Perspectives on variability of in vivo toxicology studies: considerations for next-generation toxicology

作者：Agnes L. Karmaus, Anna Kreutz, Oluwakemi Oyetade, Katie Paul Friedman, Martin Paparella, Emily N. Reinke, David Allen, Helena T. Högberg, Nicole Kleinstreuer · 发表于：Frontiers in Toxicology · 年份：2026 · DOI：10.3389/ftox.2026.1778353 · 被引用次数：3 · 研究领域：Animal testing and alternatives、Immunotoxicology and immune responses、Effects and risks of endocrine disrupting chemicals

Introduction: Animal studies have historically informed toxicological testing and safety assessments. However, assessment of the variability in both quantitative and qualitative results has been limited. Biological variability, experimental differences, interpretation of categorical endpoints, and data availability and curation approaches all contribute to the quantified variability. Methods: toxicology studies. Variability analyses were evaluated and summarized for a variety of toxicological endpoints: ocular irritation, dermal sensitization and irritation, acute oral and inhalation lethality, subchronic and chronic toxicity, carcinogenicity, neurotoxicity including DNT, endocrine, and genotoxicity. Results: This review summarizes published investigations of variability within mammalian toxicological studies that have been largely conducted in accordance with health effects test guidelines. The results of this review suggest that replicability of in vivo toxicological guideline studies varies widely by study type, endpoint complexity, and classification approach. Discussion: While any test system will have inherent variability, understanding its sources and impact on study interpretation will help ensure that appropriate confidence is applied when using the test method. Furthermore, such information aids in establishing relevant metrics to serve as baselines for informing performance characterization of new approach methodologies (NAMs). Future evaluation of NAMs should be c...