Authors
Charvi Vijayvargiya, John K Colbourne
Published in
Annual review of animal biosciences. Nov 12, 2026. Epub Nov 12, 2026.
Abstract
Safety limits on exposure to hazardous chemicals are typically treated as uniform across populations, but substantial variability exists between individuals. This review argues that susceptibility to chemical exposure should be understood as a complex genetic trait shaped by polygenic architecture, environmental context, and biological modifiers such as sex. Drawing on evidence from animal models, human-relevant test systems, and comparative genomics, we show that variation in toxic response is structured, heritable, and frequently predictable. We critically evaluate the limitations of traditional toxicology, which relies on simplified models and average responses, and highlight how this deterministic approach fails to capture population-level risk. We further examine genotype × sex interactions and the contribution of rare variants to extreme sensitivity. Finally, we discuss emerging risk assessment frameworks, including population-based and probabilistic approaches, and consider their implications for regulatory decision-making. Recognizing toxicological susceptibility as a complex trait provides a more realistic and protective basis for chemical risk assessment.
PMID:
43019457
Bibliographic data and abstract were imported from PubMed on 13 Nov 2026.
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