Critical Reviews in Toxicology最新文献

{"title":"Microbial degradation mechanisms, degradation pathways, and genetic engineering for pyrethroids: current knowledge and future perspectives.","authors":"Jiahui Wu, Hui Peng, Peng Cheng, Hongmei Liu, Ye Zhang, Maoqing Gong","doi":"10.1080/10408444.2024.2433632","DOIUrl":"https://doi.org/10.1080/10408444.2024.2433632","url":null,"abstract":"<p><p>Pyrethroids are synthetic products derived from natural pyrethroids present in flowers and are extensively used as pesticides for agriculture, animal husbandry, and household pest control. However, excessive and prolonged usage of pyrethroid insecticides can result in adverse effects on both non-target and target species. Therefore, effective technologies need to be developed to remove pyrethroid contamination and ensure environmental safety. Microbial remediation of various pesticide contaminants is highly practicable, low cost, and eco-friendly compared to physical and chemical methods. Different microbiota are screened to eliminate or degrade the contaminants. Microbial remediation technology utilizes the natural ability of microbiota to treat contaminated areas. Previous studies have mostly focused on the isolation and screening of microorganisms for pyrethroid biodegradation, as well as on the kinetics and pathways of pyrethroid biodegradation. In order to develop effective bioremediation strategies, further research based on molecular biology and bioengineering is required for a comprehensive exploration of pyrethroid-degrading microorganisms. To date, the microbial degradation of pyrethroid pesticides and the underlying mechanisms have been rarely reviewed. Therefore, this critical review encompasses the latest knowledge on synthetic pyrethroids from structural properties, bio-toxicity, and characterization of microbial degradation strains to degradation characteristics, intrinsic mechanisms, and microbial degradation pathways. The future of microbial remediation depends on combining advanced gene technology with traditional bioremediation methods to sustainably degrade pesticide contaminants. It also summarizes the factors affecting degradation efficiency and concludes with prospects, along with current challenges and limitations.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"1-25"},"PeriodicalIF":5.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of a risk prediction model of diquat poisoning based on clinical indicators.","authors":"Weiwei Qian, 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":"https://doi.org/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":"1-8"},"PeriodicalIF":5.7,"publicationDate":"2024-12-17","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":"A critical review to identify data gaps and improve risk assessment of bisphenol A alternatives for human health.","authors":"Sakina Mhaouty-Kodja, Daniel Zalko, Sabrina Tait, Emanuela Testai, Catherine Viguié, Emanuela Corsini, Nathalie Grova, Franca Maria Buratti, Nicolas J Cabaton, Lucia Coppola, Antonio De la Vieja, Maria Dusinska, Naouale El Yamani, Valentina Galbiati, Patricia Iglesias-Hernández, Yvonne Kohl, Ambra Maddalon, Francesca Marcon, Lydie Naulé, Elise Rundén-Pran, Francesca Salani, Nicoletta Santori, Mónica Torres-Ruiz, Jonathan D Turner, Ondrej Adamovsky, Kiara Aiello-Holden, Hubert Dirven, Henriqueta Louro, Maria João Silva","doi":"10.1080/10408444.2024.2388712","DOIUrl":"10.1080/10408444.2024.2388712","url":null,"abstract":"<p><p>Bisphenol A (BPA), a synthetic chemical widely used in the production of polycarbonate plastic and epoxy resins, has been associated with a variety of adverse effects in humans including metabolic, immunological, reproductive, and neurodevelopmental effects, raising concern about its health impact. In the EU, it has been classified as toxic to reproduction and as an endocrine disruptor and was thus included in the candidate list of substances of very high concern (SVHC). On this basis, its use has been banned or restricted in some products. As a consequence, industries turned to bisphenol alternatives, such as bisphenol S (BPS) and bisphenol F (BPF), which are now found in various consumer products, as well as in human matrices at a global scale. However, due to their toxicity, these two bisphenols are in the process of being regulated. Other BPA alternatives, whose potential toxicity remains largely unknown due to a knowledge gap, have also started to be used in manufacturing processes. The gradual restriction of the use of BPA underscores the importance of understanding the potential risks associated with its alternatives to avoid regrettable substitutions. This review aims to summarize the current knowledge on the potential hazards related to BPA alternatives prioritized by European Regulatory Agencies based on their regulatory relevance and selected to be studied under the European Partnership for the Assessment of Risks from Chemicals (PARC): BPE, BPAP, BPP, BPZ, BPS-MAE, and TCBPA. The focus is on data related to toxicokinetic, endocrine disruption, immunotoxicity, developmental neurotoxicity, and genotoxicity/carcinogenicity, which were considered the most relevant endpoints to assess the hazard related to those substances. The goal here is to identify the data gaps in BPA alternatives toxicology and hence formulate the future directions that will be taken in the frame of the PARC project, which seeks also to enhance chemical risk assessment methodologies using new approach methodologies (NAMs).