Environmental Genotoxins and Human Health Risks: Exposure Pathways, Mechanisms, Biomarkers and Challenges for Causal Risk Assessment

Endocrine-Disrupting Pesticides as Drivers of Human Disease: Mechanistic Toxicology and Life-Course Health Effects

Endocrine-disrupting pesticides (EDPs) are environmental toxicants capable of perturbing hormonal homeostasis through multiple molecular and cellular mechanisms. Growing evidence indicates that these compounds contribute to a broad spectrum of adverse health outcomes extending beyond classical endocrine dysfunction. This review critically synthesizes current knowledge on the toxicological mechanisms of EDPs and evaluates epidemiological evidence linking exposure to human disease. Mechanistically, EDPs act through modulation of nuclear hormone receptors, disruption of membrane-associated signaling pathways, interference with hormone synthesis, metabolism, and transport, induction of oxidative stress and mitochondrial dysfunction, and epigenetic reprogramming. These molecular events converge on shared biological pathways that affect multiple organ systems and life stages. Human and experimental evidence associates EDP exposure with reproductive dysfunction, endocrine-related cancers, metabolic disorders, thyroid abnormalities, and neurodevelopmental impairments. Particular concern surrounds exposure during critical windows of susceptibility, especially prenatal development and early childhood, when endocrine systems are highly vulnerable to disruption and developmental programming. Across disease endpoints, recurring mechanisms, including endocrine receptor perturbation, oxidative stress, inflammation, and epigenetic alterations, support a unifying toxicological framework linking diverse adverse outcomes. Despite substantial progress, important uncertainties remain regarding chronic low-dose exposure, non-monotonic dose–response relationships, cumulative effects of pesticide mixtures, and the translation of mechanistic findings into human risk assessment. Future research should integrate repeated biomonitoring, advanced mixture modeling, mechanistic biomarkers, and multi-omics approaches within longitudinal life-course studies. Improved integration of toxicological and epidemiological evidence will strengthen causal inference, refine hazard characterization, and support more protective regulatory strategies for reducing the human health burden associated with endocrine-disrupting pesticides worldwide.

Biomarkers and detection techniques for genotoxic damage in workers exposed to benzene, toluene, and xylene: a narrative review

Metal carcinogens and cancer: integrating genetic and epigenetic perspectives

People around the globe are affected by extensive environmental and occupational exposure to heavy metals, which poses a significant threat to various health hazards, with cancer being a major concern. These toxic metals are ubiquitously found in food, air, water, and industrial, agricultural, or pharmaceutical applications. Being non-biodegradable, they accumulate in the living organism. The prolong exposure to these metals can result into hazardous effects in the many organs including respiratory problems, gastrointestinal disorders, renal issues, and skin lesions etc. Arsenic (As), Cadmium (Cd), Chromium (Cr), Nickel (Ni), Mercury (Hg), and Lead (Pb) are the most common heavy metals causing carcinogenicity through both genetic and epigenetic mechanisms. The literature indicates that DNA damage, deregulation of gene expression, interference with cell signaling, etc., contribute to metal-induced carcinogenesis. Changes in epigenetic processes, such as DNA methylation, histone modification, chromatin remodeling, and non-coding RNAs, can disturb normal cell function and may even lead to cancer. However, the molecular mechanism remains poorly understood. Advancements in the field have underscored the critical roles of genetic mutations and epigenetic modifications in metal-induced tumor formation. This review gives a comprehensive overview of the function of metals in causing cancer, focusing on pathways such as genotoxicity, mutagenesis, epigenetic modification, and cancer-related signaling. Furthermore, with the ultimate goal of reducing the burden of this disease, the targeted preventive strategies, such as reducing the emission of these toxic metals into the environment from mining to industries, or other sources, and the need for social interventions, have been discussed.

Antibiotic-Induced Genotoxicity: Molecular Mechanisms, Cytogenetic Damage, and Implications for Human Health

Global antibiotic consumption continues to rise across pediatric and adult populations, while the genotoxic consequences of host eukaryotic exposure remain less systematically characterized than the parallel problem of antimicrobial resistance. Several lines of evidence, from molecular cytogenetics, redox biology, and systems toxicology, now permit a more mechanistically resolved synthesis of antibiotic-induced genome stress than was previously possible, although a substantial fraction of this evidence is preclinical and warrants cautious clinical extrapolation. This narrative review evaluates the molecular mechanisms, cytogenetic biomarkers, and translational implications of antibiotic-induced genotoxicity, with a primary focus on six clinically prominent classes (fluoroquinolones, nitroimidazoles, aminoglycosides, macrolides, β-lactams, and tetracyclines) and a brief extension to glycopeptides and glycylcyclines. We organize the evidence around three convergent mechanistic axes rather than around individual drugs. Accumulating evidence supports three intersecting off-target axes: (i) eukaryotic topoisomerase II interference, principally documented for fluoroquinolones; (ii) mitochondrial dysfunction, reflecting the evolutionary kinship between the mitoribosome and bacterial ribosomes; and (iii) inflammation-coupled redox stress, often amplified by microbiome perturbation. These pathways converge on a common spectrum of DNA lesions—including double-strand breaks, oxidatively modified bases, replication-fork stalling, and chromosomal mis-segregation) detected by complementary assays (CBMN-Cyt, comet, γH2AX, and oxidative and mitochondrial biomarkers). Pediatric, pregnant, geriatric, and oncology populations may represent biologically distinct susceptibility strata, although direct human evidence for several of these inferences remains limited. Causal inference is constrained by infection as a confounder, frequent use of supratherapeutic in vitro concentrations, reliance on immortalized cell lines that may not recapitulate primary-cell repair capacity, inter-laboratory variability across cytogenetic assays, and a marked scarcity of pediatric and pregnancy biomonitoring data. Most existing positive signals derive from preclinical models; clinically validated long-term outcomes, particularly carcinogenic endpoints, remain inconsistently demonstrated for most antibiotic classes outside metronidazole. Antibiotic-induced genotoxicity appears to be a measurable and mechanistically tractable dimension of drug safety, though its clinical magnitude in real-world exposure scenarios requires further investigation. Integrating multi-omics, microphysiological systems, single-cell genotoxicology, and AI-assisted prediction may improve risk resolution, particularly in vulnerable populations. We argue that antimicrobial stewardship discussions should consider host genome integrity alongside resistance, while remaining mindful that the mechanistic case currently outpaces clinical-endpoint validation.

