Critical Reviews in Toxicology最新文献

{"title":"Inventory of possible endocrine disrupting chemicals used in cosmetic products.","authors":"Manon C Bouwmeester, Gaby A M Eliesen, Jeroen L A Pennings, Susan W P Wijnhoven, Ellen V S Hessel","doi":"10.1080/10408444.2025.2539186","DOIUrl":"10.1080/10408444.2025.2539186","url":null,"abstract":"<p><p>There is a concern on the safety of cosmetic ingredients and their endocrine-disrupting (ED) potential. Frequent use as well as the use of a diverse range of cosmetics pose a concern for a potential health risk via aggregate exposure to endocrine disrupting chemicals (EDCs). In this study, a list of ingredients available in cosmetic products that were recently introduced to the Dutch market was retrieved from the commercially accessible Mintel database and screened for the presence of EDCs. To achieve this, a workflow was developed to crosscheck the list of cosmetic ingredients with information on potential EDCs derived from open-source initiatives (i.e. chemical lists from the European Chemicals Agency, national authorities, and non-governmental organizations). Using this workflow, 27 chemicals were identified that were categorized as \"indications for ED properties\" and one chemical as \"no concern for ED properties\" out of the 890 cosmetic ingredients reviewed. For one of these chemicals, geraniol, a preliminary safety assessment was performed. Aggregated exposure to geraniol via cosmetics was modeled using PACEMweb and compared to the lowest observed adverse effect level on thyroid histopathology derived from an extended-one-generation study. This exercise showed that, based on the current information available, geraniol can be used safely in cosmetics with regard to endocrine-related health risks. Next, the cosmetic ingredients that are currently not identified as an EDC (i.e. not present on one of the crosschecked lists, <i>n</i> = 862), were prioritized based on an aggregate exposure score for further screening of their endocrine disrupting properties (<i>n</i> = 58). For eight out of the 58 prioritized chemicals data retrieved from a literature search indicated an endocrine-mediated relationship, and were categorized as \"limited indications of ED properties\". Overall, the developed workflow is a useful tool to screen cosmetics for the presence of potential EDCs and to prioritize chemicals for further evaluation of their ED properties, as well as assessment of their safe use in cosmetics.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"693-706"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033095","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":"Evaluating health impacts of exposure to PFAS mixtures: a systematic review of epidemiological studies using mixture methods.","authors":"Megan J Kemp, Krishanth Thoppe, Kylie Jones, Meghan Maltby, Kristen Ball, Christy A Barlow","doi":"10.1080/10408444.2025.2546427","DOIUrl":"10.1080/10408444.2025.2546427","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFAS) continue to be an emerging chemical class of concern due to their long half-lives in nature and in the human body. There have been many epidemiology studies published in the scientific literature on PFAS and various health effects. Until recently, these studies have focused on assessing exposure to individual PFAS rather than exposure to mixtures of PFAS. Over the past two decades, mixture methods-statistical methods for investigating the association of mixtures-have been developed, making it possible to more accurately assess the risk of adverse health effects associated with exposure to PFAS. To help provide a resource for the overall evaluation of potential health effects of PFAS mixtures, we applied a consistent set of examination methods and criteria for all epidemiology studies that examined the potential relationship between exposure to PFAS mixtures and various types of health outcomes. We identified 233 cohort studies, 39 case-control studies, and 89 cross-sectional studies that evaluated general background-level exposures, exposure from contaminated sites, and occupational exposure to PFAS mixtures and health outcomes including metabolic, cardiovascular, and immune system effects, fetal development, pregnancy outcomes, reproductive effects, liver function, and respiratory effects. We extracted study characteristics and results in a systematic manner and performed a formal study quality evaluation and classified studies into tiers based on their methodological strengths and weaknesses. We found 42 prospective cohort studies, five nested case-control studies, and one traditional case-control study that qualified for inclusion in the highest tier of quality (Tier I). Overall, the weight of evidence from this systematic review indicates that the available epidemiology studies currently support an association between exposure to PFAS mixtures and adiposity, increased total cholesterol, and hypertension, while the evidence for all other health outcomes is suggestive or limited.