Critical Reviews in Toxicology最新文献

{"title":"United States Environmental Protection Agency's Perfluorooctanoic Acid, Perfluorooctane Sulfonic Acid, and Related Per- and Polyfluoroalkyl Substances 2024 Drinking Water Maximum Contaminant Level: Part 2 - Fifteen Misconceptions About the Health Hazards.","authors":"Dennis Paustenbach, Kylie McCauley, Jacob Siracusa, Sarah Smallets, David Brew, Michael Stevens, Blake Deckard, My Hua","doi":"10.1080/10408444.2024.2446453","DOIUrl":"10.1080/10408444.2024.2446453","url":null,"abstract":"<p><p>This paper examines widely held beliefs about the six per- and polyfluoroalkyl substances (PFAS) addressed in the final U.S. Environmental Protection Agency's (EPA) rule on PFAS in drinking water (e.g., the Maximum Contaminant Levels - MCLs). Based on our understanding of the scientific literature and the comments submitted by stakeholders regarding the EPA's regulation that was promulgated in April 2024, we identified 15 misconceptions that had a weak scientific foundation. These are now memoralized in the MCLs for the six PFAS but remain debated due to ongoing ambiguous research findings. Many critics of the MCLs found the EPA's systematic review of the published relevant information, particularly the toxicology of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), to be inadequate. The following seven views are among the most important. First, the EPA asserted that the toxicology of these six chemicals was poorly understood and lacked sufficient data to determine a safe daily intake level for chronic health effects; nonetheless, they promulgated what may be the costliest environmental regulation to date. Notably, adverse effects remain difficult to demonstrate in occupationally exposed individuals even at blood concentrations 50-100 times higher than current background PFAS levels. Second, the Agency indicated that the epidemiology data showed that exposure to PFOA and PFOS caused kidney and potentially other cancers, yet the data were equivocal and do not support that assertion. Third, it was stated that specific non-cancer effects, such as heart disease, would be prevented under the promulgated rule; however, the studies that they relied upon do not show an increased incidence of heart disease even in highly exposed populations. Fourth, the Agency relied on animal data to support its views on the likely toxic effects in humans, despite ample toxicology data that animals, particularly rodents, are poor predictors of the human response to PFAS exposures. Fifth, the EPA predicted a reduction in healthcare expenditures that would offset much of the cost of complying with the MCL, but, they did not have adequate data to support this prediction. Sixth, the EPA suggested that these six PFAS act through a shared mechanism of action (i.e., PPARα pathway induction); however, data indicate that PPARα induction in humans may be 80% less than what is observed in rodents. Also, induction of the PPARα pathway is not a cause of systemic disease. Seventh, the Agency failed to disclose that achieving the new MCL would yield negligible reductions in blood PFAS levels even among highly exposed populations, given drinking water accounts for only 20% or less of total PFAS exposure. The survey that could answer that question, the EPA's fifth Unregulated Contaminant Monitoring Rule, was only 25% complete at the time the MCL was promulgated. Overall, our analysis concluded that while the EPA's intent to regulate these chemicals due to their en","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"368-415"},"PeriodicalIF":5.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109895","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":"Correction.","authors":"","doi":"10.1080/10408444.2025.2461951","DOIUrl":"10.1080/10408444.2025.2461951","url":null,"abstract":"","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"505"},"PeriodicalIF":5.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363856","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":"<i>In vitro</i> human brain barrier models for studying thyroid hormone transport.","authors":"Kim Heikamp, Timo Hamers, Ellen V S Hessel","doi":"10.1080/10408444.2025.2540446","DOIUrl":"10.1080/10408444.2025.2540446","url":null,"abstract":"<p><p>Early brain development is dependent on the supply of thyroid hormone (TH) to the fetal brain. Disruption of TH concentrations in early brain development is associated with lower IQ and delayed motor development in children. How TH system disruption may affect brain development has mainly been studied in animal models that are not always relevant to humans and do not reflect the TH system in the developing brain. Furthermore, using animal models for safety assessments also raises ethical concerns, is still low-throughput and associated with high costs. All these reasons stress the need to develop new approach methodologies (NAMs), including <i>in vitro</i> methods that help to improve human relevant risk assessment. Initiatives are taken to develop <i>in vitro</i> assays for important key events in the fetal brain, but before TH