Critical Reviews in Toxicology最新文献

{"title":"Correction.","authors":"","doi":"10.1080/10408444.2025.2477920","DOIUrl":"https://doi.org/10.1080/10408444.2025.2477920","url":null,"abstract":"","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"1"},"PeriodicalIF":5.7,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172953","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":"Animal models of developmental toxicity induced by early life electronic-cigarettes exposure.","authors":"Lina Huang, Lanyue Gao, Danqi Chen, Qi Sun","doi":"10.1080/10408444.2025.2497754","DOIUrl":"https://doi.org/10.1080/10408444.2025.2497754","url":null,"abstract":"<p><p>The rising prevalence of electronic-cigarettes (E-cigs) use during pregnancy and lactation can be attributed, in part, to advertising campaigns promoting their safety. Nevertheless, the integrity of E-cigs as a secure substitute for conventional cigarettes necessitates further exploration. Some studies emphasize the toxic role of nicotine in E-cigs, while others underscore the significance of other distinct components whose toxicity cannot be disregarded. Increasingly, researchers are employing rodent models to elucidate the potential toxicological implications of e-cig use. Various paradigms of E-cigs exposure in early life frequently yield divergent health outcomes for offspring. This review first presents different animal model approaches to E-cig-exposure during pregnancy and lactation, referring to E-cig liquid, E-cig devices, puff topography, and inhalation methods, which would be related to the health outcomes. Moreover, the mechanisms underlying the hazardous impacts of maternal E-cig-exposure on offspring are also elucidated. Maternal exposure to E-cigs has been found to induce adverse effects on lung function, neurobehavior, glycolipid metabolism and energy homeostasis in offspring, which are probably mediated through inflammation, oxidative stress, and epigenetic modifications.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"1-22"},"PeriodicalIF":5.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126944","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":"https://doi.org/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":"1-21"},"PeriodicalIF":5.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The use of canonical dose-response models for benchmark dose analysis of continuous toxicological data.","authors":"Wout Slob, Martine I Bakker, Bas G H Bokkers, Guangchao Chen, Weihsueh A Chiu, Wim Mennes, M Alina Nicolaie, R Woodrow Setzer, Paul A White","doi":"10.1080/10408444.2025.2464067","DOIUrl":"https://doi.org/10.1080/10408444.2025.2464067","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The benchmark dose (BMD) approach employs dose-response modeling to determine the dose associated with a small change in response relative to the background response. Here, we introduce a conceptual framework for modeling continuous data that is based on key risk assessment principles and requirements. Based on this framework, we define a class of dose-response models sharing the same four biologically interpretable model parameters, while exhibiting five common properties that are essential from a risk assessment perspective: such models are denoted as \"canonical\" models. The first two canonical properties are straightforward: property 1. The models should predict positive values only (as measurements of continuous endpoints are typically positive) and property 2. the outcomes should not depend on the measurement unit. Canonical property 3 reflects the observation that toxicological dose-response data related to different subgroups (e.g. species, sexes, and exposure durations) are typically (at least approximately) parallel on a log-dose scale, which is at the same time an implicit assumption in defining fundamental toxicological concepts, such as extrapolation factors, relative potency factors (RPFs), and relative sensitivity factors (RSFs). Property 4 is needed to enable comparisons of the sensitivity of endpoints differing in maximum response. A fifth canonical property reflects our view that choices regarding the dose-response model expression, the assumed distribution for the within-group variation, and the benchmark response (BMR) that is being used should be internally consistent. The canonical models that we discuss are suitable to fit parallel dose-response curves to combined datasets related to different subgroups (e.g. species, sexes, and exposure durations). Doing so provides a tool to check canonical property 3 of the particular data analyzed. We provide a review of empirical evidence indicating that this property has general validity, which is highly fortunate, as this legitimizes the use of extrapolation factors and RPFs in risk assessment. We then evaluate to what extent the approaches in current BMD guidance by European Food Safety Authority (EFSA) or U.S. Environmental Protection Agency (US-EPA) comply with the principles of canonical dose-response modeling, concluding that this is only partly the case. The latter can have unfavorable and sometimes far-reaching consequences. For instance, some of the recommended non-canonical models result in different BMDs when changing the measurement unit (e.g. µg to mg). As another example, the BMD tool recently developed by EFSA implements covariate analysis in such a way that canonical property 3 cannot possibly be represented by any of the models. As another disadvantage, non-canonical models preclude the effective development and use of prior distributions in a Bayesian approach. Finally, we argue that a concomitant but important advantage of only using canonical models is that BM","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"1-25"},"PeriodicalIF":5.