Journal of Toxicology and Environmental Health-Part B-Critical Reviews最新文献

{"title":"Organ-specific oxidative stress induced by lipopolysaccharide, hydrogen peroxide, or iron: mechanisms and experimental models in brain, liver, kidney, and heart.","authors":"Zakaria Ejjalti, Yassir Laaziouez, Hicham Wahnou, Soufiane Rabbaa, Habiba Bouchab, Youssef El Kharrassi, Boubker Nasser, Pierre Andreoletti, Youness Limami, Mustapha Cherkaoui-Malki, Riad El Kebbaj","doi":"10.1080/10937404.2026.2746003","DOIUrl":"https://doi.org/10.1080/10937404.2026.2746003","url":null,"abstract":"<p><p>Oxidative stress arises when reactive oxygen species (ROS) production exceeds antioxidant and repair capacity, promoting lipid, protein, and DNA damage, mitochondrial dysfunction, inflammation, and regulated cell death. This review critically examined organ-specific oxidative injury induced by lipopolysaccharide (LPS), hydrogen peroxide (H₂O₂), or iron (Fe²⁺) in experimental brain, liver, kidney, and heart models. LPS primarily initiated oxidative damage through Toll-like receptor 4-dependent inflammatory signaling, cytokine release, mitochondrial impairment, and activation of apoptosis or ferroptosis-related pathways. H₂O₂ produced direct oxidant challenge disrupting redox homeostasis, damaging mitochondrial bioenergetics, and promoting oxidative injury in a concentration-, duration-, and cell type-dependent manner. Iron overload enhanced ROS formation through Fenton chemistry, lipid peroxidation, mitochondrial damage, and ferroptotic cell death. This reviewed aimed to demonstrate significant organ- and model-specific heterogeneity. Brain was especially susceptible attributed to high oxygen consumption, lipid-rich composition, and limited antioxidant reserve; the liver integrated xenobiotic metabolism, redox detoxification, and endoplasmic reticulum stress responses; the kidney was susceptible due to high mitochondrial demand and intercellular metabolic dependence within nephron-vascular niche; and heart was markedly sensitive to impaired electron-transport-chain function, calcium dysregulation, and contractile energy failure. Comparisons of <i>in vivo</i> and <i>in vitro</i> models indicated that each model captures complementary aspects of oxidative-induced pathology but may differ in dose, exposure duration, cellular complexity, and translational relevance. Overall, LPS, H₂O₂, or iron are useful but mechanistically distinct oxidative-stress inducers. Future studies need to integrate standardized exposure paradigms with spatial, single-cell, and multi-omics approaches to define intercellular redox regulation and improve translational value of experimental models.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":" ","pages":"1-28"},"PeriodicalIF":11.6,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149240301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicological insights and health risks of Didecyldimethylammonium Chloride (DDAC): an integrative review.","authors":"Eun Ah Lee, Jae Hyeon Park, Seung Jun Kwack, Sang Kyu Lee, Byung Mu Lee, Hyung Sik Kim","doi":"10.1080/10937404.2026.2740461","DOIUrl":"https://doi.org/10.1080/10937404.2026.2740461","url":null,"abstract":"<p><p>Didecyldimethylammonium chloride (DDAC) is a broad-spectrum quaternary ammonium compound (QAC) extensively utilized as a disinfectant and biocide. Widespread use of DDAC, significantly amplified during COVID-19 pandemic, increased human and environmental exposures, indicating need for updated, quantitative risk assessments. To comprehensively evaluate toxicological profile, exposure pathways, and risk characterization of DDAC, this integrative review synthesized regulatory databases (EPA, ECHA), peer-reviewed literature, and large-scale European Food Safety Authority (EFSA) monitoring data (>200,000 samples). Data demonstrated that DDAC exhibited low systemic absorption (<10%) and rapid fecal excretion, with no apparent evidence of carcinogenic, genotoxic or reproductive toxicity. Reported no observed adverse effect level (NOAEL) varied depending upon species, study design, exposure route, and toxicological endpoint, with regulatory studies reporting values ranging from approximately 10 to 93.1 mg/kg/day. Quantitative margin of exposure (MOE) analyses confirm both (1)dietary intake, despite sporadic high residues in specific animal products, and (2) routine occupational dermal exposures maintained large safety margins. Conversely, aerosol-generating applications, such as fogging and humidifier use, present narrower margins, emphasizing critical