Critical Reviews in Toxicology最新文献

{"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":"https://doi.org/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":"1-23"},"PeriodicalIF":5.7,"publicationDate":"2025-06-26","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":"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":"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":"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}

{"title":"Mode of action approach supports a lack of carcinogenic potential of six organic UV filters.","authors":"Samuel M Cohen, Alan R Boobis, David Jacobson-Kram, Rita Schoeny, Thomas J Rosol, Gary M Williams, Norbert E Kaminski, Gary M Eichenbaum, F Peter Guengerich, J F Nash","doi":"10.1080/10408444.2025.2462642","DOIUrl":"https://doi.org/10.1080/10408444.2025.2462642","url":null,"abstract":"<p><p>Ultraviolet (UV) filters, the active ingredients in sunscreens, have been used for several decades to reduce the risk of acute and chronic damage to the skin from solar UV radiation, which can lead to skin cancer. Based on recent clinical studies showing that certain UV filters are absorbed systemically at low levels in humans, the US Food and Drug Administration (FDA) has requested supplementing existing safety data with preclinical studies including oral and dermal 2-year rodent carcinogenicity studies. Although the conduct of 2-year rodent carcinogenicity studies has been the standard approach for evaluating the carcinogenic potential of chemicals and new drugs for approximately 6 decades, there are multiple examples showing that such studies are not predictive of human cancer risk. Given these concerns with 2-year rodent carcinogenicity studies, we have developed and applied an alternative approach for supplementing existing data related to carcinogenic potential for six of the most commonly used UV filters in sunscreen products (i.e. avobenzone, ensulizole, homosalate, octinoxate, octisalate, and octocrylene). This approach evaluates their mode of action (MOA) based on <i>in vivo</i>, <i>in vitro</i>, and <i>in silico</i> data combined with an assessment of exposure margins. This approach is based on the substantial progress in understanding the MOAs that are responsible for tumor induction in humans. It is consistent with those being developed by the International Council for Harmonization (ICH) and other health authorities to replace 2-year carcinogenicity studies given their limitations and questionable biological relevance to humans. The available data for the six UV filters show that they are not genotoxic and show no evidence of biologically relevant carcinogenic MOAs. Furthermore, their systemic exposure levels in humans fall well below concentrations at which they have biologic activity. In conclusion, these data support the continued safe use of these six filters in sunscreen products.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":"55 2","pages":"248-284"},"PeriodicalIF":5.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970535","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 and reproductive toxicity of acetaminophen.","authors":"Daniel G Kougias, Michael D Southall, Anthony R Scialli, Evren Atillasoy, Sadaff Ejaz, Tammi H Schaeffer, Christopher Chu, Bamidele O Jeminiwa, Andrey Massarsky, Kenneth M Unice, Michael Kovochich","doi":"10.1080/10408444.2024.2446471","DOIUrl":"10.1080/10408444.2024.2446471","url":null,"abstract":"<p><p>We previously developed a quantitative weight-of-evidence (QWoE) framework using prespecified scoring criteria for preclinical acetaminophen data to characterize potential developmental neurotoxicity outcomes with considerations for biological relevance of the response to adverse outcomes and the strength of methods and study design. The current analysis uses this framework to characterize potential developmental and reproductive toxicity (DART) outcomes following exposure to acetaminophen. Two-hundred forty-two QWoE entries were documented from <i>in vivo</i> rodent studies identified in 110 publications across five categories: DART endpoints in the context of (1) periadolescent/adulthood (nonpregnancy) exposures; (2) pregnant female exposures; and, for <i>in utero</i> or other developmental exposures, (3) anatomical abnormalities, (4) reproductive development, and (5) other physical development. A mean outcome score and methods score were calculated for 242 QWoE entries. Data analyzed in our framework were of moderate quality showing no consistent evidence of DART in male and female rodents following exposure to acetaminophen at therapeutic and/or non-systemically toxic doses. Similar results were found for the individual context- and outcome-related endpoint analyses and as segregated by sex. Overall, this QWoE analysis on the <i>in vivo</i> rodent data demonstrated no consistent evidence of adverse effects following exposure to therapeutic and/or non-systemically toxic acetaminophen on development or on the structure and function of the reproductive system.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"179-226"},"PeriodicalIF":5.