. Additionally, PBPK models provide a credible scientific methodology for route-to-route extrapolations of health guidance values, which are usually determined from a very specific set of experiments. Also, scientists at the computational toxicology laboratory are using PBPK models for advancing toxicology research in such areas as joint toxicity assessment and child-based toxicity assessments. With BMD modeling, all the information embedded in an experimentally determined dose-response relationship is used to estimate, with minimum extrapolations, human health guidance values for environmental substances. Scientists in the laboratory also rely on QSAR models in the many cases where consultations from the agency are reported for chemicals that lack adequate experimental documentation.