Critical Reviews in Toxicology最新文献

{"title":"A weight of evidence review on the mode of action, adversity, and the human relevance of xylene's observed thyroid effects in rats.","authors":"Keith Morris-Schaffer, Larry Higgins, Neslihan Aygun Kocabas, Frank Faulhammer, Alexandra Cordova, Elaine Freeman, Hennicke Kamp, Muna Nahar, Emily Richmond, Martijn Rooseboom","doi":"10.1080/10408444.2024.2422890","DOIUrl":"10.1080/10408444.2024.2422890","url":null,"abstract":"<p><p>Xylene substances have wide industrial and consumer uses and are currently undergoing dossier and substance evaluation under Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) for further toxicological testing including consideration of an additional neurotoxicological testing cohort to an extended one-generation reproduction toxicity (EOGRT) study. New repeated dose study data on xylenes identify the thyroid as a potential target tissue, and therefore a weight of evidence review is provided to investigate whether or not xylene-mediated changes on the hypothalamus-pituitary-thyroid (HPT) axis are secondary to liver enzymatic induction and are of a magnitude that is relevant for neurological human health concerns. Multiple published studies confirm xylene-mediated increases in liver weight, hepatocellular hypertrophy, and liver enzymatic induction <i>via</i> the oral or inhalation routes, including an increase in uridine 5'-diphospho-glucuronosyltransferase (UDP-GT) activity, the key step in thyroid hormone metabolism in rodents. Only minimal to slight increases in thyroid follicular cell hypertrophy have been observed in some xylene repeated dose studies, with no associated robust or consistent perturbance of thyroid hormone changes across the studies or carried through to offspring indicating adaptive homeostatic maintenance of the HPT axis. Also importantly, <i>in vitro</i> human cell line data from the United States Environmental Protection Agency (US EPA) Toxicity Forecasting (ToxCast) provides supporting evidence of xylene's inability to directly perturb thyroidal functionality. A further supplemental in-depth metabolomics analysis (MetaMap^®Tox) of xylene showed a tentative match to compounds that also demonstrate extra-thyroidal effects on the HPT axis as a consequence of liver enzyme induction. Lastly, the slight HPT axis changes mediated by xylene were well-below the published literature thresholds for developmental neurotoxicological outcomes established for thyroidal changes in animals and humans. In summary, the data and various lines of scientific evidence presented herein individually and collectively demonstrate that xylene's mediated changes in the HPT axis, <i>via</i> a secondary extra-thyroidal MOA (i.e. liver enzyme induction), do not raise a human health concern with regards to developmental neurotoxicity. As such, the available toxicological data do not support the classification of xylene as a known or suspected endocrine disruptor, specifically through the thyroid modality, per Regulations Commission Delegated Regulation (EU) 2023/707 of 19 December 2022 amending Regulation (EC) No 1272/2008 and do not support the need for a neurotoxicological cohort evaluation in any subsequent EOGRTS.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"1-26"},"PeriodicalIF":5.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945989","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 modes of action for rodent liver tumor formation by activators of the constitutive androstane receptor (CAR) and the peroxisome proliferator-activated receptor alpha (PPARα) are not relevant to human cancer risk: an updated critical evaluation.","authors":"Tomoya Yamada, Samuel M Cohen, Brian G Lake","doi":"10.1080/10408444.2025.2513332","DOIUrl":"10.1080/10408444.2025.2513332","url":null,"abstract":"<p><p>Constitutive androstane receptor (CAR) activators have long been known to enhance hepatocellular carcinogenesis in rodents, with the prototypic chemical being phenobarbital (PB). This has raised an ongoing controversy for the past 50 years as to whether this is relevant to human cancer risk. The established mode of action (MOA) for rodent liver tumor formation by CAR activators includes receptor activation, increased hepatocellular proliferation, altered liver foci and ultimately liver tumors. We previously published a critical review indicating the pivotal species difference that CAR activators are mitogenic agents in mouse and rat hepatocytes, but they do not stimulate hepatocellular proliferation in humans based on molecular downstream interaction differences, thus CAR activators pose no