化学品暴露对小鼠和大鼠造成的组织病理学影响与肝脏重量变化之间的关联：毒性参考数据库（ToxRefDB）数据分析

IF 3.4 3区医学 Q2 TOXICOLOGY

Toxicological Sciences Pub Date : 2024-04-23 DOI:10.1093/toxsci/kfae056

R Mezencev, M Feshuk, L Kolaczkowski, G C Peterson, Q J Zhao, S Watford, J A Weaver

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引用次数: 0

摘要

肝脏绝对重量（ALW）和相对重量（RLW）的变化是重复剂量啮齿动物毒性研究中的敏感终点，它们的变化经常被用于采用基准剂量-反应模型（BMD）方法对肝毒性化学品诱发的健康影响进行定量评估。为了找到与化学品暴露相关的肝脏重量生物学变化，我们评估了毒性参考数据库（ToxRefDB）中关于肝脏重量变化和相关肝脏组织病理学结果的所有可用数据。我们对 273 种化学品的 389 项亚慢性小鼠和大鼠研究进行了分析，发现在有肝脏组织病理学变化和无肝脏组织病理学变化的剂量组之间，与处理相关的 ALW 和 RLW 变化存在显著差异。此外，我们还证明了化学品治疗引起的 ALW 和 RLW 变化可以预测组织病理学结果的存在，并为 BMD 建模和毒性值的推导选择生物相关的肝脏重量变化提供信息。

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The association between histopathologic effects and liver weight changes induced in mice and rats by chemical exposures: An analysis of the data from Toxicity Reference Database (ToxRefDB)

Absolute (ALW) and relative (RLW) liver weight changes are sensitive endpoints in repeat-dose rodent toxicity studies, and their changes are often used for quantitative assessment of health effects induced by hepatotoxic chemicals using the benchmark dose-response modeling (BMD) approach. To find biologically relevant liver weight changes to chemical exposures, we evaluated all data available for liver weight changes and associated liver histopathologic findings from the Toxicity Reference Database (ToxRefDB). Our analysis of 389 subchronic mouse and rat studies for 273 chemicals found significant differences in treatment-related ALW and RLW changes between dose groups with and without liver histopathologic changes. In addition, we demonstrate that chemical treatment-induced ALW and RLW changes can predict the presence of histopathologic findings and inform the selection of biologically relevant liver weight changes for BMD modeling and derivation of toxicity values.

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来源期刊

Toxicological Sciences 医学-毒理学

CiteScore

7.70

自引率

7.90%

发文量

118

审稿时长

1.5 months

期刊介绍： The mission of Toxicological Sciences, the official journal of the Society of Toxicology, is to publish a broad spectrum of impactful research in the field of toxicology. The primary focus of Toxicological Sciences is on original research articles. The journal also provides expert insight via contemporary and systematic reviews, as well as forum articles and editorial content that addresses important topics in the field. The scope of Toxicological Sciences is focused on a broad spectrum of impactful toxicological research that will advance the multidisciplinary field of toxicology ranging from basic research to model development and application, and decision making. Submissions will include diverse technologies and approaches including, but not limited to: bioinformatics and computational biology, biochemistry, exposure science, histopathology, mass spectrometry, molecular biology, population-based sciences, tissue and cell-based systems, and whole-animal studies. Integrative approaches that combine realistic exposure scenarios with impactful analyses that move the field forward are encouraged.