The current environmental risk assessment framework for pesticides remains anchored to inadequate metrics and approaches. Although regulatory bodies incorporated chronic toxicity studies and developed advanced guidance, critical gaps in implementation undermine their effectiveness. Among these gaps are 1) continued primacy of the acute median lethal dose as a trigger for higher-tier assessments, 2) lack of standardized sublethal endpoints, 3) inadequate consideration of chemical mixtures, and 4) near-exclusive reliance on Apis mellifera as a surrogate for pollinator communities. Further, interactions between pesticides and other environmental stressors are not systematically assessed. This review critically examines the limitations of the current paradigm and proposes a structured, ecologically integrated framework for modernizing pollinator risk assessment. This review outlines 7 pillars: 1) taxonomic diversification of test species, 2) mandatory inclusion of chronic and sublethal endpoints at Tier 1, 3) standardization of sublethal behavioral assays, 4) tiered assessment of pesticide mixtures incorporating increasingly realistic ecological scenarios, 5) incorporation of landscape-scale exposure modeling, 6) explicit integration of multi-stressor interactions, and 7) in silico models to link individual-level effects to colony and population outcomes. While acknowledging the significant investment required, it is postulated that a phased transition is scientifically necessary and economically prudent, given the indispensable value of pollination services to global agriculture and ecosystem stability.
The replacement of animal testing in cosmetic safety evaluation remains an urgent scientific and regulatory imperative. Next Generation Risk Assessment (NGRA) offers a human-centric, exposure-led, hypothesis-based framework that integrates new approach methodologies (NAMs), including (1) in silico modeling and 2) mechanistically informed in vitro assays, and in chemico methods, to characterize potential human health hazards under realistic exposure conditions. The aim of this review was to critically evaluate current state of NGRA in cosmetic safety by analyzing 9 published case studies with 7 chemicals across various endpoints such as systemic toxicity, skin sensitization, reproductive and developmental toxicity, and organ-specific effects. This analysis encompassed key NGRA components including physiologically based kinetic (PBK) modeling, adverse outcome pathways (AOPs), integrated approaches to testing and assessment (IATA), threshold of toxicological concern (TTC), and defined approaches for skin sensitization. Data demonstrated that NGRA successfully identified safe concentrations for cosmetic ingredients with margins of safety above regulatory thresholds. There are currently no apparent validated NGRA frameworks for systemic toxicity endpoints where significant gaps remain for complex toxicological endpoints, even though defined approaches for skin sensitization and eye irritation have gained regulatory acceptance. Future advancement still requires integration of metabolically competent models, artificial intelligence-driven prediction tools, micro-physiological systems using multi-organs, and standardized frameworks for interpreting NAM-derived points of departure. This review provides by examining successful applications and limitations, a roadmap for strengthening NGRA as a robust, efficient, and ethically grounded approach to human health risk assessment.
Within a One Health framework, pollution is no longer a passive backdrop to host-virus interactions but actively reshapes disease dynamics across humans, animals, and ecosystems. The aim of this review was to synthesize evidence across free-ranging wildlife and wild-derived models to define environmental virotoxicology, which is the study of how environmental contaminants alter susceptibility, replication, shedding, transmission, pathogenesis, persistence, and viral evolution in hosts. A systematic search of PubMed, Scopus, and Web of Science (26 Oct 2025), augmented by citation-chasing, yielded 162 eligible studies spanning more than 100 taxa (marine mammals, birds, amphibians, reptiles, fish, invertebrates) and major DNA/RNA virus families. Across 9 contaminant classes (>180 chemicals), including legacy persistent organic pollutants, petroleum hydrocarbons/polycyclic aromatic hydrocarbons (PAHs), metals, agrochemicals, pharmaceuticals, per- and polyfluoroalkyl substances (PFAS), and micro/nanoplastics, recurrent patterns emerge: (1) suppression or dysregulation of antiviral immunity, (2) reactivation of latent infections, and (3) increases in viral load, severity, and epizootic magnitude. Effects are context-dependent, with documented null or mixed outcomes shaped by dose, timing, life stage, immune compartment, and host ecology. Two broad implications follow: 1) contaminants might amplify wildlife epizootics and reshape reservoir competence, and in at least one well-supported case (2) low, environmentally realistic exposure to antiviral residues in wild waterfowl may impose selective pressure on viral populations and select for antiviral resistance. It is recommended to integrate contaminant surveillance with viral infectious disease monitoring and prioritizing multifactor, mechanistic designs that couple exposure history, immune phenotype, and virological endpoints.
