Critical Reviews in Toxicology最新文献

{"title":"Mechanisms of developmental neurotoxicity mediated by perturbed thyroid hormone homeostasis in the brain: an adverse outcome pathway network.","authors":"Nathalie T O M Dierichs, Aldert H Piersma, Robin P Peeters, W Edward Visser, Marcel E Meima, Ellen V S Hessel","doi":"10.1080/10408444.2025.2461076","DOIUrl":"10.1080/10408444.2025.2461076","url":null,"abstract":"<p><p>Thyroid hormone (TH) is crucial for proper neurodevelopment. Insufficient TH concentrations in early life are associated with lower IQ and delayed motor development in children. Intracellular levels of TH are modulated via the transmembrane transport of TH and intracellular deiodination, and can mediate gene transcription via binding to the nuclear TH receptor. Chemical exposure can disrupt TH homeostasis via modes of action targeting intracellular mechanisms, thereby potentially influencing TH transport, deiodination or signaling. Understanding the cause and effect relationships of chemical hazards interfering with TH homeostasis in the developing brain is necessary to identify how chemicals might disturb brain development and result in neurodevelopmental disorders. Adverse Outcome Pathways (AOPs) can provide a template for mapping these relationships, and so far multiple AOPs have been developed for TH homeostasis and adverse effects on cognition. The present review aims to expand current AOP networks by (1) summarizing the most important factors in the regulation of brain development under influence of TH, (2) integrating human-based mechanistic information of biological pathways which can be disturbed by TH disrupting chemicals, and (3) by incorporating brain-specific TH-mediated physiology, including barriers and cell specificity, as well as clinical knowledge. TH-specific pathways in the fetal brain are highlighted and supported by distinguishing cell type specific Molecular Initiating Events (MIEs) and downstream Key Events (KEs) for astrocytes, neurons and oligodendrocytes. Two main pathways leading to adverse outcomes (AOs) in the areas of 'cognition' and 'motor function' are decreased myelination due to oligodendrocyte dysfunction, and decreased synaptogenesis and network formation via the neurons. The proposed AOP framework can form a basis for selecting developmental neurotoxic <i>in vitro</i> and <i>in silico</i> test systems for an innovative human-focused hazard testing strategy and risk assessment of chemical exposure.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"304-320"},"PeriodicalIF":5.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585003","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":"United States Environmental Protection Agency's Perfluorooctanoic Acid, Perfluorooctane Sulfonic Acid, and Related Per- and Polyfluoroalkyl Substances 2024 Drinking Water Maximum Contaminant Level: Part 1 - Analysis of Public Comments.","authors":"My Hua, Kylie McCauley, David Brew, Jonathan Heywood, Jacob Siracusa, Michael Stevens, Dennis Paustenbach","doi":"10.1080/10408444.2024.2415893","DOIUrl":"10.1080/10408444.2024.2415893","url":null,"abstract":"<p><p>In March 2023, the EPA proposed a 4.0 ppt maximum contaminant level (MCL) for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) (each) and a hazard index approach for four other PFAS. The EPA sought public feedback on the proposed MCL in early 2023 and received 1626 comment submissions <i>via</i> the PFAS docket website (Docket ID: EPA-HQ-OW-2022-0114). Final MCLs were promulgated on April 10, 2024. Our analysis of the PFAS docket identified 128 comments that had a reasonable degree of scientific merit, with 57 comments endorsing the regulations and 71 questioning the MCLs public health utility. Critics noted the lack of evidence for adverse health effects at low PFAS exposures, the rule's significant impact on the economy, and the EPA's selection of published papers which the Agency chose to support their views. Many well-substantiated comments highlighted that few, if any, adverse health effects were reported at doses as much as 100-1000 times above those associated with the proposed drinking water guidelines. We found that the comments which discussed the evidence linking PFAS exposures below 200 ppt in drinking water to adverse health effects were equivocal. Most of the well-documented science based comments indicated that the data did not justify setting a 4.0 ppt MCL. It was noted that the EPA MCL was quite different from drinking water standards in other countries (up to 8-140 fold lower). During the review, it became apparent that a 4.0 ppt MCL may have little effect on PFAS blood concentrations in most Americans since drinking water accounts for less than 20% of their total PFAS intake. Additionally, a significant portion of the American population consumes minimal amounts of tap water. Commenters noted that the financial burden for treatment and cleanup was much higher than what was reported in the justification for the final MCL which was submitted to the Office of Management and Budget (OMB) and eventually promulgated. It is possible that EPA underestimated the financial impact on the nation by