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810724","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":"Toxicity effects of cadmium exposure on early development: a review of current evidence.","authors":"Nur Batrisyia Azlan, Siti Sarah Mohamad Zaid, Siti Rosmani Md Zin","doi":"10.1080/10408444.2025.2462653","DOIUrl":"https://doi.org/10.1080/10408444.2025.2462653","url":null,"abstract":"<p><p>In recent decades, cadmium (Cd) has garnered significant global attention due to its extensive and potentially harmful health effects, even at low exposure levels. Improper management of cadmium waste can lead to severe environmental pollution, ultimately affecting living organisms through various exposure routes. This study aims to compile and review the latest data on the toxic effects of Cd exposure on critical body systems and functions, with a particular focus on the early stages of development (prepubertal period) across different species. The review highlights Cd's impact on the reproductive, neurobehavioral, cognitive, immune, renal systems, gastrointestinal, and endocrine systems. Additionally, it provides valuable insights into how early Cd exposure may contribute to the development of various diseases in later life.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"1-20"},"PeriodicalIF":5.7,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794801","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 risk assessment of mechanics who changed chrysotile asbestos containing brakes and other vehicle components in the 1950s-early 2000s era: an update on the 2004 evaluation.","authors":"David W Brew, Michael E Stevens, Arthur M Langer, Dennis J Paustenbach","doi":"10.1080/10408444.2024.2427222","DOIUrl":"https://doi.org/10.1080/10408444.2024.2427222","url":null,"abstract":"<p><p>For the past 50 years, there has been an ongoing interest in understanding the potential health hazards, if any, to vehicle mechanics who worked with asbestos-containing brakes in the 1950s-early 2000s era. Two reviews have been published on this topic, one by Langer (2003) (\"Reduction of the biological potential of chrysotile asbestos arising from conditions of service on brake pads\") and another by Paustenbach, et al. (2004) (\"Environmental and occupational health hazards associated with the presence of asbestos in brake linings and pads (1900 to present): a 'state-of-the-art' review\"). This analysis is an update on those papers since a considerable amount of research has been published over the past 20 years on this topic. The following important aspects are addressed in this review: new information on the toxicology of chrysotile, toxicology studies of brake dust associated with grinding, additional epidemiology studies and meta-analyses published on auto mechanics of the era, previously unfound data on how brakes (during the era when chrysotile was used) were manufactured, and new work describing the transformation of chrysotile to various degradation products during vehicle braking. This update also addresses questions about the health hazards associated with asbestos in vehicle clutches, transmissions, and gaskets. The exposure data indicate that the airborne concentrations of chrysotile fibers associated with vehicle mechanic work when asbestos was in auto brakes were, on average, less than 0.04 f/cm³ (8-h TWA) and the average lifetime cumulative dose was in the vicinity of 0.5-3 f/cm³-year for mechanics of that era. Although many of these fibers may have no toxicity due to thermal degradation and the conversion to degradation products, 31 epidemiology studies have evaluated the risks of mesothelioma for vehicle mechanics of this era and all but one indicate that there was no increased incidence of this disease in these workers. The weight of evidence continues to indicate that the asbestos-related health risks to vehicle mechanics from asbestos-containing components were <i>de minimis</i>. The risks associated with take-home and bystander exposure of a mechanic were also addressed and they were found to pose a <i>de minimis</i> or zero health risk to those potentially exposed. Based on our evaluation, there is no indication that asbestos from asbestiform tremolite was present at detectable concentrations in bulk samples of brakes or in the air during brake work. The recent U.S. Environmental Protection Agency (EPA) risk assessment of 2024 on chrysotile and their views of the hazards of asbestos-containing brakes were discussed. Their analyses did not alter our views that exposures to mechanics posed no increased risk of asbestos related disease. The latest knowledge about the role of genetic susceptibility on the development of mesothelioma is also addressed.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"1-50"},"PeriodicalIF":5.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499639","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":"1"},"PeriodicalIF":5.7,"publicationDate":"2025-02-07","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":"Perspectives on aerosol inhalability: concepts and applications.","authors":"Robert F Phalen, Mark D Hoover, Roger O McClellan","doi":"10.1080/10408444.2025.2458276","DOIUrl":"10.1080/10408444.2025.2458276","url":null,"abstract":"<p><p>The original motivation for the aerosol inhalability convention was to account for the fact that the inhalation efficiency of particles can cause the composition of the particle-containing air that is inhaled into the mouth and nose to differ significantly from the composition of the ambient air. Therefore, without appropriate adjustments for the inhalation efficiency of particles, air samples could over- or underestimate the actual exposures of inhaled materials, possibly compromising some workplace air standards. Subsequently, the concepts and applications of inhalability and inhalability sampling have been expanded to inhalation exposures outside of the workplace, including general human populations, medical patients, cell cultures, and animal research subjects. As described in this commentary, some of these applications have occurred in ways that could misrepresent actual exposures. Scientific advances in the understanding and applications of inhalability-related concepts are needed. Such advances will best be achieved through multidisciplinary collaborations involving modeling, wind tunnel mannequin and human subject studies, and health effects studies involving input from aerosol scientists, engineers, physiologists, anatomists, physicians, veterinarians, mathematical modelers, and regulators.