Libby amphibole asbestos (LAA) remains a persistent source of environmental exposure within Operable Unit 3 (OU3) of the Libby Asbestos Superfund Site. This review evaluates ecological evidence relevant to OU3, including the U.S. EPA's Baseline Ecological Risk Assessment (BERA), published toxicology studies, fiber-burden data, and recent federal actions under the Toxic Substances Control Act (TSCA). BERA provided valuable initial information but did not evaluate many endpoints now recognized as sensitive indicators of asbestos-related injury, including immune disruption, early physiological stress, altered behavior, genomic and epigenetic changes, and subclinical effects in longer-lived wildlife. Several exposure pathways, including soil, sediment, vegetation, prey species, and trophic transfer, were incompletely assessed. Fiber-burden analyses in OU3 fish confirm biologically relevant exposure, and findings from amphibole-exposed laboratory animals examining respiratory injury, oxidative stress, growth impairment, and altered immune function, indicate that these injury pathways are plausible in wild species. Recent TSCA risk evaluations remain focused on human health and exposures, with minimal treatment of ecological pathways. This regulatory gap parallels the scientific limitations of the BERA and highlights the need for modernized ecological assessment tools. Evidence from other asbestos-impacted regions underscores that these issues are not unique to Libby; legacy amphibole fiber contamination continues to affect soils, sediments, vegetation, and wildlife elsewhere. The collective evidence indicates a reasonable probability that LAA is affecting natural resources in OU3 through both direct and indirect mechanisms.
The northern fulmar (Fulmarus glacialis) is well suited to contribute to a "One Health" approach for understanding plastic-associated toxicity. Plastics contain additives that act as endocrine-disrupting chemicals (EDCs), which leach into the environment, often disrupting hormonal signaling in wildlife. As an ecotoxicological model, the fulmar, a seabird, provides a unique opportunity to investigate these effects under real-world exposure conditions. Fulmars are currently utilized in The EU's Marine Strategy Framework Directive as passive bioindicators of marine litter in the Northeast Atlantic, based upon the proportion of individuals with significant plastic burdens in their stomachs. The aim of this review is to advocate for elevating the fulmar's role from a passive indicator to active sentinel species to better understand long-term environmental health impacts of chronic plastic exposure. The fulmar's unique ecological niche, high trophic level, and wide-ranging foraging behavior make it particularly vulnerable to plastic ingestion, providing a relevant model for exposure assessment. The role of epigenetic mechanisms was examined in mediating gene-environment interactions, particularly how plastic exposure may influence gene expression and contribute to adverse health outcomes. Further, advances in genome sequencing and annotation enabled identification of molecular pathways affected by plastic-derived EDCs, contributing to the development of complex adverse outcomes that might be characterized through systems biology. Finally, practical benefits and methodological challenges of integrating molecular and genomic analyses into fulmar-based monitoring, focusing upon bycaught individuals and long-term study cohorts, was determined. This framework supports the fulmar's potential as a sentinel species for monitoring plastic-related health risks in marine ecosystems.
