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The association between histopathologic effects and liver weight changes induced in mice and rats by chemical
Roman Mezencev1, Madison Feshuk2, Lori Kolaczkowski2,3
1Center for Public Health and Environmental Assessment, Office of Research and Development, US EPA, Washington, District of Columbia, USA.
Summary
Liver weight changes in rodents can predict chemical-induced liver damage. Analyzing liver weight changes and histopathology helps identify biologically relevant effects for toxicity assessments.
Area of Science:
- Toxicology
- Pharmacology
- Biostatistics
Background:
- Absolute (ALW) and relative (RLW) liver weight changes are key indicators in rodent toxicity studies.
- These changes are frequently used in benchmark dose-response modeling (BMD) for quantitative health risk assessment of hepatotoxic chemicals.
Purpose of the Study:
- To determine biologically relevant liver weight changes in response to chemical exposures.
- To correlate liver weight alterations with histopathologic findings in rodent toxicity studies.
Main Methods:
- Analysis of 389 subchronic mouse and rat studies from the Toxicity Reference Database (ToxRefDB).
- Evaluation of data linking liver weight changes (ALW and RLW) with liver histopathology for 273 chemicals.
Main Results:
- Significant differences in ALW and RLW were observed between dose groups with and without liver histopathologic changes.
- Chemical-induced ALW and RLW changes effectively predicted the presence of histopathologic findings.
Conclusions:
- Liver weight changes serve as reliable predictors of chemical-induced liver histopathology.
- ALW and RLW data can inform the selection of biologically relevant endpoints for BMD modeling and toxicity value derivation.
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