up to 100 to 200-fold. Our analysis indicates that many, if not most, of the scientifically rigorous comments on the EPA's proposed MCL were not acknowledged or considered by the Agency. We conclude the article by offering sixteen recommendations for the EPA to consider if Congress or the courts choose to reopen the evaluation of these MCLs. These included convening an international expert panel, reevaluating the appropriateness of the LNT model for PFAS, ensuring adequate time for study quality assessment and cost-benefit analysis, considering an approach to implementing a series of MCLs, critically reevaluating scientific studies, adhering to EPA risk assessment guidelines, addressing SDWA compliance concerns, revisiting the Hazard Index approach, and ensuring thorough and transparent review of public comments.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"321-367"},"PeriodicalIF":5.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109868","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":"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":"&lt;p&gt;&lt;p&gt;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":"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":"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":"Dietary psychoactive xenobiotics: an updated review on food contamination with ergot, tropane and opium alkaloids and their toxicological effects.","authors":"Inês Margarido Martins, Ricardo Jorge Dinis-Oliveira, João G Costa, Félix Carvalho, Nuno G Oliveira","doi":"10.1080/10408444.2025.2508996","DOIUrl":"10.1080/10408444.2025.2508996","url":null,"abstract":"<p><p>Food contamination has been a major health issue since the beginning of human existence. Some food contaminants trigger important psychological manifestations, such as delirium, hallucinations, and psychosis, which may cause distress, aggravate pre-existing conditions, and dangerously interact with certain medications. Exposure to psychoactive food contaminants can ultimately lead to severe health problems or even death. As such, it is important to further study these substances to prevent contamination and identify and treat intoxications. Among these substances, three classes of food contaminants are addressed herein due to their toxicological relevance: (i) ergot alkaloids (ergotamine and ergometrine), (ii) tropane alkaloids (atropine, hyoscyamine, and scopolamine), and (iii) opium alkaloids (codeine and morphine). An historical perspective relative to each contaminant is briefly described in this review, as well as the dietary sources and key chemical properties. Guidance values and analytical methods that allow the detection and quantification of these toxic agents are also provided. In addition, relevant toxicokinetic and toxicodynamic aspects are summarized. Finally, for each xenobiotic, registered intoxication cases, from epidemics and outbreaks to case reports, are described, as well as the detection of contaminants in screening procedures. Overall, this review reinforces that dietary exposure to psychoactive contaminants constitutes a toxicological issue that should be duly considered.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"526-548"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144495065","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":"Necessary conditions for valid causal inference from observational data.","authors":"Louis Anthony Cox","doi":"10.1080/10408444.2025.2611827","DOIUrl":"10.1080/10408444.2025.2611827","url":null,"abstract":"<p><p>Observational studies often guide policy, regulation, litigation, and public health decisions. However, causal claims from such studies can be misleading if key logical and methodological requirements are not met. We synthesized insights from foundational causal theory, contemporary methods, and critiques of common practices to develop a framework of necessary conditions for valid interventional causal inferences predicting the effects of changes in exposure on changes in risk. The framework organizes these conditions into five domains: (A) conceptual and definitional clarity, (B) study design prerequisites, (C) data analysis requirements for valid causal modeling and effect estimation, (D) interpretation and result integrity, and (E) robustness, generalizability, and external validity of results. Each domain includes criteria, rationale, and practical evaluation tools, integrating Potential Outcomes (PO), Structural Causal Models (SCM), Directed Acyclic Graphs (DAG), information-theoretic measures, and machine-learning (ML) approaches for heterogeneity. Summary tables and STROBE-style checklists translate the framework into actionable guidance. Producing trustworthy, decision-relevant causal claims from observational data requires meeting all necessary conditions across the five domains. Modern study designs, methods, and software make it increasingly practical to do so.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"995-1110"},"PeriodicalIF":5.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147527432","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":"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}