Methyl isothiocyanate (MITC), a soil fumigant, induced nasal tumors in Sprague Dawley rats exposed by inhalation to a high concentration (20 ppm), but not at 0.5 or 5 ppm. In an inhalation study (1 day, 5 days, or 4 weeks) with MITC, nasal lesions were observed at the tumorigenic concentration, including acute/subacute inflammation, epithelial cell degeneration/necrosis, epithelial cell proliferation (epithelial hyperplasia, increased DNA synthesis, and regeneration), olfactory sensory neuron apoptosis and loss resulting in atrophy/loss of olfactory epithelium, and/or respiratory cell metaplasia. The available toxicity data were examined using the International Programme on Chemical Safety framework and a mode of action (MOA) was proposed that included key events: 1) direct cytotoxicity in nasal mucosa because of irritation; 2) consequent regenerative cell proliferation; 3) onset and persistence of squamous cell metaplasia as an adaptive response; and 4) development of tumors. Data in support of the key events are discussed, along with possible alternative MOAs as well as human relevance of the proposed MOA. Findings are consistent with the proposed MOA and indicated that tumorigenicity of MITC exhibits exposure thresholds but is not likely to pose a carcinogenic risk to humans under normal use patterns and corresponding exposure levels.
Chronic inhalation exposure of mice to high concentrations of cumene resulted in liver tumors. The aim of this review was to investigate the mode of action (MOA) for these tumors and their relevance to humans. A pilot study demonstrated the activation of constitutive-androstane receptor (CAR) and induction of hepatocyte proliferation following 7-day oral gavage of 1000 mg/kg/day cumene to female C57BL/6 mice. The induction of hepatic enzyme activities in the pilot study was consistent with CAR activation. In a 5-day inhalation study, activation of the CAR nuclear receptor, as indicated by induction of hepatic Cyp2b10 transcripts, was observed in C57BL/6 and B6C3F1, but not in CAR/Pregnane-X-Receptor knock-out (CAR/PXR-KO) female mice. Hepatocyte proliferation was identified only in cumene-exposed wild-type, but not in CAR/PXR-KO, mice. The MOA data were integrated with other existing findings for alignment with CAR-mediated MOA to determine whether alternative mechanisms may be excluded. The weight-of-evidence was evaluated using the evolved Bradford Hill criteria for causality. In addition, a human relevance framework analysis of cumene-induced liver tumors was conducted. This evaluation concluded that the CAR-mediated MOA is responsible for cumene-induced mouse liver tumors, and these tumors are not relevant to humans based upon qualitative and quantitative differences between species.
Mosquito-borne diseases remain a major public health challenge, intensified by growing resistance to conventional insecticides. In this context, the green synthesis of silver nanoparticles (AgNPs), especially using plant extracts from the Annonaceae family, has emerged as an effective and environmentally sustainable alternative. This systematic review aimed to examine the use of aqueous extracts of Annonaceae plants in the synthesis of AgNPs, compiling data on synthesis methods, nanoparticle (NP) characteristics, and biological activity. The review followed PRISMA guidelines and included studies identified in 11 databases and gray literature, selected according to the PEO strategy. Five studies met the inclusion criteria and were independently assessed by three reviewers. Methodological quality, evaluated using ARRIVE 2.0, ranged from 79 to 94%, with limitations mainly related to ethical reporting, blinding, and inclusion/exclusion criteria. AgNPs were synthesized using leaves or seeds of Annona glabra, Annona squamosa, and Annona muricata, with synthesis conditions influencing particle size (14-500 nm), morphology, dispersion, and stability (4-8 weeks). In bioassays, AgNPs demonstrated potent larvicidal activity against Aedes, Anopheles, and Culex species, particularly in early larval stages and with smaller particles, surpassing effectiveness of crude extracts. Observed mechanisms included cuticle penetration, molting interference, enzyme inhibition, and metabolic disruption. Overall, Annona-mediated green synthesis of AgNPs constitutes a promising, low-cost, and sustainable strategy, although further standardization, toxicity assessment, and field studies are needed.