</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"696-753"},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460007","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":"Examining the relationship between per-and polyfluoroalkyl substances and breast, colorectal, prostate, and ovarian cancers: a meta-analysis.","authors":"Ahmad Habibian Sezavar, Nima Rastegar-Pouyani, Nader Rahimi Kakavandi, Fatemeh Fakhari, Emad Jafarzadeh, Shima Aliebrahimi, Seyed Nasser Ostad","doi":"10.1080/10408444.2024.2425669","DOIUrl":"10.1080/10408444.2024.2425669","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used widely in industrial and commercial applications. Concerns exist about their potential link to cancer risk as possible endocrine-disrupting chemicals. We conducted a meta-analysis to evaluate the dose-response relationship between PFAS, perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorohexanesulfonic acid (PFHxS) exposure and risk of breast, prostate, colorectal, and ovarian cancers. We systematically searched major databases through May 2022 and identified 13 observational studies for inclusion. Using random-effects models, we calculated summary odds ratios (ORs) and 95% confidence intervals (CIs) comparing the highest versus lowest PFAS exposure categories. Additionally, we analyzed the dose-response correlation between PFAS and cancer risk in a subset of studies. The study revealed no substantial correlation between exposure to PFASs and the incidence of breast cancer (BC) (OR_PFOS = 1.15, 95% CI = 0.91-1.46, OR_PFOA = 1.01, 95% CI = 0.68-1.50, OR_PFNA = 0.88, 95% CI = 0.64-1.21, OR_PFHxS = 1.22, 95% CI = 0.40-3.77, and OR_PFDA = 1.29, 95% CI = 0.41-4.10), ovarian cancer (OR_PFOA = 1.43, 95% CI = 0.84-2.42), prostate cancer (OR_PFOA = 1.05, 95% CI = 0.88-1.26), and colorectal cancer (OR_PFOA = 0.77, 95% CI = 0.53-1.12) in the highest versus lowest exposure analysis. However, dose-response analysis showed that for every 1 ng/ml increase in PFNA and 2 ng/ml increase in PFOA, the relative risk for BC decreased significantly (RR 0.67, 95% CI 0.45-0.99 and RR 0.94, 95% CI 0.89-0.98, respectively). Non-linear dose-response analysis found no significant changes in BC risk with increasing PFAS levels. In conclusion, while the highest versus lowest analysis does not support associations between PFAS exposure and the risk of these cancers, linear dose-response analysis suggests potential inverse relationships between PFNA/PFOA levels and BC risk. Further research is warranted on these potential protective effects.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"981-995"},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784392","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":"Review of epidemiological and toxicological studies on health effects from ingestion of asbestos in drinking water.","authors":"Jennifer Go, Nawal Farhat, Karen Leingartner, Elvin Iscan Insel, Franco Momoli, Richard Carrier, Daniel Krewski","doi":"10.1080/10408444.2024.2399840","DOIUrl":"10.1080/10408444.2024.2399840","url":null,"abstract":"<p><p>Asbestos is a group of naturally occurring fibrous minerals that were commonly used in the construction of cement pipes for drinking water distribution systems. These pipes deteriorate and can release asbestos fibers into drinking water, raising concerns about potential risk to human health. The objective of this work was to synthesize human, animal, and <i>in vitro</i> evidence on potential health risks due to ingested asbestos in drinking water and evaluate the weight of evidence (WoE) of human health risk. A systematic review of epidemiological evidence was conducted, along with critical review of animal and <i>in vitro</i> evidence, followed by WoE evaluation that integrated human, animal, and <i>in vitro</i> evidence. The systematic review included 17 human studies with health outcomes mostly related to various cancer sites, with the majority focusing on the gastrointestinal system. The WoE evaluation resulted in very low levels of confidence or insufficient evidence of a health effect for cancers in 15 organ systems and for three non-cancer endpoints. While eight studies reported possible associations with stomach cancer in males, few high-quality studies were available to verify a causal relationship. Based on high-quality animal studies, an increased risk for cancer or non-cancer endpoints was not supported, aligning with findings from human studies. Overall, the currently available body of evidence is insufficient to establish a clear link between asbestos contamination in drinking water and adverse health effects. Due to the lack of both high-quality epidemiological studies and a validated kinetic model for ingested asbestos, additional research on this association is warranted.