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"777-795"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069370","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":"Human biomonitoring and risks of hazardous occupational exposure to polycyclic aromatic hydrocarbons in wildland fires: a critical review.","authors":"Rafael Araújo Silva, Elizeu Chiodi Pereira, Kelly Polido Kaneshiro Olympio, Maria José Nunes de Paiva, Isarita Martins","doi":"10.1080/10408444.2025.2522814","DOIUrl":"10.1080/10408444.2025.2522814","url":null,"abstract":"<p><p>The increase in global temperatures associated with climate change has intensified the frequency, duration, and severity of wildfires, resulting in exposure to a range of hazardous compounds, including polycyclic aromatic hydrocarbons (PAHs). The work of wildland firefighters involves exposure to several physical, chemical, and biological hazards. The present study evaluated the health effects of PAH exposure from wildfires on firefighters. A systematic literature review was conducted using the Web of Science, PubMed, Scopus, CINAHL, and Lilacs databases, covering the period from January 2019 to June 2025, according to PRISMA guidelines. Out of 766 papers retrieved, 16 met the inclusion criteria. Biomonitoring was employed to quantify the levels of biomarkers of exposure, specifically monohydroxylated PAHs (OH-PAHs), in most studies, and biomarkers of effect, such as biochemical or cellular changes, in over half of them. Most studies have indicated significant post-exposure increases (up to 12-fold) in urinary PAH metabolite levels, either during simulated burn training or actual wildfire events. The primary health effects observed were oxidative stress, increased DNA damage, and alterations in inflammatory markers and immunological cells. Both respiratory and dermal exposure routes are significant, with dermal absorption identified as a key pathway even when respiratory protection is used. However, there is no specific certified respiratory personal protective equipment (PPE) for use in wildfires. In consideration of these findings, it is recommended that specialized equipment be developed for forest firefighting to reduce smoke exposure. The review highlights the need to mitigate these risks as the workers presented a high body burden of PAHs, and current exposure limits may be insufficient. Further occupational exposure studies, particularly in under-researched, high-impact geographical regions, are crucial to guide the development of public health policies and enhance risk management strategies for wildland firefighters.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"601-619"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759403","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":"Microbial degradation mechanisms, degradation pathways, and genetic engineering for pyrethroids: current knowledge and future perspectives.","authors":"Jiahui Wu, Hui Peng, Peng Cheng, Hongmei Liu, Ye Zhang, Maoqing Gong","doi":"10.1080/10408444.2024.2433632","DOIUrl":"10.1080/10408444.2024.2433632","url":null,"abstract":"<p><p>Pyrethroids are synthetic products derived from natural pyrethroids present in flowers and are extensively used as pesticides for agriculture, animal husbandry, and household pest control. However, excessive and prolonged usage of pyrethroid insecticides can result in adverse effects on both non-target and target species. Therefore, effective technologies need to be developed to remove pyrethroid contamination and ensure environmental safety. Microbial remediation of various pesticide contaminants is highly practicable, low cost, and eco-friendly compared to physical and chemical methods. Different microbiota are screened to eliminate or degrade the contaminants. Microbial remediation technology utilizes the natural ability of microbiota to treat contaminated areas. Previous studies have mostly focused on the isolation and screening of microorganisms for pyrethroid biodegradation, as well as on the kinetics and pathways of pyrethroid biodegradation. In order to develop effective bioremediation strategies, further research based on molecular biology and bioengineering is required for a comprehensive exploration of pyrethroid-degrading microorganisms. To date, the microbial degradation of pyrethroid pesticides and the underlying mechanisms have been rarely reviewed. Therefore, this critical review encompasses the latest knowledge on synthetic pyrethroids from structural properties, bio-toxicity, and characterization of microbial degradation strains to degradation characteristics, intrinsic mechanisms, and microbial degradation pathways. The future of microbial remediation depends on combining advanced gene technology with traditional bioremediation methods to sustainably degrade pesticide contaminants. It also summarizes the factors affecting degradation efficiency and concludes with prospects, along with current challenges and limitations.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"80-104"},"PeriodicalIF":5.