Most ecological and human environmental health researchers are motivated both by curiosity and a desire to do work that will be useful sooner rather than later. However, the academic research process does not always produce and present results that meet the needs of those we imagine using it beyond other researchers. The aim of this review was to discuss needs and opportunities associated with research question development, experimental design, data sharing, science communication, and community engagement, with the goal of supporting regulators, policymakers, environmental nonprofits, and pollution-impacted communities. For example, each regulatory agency has unique policies regarding study characteristics required before the agency includes the study results in its policy-making. To illustrate the extent of this problem: systematic reviews used by policymakers often keep only approximately 5% of papers originally found, because others fail to meet inclusion criteria of which academics are often unaware. The review also details the importance of data sharing via databases and science communication and opportunities for engagement with policy-makers, nonprofits, and communities, and obstacles that researchers face in conducting research that generates data useful to such groups. Our findings demonstrate that while not all academic research can or needs to be designed to be quickly applicable, opportunities exist where this is possible with relatively minor changes to typical academic practices. It is hoped that this review will help identify ways that academic researchers might both address fundamental, basic research knowledge gaps and contribute more directly and rapidly to policy making and community needs.
Environmentally persistent free radicals (EPFRs) are stable free radicals formed on particulate matter (PM) through processes such as combustion and pyrolysis. These free radicals are generated on transition metal oxide surfaces in the presence of aromatic precursors. Exposure to EPFRs occurs primarily via inhalation of PM deriving from combustion, traffic, industrial activities, and both indoor and outdoor burning. Other environmental factors that might generate EPFRs are radon, electronic and tobacco cigarettes. EPFRs exhibit unexpectedly long half-lives, ranging from several weeks to, in some cases, several years. EPFRs may be carbon-centered, oxygen-centered or mixed, identified by g-values exhibited in electron paramagnetic resonance analysis. The radicals undergo redox cycling within aqueous solutions and in biological tissues/fluids triggering production of reactive oxygen species (ROS), comprised primarily of hydroxyl, superoxide, and peroxyl radicals. The stability of EPFRs, their association with PM2.5, and their ability to generate ROS may pose significant concerns for human health. To determine whether there are sufficient data for risk assessment, recent advances were examined in the following important aspects of EPFR research: (1) atmospheric chemistry, (2) human exposures, (3) animal toxicity, and (4) epidemiology. Our review found insufficient epidemiological and exposure studies; however, toxicological data in animals suggested that EPFR inhalation contributes to cardiovascular, respiratory, and metabolic diseases. Although EPFRs are not currently surveyed by a regulatory monitoring system, data indicate their widespread presence in the environment and their potential to initiate/exacerbate diseases.
Methicillin-resistant Staphylococcus aureus (MRSA) is among the most prevalent nosocomial pathogens. However, in recent decades, infections were reported in communities, infecting individuals without previous hospitalization, and in livestock. Given this public health concern, this systematic review aimed to analyze studies that isolated MRSA from environmental and animal matrices, with an emphasis on the implications of this pathogen's presence from a One Health perspective. A total of 183 articles were selected between 2005 and 2025. These investigations were conducted in 43 countries, with 44% in Europe and 5% in North America. In South America, only studies from Brazil were identified, indicating a lack of data from other countries in the region. The animal matrix was the most extensively investigated source of MRSA, comprising 153 studies (85%) across a range of wild, domestic, and farm species. In the environmental context, MRSA was primarily identified in water (65.8%), followed by soil (21%), and air (13.2%). The predominance of MRSA isolation in the aquatic environment indicates that water is a critical reservoir for the spread of antimicrobial resistance (AMR). The MRSA isolates exhibited a multidrug resistance profile. Resistance was most frequent to tetracycline (11.51%) and erythromycin (11.51%), followed by clindamycin (9.04%) and penicillin (7.67%). Further, some studies have identified MRSA in foods of animal origin, representing a potential route of transmission to humans. Finally, this study indicates that the MRSA contamination cycle, which involves hospitals, the community, environment, and animals, is a growing One Health problem that necessitates a global multisectoral approach.