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"856-894"},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460009","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":"Mechanistic insights regarding neuropsychiatric and neuropathologic impacts of air pollution.","authors":"Katherine M Rentschler, Urmila P Kodavanti","doi":"10.1080/10408444.2024.2420972","DOIUrl":"10.1080/10408444.2024.2420972","url":null,"abstract":"<p><p>Air pollution is a significant environmental health risk for urban areas and developing countries. Air pollution may contribute to the incidence of cardiopulmonary and metabolic diseases. Evidence also points to the role of air pollution in worsening or developing neurological and neuropsychiatric conditions. Inhaled pollutants include compositionally differing mixtures of respirable gaseous and particulate components of varied sizes, solubilities, and chemistry. Inhalation of combustibles and volatile organic compounds (VOCs) or other irritant particulate matter (PM) may trigger lung sensory afferents which initiate a sympathetic stress response <i>via</i> activation of the hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes. Activation of SAM and HPA axes are associated with selective inhibition of hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-thyroid (HPT) axes following exposure. Regarding chronic exposure in susceptible hosts, these changes may become pathological by causing neuroinflammation, neurotransmitter, and neuroendocrine imbalances. Soluble PM, such as metals and nano-size particles may translocate across the olfactory, trigeminal, or vagal nerves through retrograde axonal transport, or through systemic circulation which may disrupt the blood-brain barrier (BBB) and deposit in neural tissue. Neuronal deposition of metallic components can have a negative impact through multiple molecular mechanisms. In addition to systemic translocation, the release of pituitary and stress hormones, altered metabolic hormonal status and resultant circulating metabolic milieu, and sympathetically and HPA-mediated changes in immune markers, may secondarily impact the brain through a variety of regulatory adrenal hormone-dependent mechanisms. Several reviews covering air pollution as a risk factor for neuropsychiatric disorders have been published, but no reviews discuss the in-depth intersection between molecular and stress-related neuroendocrine mechanisms, thereby addressing adaptation and susceptibility variations and link to peripheral tissue effects. The purpose of this review is to discuss evidence regarding neurochemical, neuroendocrine, and molecular mechanisms which may contribute to neuropathology from air pollution exposure. This review also covers bi-directional neural and systemic interactions which may raise the risk for air pollution-related systemic illness.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"953-980"},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799679","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":"Thank you to authors and reviewers of papers in Critical Reviews in Toxicology (CRT) volume 54, 2024.","authors":"Roger O McClellan","doi":"10.1080/10408444.2024.2440252","DOIUrl":"https://doi.org/10.1080/10408444.2024.2440252","url":null,"abstract":"","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":"54 10","pages":"695"},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876605","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":"Objective causal predictions from observational data.","authors":"Louis Anthony Cox","doi":"10.1080/10408444.2024.2399856","DOIUrl":"10.1080/10408444.2024.2399856","url":null,"abstract":"<p><p>Many recent articles in public health risk assessment have stated that causal conclusions drawn from observational data must rely on inherently untestable assumptions. They claim that such assumptions ultimately can only be evaluated by informed human judgments. We call this the <i>subjective approach</i> to causal interpretation of observational results. Its theoretical and conceptual foundation is a potential outcomes model of causation in which counterfactual outcomes cannot be observed. It risks depriving decision-makers and the public of the key benefits of traditional objective science, which invites scrutiny and independent verification through testable causal models and interventional hypotheses. We introduce an alternative <i>objective approach</i> to causal analysis of exposure-response relationships in observational data. This is designed to be more objective in the specific sense that it is independently verifiable (or refutable) and data-driven, requiring no inherently untestable assumptions. This approach uses empirically testable interventional causal models, specifically causal Bayesian networks (CBNs), instead of untestable potential outcomes models. It enables empirical validation of causal claims through Invariant Causal Prediction (ICP) tests across multiple studies. We explain how to use CBNs and individual conditional expectation (ICE) plots to quantify the effects on health risks of changing exposures while taking into account realistic complexities such as imperfectly controlled confounding, missing data, and measurement error. By ensuring that all causal assumptions are explicit and empirically testable, our framework may help to improve the reliability and transparency of causal inferences in health risk assessments.