Exposure–Adaptive Capacity Framework for Environmental Chemical Mixtures and Metabolic Resilience: A Critical Review and Operational Proposal

Environmental chemical exposures are increasingly recognized as contributors to metabolic dysfunction, particularly when they occur as chronic, low-dose mixtures rather than as isolated high-dose toxicants. However, current approaches often focus on exposure intensity, single-compound hazard or isolated biomarker associations, and provide limited explanation for why individuals with comparable exposure profiles may develop markedly different metabolic outcomes. This semi-systematic review proposes an Exposure–Adaptive Capacity (EAC) framework to interpret the metabolic consequences of environmental chemical mixtures through the interaction between exposure burden and host adaptive capacity. A structured literature search covered PubMed/MEDLINE, Scopus and Web of Science records published through 30 June 2026; a reviewer-triggered PubMed/MEDLINE update was executed on 30 July 2026 using harmonized British and American dyslipidaemia/dyslipidemia terms, explicit eligibility domains and evidence-mapping procedures. The review integrates epidemiological, mechanistic, toxicological and translational evidence related to environmental chemicals, metabolic dysfunction, mitochondrial impairment, oxidative stress, inflammation, endocrine disruption, metabolic resilience and biomarkers. The evidence indicates that several chemical classes, including per- and polyfluoroalkyl substances, bisphenols, phthalates, pesticides, persistent organic pollutants and selected metals, converge on mitochondrial bioenergetics, redox regulation, inflammatory signalling, endocrine and nuclear receptor activity, nutrient-sensing networks and adipose tissue function. The EAC framework defines exposure burden as the cumulative biological pressure imposed by chemical mixtures and adaptive capacity as the organism’s functional ability to buffer, compensate for or recover from exposure-induced metabolic stress. To make the framework empirically testable, we specify measurable domains for exposure burden, adaptive capacity and EAC mismatch, and distinguish biomarkers of exposure, early biological effect, adaptive capacity, metabolic dysfunction and vulnerability. A quotient-based expression is retained only as a heuristic representation, while empirical testing is proposed through exposure-by-adaptive-capacity interaction models and complementary multidimensional approaches. The framework provides a structured basis for future exposomic, epidemiological and translational studies by shifting attention from exposure alone to the balance between environmental pressure and biological resilience.

Formaldehyde in pathology services: from molecular toxicity to histopathological change and occupational risk.

BACKGROUND AND OBJECTIVE Formaldehyde (FA), classified as a Group 1 human carcinogen by the International Agency for Research on Cancer (IARC), constitutes a significant occupational hazard within hospital pathology service, where it remains the "gold standard" fixative for tissue preservation. Despite widespread recognition of its toxicological properties, the specific carcinogenic and non-carcinogenic health risks confronting pathology personnel subjected to chronic, low-level, and intermittent exposures remain incompletely characterized. This review synthesizes the current body of evidence regarding the cellular and molecular mechanisms of FA toxicity, histopathological (HP) alterations in target tissues, and associated occupational health risks among pathology staff. Study selection for review: A comprehensive literature search was conducted across PubMed∕MEDLINE, Web of Science, and Scopus databases, encompassing publications through December 2025. Studies were selected based on relevance to FA toxicity mechanisms, HP effects, and occupational exposure in pathology settings. Given the heterogeneity of study designs and outcomes, a narrative synthesis approach was adopted. EVIDENCE SYNTHESIS The synthesized evidence demonstrates that pathology personnel are routinely exposed to FA concentrations exceeding recommended occupational exposure limits (OELs). At the cellular level, FA exerts toxicity through deoxyribonucleic acid (DNA)-protein crosslink formation, oxidative stress induction, and inflammatory pathway activation. HP examination of exposed individuals reveals a characteristic progression from ciliary loss and goblet cell hyperplasia through squamous metaplasia to epithelial dysplasia in the nasal mucosa. Non-carcinogenic health effects, including respiratory symptoms and genotoxicity biomarker elevation, are highly prevalent. However, direct epidemiological evidence substantiating elevated cancer risk within this specific occupational cohort remains limited, mainly due to improper (occupational medicine) reporting. CONCLUSIONS This review confirms substantial non-carcinogenic health effects among pathology personnel, with documented HP alterations representing preneoplastic changes at the portal of entry. The mechanistic evidence supports biological plausibility for carcinogenic risk, though epidemiological confirmation specific to this workforce remains lacking, highlighting a critical research gap.