role of ventilation parameters. Overall, DDAC exhibited low systemic toxicity under typical exposure conditions due to limited absorption and rapid elimination. However, accumulating mechanistic evidence indicates that DDAC might initiate portal-of-entry toxicity, including dermal, ocular, and respiratory irritation related to membrane disruption, mitochondrial dysfunction, oxidative stress, and inflammatory responses. Integrating regulatory evaluations with recent mechanistic findings provides a more comprehensive understanding of DDAC-induced toxicity, identifies important uncertainties regarding chronic aerosol exposure and environmental persistence, supporting continued refinement of human health and environmental risk assessments.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":" ","pages":"1-34"},"PeriodicalIF":11.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factors for frailty in aging: from sex and gender and genetic determinants to the exposome.","authors":"Ali Hemadeh, Carlota Lema-Arranz, Natalia Fernández-Bertólez, Laura Lorenzo-López, Vanessa Valdiglesias, Blanca Laffon","doi":"10.1080/10937404.2026.2727613","DOIUrl":"https://doi.org/10.1080/10937404.2026.2727613","url":null,"abstract":"<p><p>Frailty is a multidimensional geriatric syndrome of loss of physical and cognitive reserves and increased vulnerability that leads to an increased risk of adverse health outcomes. Although age is recognized as the strongest driver of frailty, dynamic nature of this syndrome enables bidirectional changes in the frailty continuum, implying that this syndrome might be prevented and even reverted when detected in early stages. The pathophysiological changes underlying frailty syndrome are initiated by prolonged exposure to a series of risk factors, in a downward spiral of events leading to manifestation of frailty-associated symptomatology. This review is focused on key factors influencing frailty onset. Accumulated evidence demonstrates that the pathway for frailty development starts in early life and might be influenced by (1) sex/gender-related factors, (2) behavioral and social differences, (3) genetic load, and (4) a series of modifiable risk factors including lifestyle and consumption habits, environmental pollution, occupational conditions, as well as other exposures experienced throughout life. In addition, psychosocial and economic factors such as depression, cognitive decline, and limited access to healthcare resources, which influence cognitive reserve, play a critical role in accelerating physiological vulnerability and functional decline, thereby facilitating transition from robustness to frailty. Advancing our knowledge on the risk factors associated with frailty is crucial to implementing effective preventive measures, particularly when the detrimental effects of these factors may be corrected or mitigated through targeted interventions.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":" ","pages":"1-26"},"PeriodicalIF":11.6,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protecting pollinators: moving towards an ecologically integrated risk assessment framework.","authors":"Fabio Castagna, Stefano Ruga, Roberto Bava, Giovanna Liguori, Rosa Maria Bulotta, Domenico Brosio, Luigi Montano, Antonio Giordano, Ernesto Palma, Domenico Britti","doi":"10.1080/10937404.2026.2726750","DOIUrl":"https://doi.org/10.1080/10937404.2026.2726750","url":null,"abstract":"<p><p>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 <i>Apis mellifera</i> 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) <i>in silico</i> 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.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":" ","pages":"1-21"},"PeriodicalIF":11.6,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Telomere stability pathway genes as predictors of susceptibility and prognosis in urothelial bladder cancer: review and bioinformatics analyses.","authors":"Isabely Mayara da Silva, Luiza Magosso Oliveira Rocha, Quezia Geromel de Andrade, Luan Vitor Alves de Lima, Beatriz Geovana Leite Vacario, Tacieli Maria de Almeida, Flora Troina Maraslis, Wilner Martinez-López, Nicole Debia, Athanara Alves de Sousa, João Marcelo de Castro E Sousa, Juliana Mara Serpeloni","doi":"10.1080/10937404.2026.2707570","DOIUrl":"https://doi.org/10.1080/10937404.2026.2707570","url":null,"abstract":"<p><p>Telomeres play a crucial role in carcinogenesis, particularly environmentally related cancers such as urothelial bladder cancer (UBC). Evidence indicates that exposure to environmental pollutants