can enter the fetal brain, it has to pass the developing blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). During brain development, the composition of the barriers change over time, as well as the interplay between the two different barriers. Therefore, barrier models need to be included in testing strategies for TH system disruption in the developing brain and these models should take the timepoint of development into account. Barriers are crucial for the supply of TH in the brain. TH is actively transported through these barriers via TH transmembrane transporters (THTMTs) such as MCT8 and OATP1C1, but alternatively, other THTMTs may be involved too. Furthermore, transport of TH across the brain barriers can be disrupted by chemicals. Currently, the extent of THTMT inhibition and its subsequent adverse effects on brain development is largely undiscovered. To further investigate TH transport across the BBB and BCSFB, human cell-based NAMs are being developed that more closely resemble the human brain barriers. These models take the complex cellular composition of the brain barriers into account and in case of organ-on-chip models, the blood/cerebrospinal fluid flow as well. In this review, aspects of accurate <i>in vitro</i> models ranging from simple mono-cultures to extended 3D cultures of the brain barriers are discussed as well as how (a combination of) these <i>in vitro</i> models can be utilized to study TH transport and its disruption in the brain.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"645-661"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854835","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":"European Food Safety Authority database for <i>in vivo</i> developmental neurotoxicity studies of pesticides.","authors":"Iris Mangas, Eliana Spilioti, Andrea Terron, Martina Panzarea, Monica Nepal, Barbara Viviani, Marco Binaglia, Kevin M Crofton","doi":"10.1080/10408444.2025.2521280","DOIUrl":"10.1080/10408444.2025.2521280","url":null,"abstract":"<p><p>Current evidence on the prevalence of neurodevelopmental disorders has raised concerns over the environmental etiology for developmental neurotoxicity. As the use of standardized <i>in vivo</i> developmental neurotoxicity methods has been restricted due to high costs, limited testing capacity and extrapolation uncertainties, a shift to implementation of higher throughput technologies is urgently needed. A fit-for-purpose Developmental Neurotoxicity <i>In Vitro</i> Battery based on New Approach Methodologies has been recently developed to support the regulatory decision-making process. To increase confidence in its predictive performance and readiness, the authors, under the auspices of European Food Safety Authority, have created a curated database of <i>in vivo</i> study results from developmental neurotoxicity guideline or guideline-like <i>in vivo</i> studies. Methods, data and results from publicly available US Environmental Protection Agency Data Evaluation Records have been entered into a standardized data extraction model, developed to facilitate quantitative data collection and harmonization. The goal of the present work was to build a transparent and publicly available database of developmental neurotoxicity data from guideline studies, suitable for comparison with outputs from NAM assays such as the Developmental Neurotoxicity <i>In Vitro</i> battery. This effort represents a significant advancement for future analyses and will serve as a key stone for the development of transparent and publicly accessible databases of developmental neurotoxicity data.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"587-598"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741533","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":"In search of certainty beyond the cholinergic system: a systematic review of developmental chlorpyrifos exposure and neurotransmitter systems disruption in preclinical models.","authors":"Cristian Perez-Fernandez, Diego Ruiz-Sobremazas, Mario Ruiz-Coca, Fernando Sánchez-Santed, Miguel Morales-Navas","doi":"10.1080/10408444.2025.2543405","DOIUrl":"10.1080/10408444.2025.2543405","url":null,"abstract":"<p><p>Chlorpyrifos (CPF) is one of the most widely used pesticides globally, despite being strictly regulated and banned in several developed countries. It remains in use across many developing and underdeveloped nations. While its primary mechanism of action is acetylcholinesterase inhibition, multiple preclinical and clinical studies have reported developmental and cognitive alterations at lower doses that do not trigger this mechanism. These effects are particularly concerning during early development, when the central nervous system is immature and more vulnerable. Although various alternative molecular targets have been proposed, growing attention has been given to neurotransmitter systems beyond the cholinergic pathway. However, empirical data is inconsistent, and no qualitative or quantitative reviews have provided a clear understanding of these mechanisms. This systematic review aims to address this gap, focusing on