Critical Reviews in Toxicology最新文献

{"title":"Microplastics-PFAS interactions in environmental matrices: quantitative evidence for antagonistic and synergistic toxicity.","authors":"Niyati Kuriyal, Abhishek Nandan","doi":"10.1080/10408444.2026.2686292","DOIUrl":"10.1080/10408444.2026.2686292","url":null,"abstract":"<p><p>Microplastics (MPs) and per- and polyfluoroalkyl substances (PFAS) increasingly co-occur across aquatic, terrestrial, and biological systems, yet their combined toxicological behavior remains poorly resolved. To address this gap, we conducted a systematic review and meta-analysis of 47 controlled experimental studies encompassing aquatic organisms, soil invertebrates, and mammalian models. Using standardized mean differences (Hedges' <i>g</i>) under a random-effects REML framework, supported by subgroup analysis, meta-regression, and bias diagnostics, we quantitatively compared biological responses induced by MPs, PFAS, and their co-exposure. PFAS produced the strongest and most consistent toxic effects across systems (<i>g</i> = 4.71; 95% CI: 2.32-7.09), with pronounced impacts on oxidative balance, hepatic function, immune regulation, and reproductive performance. MPs also induced widespread biological stress, though with lower and more variable intensity (<i>g</i> = 2.19; 95% CI: -0.29-4.66), affecting oxidative, reproductive, and inflammatory pathways. Notably, co-exposure to MPs and PFAS frequently resulted in attenuated or antagonistic responses rather than additive toxicity (g = -2.98; 95% CI: -8.89-2.93), suggesting that PFAS adsorption onto MP surfaces can reduce bioavailability and tissue uptake. However, synergistic effects emerged under specific conditions, particularly at high PFAS concentrations, with small or weathered particles and prolonged exposure durations. Dose response relationships were evident across exposure categories, with aquatic species displaying the greatest sensitivity. Overall, these findings demonstrate that mixture toxicity is context-dependent and cannot be inferred from single-compound data alone. This study provides a quantitative foundation for advancing mixture-aware environmental risk assessment and regulatory frameworks.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"364-388"},"PeriodicalIF":5.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419450","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":"Letter to the Editor: Comprehensive review of octocrylene toxicology data and human exposure assessment for personal care products.","authors":"Joseph C DiNardo","doi":"10.1080/10408444.2026.2640891","DOIUrl":"10.1080/10408444.2026.2640891","url":null,"abstract":"","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"229-230"},"PeriodicalIF":5.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670960","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":"Comments on the article \"The IARC re-classification of talc carcinogenicity: a move in the wrong direction?\" by A.A. Korchevskiy and A.G. Wylie (2025).","authors":"Alessandro Francesco Gualtieri","doi":"10.1080/10408444.2026.2641755","DOIUrl":"10.1080/10408444.2026.2641755","url":null,"abstract":"","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"38-47"},"PeriodicalIF":4.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590745","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":"Setting occupational exposure limits (OELs) for carcinogens: a focus on benzene.","authors":"Maria de Fatima M Pedrozo, Monica M B Paoliello","doi":"10.1080/10408444.2026.2669526","DOIUrl":"10.1080/10408444.2026.2669526","url":null,"abstract":"<p><p>Since the 1950s, regulation of occupational carcinogen exposure has progressed from hazard identification to quantitative evaluation, driven by advances in cancer biology. This narrative review compares two approaches for setting Occupational Exposure Limits (OELs) for carcinogens, focusing on benzene. The first one applies a mode of action (MOA)-based approach to genotoxicity stratification, using linear extrapolation for direct genotoxicants and non-linear extrapolation for indirect genotoxicants. The second approach quantifies <i>in vivo</i> genotoxicity data, employing mathematical modeling to define the point of departure (POD) for non-linear extrapolation, regardless of the MOA. As benzene is an indirect genotoxicant, it is considered to have a threshold value. Applying the MOA-based approach to genotoxicity stratification, different European institutions and commissions have proposed OELs ranging from 0.05 to 0.25 ppm. The ACGIH has recommended a TLV-TWA of 0.02 ppm (skin notation). Based on a quantitative genotoxicity approach, the proposed OELs range from 0.021 to 0.07 ppm for benzene. Current evidence indicates that workplace benzene concentrations above 0.3 ppm do not adequately protect the health of exposed workers. Extending follow-up of existing cohorts and conducting robust quantitative genotoxicity assays in well-designed epidemiological and experimental studies are essential to reduce uncertainties and to confirm the most sensitive toxic effect, thereby supporting the establishment of a more realistic OEL for benzene and minimizing the likelihood of over- or underestimating the associated risks.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"409-424"},"PeriodicalIF":5.