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467252","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":"Nomograms applicability in clinical toxicology - enhancing precision in clinical decision-making: a systematic review.","authors":"Asmaa Fady Sharif, Zeinab A Kasemy, Khalid Saeed Alshalawi, Zahraa Khalifa Sobh","doi":"10.1080/10408444.2024.2445021","DOIUrl":"10.1080/10408444.2024.2445021","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Nomograms represent powerful predictive tools that could be easily applied to guide managing acutely intoxicated patients. Thus, several nomograms were developed and validated in the last few decades to predict various outcomes following acute poisoning. However, the adopted nomograms remain sporadic efforts of researchers that limited their usefulness in clinical settings. We aimed to bridge the gap between theoretical formulation and hands-on application of the developed nomograms to benefit acutely poisoned patients. In this context, this systematic review was conducted to be a reference guide for implementing these nomograms in clinical toxicology practice. This review included 27 studies that were published over 60 years. A total of 60,883 patients ranging between 2 and 91 years were enrolled. These studies elaborated 38 nomograms; 13 nomograms addressed acute poisoning in general, and 25 nomograms were specially designed for six poisons/categories, including pesticides (&lt;i&gt;n&lt;/i&gt; = 9), psychotropic drugs (&lt;i&gt;n&lt;/i&gt; = 5), alcohol (&lt;i&gt;n&lt;/i&gt; = 4), analgesics, and anti-inflammatory medications (&lt;i&gt;n&lt;/i&gt; = 3), carbon monoxide (&lt;i&gt;n&lt;/i&gt; = 2), and digoxin (&lt;i&gt;n&lt;/i&gt; = 2). Despite the first nomogram was published in 1960, 81.5% of nomograms emerged after 2016, with a significant increase in the trend of published nomograms (&lt;i&gt;p&lt;/i&gt; &lt; .001). The Glasgow Coma Scale, patient age, poison concentration, bicarbonate level, and blood pressure were the most frequently used predictors. The nomograms were designed to predict eight outcomes, including mortality (&lt;i&gt;n&lt;/i&gt; = 14, 36.8%), need for intensive care unit (ICU) admission (&lt;i&gt;n&lt;/i&gt; = 9, 23.7%), complications of poisoning (&lt;i&gt;n&lt;/i&gt; = 6, 15.8%), optimization of therapy (&lt;i&gt;n&lt;/i&gt; = 4, 10.5%), and poisoning severity (&lt;i&gt;n&lt;/i&gt; = 2, 5.3%). Also, the need for mechanical ventilation (MV), diagnosis of poisoning, and suicidal poisoning were predicted by one nomogram for each of them. The developed nomograms' performances were tested using receiver operating characteristic analysis and the area under a curve of 26 derived nomograms ranged between 0.839 and 0.999. External validation was conducted on 16 nomograms only; 15 nomograms were validated using validation cohorts within the same studies that developed the nomograms. However, only one nomogram was subjected to external validation by other studies. The externally validated nomograms consist of 10 nomograms for managing particular poisoning and, six nomograms for un-specified poisoning. The poison-specific nomograms were concerned with acute poisoning with pesticides (&lt;i&gt;n&lt;/i&gt; = 4), methanol (&lt;i&gt;n&lt;/i&gt; = 2), opioid (&lt;i&gt;n&lt;/i&gt; = 1), clozapine (&lt;i&gt;n&lt;/i&gt; = 1), carbon monoxide (&lt;i&gt;n&lt;/i&gt; = 1), and digoxin (&lt;i&gt;n&lt;/i&gt; = 1). Regarding six validated nomograms in a general poisoning approach, two nomograms predicted mortality. Nevertheless, four separate nomograms were concerned with the prediction of poisoning complications, the need for ICU admission, the need for ","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"285-303"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406209","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 avobenzone (butyl methoxydibenzoylmethane) toxicology data and human exposure assessment for personal care products.","authors":"Kimberly G Norman, Lewis E Kaufman, 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":"10.1080/10408444.2025.2535394","DOIUrl":"10.1080/10408444.2025.2535394","url":null,"abstract":"<p><p>A comprehensive review of existing toxicity and human exposure data for the ultraviolet filter avobenzone (butyl methoxydibenzoylmethane) was conducted to assess its safety as currently used in over-the-counter sunscreen formulations. Avobenzone has a suitable safety profile without any clear markers of toxicity or endpoints of concern. There are sufficient clinical studies and <i>in vitro</i> and <i>in vivo</i> toxicity studies in animal models to assess avobenzone's pharmacokinetics, pharmacodynamics, and potential toxicological properties, supportive of its long history of safe use. No harmonized dermal absorption value was available, but the clinical data indicate low percutaneous absorption of avobenzone in humans (≤0.59% of the applied dose). There were no data to characterize the distribution of avobenzone; however, four tentative metabolites of avobenzone have been identified, and limited excretion in urine was demonstrated in human biomonitoring studies. Avobenzone generally did not cause dermal irritation or sensitization, but indications of photoallergy have been reported in clinical case studies. The acute toxicity profile indicated that avobenzone has minimal toxicity. The no-observed-adverse-effect level (NOAEL) for general toxicity from a rat dietary subchronic toxicity study was 450 mg/kg/day. There was no evidence of avobenzone effects on immune tissues or the estrogen, androgen, or thyroid systems. Although there were no formal 2-year carcinogenicity studies for avobenzone, a 90-day dietary exposure study in rats did not show any increase in hyperplasia of any tissue or evidence of cytotoxicity, and avobenzone has not shown any indication of genotoxicity either <i>in vitro</i> or <i>in vivo</i>. Together, this indicates that key events for modes of action for avobenzone are absent and carcinogenicity in humans is unlikely. Based on the selected rat subchronic NOAEL and conservative assumptions for estimating the systemic exposure dose (SED) from the application of sunscreen products, margins of exposure (defined as the ratio of NOAEL to SED) greater than 100 were obtained for avobenzone. Therefore, the available data show that avobenzone is unlikely to pose a risk to human health when used in sunscreen products at concentrations up to the permitted maximum usage levels in the United States and Canada, which is 3%.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"662-692"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999886","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}