In recent decades, evidence has continuously mounted regarding the myriad adverse health effects that environmental exposures exert on human health, yet little attention has been given to skeletal muscle-related outcomes. With its important metabolic, hormonal, and functional properties, skeletal muscle exerts a critical effect on human health and quality of life. The aim of this review was to survey the literature regarding potential impacts of environmental exposures on skeletal muscle health. The focus was on 10 substances atop the Agency for Toxic Substances and Disease Registry's Substance Priority List including arsenic, lead, mercury, vinyl chloride, polychlorinated biphenyls, benzene, cadmium, benzo(a)pyrene, polycyclic aromatic hydrocarbons, and benzo(b)fluoranthene. In addition, per- and poly-fluoroalkyl compounds were included due to an increasing interest in the field of toxicology. Cell, animal, human, and population studies were all examined to determine toxicant effects on skeletal muscle, though the literature is scarce for many individual agents. Some commonalities, such as effects on mitochondrial function and sexually dimorphic consequences, were observed across compounds. Evidence indicates the need for further investigation of this important topic, with an emphasis on longitudinal large-scale population studies, and investigations which synthesize population and mechanistic research to interrogate causality.
Inorganic nitrate and nitrite are naturally occurring anions that play an essential role in Earth's nitrogen cycle. The general population is exposed to nitrate and nitrite from both food and drinking water sources. However, there is evidence that under certain exposure conditions, nitrate and nitrite may be associated with adverse health effects across multiple organ systems. Therefore, a systematic review was undertaken to identify, evaluate, and synthesize the available human evidence for adverse health effects following oral exposure to inorganic nitrate and nitrite. This review includes a literature search that builds upon health assessments by federal, state, and international health agencies, supplemented by a comprehensive search for recently published literature (January 2016-August 2024). Studies underwent screening in two stages (title and abstract, full-text) using a Populations, Exposures, Comparators, Outcomes (PECO) criteria. PECO-relevant studies were evaluated for risk of bias and sensitivity, then synthesized by health effect type. Overall, 267 PECO-relevant human studies were identified examining cancer and non-cancer health outcomes. Database characteristics varied widely across health effects, as did the characterization of nitrate and nitrite exposure. Overall, there were more consistent patterns of increased risk for certain cancer sites (urinary tract, bladder, and kidney; prostate; thyroid), type 2 diabetes, and birth defects. For other endpoints, there was less consistency across studies, and in some cases, evidence was too sparse to identify patterns of association. This review serves not only to identify potential hazards of nitrate and nitrite exposure but also data gaps that would benefit from further research.
The increasing detection of emerging mycotoxins in food and feed emphasizes the need to assess their potential adverse health risks. Unlike regulated compounds, many mycotoxins lack toxicological data, especially regarding genotoxicity or carcinogenic potential. This systematic review aimed to identify and prioritize emerging mycotoxins for future research and risk assessment. From an initial list of 102 compounds, 32 were excluded for having already been assessed by EFSA, with 15 also regulated in Europe. The remaining 70 were classified as "emerging" and examined through a PubMed and a Web of Science search. A total of 63 articles were included, encompassing in vitro, in vivo, or both types of studies, in conjunction with contextual data from reviews and human studies. Data were extracted from validated or widely used assays and clustered following international genotoxicity testing guidelines (OECD, EFSA, ICH). In the few studies available, genotoxicity was observed for kojic acid, apicidin, tryptophol and, to a lesser extent, with equivocal or conflicting results, for 3-nitropropionic acid, aurofusarin, averufin, fusaric acid, secalonic acids D and F, and mycophenolic acid. Butenolide was also positive but was only tested in one experiment. Bikaverin, culmorin, and skyrin showed no marked genotoxic effects but were only tested once or twice or in protocols not following OECD standards, yielding limited or conflicting results. Overall, the limited number of assays, significant data gaps and methodological limitations hinder conclusive human health risk assessment, emphasizing the need for standardized and comprehensive genotoxicological testing of the emerging mycotoxins.
