Office of Research and Development, Emeritus, U.S. Environmental Protection Agency, 26 W. Martin L. King Drive, Cincinnati, OH, 45268, USA.
Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, 26 W. Martin L. King Drive, Cincinnati, OH, 45268, USA.
Regul Toxicol Pharmacol. 2022 Mar;129:105111. doi: 10.1016/j.yrtph.2021.105111. Epub 2021 Dec 30.
This paper provides a systematic weight-of-evidence method for read-across analyses of data-poor chemicals. The read-across technique extrapolates toxicity from analogous chemicals for which suitable test data are available to a target chemical. To determine that a candidate analogue is the 'best' and is sufficiently similar, the evidence for similarity of each candidate analogue to the target is weighed. We present a systematic weight of evidence method that provides transparency and imposes a consistent and rigorous inferential process. The method assembles relevant information concerning structure, physicochemical attributes, toxicokinetics, and toxicodynamics of the target and analogues. The information is then organized by evidence types and subtypes and weighted in terms of properties: relevance, strength, and reliability into weight levels, expressed as symbols. After evidence types are weighted, the bodies of evidence are weighted for collective properties: number, diversity, and coherence. Finally, the weights for the types and bodies of evidence are weighed for each analogue, and, if the overall weight of evidence is sufficient for one or more analogues, the analogue with the greatest weight is used to estimate the endpoint effect. We illustrate this WoE approach with a read-across analysis for screening the organochlorine contaminant, p,p'-dichlorodiphenyldichloroethane (DDD), for noncancer oral toxicity.
本文提供了一种系统的证据权重方法,用于对数据匮乏的化学品进行同类分析。 同类分析技术将毒性从具有合适测试数据的类似化学物质外推到目标化学物质。 为了确定候选类似物是“最佳”且足够相似,需要权衡每个候选类似物与目标物相似性的证据。 我们提出了一种系统的权重证据方法,该方法提供了透明度,并施加了一致且严格的推断过程。 该方法汇集了有关目标物和类似物的结构、物理化学特性、毒代动力学和毒效动力学的相关信息。 然后,信息按证据类型和亚型进行组织,并根据属性(相关性、强度和可靠性)加权到权重级别,用符号表示。 在对证据类型进行加权后,根据集体属性(数量、多样性和一致性)对证据体进行加权:对每个类似物的类型和证据体进行加权,如果一个或多个类似物的证据总权重足够,则使用权重最大的类似物来估计终点效应。 我们用一种同类分析方法来阐明这种 WoE 方法,该方法用于筛选有机氯污染物 p,p'-二氯二苯二氯乙烷(DDD)的非致癌性口服毒性。