might accelerate telomere erosion and further induce premature senescence, increasing morbidity and mortality rates of cancer. In addition to environmental exposure, variants in telomere-related genes may influence relative telomere length (RTL). This systematic review discusses the pathophysiological aspects of UBC, the mechanisms regulating telomere homeostasis, and factors contributing to telomere dysfunction, with a focus on genetic variations. The available literature on genetic variants and their impact on UBC susceptibility, prognosis, and RTL was summarized and discussed. A total of 17 eligible studies examining 63 polymorphisms across 11 telomere-related genes/loci were included, with telomerase reverse transcriptase (<i>TERT</i>) being the most investigated gene. Most studies focused on disease susceptibility, whereas fewer explored prognostic implications or associations with RTL. Further, bioinformatics analyses were conducted to explore mutation and expression patterns of these genes in UBC. Data from The Cancer Genome Atlas (TCGA) demonstrated that tumors with mutations in genes related to RTL exhibit a higher tumor mutation burden than those without such mutations, and that <i>TEP1</i> and <i>POT1</i> are the most frequently mutated genes in UBC. These findings reinforce the role of telomere instability as a key mechanism in bladder carcinogenesis. This review suggests that variants in genes encoding telomerase and telomere-related proteins play a critical role in UBC susceptibility and prognosis, and that personalized treatment targeting telomere disruption may be expanded to bring clinical benefits for UBC patients.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":" ","pages":"1-26"},"PeriodicalIF":11.6,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148609580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental virotoxicology: how pollutant exposure modulates viral infections - a systematic review of wildlife-associated evidence.","authors":"Younes Aftabi, B Paige Lawrence, Sasan Fereidouni","doi":"10.1080/10937404.2026.2697419","DOIUrl":"https://doi.org/10.1080/10937404.2026.2697419","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":" ","pages":"1-93"},"PeriodicalIF":11.6,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-Generation Risk Assessment for cosmetic ingredients: a critical evaluation of published case studies.","authors":"Rahul Upadhyay Nepal, Seok Kwon, Kyu-Bong Kim","doi":"10.1080/10937404.2026.2702958","DOIUrl":"https://doi.org/10.1080/10937404.2026.2702958","url":null,"abstract":"<p><p>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) <i>in silico</i> modeling and 2) mechanistically informed <i>in vitro</i> assays, and <i>in chemico</i> 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.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":" ","pages":"1-49"},"PeriodicalIF":11.6,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ecotoxicological pathways overlooked: a critical evaluation of the baseline ecological risk assessment and potential natural resource injury from Libby Amphibole Asbestos.","authors":"Jean C Pfau, Deborah E Keil","doi":"10.1080/10937404.2026.2671074","DOIUrl":"https://doi.org/10.1080/10937404.2026.2671074","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":" ","pages":"1-26"},"PeriodicalIF":8.1,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148165240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The northern fulmar as a sentinel species for monitoring the environmental health impacts of plastic exposure.","authors":"Christina Biamis, Susanne Kühn, Ana Payo-Payo, Jaimie Dick, Pierre Bize, Jan van Franeker, Gary Hardiman","doi":"10.1080/10937404.2026.2674012","DOIUrl":"https://doi.org/10.1080/10937404.2026.2674012","url":null,"abstract":"<p><p>The northern fulmar (<i>Fulmarus glacialis</i>) 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.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":" ","pages":"1-27"},"PeriodicalIF":8.1,"publicationDate":"2026-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148018503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic review of adverse human health effects following oral exposure to inorganic nitrate and nitrite.","authors":"Krista Y Christensen, Paige A Bommarito, Rachel M Shaffer, Benjamin Davis, Alexandra L Lee","doi":"10.1080/10937404.2025.2559344","DOIUrl":"10.1080/10937404.2025.2559344","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":" ","pages":"169-235"},"PeriodicalIF":8.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}