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419410","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":"Wildfires in the Pan-Amazon: what is known about health impacts on affected populations?","authors":"Elizeu Chiodi Pereira, Dayane da Fonseca Barbosa, Fernando Viana Rodovalho, Thiago Nogueira, Kelly Polido Kaneshiro Olympio","doi":"10.1080/10408444.2025.2606263","DOIUrl":"10.1080/10408444.2025.2606263","url":null,"abstract":"<p><p>According to the World Health Organization, climate change is associated with detrimental health effects through air pollution, increased risk of infectious diseases, as well as extreme heat and drought. The rise in wildfires, exacerbated by climate change, plays a fundamental role in air pollution by emitting diverse pollutants responsible for adverse health effects, environmental and economic damage, directly impacting the health of populations, especially the most vulnerable. This study aimed to evaluate the effects on human health stemming from exposure to wildfire smoke in the Amazon region. For this purpose, a literature review following the PRISMA methodology was conducted in the Web of Science, PubMed, LILACS, and Scopus databases, with no restrictions for biological sex or time frame using descriptors such as \"Exposure\", \"Health effect*\", \"Wildfire*\", and \"Air pollution\". Articles in English, Spanish, and Portuguese were included. A total of 302 articles were identified, of which 30 met the inclusion and exclusion criteria. Studies were identified only in the Brazilian Amazon, and the groups most susceptible to smoke effects were children up to 5 years old and the elderly aged 60 and above, in addition to individuals with preexisting comorbidities. Only one article conducted a biomonitoring study in the region; the others worked with hospital admission data. Coordinated health actions are necessary to protect the health of exposed populations, especially those in conditions of social vulnerability, to ensure health protection and adequate environmental safety.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"1-22"},"PeriodicalIF":5.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017372","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":"Response to Mr. DiNardo's \"Letter to the Editor: Comprehensive review of octocrylene toxicology data and human exposure assessment for personal care products\".","authors":"Kimberly G Norman, Lewis E Kaufman, Peter Griem, Carl D'Ruiz, 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":"10.1080/10408444.2026.2640896","DOIUrl":"10.1080/10408444.2026.2640896","url":null,"abstract":"","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"231-233"},"PeriodicalIF":5.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147671051","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 formaldehyde dispute - Part B: scientific critique of EPA's formaldehyde occupational exposure values (OEVs) and proposed alternative occupational exposure limits (OELs).","authors":"Quincy Perry, Jacob Siracusa, Michael Stevens, Patricia Underwood, Dennis Paustenbach","doi":"10.1080/10408444.2026.2630662","DOIUrl":"10.1080/10408444.2026.2630662","url":null,"abstract":"<p><p>In 2024, the U.S. Environmental Protection Agency (EPA) finalized its Integrated Risk Information System (IRIS) Toxicological Review and Toxic Substances Control Act (TSCA) Risk Evaluation for formaldehyde. After analyzing all the data that they deemed relevant, TSCA relied on IRIS's proposed inhalation reference values to establish an 8-hour occupational exposure value (OEV) of 0.11 ppm derived from epidemiological evidence of nasopharyngeal cancer. They also developed a 15-minute OEV of 0.17 ppm based on the goal of preventing sensory irritation. In an earlier draft of EPA's TSCA Risk Evaluation, they initially proposed an 8-hour OEV of 0.011 ppm derived from residential exposure studies of children, but this was withdrawn. This review examined EPA's methodology, the nearly 40 years of scientific literature underlying the EPA's conclusions, and the more than 300 public comments, which were submitted to the draft IRIS Toxicological Review (Docket ID: [EPA-HQ-ORD-2010-0396]) and draft TSCA Risk Evaluation (Docket ID: [EPA-HQ-OPPT-2023-0613]). A minimum of five significant flaws were identified and discussed: (1) heavy reliance on epidemiological studies which had serious confounding factors and design limitations; (2) application of default uncertainty factors which were too high given the robust human data; (3) use of exclusion criteria which dismissed high-quality studies from being considered; (4) the use of a linear no-threshold (LNT) model despite decades of substantial evidence for a threshold-driven mode of action (MOA); and (5) neglect for a validated biologically based dose-response (BBDR) model which may have been the most robust ever developed. Based on our weight-of-evidence evaluation of toxicological, mechanistic, and epidemiological data, we propose occupational exposure limits (OELs) of 0.3 ppm (8-hour TWA) and 1 ppm (15-min STEL). These values are grounded in controlled human exposure studies of asthmatics and non-asthmatics and supported by an internationally accepted BBDR model estimating an approximately 1 in 940,000 increased cancer risk for workers. As such, these OELs protect against sensory irritation, asthma, and other adverse effects, as well as carcinogenicity. They are also aligned with limits adopted by other domestic and international regulatory bodies. Immediately before this paper was accepted, EPA released their <i>Updated Draft Risk Calculation Memorandum: Formaldehyde</i> for public comment, which proposed to drop their promulgated OEVs (0.11 ppm and 0.17 ppm) and adopt an 8-hour OEV of 0.3 ppm to protect against sensory irritation and cancer, similarly to what was recommended in this paper.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"176-203"},"PeriodicalIF":4.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856189","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":"Addendum.","authors":"","doi":"10.1080/10408444.2026.2686569","DOIUrl":"10.1080/10408444.2026.2686569","url":null,"abstract":"","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"322"},"PeriodicalIF":5.