Critical Reviews in Toxicology最新文献

{"title":"Mechanisms of developmental neurotoxicity mediated by perturbed thyroid hormone homeostasis in the brain: an adverse outcome pathway network.","authors":"Nathalie T O M Dierichs, Aldert H Piersma, Robin P Peeters, W Edward Visser, Marcel E Meima, Ellen V S Hessel","doi":"10.1080/10408444.2025.2461076","DOIUrl":"https://doi.org/10.1080/10408444.2025.2461076","url":null,"abstract":"<p><p>Thyroid hormone (TH) is crucial for proper neurodevelopment. Insufficient TH concentrations in early life are associated with lower IQ and delayed motor development in children. Intracellular levels of TH are modulated via the transmembrane transport of TH and intracellular deiodination, and can mediate gene transcription via binding to the nuclear TH receptor. Chemical exposure can disrupt TH homeostasis via modes of action targeting intracellular mechanisms, thereby potentially influencing TH transport, deiodination or signaling. Understanding the cause and effect relationships of chemical hazards interfering with TH homeostasis in the developing brain is necessary to identify how chemicals might disturb brain development and result in neurodevelopmental disorders. Adverse Outcome Pathways (AOPs) can provide a template for mapping these relationships, and so far multiple AOPs have been developed for TH homeostasis and adverse effects on cognition. The present review aims to expand current AOP networks by (1) summarizing the most important factors in the regulation of brain development under influence of TH, (2) integrating human-based mechanistic information of biological pathways which can be disturbed by TH disrupting chemicals, and (3) by incorporating brain-specific TH-mediated physiology, including barriers and cell specificity, as well as clinical knowledge. TH-specific pathways in the fetal brain are highlighted and supported by distinguishing cell type specific Molecular Initiating Events (MIEs) and downstream Key Events (KEs) for astrocytes, neurons and oligodendrocytes. Two main pathways leading to adverse outcomes (AOs) in the areas of 'cognition' and 'motor function' are decreased myelination due to oligodendrocyte dysfunction, and decreased synaptogenesis and network formation via the neurons. The proposed AOP framework can form a basis for selecting developmental neurotoxic <i>in vitro</i> and <i>in silico</i> test systems for an innovative human-focused hazard testing strategy and risk assessment of chemical exposure.</p>","PeriodicalId":10869,"journal":{"name":"Critical Reviews in Toxicology","volume":" ","pages":"1-17"},"PeriodicalIF":5.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585003","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":"https://doi.org/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":"1-21"},"PeriodicalIF":5.7,"publicationDate":"2025-02-27","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 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":"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":"https://doi.org/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":"1-55"},"PeriodicalIF":5.7,"publicationDate":"2025-02-21","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":"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":"https://doi.org/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":"1-48"},"PeriodicalIF":5.7,"publicationDate":"2025-02-21","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":"https://doi.org/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":"1-19"},"PeriodicalIF":5.7,"publicationDate":"2025-02-13","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":"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":"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":"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":"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}