liver carcinogenic risk to humans (Yamada et al. <i>Crit Rev Toxicol 2021</i>). Peroxisome proliferator-activated receptor alpha (PPARα) activators induce rodent liver tumors through a similar MOA, again involving increased hepatocellular proliferation, but are generally considered not relevant to human cancer risk. As with CAR activators, PPARα activators are mitogenic in rodent liver but not in other species, including humans. This species-specific effect of CAR and PPARα activators provides critical information useful for the overall risk assessments of these molecules, including pharmaceuticals, agrochemicals, food additives, and other chemicals. Overall, based on the available data for the specific molecular effects of these agents, the time has come to consider that chemicals for which the MOA of liver carcinogenicity observed in rodents has been clearly identified as either CAR- or PPARα-mediated (with other MOAs having been excluded) can be judged as having no relevance to human cancer risk without further investigations being necessary.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"549-586"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505066","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":"Effects of statins on male reproductive health: a systematic review of rodent studies and their potential implications to human male reproduction.","authors":"Gabriel Adan Araújo Leite, Virgínia Meneghini Lazzari, Vinícius Augusto Simão, Marciana Sanabria","doi":"10.1080/10408444.2025.2504395","DOIUrl":"10.1080/10408444.2025.2504395","url":null,"abstract":"<p><p>Statins are the drugs recommended for the treatment of dyslipidemia and for preventing cardiovascular risks in humans. However, it is reported that statins may impair reproductive parameters in males at different periods of exposure in pre-clinical studies. This work carried out a systematic review of the literature concerning the primary studies that evaluated the reproductive outcomes in male rats and mice exposed to several statins available on the market. The literature search was performed employing several databases, including Embase, Web of Science, PubMed, LILACS, Scopus, and SciELO, by using different combinations of the search terms \"statins,\" \"mice,\" \"rats,\" \"male reproduction,\" \"fertility\" and \"sperm,\" followed by the Boolean operators AND or OR. Then, duplicated articles or studies that did not meet the eligibility criteria were excluded. Posteriorly, the risk of bias was assessed following the essential ten points of the ARRIVE guidelines. Afterward, the extraction and qualitative analysis of the data were performed, and when possible, a meta-analysis was carried out. The results indicated that normolipidemic healthy rodents exposed to statins showed reproductive impairment, such as reduced sperm quality, diminished testosterone production, and delayed puberty onset. Additionally, <i>in vitro</i> and <i>ex vivo</i> studies demonstrated a decrease in testosterone synthesis after statin exposure. However, when rodents were induced to diabetes and erectile dysfunction or were fed a high-fat diet, these diseased animals exposed to statins exhibited improved erectile function, increased sperm quality, and no changes or augmented testosterone levels. Given the reproductive toxicity generated by statin exposure in healthy male rodents without any previous dysfunction, these drugs should be reserved for treating dyslipidemia or, when appropriate, as an adjunct therapy for erectile dysfunction.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"507-525"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144495066","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":"Meta-analysis of the safety and efficacy of fresh frozen plasma exchange in the treatment of organophosphate pesticide poisoning.","authors":"Binrong Cai, Xian Yu, Xiaoyan Xian, Lipeng Liu, Bin He, Shuyun Xu","doi":"10.1080/10408444.2025.2540432","DOIUrl":"10.1080/10408444.2025.2540432","url":null,"abstract":"<p><p>This study evaluates whether fresh frozen plasma (FFP) improves outcomes compared to conventional therapy alone in organophosphorus poisoning (OP). Relevant literature was searched in PubMed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang, and VIP databases, applying predefined inclusion/exclusion criteria to select studies. Data from included studies were extracted for analysis. Seven randomized clinical trials involving 391 patients were included in the analysis, with 191 patients in the FFP combined with conventional therapy group (combination therapy group) and 200 patients