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148351038","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":"Mammalian reproductive and developmental toxicity of micro- and nanoplastics: a critical appraisal of evidence using the SciRAP tool.","authors":"Ida Due, Laura Rubio, Julia Catalán, Laura Tusell, Ester Anton, Steffen Foss Hansen, Anders Baun, Elena Ibáñez","doi":"10.1080/10408444.2026.2686289","DOIUrl":"10.1080/10408444.2026.2686289","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Human exposure to micro- and nanoplastics (MNPs) is increasingly documented, yet their potential effects on reproductive and developmental health remain inadequately explored. Preliminary findings presented in scientific literature suggest that MNPs may translocate systemically and localize in reproductive tissues, prompting growing concern among both researchers and regulators. However, existing toxicological studies differ in terms of methodological adequacy and regulatory applicability. The aim of this study is to provide a systematic evaluation of current scientific evidence regarding the reproductive and developmental effects of MNPs, addressing both scientific findings and study quality for regulatory purposes. We structured our study by first conducting a systematic review focused on &lt;i&gt;in vivo&lt;/i&gt; mammalian studies examining the effects of MNPs on reproductive and developmental endpoints. This was followed by an assessment of the quality of these studies in terms of regulatory reliability and relevance using the Science in Risk Assessment and Policy (SciRAP) tool, version 2.3, originally developed for evaluating chemical toxicity studies. Recognizing that this tool does not fully capture MNPs-specific challenges, we supplemented the evaluation with additional criteria, including polymer type, particle size and shape, preparation methods, and plastic test item characterization. Due to common gaps in reporting, particularly regarding exposure doses, we incorporated a \"&lt;i&gt;not reported&lt;/i&gt;\" option in the Relevance assessment. Each study's overall Critical Appraisal of Evidence Score was then estimated based on its SciRAP score and the extent to which it addressed MNPs-specific criteria. To our knowledge, this represents the first systematic application of SciRAP to studies on MNPs toxicity. Following a tiered and targeted search strategy, the review included 102 studies, with findings grouped into three categories: Biodistribution, Reproductive System, and Fertility and Development. Our analysis found evidence of MNPs presence in reproductive organs, resulting in disruptions to testicular, ovarian, and uterine functions. Both male and female gamete quantity and quality were negatively affected. Additionally, we identified studies indicating maternal transfer of MNPs &lt;i&gt;via&lt;/i&gt; the placenta and lactation, with consequences for fetal development and offspring fertility. The outcome of the critical appraisal of evidence evaluation was that 7 studies were classified as strong, 89 as moderate, and 6 as weak for risk assessment e.g. in a weight of evidence assessment of MNPs effects on biodistribution, the reproductive system, fertility and development. Although many studies report adverse reproductive and developmental outcomes following MNPs exposure, methodological shortcomings and insufficient reporting hinder data synthesis and integration into structured assessments, such as weight-of-evidence approaches. Critical information, such as p","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"323-351"},"PeriodicalIF":5.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789328","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":"Role of constitutive androstane receptor in developmental toxicology: linking chemical exposure, nutrition, and disease susceptibility.","authors":"Ryota Shizu, Kouichi Yoshinari","doi":"10.1080/10408444.2026.2623026","DOIUrl":"10.1080/10408444.2026.2623026","url":null,"abstract":"<p><p>The constitutive androstane receptor (CAR) is a xenobiotic-sensing nuclear receptor that regulates gene transcription involved in drug metabolism, especially in the liver. CAR activation influences detoxification pathways and disrupts endocrine homeostasis, notably thyroid hormone (TH) signaling. THs are crucial for neurodevelopment, skeletal maturation, and metabolic regulation. When activated by antiseizure medications, such as phenobarbital, or environmental chemicals, such as perfluoroalkyl substances, CAR induces hepatic enzymes, including UDP-glucuronosyltransferases (UGTs), which increase the clearance of THs and raise thyroid-stimulating hormone levels. Developmental exposure to CAR activators in rodents has been linked to reduced circulating and brain TH levels, resulting in impaired neurodevelopmental outcomes. Given that CAR expression is very low in fetal and neonatal livers, maternal CAR activation may significantly disrupt fetal TH signaling. Additionally, CAR modulates host gene expression affecting microbial composition and bile acid homeostasis, with emerging evidence connecting it to early-life metabolic programming, including low birth weight. Epigenetic changes caused by CAR agonists during the neonatal period can persist into adulthood at least in rodents, suggesting a potential role of CAR in the developmental origins of health and disease, or DOHaD. While it is essential to consider species differences in ligand specificity and UGT isoform expression when extrapolating findings from rodents into humans, CAR is increasingly recognized as a mediator between environmental exposure and endocrine-metabolic disruption. This review integrates animal and human evidence to highlight the critical yet underappreciated functions of CAR in mediating developmental toxicity and long-term health outcomes.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"76-92"},"PeriodicalIF":5.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282884","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}