The global spread of Aedes aegypti poses increasing challenges for vector control programs, especially in the context of insecticide resistance and growing environmental concerns. Innovative control strategies include integrated vector management and use of biopesticides as sustainable alternatives to conventional insecticides. However, despite recent advances, critical knowledge gaps remain regarding the efficacy, safety, and sustainability of integrated biopesticide-based strategies for environmentally friendly Aedes aegypti management. The aim of this review was to critically examine the ecotoxicological risks associated with isolated use of conventional pesticides and highlight the benefits and limitations of integrated vector management approaches. Publications from the last 10 years were searched in PubMed, Scopus, Web of Science, and Google Scholar, with inclusion criteria focusing on studies addressing ecotoxicological effects and sustainability of integrated biopesticide-based strategies. Recent evidence demonstrated that integrated strategies provide enhanced efficacy and reduced environmental impact compared to chemical-only interventions. However, knowledge gaps remain regarding long-term ecological safety, operational feasibility, and resistance development. Comprehensive toxicological assessments and further studies are crucial to ensure the safe, effective, and sustainable use of integrated vector control approaches, with a focus on minimizing adverse environmental impacts and delaying insecticidal resistance development.
The US Environmental Protection Agency (US EPA) and other regulatory agencies routinely assess whether certain chemical exposures might result in harmful health effects. Traditional human health assessments rely upon expert judgment of dose-effect linkages observed in animal toxicology or human studies. Because both collection of toxicology data and synthesis of information might take multiple years to complete, there are relatively few available assessments for decision-making. Identifying methods that yield significant time and resource efficiencies to the process will have scalable public health benefits. To address the need, US EPA developed the database-calibrated assessment process (DCAP) to generate oral, non-cancer human health toxicity values that builds on previously published approaches and guidance. The approach uses the US EPA Toxicity Values Database (ToxValDB) that contains dose-response summary values (DRSVs) from in vivo toxicity studies. The DRSVs are converted to an oral, chronic, human equivalent dose using a series of standard conversion factors. A point-of-departure (POD) is then calculated across a distribution of studies for a given chemical using a calibration percentile that is benchmarked to critical effect PODs from published human health assessments. Traditional and process-specific uncertainties are incorporated to derive a calibrated toxicity value (CTV), defined as an estimate of a daily oral dose to the human population that is likely to be without appreciable risk of adverse non-cancer health effects over a lifetime. This review presents the rationale and methods for the approach, resulting in reporting of 1001 CTVs for chemicals that currently lack a human health assessment.
Per- and polyfluoroalkyl substances (PFAS) comprise a large class of human-made chemicals that are in widespread use and present concerns for persistence, bioaccumulation and toxicity. Whilst a handful of PFAS have been characterized for their hazard profiles, the vast majority of PFAS have not been extensively studied. A comprehensive evaluation to characterize the hazard profiles of the thousands of available PFAS would require extensive resources in terms of cost, number of animals and time. An alternative and more efficient approach is to develop a structural chemical categorization approach to prioritize which PFAS or categories of PFAS should be subject to additional study. To that end, the U.S. Environmental Protection Agency (EPA), in collaboration with the National Institute of Environmental Health Sciences (NIEHS) Division of Translational Toxicology (DTT), initiated a research project in 2018 to screen approximately 150 PFAS through a battery of alternative model organisms, in vitro cell and biochemical assays, and in vitro toxico kinetic (TK) assays in order to inform chemical category and read-across approaches. The aim of this review summarizes the experimental testing undertaken, how data were processed, what insights were derived from a category perspective and how these might potentially inform subsequent tiered testing.