preclinical rodent studies. Using a rigorous methodology, 41 studies were included in the qualitative analysis, covering 126 outcomes related to the dopaminergic, serotonergic, GABAergic, glutamatergic, and endocannabinoid systems. Overall, the included studies showed a low level of methodological quality and a high risk of bias. Only a few molecular targets were systematically investigated. We introduce two new evaluative metrics-Weight of Evidence and Percentage of Convergence-to highlight five key findings. Notably, preweaning CPF exposure consistently reduced the activity of endocannabinoid-degrading enzymes (FAAH and MAGL), resulting in elevated endocannabinoid tone, particularly increased levels of AEA. Additionally, there is consistent support for CPF-induced serotonergic alterations, particularly upregulation of 5HT2 and 5HT1A receptors following neonatal exposure. Due to insufficient data convergence across laboratories, a meta-analysis was deemed inappropriate. In conclusion, while numerous molecules have been linked to low-dose developmental CPF exposure, only a limited number show consistent empirical support, and only under postnatal exposure conditions. Future research should investigate prenatal exposure effects more systematically and replicate postnatal findings across independent laboratories to strengthen the reliability of these promising results through robust, quantitative analyses.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"751-776"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945897","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":"Comprehensive review of ensulizole toxicology data and human exposure assessment for personal care products.","authors":"Kimberly G Norman, Lewis E Kaufman, Peter Griem, Linda Loretz, Alexandra Kowcz, Samuel M Cohen, Anthony R Scialli, Alan R Boobis, David Jacobson-Kram, Rita Schoeny, Thomas J Rosol, Gary M Williams, Norbert E Kaminski, F Peter Guengerich, J F Nash","doi":"10.1080/10408444.2025.2541392","DOIUrl":"10.1080/10408444.2025.2541392","url":null,"abstract":"<p><p>A comprehensive review of existing toxicity and human exposure data for the ultraviolet filter ensulizole (2-phenylbenzimidazole-5-sulfonic acid) as currently used in over-the-counter sunscreen formulations was conducted. Authorized maximum ensulizole usage levels in consumer end-use products worldwide range from 3% to 8%, with the maximum usage level limited to 4% in the United States, Canada, and Australia. Postmarketing clinical safety studies of ensulizole have reported only occasional local skin effects, none of which were associated with systemic toxicity. Ensulizole has been investigated <i>in vitro</i>, in animal toxicity studies, and in human studies for its pharmacokinetics, pharmacodynamics, and potential toxicological properties. Experimentally determined values of 4% for oral absorption in rats and of 0.26% for dermal absorption in humans were used for risk calculation purposes. There was no evidence of ensulizole bioaccumulation from rat <i>in vivo</i> studies, consistent with its high water solubility and low octanol/water partition coefficient. Ensulizole is not classifiable as an irritant, although local skin irritation with no systemic effects was noted in a 3-month repeated-dose dermal toxicity study in rabbits. Ensulizole is non-(photo)sensitizing, non-phototoxic, and has demonstrated low toxicity in acute (oral, dermal, and intraperitoneal) and subchronic repeated-dose studies in mammalian species. Subchronic 3-month no-observed-adverse-effect levels (NOAELs) were identified at 100 mg/kg/day (dermal rabbit) and 1000 mg/kg/day (oral rat OECD 408 study), the highest doses tested, respectively. Ensulizole is considered non-genotoxic, based on negative <i>in vitro</i> studies. No <i>in vivo</i> genotoxicity or long-term carcinogenicity studies were identified. Carcinogenicity risk is not expected based on the negative genotoxicity data, empirical evidence from repeated-dose toxicity and developmental toxicity studies, and the absence of effects on the androgen, estrogen, thyroid, immune, developmental, or reproductive systems. Based on the selected rat subchronic NOAEL of 1000 mg/kg/day and conservative assumptions for estimating the systemic exposure dose (SED) from the application of sunscreen products, margins of safety (defined as NOAEL/SED) >100 were obtained for ensulizole. Therefore, the available data show that ensulizole does not pose risks to human health when used in sunscreen products at concentrations up to 4%, the permitted maximum usage level in the United States, Canada, and Australia.