Toxicology principles are essential to establishing plausibility of environmental epidemiology studies**

SUMMARY Environmental epidemiology studies that report associations between chemical exposures and adverse health outcomes are increasingly used in hazard identification, risk assessment, regulatory decision-making, litigation, and public communication. Although well-conducted epidemiology studies can provide important evidence of human health hazards, reported associations require interpretation in the context of toxicology, exposure science, and biological plausibility before they are given preferential weight in chemical risk assessment. This manuscript, based on an informational session held at the Society of Toxicology 65 th Annual Meeting (March 2026, San Diego, CA), proposes that toxicologists should formulate explicit plausibility statements for epidemiology findings involving naturally occurring, industrial, and agricultural chemicals. Although epidemiology studies may suggest association, they do not establish causality. Plausibility is a component of causality. Thus, plausibility/implausibility statements by toxicologists address causality. Such statements should consider exposure magnitude, frequency, and timing; the nature and pathophysiology of the reported adverse outcome; chemical structure and reactivity; known toxicity in animals and in vitro systems; pharmacokinetics and pharmacodynamics; mode of action; availability of supporting data; and the adequacy of statistical analysis. The central toxicological principle that “the dose makes the poison” is emphasized as essential to evaluating whether reported adverse outcomes are dosimetrically and biologically plausible. Examples involving chlorpyrifos, glyphosate, 2,4-dichlorophenoxyacetic acid (2,4-D) and n -nitrosodimethylamine illustrate how exposure, mode-of-action, biomonitoring, and mechanistic data can support either implausible, plausible, or conditionally plausible interpretations of epidemiological associations. The manuscript further argues that transparent, science-based plausibility statements would benefit epidemiologists, toxicologists, regulators, funding agencies, industry, courts, journal editors, and the public by clarifying the scientific basis for accepting or challenging reported associations. Future work should focus on developing standardized criteria and independent processes for preparing plausibility statements that integrate science with rigorous epidemiological evaluation, using current promising advances in toxicology and exposure sciences.