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"227-247"},"PeriodicalIF":5.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514973","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 evaluation of rodent carcinogenicity studies on butyl methacrylate demonstrates a lack of carcinogenic potential.","authors":"Susan A Elmore, Joseph K Haseman, Mark Pemberton, B Bhaskar Gollapudi, Samuel M Cohen","doi":"10.1080/10408444.2025.2451885","DOIUrl":"10.1080/10408444.2025.2451885","url":null,"abstract":"<p><p>Assessments of a chemical agent's carcinogenicity based on rodent bioassays rely on their appropriate interpretation. This involves attention to study details, including reliable histopathologic diagnoses, and proper statistical analyses, including consideration of multiple comparisons, concurrent and historical controls. A major factor is evaluation of their likely mode of action and the human relevance of any identified tumors. We present a critical evaluation of the assessment of the 2-year inhalation bioassays of n-butyl methacrylate (n-BMA) in rats and mice performed by the Japan Bioassay Research Center (JBRC) and an assessment of the International Agency for Research on Cancer (IARC) review and classification as Group 2B, possible human carcinogen. The tumors of concern for assessment of its carcinogenicity included mononuclear cell leukemia (MCL) in male rats, thyroid C-cell tumors in female rats, liver tumors and histiocytic sarcomas in male mice, and hemangiosarcomas in female mice. Our review of these studies raises concerns regarding the accuracy of histopathology diagnoses and human relevance of MCL. Most critically, the statistical evaluation/interpretation of all tumor types indicates no carcinogenic effects, since the frequency of increases (at <i>p</i> < 0.05) in tumor incidences in the study is totally consistent with chance expectation (i.e. not treatment related). Furthermore, the plausibility of n-BMA being carcinogenic is questionable since it is non-genotoxic, and the weight of evidence including read-across to the close structural analog methyl methacrylate indicates no concern for cancer. After thorough review of these bioassays, we conclude that there is no convincing evidence of carcinogenicity for n-BMA, contrary to the conclusion of the JBRC and the decision by the IARC.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"105-123"},"PeriodicalIF":5.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729149","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 quantitative weight-of-evidence review of preclinical studies examining the potential developmental neurotoxicity of acetaminophen.","authors":"Daniel G Kougias, Evren Atillasoy, Michael D Southall, Anthony R Scialli, Sadaff Ejaz, Christopher Chu, Bamidele O Jeminiwa, Andrey Massarsky, Kenneth M Unice, Tammi H Schaeffer, Michael Kovochich","doi":"10.1080/10408444.2024.2442344","DOIUrl":"10.1080/10408444.2024.2442344","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Acetaminophen [paracetamol; &lt;i&gt;N&lt;/i&gt;-acetyl-&lt;i&gt;para&lt;/i&gt;-aminophenol (APAP)] is an antipyretic/analgesic commonly used in the treatment of fever and mild to moderate pain, headache, myalgia, and dysmenorrhea. Recent literature has questioned the safety of acetaminophen use during pregnancy, with an emphasis on whether exposure to the developing nervous system results in behavioral changes consistent with autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and/or other cognitive deficits in the offspring. No previous review has used a fully detailed, quantitative weight-of-evidence (QWoE) approach to critically examine the preclinical acetaminophen data with regards to potential developmental neurotoxicity (DNT). Following regulatory guidance, a QWoE framework using prespecified scoring criteria was developed consistent with previous approaches to characterize potential adverse DNT outcomes with considerations for biological relevance of the response to adverse outcomes (outcome score) and the strength of methods and study design (methods score). Considerations for the methods score included (1) experimental design, (2) details/reliability of measurement(s), (3) data transparency, and (4) translational/methodological relevance. Considerations for the outcome score included response-related (1) statistical significance, (2) dose-response, (3) relevance/reliability/magnitude, (4) plausibility, and (5) translational relevance, including consideration of systemic toxicity/hepatotoxicity and therapeutic and/or non-systemically toxic doses and durations of use. Application of this QWoE framework to the 34 &lt;i&gt;in vivo&lt;/i&gt; studies identified that assess the potential DNT of acetaminophen resulted in 188 QWoE entries documented across 11 DNT endpoints: social behavior, stereotypic behavior, behavioral rigidity, attention/impulsivity, hyperactivity, anxiety-like behavior, sensorimotor function, spatial learning/memory, nonspatial learning/memory, neuroanatomy, and neurotransmission. For each endpoint, the mean outcome score and methods score were calculated for total entries and for entries segregated by sex to assist in determining data quality and potential adversity. Informed by all 188 entries, the QWoE analysis demonstrated data of moderate quality showing no consistent evidence of DNT in male and female rodents following exposure to acetaminophen at therapeutic and/or nonsystemically toxic doses. Although some of the DNT endpoints (behavioral rigidity, attention/impulsivity, spatial learning/memory, neuroanatomy, and neurotransmission) generally displayed a more limited dataset and/or relatively lower data quality, similar conclusions were drawn based on results indicating a lack of biological relevance and reliability of reported adverse effects. Overall, this QWoE analysis on the preclinical &lt;i&gt;in vivo&lt;/i&gt; data demonstrates no consistent evidence of adverse effects following developmental exposure to acetaminophen at","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"124-178"},"PeriodicalIF":5.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467254","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}