in the conventional therapy alone group (control group). Compared with the control group, the combination therapy group demonstrated a lower case fatality rate (relative risk (RR) = 0.58, 95% confidence interval [CI] [0.34, 0.97], <i>p</i> < .05), reduced utilization of mechanical ventilation (RR = 0.78, 95% CI [0.64, 0.95], <i>p</i> < .05), and superior cholinesterase recovery levels (standardized mean difference (SMD) = 1.70, 95% CI [-0.02, 3.43], <i>p</i> = .05). However, no significant differences were observed between the two groups in hospitalization duration or ICU length, incidence of intermediate syndrome, and duration of mechanical ventilation maintenance (<i>p</i> > .05). Current evidence indicates that FFP combined with conventional therapy may reduce mortality rates, mechanical ventilation utilization, and enhance cholinesterase activity recovery levels in OP patients. Nevertheless, multicenter randomized double-blind controlled trials remain necessary to validate these findings in the future.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"707-715"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945959","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":"10.1080/10408444.2025.2464067","url":null,"abstract":"<p><p>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":"437-461"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12318563/pdf/","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":"OA","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":"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":"417-436"},"PeriodicalIF":5.7,"publicationDate":"2025-01-01","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":"The tradeoff between the efficacy of calcineurin inhibitors: prevention of allograft rejection vs. post-transplant renal and cardiovascular complications.","authors":"Kalpanarani Dash, Monalisa Mishra","doi":"10.1080/10408444.2024.2433631","DOIUrl":"10.1080/10408444.2024.2433631","url":null,"abstract":"<p><p>Solid organ transplantation has emerged as a crucial intervention in the field of medicine. During transplantation, our human body perceives the organ as an exogenous entity or graft, initiating an immune reaction to eliminate it. This immune response ultimately culminates in the rejection of the graft. So, to mitigate the possibility of graft rejection, implementing immune suppression is imperative. In this context, the utilization of calcineurin inhibitors (CNIs) assumes a pivotal role. Calcineurin inhibitors significantly preserve immunosuppression following solid organ transplantation. Calcineurin inhibitors have considerably improved short-term results in renal transplantation by reducing acute rejection rates. Concerning the limited therapeutic window of these medications, careful monitoring of pharmacological treatment and individual doses is required. However, a significant number of patients do experience CNI toxicity. Side effects of CNIs include renal failure, hypertension, respiratory disorders, gastrointestinal damage, gingivitis, and so on. Higher trough level of the drug causes acute nephrotoxicity, which is of three types: functional toxicity, tubular toxicity, and vascular toxicity. Acute nephrotoxicity, if untreated, leads to irreversible, progressive deterioration of allograft function, leading to chronic nephrotoxicity. Cardiovascular toxicity of CNIs includes atrial hypertension caused by vasoconstriction of the afferent arteriole, vascular remodeling, hypertrophy, dyslipidemia, and also the onset of diabetes. Such clinical complications further affect the patient's survivability and subjective well-being, possibly leading to graft loss. This review focuses on the most severe side effects of CNIs: renal and cardiovascular toxicity.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"63-79"},"PeriodicalIF":5.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977932","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":"Construction of a risk prediction model of diquat poisoning based on clinical indicators.","authors":"Weiwei Qian, Xuxin Xie, Jian Zhou, Yan Ren, Yangjuan Bai, Aihua Peng, Lin Lv, Zengwen Ma, Chengtong He, Yue Zhou, Jiale Tong, Yanzi Zhang, Yu Cao, Shuyun Xu","doi":"10.1080/10408444.2024.2433242","DOIUrl":"10.1080/10408444.2024.2433242","url":null,"abstract":"<p><p>This study aims to explore the clinical characteristics and prognostic factors in patients with diquat (DQ) poisoning and to develop a clinical risk assessment model to improve diagnosis and treatment strategies. Data from 60 patients with DQ poisoning, including basic characteristics, poisoning