Human biomonitoring (HBM) is an essential approach for assessing exposure to environmental toxicants and for informing risk assessment frameworks. However, the global expansion of HBM has (1) outpaced efforts to harmonize methodologies, (2) addressed contextual inequalities, and (3) translated findings into public health interventions. This review examined literature regarding HBM across different contaminant categories including atmospheric pollutants, heavy metals, mycotoxins, persistent organic pollutants (POPs) and per- and polyfluoroalkyl substances (PFAS). Drawing on recent studies, key trends, methodological inconsistencies, and systemic biases in research design and population coverage were identified. This review noted an overrepresentation of studies in high-income countries, limited data from vulnerable populations, and a persistent reliance on cross-sectional designs. There is significant heterogeneity in biomarker selection, analytical protocols, and interpretation of exposure-health relationships. Further, many investigations failed to control for confounding variables or explore toxicokinetic and toxicodynamic mechanisms, limiting causal inference. Further, exposure to complex chemical mixtures was routinely underexplored, despite evidence of potential interactive effects. The review presents critical gaps in current knowledge, particularly regarding long-term health effects and translation of biomonitoring data into risk management policies. This review emphasizes the need for standardized methodologies, expanded research in low- and middle-income settings, and integration of biomonitoring with community-based surveillance and environmental justice frameworks. Future research needs to prioritize longitudinal designs, interdisciplinary approaches, and greater inclusion of socially and geographically marginalized groups. By reconceptualizing HBM as both a scientific and socio-political endeavor, the field might more effectively contribute to global environmental health protection.
Manganese (Mn) is an essential trace element that, in excess, may initiate adverse health effects. Recent evidence suggested that environmental exposure to Mn may produce thyroid hormone imbalances leading to adverse neurodevelopmental outcomes. The aim of this review was to summarize available evidence regarding Mn exposure and consequent adverse thyroid effects, including potential implications for neurodevelopmental impairment in children. Medline, EMBASE, and Scopus were systematically searched using two concepts: Mn exposure and thyroid function. A total of 31 studies (17 human studies, 14 toxicological studies) fulfilled eligibility criteria. Evidence for effects attributed to Mn on the thyroid from human studies is inconclusive. No apparent studies were identified to directly characterize Mn thyroid-mediated effects on neurodevelopmental outcomes. Although limited evidence from animal studies provides some support for the effects of Mn on thyroid-related hormones, it is unclear whether such hormonal imbalance is a result of a direct or indirect biological mechanism of action. Toxicokinetic data demonstrated that Mn accumulates in thyroid tissue and might interfere with thyroid function. Currently, there are limited data on biological mechanisms of action for the effects of Mn on the thyroid. Although evidence to date is suggestive of Mn thyroid-related activity, the lack of adequate studies precludes a causal interpretation.
Atrazine is a chlorotriazine herbicide that is one of the most widely used herbicides in the USA and the world. For over 60 years atrazine has been used on major crops including corn, sorghum, and sugarcane to control broadleaf and grassy weed emergence and growth. Atrazine has exerted a major economic and environmental impact over that time, resulting in reduced production costs and increased conservation tillage practices. However, widespread use and a long half-life led to a high prevalence of atrazine in the environment. Indeed, atrazine is the most frequent herbicide contaminant detected in water sources in the USA. Due to its almost ubiquitous presence and questions regarding its safety, atrazine has been well-studied. First reported to affect reproduction with potential disruptive effects which were later linked to the immune system, cancer, stress response, neurological disorders, and cardiovascular ailments in experimental models. Atrazine impact on multiple interwoven systems broadens the significance of atrazine exposure. The endeavor to uncover the mechanisms underlying atrazine-induced dysfunction in mammals is ongoing, with new genetic and pharmacological targets being reported. This review aims to summarize the prominent effects of atrazine on mammalian physiology, primarily focusing on empirical studies conducted in lab animal models and establish correlations with epidemiological human studies when relevant. In addition, current common patterns of toxicity and potential underlying mechanisms of atrazine action will be examined.