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"716-734"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063411","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":"A critical review to identify data gaps and improve risk assessment of bisphenol A alternatives for human health.","authors":"Sakina Mhaouty-Kodja, Daniel Zalko, Sabrina Tait, Emanuela Testai, Catherine Viguié, Emanuela Corsini, Nathalie Grova, Franca Maria Buratti, Nicolas J Cabaton, Lucia Coppola, Antonio De la Vieja, Maria Dusinska, Naouale El Yamani, Valentina Galbiati, Patricia Iglesias-Hernández, Yvonne Kohl, Ambra Maddalon, Francesca Marcon, Lydie Naulé, Elise Rundén-Pran, Francesca Salani, Nicoletta Santori, Mónica Torres-Ruiz, Jonathan D Turner, Ondrej Adamovsky, Kiara Aiello-Holden, Hubert Dirven, Henriqueta Louro, Maria João Silva","doi":"10.1080/10408444.2024.2388712","DOIUrl":"10.1080/10408444.2024.2388712","url":null,"abstract":"<p><p>Bisphenol A (BPA), a synthetic chemical widely used in the production of polycarbonate plastic and epoxy resins, has been associated with a variety of adverse effects in humans including metabolic, immunological, reproductive, and neurodevelopmental effects, raising concern about its health impact. In the EU, it has been classified as toxic to reproduction and as an endocrine disruptor and was thus included in the candidate list of substances of very high concern (SVHC). On this basis, its use has been banned or restricted in some products. As a consequence, industries turned to bisphenol alternatives, such as bisphenol S (BPS) and bisphenol F (BPF), which are now found in various consumer products, as well as in human matrices at a global scale. However, due to their toxicity, these two bisphenols are in the process of being regulated. Other BPA alternatives, whose potential toxicity remains largely unknown due to a knowledge gap, have also started to be used in manufacturing processes. The gradual restriction of the use of BPA underscores the importance of understanding the potential risks associated with its alternatives to avoid regrettable substitutions. This review aims to summarize the current knowledge on the potential hazards related to BPA alternatives prioritized by European Regulatory Agencies based on their regulatory relevance and selected to be studied under the European Partnership for the Assessment of Risks from Chemicals (PARC): BPE, BPAP, BPP, BPZ, BPS-MAE, and TCBPA. The focus is on data related to toxicokinetic, endocrine disruption, immunotoxicity, developmental neurotoxicity, and genotoxicity/carcinogenicity, which were considered the most relevant endpoints to assess the hazard related to those substances. The goal here is to identify the data gaps in BPA alternatives toxicology and hence formulate the future directions that will be taken in the frame of the PARC project, which seeks also to enhance chemical risk assessment methodologies using new approach methodologies (NAMs).</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"696-753"},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460007","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":"Examining the relationship between per-and polyfluoroalkyl substances and breast, colorectal, prostate, and ovarian cancers: a meta-analysis.","authors":"Ahmad Habibian Sezavar, Nima Rastegar-Pouyani, Nader Rahimi Kakavandi, Fatemeh Fakhari, Emad Jafarzadeh, Shima Aliebrahimi, Seyed Nasser Ostad","doi":"10.1080/10408444.2024.2425669","DOIUrl":"10.1080/10408444.2024.2425669","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used widely in industrial and commercial applications. Concerns exist about their potential link to cancer risk as possible endocrine-disrupting chemicals. We conducted a meta-analysis to evaluate the dose-response relationship between PFAS, perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorohexanesulfonic acid (PFHxS) exposure and risk of breast, prostate, colorectal, and ovarian cancers. We systematically searched major databases through May 2022 and identified 13 observational studies for inclusion. Using random-effects models, we calculated summary odds ratios (ORs) and 95% confidence intervals (CIs) comparing the highest versus lowest PFAS exposure categories. Additionally, we analyzed the dose-response correlation between PFAS and cancer risk in a subset of studies. The study revealed no substantial correlation between exposure to PFASs and the incidence of breast cancer (BC) (OR_PFOS = 1.15, 95% CI = 0.91-1.46, OR_PFOA = 1.01, 95% CI = 0.68-1.50, OR_PFNA = 0.88, 95% CI = 0.64-1.21, OR_PFHxS = 1.22, 95% CI = 0.40-3.77, and OR_PFDA = 1.29, 95% CI = 0.41-4.10), ovarian cancer (OR_PFOA = 1.43, 95% CI = 0.84-2.42), prostate cancer (OR_PFOA = 1.05, 95% CI = 0.88-1.26), and colorectal cancer (OR_PFOA = 0.77, 95% CI = 0.53-1.12) in the highest versus lowest exposure analysis. However, dose-response analysis showed that for every 1 ng/ml increase in PFNA and 2 ng/ml increase in PFOA, the relative risk for BC decreased significantly (RR 0.67, 95% CI 0.45-0.99 and RR 0.94, 95% CI 0.89-0.98, respectively). Non-linear dose-response analysis found no significant changes in BC risk with increasing PFAS levels. In conclusion, while the highest versus lowest analysis does not support associations between PFAS exposure and the risk of these cancers, linear dose-response analysis suggests potential inverse relationships between PFNA/PFOA levels and BC risk. Further research is warranted on these potential protective effects.