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)-Reference-Cited by-同舟云学术

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)

Published:2024-04-24 Issue:2 Volume:200 Page:404-413
ISSN:1096-6080
Container-title:Toxicological Sciences
language:en
Short-container-title:

Author:

Mezencev Roman¹^ORCID,Feshuk Madison²^ORCID,Kolaczkowski Lori²³,Peterson Geoffrey Colin¹,Zhao Q Jay⁴,Watford Sean¹^ORCID,Weaver J Andre⁵

Affiliation:

1. Center for Public Health and Environmental Assessment, Office of Research and Development, US EPA , Washington, District of Columbia, USA

2. Center for Computational Toxicology and Exposure, Office of Research and Development, US EPA, Research Triangle Park , North Carolina, USA

3. Oak Ridge Associated Universities, National Student Services Contract , Oak Ridge, Tennessee, USA

4. Center for Public Health and Environmental Assessment, Office of Research and Development, US EPA , Cincinnati, Ohio, USA

5. Center for Public Health and Environmental Assessment, Office of Research and Development, US EPA, Research Triangle Park , North Carolina, USA

Abstract

Abstract 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.

Publisher

Oxford University Press (OUP)

Link

https://academic.oup.com/toxsci/advance-article-pdf/doi/10.1093/toxsci/kfae056/58213151/kfae056.pdf

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