Critical Reviews in Toxicology最新文献

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], p < .05), reduced utilization of mechanical ventilation (RR = 0.78, 95% CI [0.64, 0.95], p < .05), and superior cholinesterase recovery levels (standardized mean difference (SMD) = 1.70, 95% CI [-0.02, 3.43], p = .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 (p > .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.

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.

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

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, in vitro and ex vivo 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.

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.

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 (p < .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) (p < .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.

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.

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.

There is a concern on the safety of cosmetic ingredients and their endocrine-disrupting (ED) potential. Frequent use as well as the use of a diverse range of cosmetics pose a concern for a potential health risk via aggregate exposure to endocrine disrupting chemicals (EDCs). In this study, a list of ingredients available in cosmetic products that were recently introduced to the Dutch market was retrieved from the commercially accessible Mintel database and screened for the presence of EDCs. To achieve this, a workflow was developed to crosscheck the list of cosmetic ingredients with information on potential EDCs derived from open-source initiatives (i.e. chemical lists from the European Chemicals Agency, national authorities, and non-governmental organizations). Using this workflow, 27 chemicals were identified that were categorized as "indications for ED properties" and one chemical as "no concern for ED properties" out of the 890 cosmetic ingredients reviewed. For one of these chemicals, geraniol, a preliminary safety assessment was performed. Aggregated exposure to geraniol via cosmetics was modeled using PACEMweb and compared to the lowest observed adverse effect level on thyroid histopathology derived from an extended-one-generation study. This exercise showed that, based on the current information available, geraniol can be used safely in cosmetics with regard to endocrine-related health risks. Next, the cosmetic ingredients that are currently not identified as an EDC (i.e. not present on one of the crosschecked lists, n = 862), were prioritized based on an aggregate exposure score for further screening of their endocrine disrupting properties (n = 58). For eight out of the 58 prioritized chemicals data retrieved from a literature search indicated an endocrine-mediated relationship, and were categorized as "limited indications of ED properties". Overall, the developed workflow is a useful tool to screen cosmetics for the presence of potential EDCs and to prioritize chemicals for further evaluation of their ED properties, as well as assessment of their safe use in cosmetics.

Per- and polyfluoroalkyl substances (PFAS) continue to be an emerging chemical class of concern due to their long half-lives in nature and in the human body. There have been many epidemiology studies published in the scientific literature on PFAS and various health effects. Until recently, these studies have focused on assessing exposure to individual PFAS rather than exposure to mixtures of PFAS. Over the past two decades, mixture methods-statistical methods for investigating the association of mixtures-have been developed, making it possible to more accurately assess the risk of adverse health effects associated with exposure to PFAS. To help provide a resource for the overall evaluation of potential health effects of PFAS mixtures, we applied a consistent set of examination methods and criteria for all epidemiology studies that examined the potential relationship between exposure to PFAS mixtures and various types of health outcomes. We identified 233 cohort studies, 39 case-control studies, and 89 cross-sectional studies that evaluated general background-level exposures, exposure from contaminated sites, and occupational exposure to PFAS mixtures and health outcomes including metabolic, cardiovascular, and immune system effects, fetal development, pregnancy outcomes, reproductive effects, liver function, and respiratory effects. We extracted study characteristics and results in a systematic manner and performed a formal study quality evaluation and classified studies into tiers based on their methodological strengths and weaknesses. We found 42 prospective cohort studies, five nested case-control studies, and one traditional case-control study that qualified for inclusion in the highest tier of quality (Tier I). Overall, the weight of evidence from this systematic review indicates that the available epidemiology studies currently support an association between exposure to PFAS mixtures and adiposity, increased total cholesterol, and hypertension, while the evidence for all other health outcomes is suggestive or limited.