Williams Antony J, Lambert Jason C, Thayer Kris, Dorne Jean-Lou C M
Center for Computational Toxicology and Exposure, Office of Research and Development, U.S. Environmental Protection Agency (U.S. EPA), Research Triangle Park, NC, USA.
Center for Computational Toxicology and Exposure, Office of Research and Development, U.S. Environmental Protection Agency (U.S. EPA), Research Triangle Park, NC, USA.
Environ Int. 2021 Sep;154:106566. doi: 10.1016/j.envint.2021.106566. Epub 2021 Apr 29.
For the past six decades, human health risk assessment of chemicals has relied on in vivo data from human epidemiological and experimental animal toxicological studies to inform the derivation of non-cancer toxicity values. The ongoing evolution of this risk assessment paradigm in an environmental landscape of data-poor chemicals has highlighted the need to develop and implement non-testing methods, so-called New Approach Methodologies (NAMs). NAMs include a growing number of in silico and in vitro data streams designed to inform hazard properties of chemicals, including kinetics and dynamics at different levels of biological organization, environmental fate and transport, and exposure. NAMs provide a fit-for-purpose science-basis for human hazard and risk characterization of chemicals ranging from data-gap filling applications to broad evidence-based decision-making. Systematic assembly and delivery of empirical and predicted data for chemicals are paramount to advancing chemical evaluation, and software tools serve an essential role in delivering these data to the scientific community. The CompTox Chemicals Dashboard (from here on referred to as the "Dashboard") is one such tool and is a publicly available web-based application developed by the US Environmental Protection Agency to provide access to chemistry, toxicity and exposure information for ~900,000 chemicals. The Dashboard is increasingly becoming a valuable resource for assessors tasked with the evaluation of potential human health risks associated with chemical exposures. In this context, the significant amount of information present in the Dashboard facilitates: 1) assembly of information on physicochemical properties and environmental fate and transport and exposure parameters and metrics; 2) identification of cancer and non-cancer health effects from extant human and experimental animal studies in the public domain and/or information not available in the public domain (i.e., "grey literature"); 3) systematic literature searching and review for developing cancer and non-cancer hazard evidence bases; and 4) access to mechanistic information that can aid or augment the analysis of traditional toxicology evidence bases, or potentially, serve as the primary basis for informing hazard identification and dose-response when traditional bioassay data are lacking. Finally, in silico predictive tools developed to conduct structure-activity or read-across analyses are also available within the Dashboard. This practical tutorial is intended to address key questions from the human health risk assessment community dealing with chemicals in both food and in the environment. Perspectives for future development or refinement of the Dashboard highlight foreseen activities to further support the research and risk assessment community in cancer and non-cancer chemical evaluations.
在过去的六十年里,对化学品的人类健康风险评估一直依赖于来自人类流行病学和实验动物毒理学研究的体内数据,以推导非癌症毒性值。在数据匮乏的化学品环境中,这种风险评估范式的不断演变凸显了开发和实施非测试方法(即所谓的新方法学,NAMs)的必要性。NAMs包括越来越多的计算机模拟和体外数据流,旨在了解化学品的危害特性,包括不同生物组织水平的动力学和动态、环境归宿和迁移以及暴露情况。NAMs为化学品的人类危害和风险特征描述提供了一个适用的科学基础,范围从填补数据空白应用到广泛的基于证据的决策制定。系统地收集和提供化学品的经验数据和预测数据对于推进化学品评估至关重要,软件工具在将这些数据提供给科学界方面发挥着重要作用。综合毒性化学品仪表盘(以下简称“仪表盘”)就是这样一种工具,它是美国环境保护局开发的一个基于网络的公开应用程序,可提供约90万种化学品的化学、毒性和暴露信息。仪表盘正日益成为评估人员评估与化学品暴露相关的潜在人类健康风险的宝贵资源。在此背景下,仪表盘中存在的大量信息有助于:1)收集有关物理化学性质、环境归宿和迁移以及暴露参数和指标的信息;2)从公共领域现存的人类和实验动物研究以及/或公共领域不可用的信息(即“灰色文献”)中识别癌症和非癌症健康影响;3)系统地检索和审查文献,以建立癌症和非癌症危害证据库;4)获取有助于或增强对传统毒理学证据库分析的机制信息,或者在缺乏传统生物测定数据时,有可能作为危害识别和剂量反应的主要依据。最后,仪表盘中还提供了用于进行结构活性或类推分析的计算机模拟预测工具。本实用教程旨在解决人类健康风险评估界在处理食品和环境中的化学品时的关键问题。对仪表盘未来发展或改进方向的展望突出了预期活动,以进一步支持癌症和非癌症化学品评估方面的研究和风险评估界。