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"895-924"},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460008","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":"Xylene: weight of evidence approach case study to determine the need for an extended one generation reproductive study with a developmental neurotoxicity animal cohort.","authors":"Frank Faulhammer, Martijn Rooseboom, Neslihan Aygun Kocabas, Josje H E Arts, Alexandra Cordova, Elaine Freeman, Larry G Higgins, Muna Nahar, Emily Richmond, Steffen Schneider, Keith Morris-Schaffer","doi":"10.1080/10408444.2024.2413073","DOIUrl":"10.1080/10408444.2024.2413073","url":null,"abstract":"<p><p>Xylene is a high production volume chemical that is widely used as a solvent and polymer precursor, and is currently undergoing substance evaluation under Registration, Evaluation, Authorization and Restriction of Chemicals (REACH). Xylenes recently received testing decisions on one-generation reproductive toxicity (EOGRT) studies with additional developmental neurotoxicity (DNT) cohorts for each of the three isomers. Xylene presents a unique opportunity to investigate the need for additional animal DNT toxicology testing because it is a legacy industrial chemical for which a significant amount of animal and human data already exists on its toxicity profile, including central nervous system effects. Therefore, to address the need for further vertebrate testing, a comprehensive weight of evidence (WOE) review of published and previously unpublished new studies of xylene substances was performed. Evidence topics included the pharmacokinetics, narcotic effects in humans and animals, narcotic mode of action (MOA), and strength of DNT signal for xylene. Pharmacokinetic data indicate minimal distribution of the unmetabolized parent compound to the fetus relative to parental brain tissue, and rapid metabolism of xylene to methyl hippuric acid (MHA), which is also rapidly excreted in both humans and animals. Xylene exposure has also resulted in transient, nonspecific neurological effects including delays in reaction time of human volunteers and reductions in motor activity of animals. This narcotic MOA for xylene occurs by the nonspecific perturbation of nervous cell membrane phospholipids, such that membrane-bound proteins and their respective functions are impaired. Furthermore, an in-depth review of the available DNT data indicates significant methodological deficiencies in several studies in the literature purported to provide evidence of a DNT concern following xylene exposure and no DNT concern reported in one reliable study. In conclusion, based on xylene's pharmacokinetics, narcotic effects on the central nervous system observed in animal and human studies, its narcotic MOA, and the lack of a robust signal from the published DNT studies, there is no trigger for the additional EOGRT study DNT cohort to be conducted for xylene. Further, the findings on narcotic effects and MOA underscore the difficulty in separating transient, acute intoxication effects <i>via</i> direct exposure of the offspring from investigating DNT effects (as investigated in a standard guideline (426) DNT study) in the EOGRT study, therefore producing unreliable data, which is ethically at odds with REACH and 3 R principles.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"925-952"},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616363","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 analysis of the toxicity-related findings from repeated-dose subacute toxicity studies of industrial chemicals in male rats.","authors":"Jun-Ichi Takeshita, Yoshitaka Goto, Shinji Yamamoto, Takamitsu Sasaki, Kouichi Yoshinari","doi":"10.1080/10408444.2024.2427221","DOIUrl":"10.1080/10408444.2024.2427221","url":null,"abstract":"<p><p>The demand for alternatives to animal testing has increased, but there has been no significant progress in developing alternatives for repeated-dose toxicity tests despite their importance in chemical risk assessment. A comprehensive analysis of existing toxicity studies is the first step toward understanding toxicity and developing alternatives. However, such an analysis has yet to be performed for industrial chemicals. Therefore, we collected and organized publicly available repeated-dose subacute toxicity studies in male rats and constructed a database consisting of more than 2000 toxicity studies with about 500 toxicity-related findings. We then analyzed the no observed effect and lowest observed effect levels, toxicity-related findings, and organ categories in the database. The analyses revealed commonly and uncommonly observed toxicity-related findings and organ categories, as well as toxicity-related findings and organ categories with low and high median lowest observed effect levels. In addition, we extracted the toxicity studies registered in the Japanese and European chemical regulatory systems and conducted the same analysis for these datasets as the entire database. The results suggest that commonly observed toxicity-related findings were similar, but some toxicity-related findings differed in the frequency of observations between the two datasets.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"996-1010"},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784390","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}