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863479","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":"Use and limitations of clinical data in the identification and classification of low molecular weight chemicals (LMWCs) as respiratory sensitizers: recommendations for improvement.","authors":"Julia Scheel, Nora L Krutz, Ramya Rajagopal, Nikaeta Sadekar, Stuart Hindle, Christina Hickey, Clive Campbell, Phil Botham","doi":"10.1080/10408444.2024.2433222","DOIUrl":"10.1080/10408444.2024.2433222","url":null,"abstract":"<p><p>While progress has been made in recent years, there are still no suitable and accepted <i>in silico</i>, <i>in vitro,</i> or <i>in vivo</i> models that can be used to accurately predict whether a chemical substance has the intrinsic property to cause immune-mediated chemical respiratory allergy, typically manifested as allergic asthma or allergic rhinitis which represents a severe health hazard. Regulatory authorities have relied primarily on clinical evidence (case reports, clinical databases, worker exposure studies) to classify substances as respiratory sensitizers, but this evidence can lack a proven immunological mechanism which is necessary to identify substances which can cause life-long sensitization and clinically relevant allergic symptoms in the respiratory tract in an exposed population (such respiratory allergens may be considered as \"true\" sensitizers, in analogy to the definition of skin sensitization, and in contrast to respiratory irritants). In light of this, the European Center for Ecotoxicology and Toxicology of Chemicals convened a Task Force to evaluate the types of clinical methods and data sources and the implications of relying on such data for regulatory decision making from a scientific perspective. Recognizing that there are benefits and important insights from using such data, significant shortcomings were identified. With clinical work being focused on treatment and diagnosis of individual patients, the approaches and methods used for clinical guidance, diagnostics and reporting have serious limitations in proving the respiratory sensitization potential of a specific chemical, definitely restricting their suitability in deriving legally binding hazard classifications for human health protection. Even within the current broader regulatory definition of respiratory sensitization, a robust assessment and sound evidence of causation by a specific chemical seems mandatory in order to avoid misclassifications. Application of a systematic weight-of-evidence approach is considered suitable to determine the level of confidence, including a thorough assessment of the specificity or non-specificity of observed bronchial hyperreactivity. Recommendations proposed in this publication may not only aid industry and regulators in their decision making but also facilitate a further exchange between stakeholders to improve the data used to (a) more precisely identify true respiratory sensitizers to effectively protect human health, (b) aid evaluation of potential predictive models, and (c) encourage regulators to clarify guidance and to consider a re-evaluation of the current regulatory definition of respiratory sensitizers.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"27-54"},"PeriodicalIF":5.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945992","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":"Per- and polyfluoroalkyl substances (PFAS): immunotoxicity at the primary sites of exposure.","authors":"Emma Arnesdotter, Charlotte B A Stoffels, Wiebke Alker, Arno C Gutleb, Tommaso Serchi","doi":"10.1080/10408444.2025.2501420","DOIUrl":"10.1080/10408444.2025.2501420","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals widely used in industrial and consumer products, leading to environmental contamination and human exposure. This review focuses on perfluoroalkyl acids, a subset of PFAS, which are primarily encountered through diet, including drinking water, and other pathways such as dust ingestion, and dermal contact. Impaired vaccine antibody response has been identified as the most critical effect for risk assessment by the European Food Safety Authority. Furthermore, human epidemiological studies have linked exposure to certain PFAS to various immune-related outcomes, such as asthma, allergies, and inflammatory bowel disease. This review examines potential immunomodulatory effects of perfluoroalkyl acids at the primary sites of exposure: lungs, intestines, and skin, using human epidemiological data as the basis for investigating these impacts. While animal studies are referenced for context, this paper highlights the need for further human-based research to address key questions about PFAS and their immunological impacts. The state of <i>in vitro</i> toxicity testing related to these effects is thoroughly reviewed and critical issues pertaining to this topic are discussed.