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"981-995"},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784392","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":"Mechanistic insights regarding neuropsychiatric and neuropathologic impacts of air pollution.","authors":"Katherine M Rentschler, Urmila P Kodavanti","doi":"10.1080/10408444.2024.2420972","DOIUrl":"10.1080/10408444.2024.2420972","url":null,"abstract":"<p><p>Air pollution is a significant environmental health risk for urban areas and developing countries. Air pollution may contribute to the incidence of cardiopulmonary and metabolic diseases. Evidence also points to the role of air pollution in worsening or developing neurological and neuropsychiatric conditions. Inhaled pollutants include compositionally differing mixtures of respirable gaseous and particulate components of varied sizes, solubilities, and chemistry. Inhalation of combustibles and volatile organic compounds (VOCs) or other irritant particulate matter (PM) may trigger lung sensory afferents which initiate a sympathetic stress response <i>via</i> activation of the hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes. Activation of SAM and HPA axes are associated with selective inhibition of hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-thyroid (HPT) axes following exposure. Regarding chronic exposure in susceptible hosts, these changes may become pathological by causing neuroinflammation, neurotransmitter, and neuroendocrine imbalances. Soluble PM, such as metals and nano-size particles may translocate across the olfactory, trigeminal, or vagal nerves through retrograde axonal transport, or through systemic circulation which may disrupt the blood-brain barrier (BBB) and deposit in neural tissue. Neuronal deposition of metallic components can have a negative impact through multiple molecular mechanisms. In addition to systemic translocation, the release of pituitary and stress hormones, altered metabolic hormonal status and resultant circulating metabolic milieu, and sympathetically and HPA-mediated changes in immune markers, may secondarily impact the brain through a variety of regulatory adrenal hormone-dependent mechanisms. Several reviews covering air pollution as a risk factor for neuropsychiatric disorders have been published, but no reviews discuss the in-depth intersection between molecular and stress-related neuroendocrine mechanisms, thereby addressing adaptation and susceptibility variations and link to peripheral tissue effects. The purpose of this review is to discuss evidence regarding neurochemical, neuroendocrine, and molecular mechanisms which may contribute to neuropathology from air pollution exposure. This review also covers bi-directional neural and systemic interactions which may raise the risk for air pollution-related systemic illness.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"953-980"},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review of epidemiological and toxicological studies on health effects from ingestion of asbestos in drinking water.","authors":"Jennifer Go, Nawal Farhat, Karen Leingartner, Elvin Iscan Insel, Franco Momoli, Richard Carrier, Daniel Krewski","doi":"10.1080/10408444.2024.2399840","DOIUrl":"10.1080/10408444.2024.2399840","url":null,"abstract":"<p><p>Asbestos is a group of naturally occurring fibrous minerals that were commonly used in the construction of cement pipes for drinking water distribution systems. These pipes deteriorate and can release asbestos fibers into drinking water, raising concerns about potential risk to human health. The objective of this work was to synthesize human, animal, and <i>in vitro</i> evidence on potential health risks due to ingested asbestos in drinking water and evaluate the weight of evidence (WoE) of human health risk. A systematic review of epidemiological evidence was conducted, along with critical review of animal and <i>in vitro</i> evidence, followed by WoE evaluation that integrated human, animal, and <i>in vitro</i> evidence. The systematic review included 17 human studies with health outcomes mostly related to various cancer sites, with the majority focusing on the gastrointestinal system. The WoE evaluation resulted in very low levels of confidence or insufficient evidence of a health effect for cancers in 15 organ systems and for three non-cancer endpoints. While eight studies reported possible associations with stomach cancer in males, few high-quality studies were available to verify a causal relationship. Based on high-quality animal studies, an increased risk for cancer or non-cancer endpoints was not supported, aligning with findings from human studies. Overall, the currently available body of evidence is insufficient to establish a clear link between asbestos contamination in drinking water and adverse health effects. Due to the lack of both high-quality epidemiological studies and a validated kinetic model for ingested asbestos, additional research on this association is warranted.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"856-894"},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460009","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}