Environmental Genotoxins and Human Health Risks: Exposure Pathways, Mechanisms, Biomarkers and Challenges for Causal Risk Assessment
TL;DR
This critical narrative review integrates evidence on major environmental genotoxin classes, exposure routes, molecular mechanisms, human biomonitoring, disease associations and risk-assessment practice for well-established and less mature evidence domains.
Abstract
Environmental genotoxins are exogenous chemical agents or complex particulate mixtures capable of damaging DNA, chromosomes or genome-maintenance systems. Their public-health importance extends beyond cancer because persistent or poorly repaired lesions may contribute to reproductive impairment, developmental disturbance, haematological toxicity and other chronic disease pathways. This critical narrative review integrates evidence on major environmental genotoxin classes, exposure routes, molecular mechanisms, human biomonitoring, disease associations and risk-assessment practice. Literature published from 1 January 2000 to 31 May 2026 was examined through accessible scholarly indexes and authoritative sources, with earlier foundational studies retained where necessary. The evidence is strongest when exposure characterisation, mechanistic plausibility, internal-dose biomarkers and prospective health outcomes converge. Such convergence is clearest for aflatoxin B1 and hepatocellular carcinoma, benzene and haematological malignancy, inorganic arsenic and several cancers, inhaled hexavalent chromium and respiratory cancer, and ambient particulate pollution and lung cancer. For many pesticides, drinking-water by-products, metals and emerging particulate contaminants, genotoxic signals are credible but heterogeneous because exposure mixtures, assay protocols, tissue choice, confounding and dose relevance differ markedly. Comet, micronucleus, chromosome-aberration and DNA-adduct assays provide complementary information, yet none independently quantifies disease risk. Mutational signatures and adductomics offer stronger source attribution, but translation from experimental systems to population-level causation remains incomplete. Current single-chemical regulation also underrepresents cumulative exposure, susceptibility, co-exposures and environmental inequity. More defensible risk assessment requires harmonised longitudinal biomonitoring, repeated personal exposure measurement, mechanistically anchored dose-response analysis, transparent mixture methods and explicit separation of hazard identification from exposure-specific risk. Prevention should prioritise source control for well-established hazards while uncertainty is reduced for less mature evidence domains.