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"484-504"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119155","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":"Toxicological insights into hydrogen sulfide biology in <i>Caenorhabditis elegans</i>: detection, metabolism, and functional outcomes.","authors":"Bobo Yang, Michael Aschner, Rongzhu Lu","doi":"10.1080/10408444.2025.2543396","DOIUrl":"10.1080/10408444.2025.2543396","url":null,"abstract":"<p><p>Hydrogen sulfide (H₂S), while historically recognized as a poisonous substance, also serves as a gasotransmitter that mediates a wide spectrum of physiological processes across species and is involved in the mechanisms of various exogenous toxicants. The <i>Caenorhabditis elegans (C. elegans)</i> is a valuable tool in toxicology, featuring both a conserved enzymatic H₂S metabolic pathway and a unique dietary bacteria-derived H₂S generation mechanism. Notably, existing data demonstrate that H₂S can extend lifespan, strengthen stress resistance, and preserve mitochondrial function in <i>C. elegans</i>. Its molecular mechanisms may be related to regulating HIF-1 and SKN-1 signaling, enhancing deacetylase SIR-2.1 activity, and exerting epigenetic effects, including methylation of histone H3K4 and protein persulfidation. More recently, H₂S has also been utilized to develop novel multi-target drugs for Alzheimer's disease using the <i>C. elegans</i> model. The present review summarizes recent advances in H₂S-based detection, metabolism and its functional outcomes, as well as molecular underpinnings of H₂S effects in <i>C. elegans</i>, offering valuable insight into the potential of this alternative model system for investigating H₂S-related physiological and toxicological mechanisms.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"735-750"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945910","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":"Female reproductive toxicity after exposure to malathion or diazinon: a systematic review of rodent and human studies.","authors":"Indiamara Guesser Barbosa, Virgínia Meneghini Lazzari, Gabriel Adan Araújo Leite","doi":"10.1080/10408444.2025.2548581","DOIUrl":"10.1080/10408444.2025.2548581","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Malathion and diazinon are pesticides widely used in agriculture as well as for domestic and veterinary purposes to control pests, such as scale insects, aphids, and fleas. However, these compounds may have harmful effects on the female genital system in humans and animals. This study conducted a systematic review of the scientific literature on the female reproductive effects in humans and rodents exposed to malathion or diazinon. The search was conducted from March to September 2024 and was updated in July 2025. It was carried out in the Embase, LILACS, PubMed, SciELO, Scopus, and Web of Science databases by using different combinations of the terms \"diazinon\", \"malathion\", \"ovary\", \"uterus\", \"female reproduction\", \"humans\", \"rats\", and \"mice\" accompanied by the Boolean operators AND or OR. A total of 241 articles were found when the search was conducted using rats or mice as exposed organisms. After removing the duplicates and excluding the articles that showed administration routes not applicable to humans and the studies that were unavailable in full, only seven articles were included in this systematic review. These studies were assessed in relation to the risk of bias as recommended by the SYRCLE's risk of bias tool. For the search involving human studies, 291 articles were found; however, only four articles were deemed relevant for this review after removing the duplicates and the studies that did not meet the eligibility criteria. Then, the included studies were evaluated in relation to the risk of bias as recommended by the Newcastle-Ottawa Scale. Afterwards, the extraction of the results was performed, and the outcomes were organized in tables. When possible, a meta-analysis was carried out with all the studies that assessed the same sexual steroid and gonadotrophic hormones in females. In this review, the results demonstrated that malathion and diazinon impair female reproduction in rodents by reducing ovarian hormone production, increasing oxidative stress, diminishing oocyte quality, and inducing histopathological changes in the reproductive organs. In humans, the included studies demonstrated that exposure to these pesticides is associated with a higher risk for developing endometriosis and an increased risk of ovarian, uterine, and thyroid cancers. After assessing the effects of these organophosphates on hormonal levels by meta-analysis in this review, it was shown a reduction in progesterone concentrations (reduction of 37.43%; overall effect size: &lt;i&gt;Z&lt;/i&gt; = 2.05, &lt;i&gt;p&lt;/i&gt; = 0.04; mean difference and confidence interval: -9.33 [-18.23, -0.43]) but there were no effects in estradiol (overall effect size: &lt;i&gt;Z&lt;/i&gt; = 0.31, &lt;i&gt;p&lt;/i&gt; = 0.76; mean difference and confidence interval: 2.66 [-14.21, -19.54]), testosterone (overall effect size: &lt;i&gt;Z&lt;/i&gt; = 0.91, &lt;i&gt;p&lt;/i&gt; = 0.36; mean difference and confidence interval: 0.08 [-0.09, 0.24]), FSH (overall effect size: &lt;i&gt;Z&lt;/i&gt; = 0.86, &lt;i&gt;p&lt;/i&gt; = 0.39; mean difference and confidence inte","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"796-807"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991733","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":"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}