severity, and inflammatory response indicators, were collected. The plasma concentration of DQ was measured using liquid chromatography-mass spectrometry. The included patients were categorized into survival and death groups based on their 30-day outcomes. Fisher's exact test was used to identify statistically significant clinical indicators (<i>p</i> < .05), and logistic regression within a generalized linear model (GLM) framework was employed to analyze these indicators alongside the severity index of diquat poisoning (SIDP), followed by the construction of a prognostic model. The performance of the model was evaluated through receiver operating characteristic (ROC) analysis, and the accuracy of the model was assessed. Additionally, two independent sample Wilcoxon tests compared the clinical indicators between high-risk and low-risk groups. Fisher's exact test identified significant differences in variables such as oral drug dosage (ODD), time from poisoning to admission (TFPTA), state of consciousness (SOC), Glasgow Coma Scale (GCS), white blood cells (WBC), myoglobin (Myo), high-flow nasal cannula (HFNC), invasive mechanical ventilation (IMV), acute kidney injury (AKI), and acute lung injury (ALI) (<i>p</i> < .05) between the survival and death groups. The GLM-based risk assessment model demonstrated high predictive accuracy, with an area under the ROC curve (AUC) of 0.97 (SE 0.017, 95% CI 0.939-1.001), indicating potent prognostic capability. The Wilcoxon test revealed that ODD, Myo, SIDP, aspartate transferase (AST), creatine kinase (CK), hemoglobin (Hb), cardiac troponin (cTnT), and serum creatinine (Cr) levels were significantly higher in the high-risk group. The clinical risk assessment model effectively predicts the prognosis of patients with DQ poisoning, aiding clinicians in personalizing treatment strategies to improve patient outcomes.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"55-62"},"PeriodicalIF":5.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834482","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":"Development and application of meta-analysis in environmental health research.","authors":"Qingyuan Li, Xiaoxing Liang, Renjun Yang, Nuoya Yin, Francesco Faiola","doi":"10.1080/10408444.2025.2530972","DOIUrl":"10.1080/10408444.2025.2530972","url":null,"abstract":"<p><p>The Adverse Outcome Pathway (AOP) framework is a foundational approach in environmental pollutant research, encompassing the detrimental effects of pollutants across biological levels from molecules to populations. Toxicogenomics (TGx), which integrates omics technologies with toxicology, plays a crucial role in AOPs by elucidating the relationships between chemical exposure, molecular initiating events (MIEs), and key events (KEs) across various biological levels using animal and cell model-based data. However, since some MIEs (e.g. changes in specific enzyme activities or receptor binding/activation) cannot be confirmed by omics data alone, TGx data must be integrated with classical enzymatic assays, receptor function analyses, and related methods when constructing AOPs to ensure comprehensive, accurate identification of MIEs and their associated KEs. Epidemiology examines the links between environmental exposures, KEs and adverse outcomes (AOs) in human populations, contributing to the understanding of population-level disease outcomes. With the advent of big data, both epidemiology and TGx studies have generated substantial datasets. To synthesize these extensive data resources, meta-analysis emerges as a robust tool, effectively integrating environmental epidemiology and TGx data to provide a coherent and strong evidence base, revealing the correlative and causative relationships between environmental pollutants and human health outcomes. This review focuses on the role of meta-analysis in environmental health research, particularly on integrating environmental health epidemiology and TGx data. Additionally, we explore the challenges in applying meta-analysis and discuss future directions. Our aim is to provide researchers with a comprehensive understanding of meta-analysis methods and processes in environmental health research, encouraging wider adoption and further development of this analytical approach.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"620-644"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752645","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":"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":"462-483"},"PeriodicalIF":5.7,"publicationDate":"2025-01-01","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}