Frontiers in toxicology最新文献

Introduction: Exposure to waterpipe smoke (WPS) in humans and experimental animals has been reported to cause oxidative stress and thrombotic complications. L-2-Oxothiazolidine-4-carboxylic acid (OTC) is a cysteine prodrug that maintains glutathione (GSH) in tissues. Nevertheless, the possible mitigating effects of OTC on platelet aggregation induced by WPS inhalation, and its underlying mechanisms of action remain unexplored. This is the goal of the present work in BALB/c mice.

Methods: Animals were exposed to either WPS or air (control) by inhalation daily for 30 min for 1 month. OTC was given 1 h before each exposure session by gavage at a dose of 80 mg/kg.

Results: WPS inhalation increased various markers of platelet aggregation, coagulation, fibrinolysis and endothelial integrity (platelet factor 4, tissue factor, fibrinogen, thrombin-antithrombin complexes, plasminogen activator inhibitor, P-selectin, E-selectin, intercellular adhesion molecule 1 and vascular cell adhesion molecule 1). It also shortened the prothrombin time and partial thromboplastin time and augmented the plasma concentrations of C-reactive protein and triglycerides. All these effects were attenuated by OTC treatment. Likewise, OTC administration significantly mitigated platelet aggregation in vivo. Platelets isolated from mice exposed to WPS showed high levels of markers of oxidative and nitrosative stress, calcium, annexin V and calpain. The latter effects were significantly alleviated by OTC treatment.

Discussion: Our data show that OTC administration significantly mitigated WPS-induced in vivo endothelial injury and thrombotic events, as well as platelet oxidative stress and apoptosis. This finding provides evidence on the mechanisms of toxicity of WPS on platelet physiology, and the alleviative action of OTC.

Objective: Pediatric poisonings account for a significant proportion of poison center consultations. Gastrointestinal decontamination (GD) is a crucial intervention in cases of acute poisoning, yet its effectiveness remains debated. This study aims to evaluate the role of esophagogastroduodenoscopy (EGD) in pediatric GD by retrospectively analyzing cases of suspected or confirmed toxic ingestions in which EGD was employed as a decontamination technique.

Methods: A retrospective review was conducted on medical records from our hospital between 1 January 2015, and 31 March 2025. Pediatric patients (<18 years) who underwent EGD for GD following suspected or confirmed ingestion of toxic drugs were included.

Results: A total of 19 cases met the inclusion criteria. In all cases, a potentially toxic drug dose was ingested. EGD was primarily indicated in the presence of sustained-release (SR) formulations, delayed gastric emptying, or severe clinical presentation. In 15 cases, xenobiotic residues (pharmacobezoars, intact tablets, or gastric contents containing drug material) were successfully removed via EGD. No complications were reported, and all patients had favorable outcomes.

Conclusion: EGD appears to be an effective GD technique in selected pediatric poisoning cases, particularly those involving bezoar-forming drugs, SR formulations, and substances that impair gastrointestinal motility. It may also be useful in cases of massive ingestion of potentially harmful substances. Further research is needed to establish standardized guidelines for its use in pediatric toxicology.

Background: Chemotherapy during pregnancy presents a clinical challenge, balancing maternal treatment efficacy with fetal safety. While chemotherapy after the first trimester is generally considered safe, its impact on placental development remains underexplored. This study investigates the effects of commonly used chemotherapeutic agents (CAs), including anthracyclines, taxanes, and platinum-based compounds, on maternal, placental, and fetal outcomes using a mouse model.

Methods: To model the chemotherapy exposure during pregnancy, pregnant mice received a single CA dose at embryonic day 13.5 (E13.5), equivalent to the beginning of the second trimester in human gestation. Placental and fetal outcomes were assessed at E15.5 and E18.5 using contrast-enhanced microtomography (micro-CT) and histopathological analyses to investigate the alterations associated to the exposure to differen CAs.

Results: Platinum-based agents, particularly carboplatin, significantly reduced fetal and placental weights and altered placental morphology, with persistent effects observed at E18.5. Contrast-enhanced microtomography (micro-CT) and histopathological analyses revealed reduced placental volumes, in both the labyrinth and junctional zones, and increased signs of trophoblast degeneration. Despite these changes, embryonic viability and litter size remained unaffected, suggesting that fetal growth restriction may be driven by placental insufficiency rather than direct fetal toxicity.

Conclusion: These findings underscore the importance of placental assessment in evaluating chemotherapy safety during pregnancy and highlight the potential long-term implications of platinum-based treatments on fetal development.

Background: Microplastic pollution has emerged as a global environmental crisis with potential adverse consequences on human health. Mixtures of microplastics with fungal particles including mycelial fragments or spores are highly probable exposure scenarios occurring in various occupational settings or in moldy built indoor environments. However, immunotoxic outcomes associated with such exposure remain poorly characterized. Most studies have focused on single-exposure components. Here, we investigated, for the first time, the immunotoxic effects of microplastics mixed with spores or mycelial fragments from Aspergillus fumigatus on human neutrophil-like cells.

Materials and methods: Differentiated HL60 neutrophil-like cells were exposed to 0-100 μg/mL HDPE microplastics mixed with 10⁶ heat-inactivated mycelial fragments or spores for 24 h.

Results and discussion: HDPE combined with fungal fragments induced significant release of IL-6 and IL-8 while the mixtures with fungal spores induced only IL-6 release from the neutrophil-like cells. Most importantly, we observed a trend of decreasing IL-6 levels with increasing doses of HDPE microplastics in mixture with fungal particles, indicating possible dysregulation of the pro-inflammatory response. The tested doses of HDPE microplastics in mixture with fungal particles showed no significant acute effects on the cell viability. Using HEK293-TLR reporter cells, we found no significant activation of TLR2 and TLR4 by HDPE microplastics, fungal particles, or their combination, suggesting that the release of IL-6 and IL-8 is induced through other innate immune-signaling pathways. Taken together, fungal particles as microbial contaminants, seem to be the main drivers of the immune responses triggered by exposure to mixed HDPE microplastics and fungal particles. Among these, fungal mycelial fragments appear to be the most potent compared to fungal spores that are typically monitored for risk assessments.

The Partnership for the Assessment of Risks from Chemicals (PARC) represents a joint effort among risk assessors, regulatory authorities, and the scientific community to advance the implementation of next-generation risk assessment (NGRA) in line with the objectives of the EU Chemicals Strategy for Sustainability. Addressing the challenges faced by the national and European regulators by integrating data generated through innovative methodologies is central to achieving this goal. Following an initial phase of the partnership, in which projects were defined based on a first prioritization of methodologies, a second prioritization round was conducted with input from the Governing Board representatives of all participating entities. This second process also considered the Key Areas of Regulatory Challenge introduced by the European Chemicals Agency in 2023, ensuring that the evolving research agenda within PARC is closely aligned with current and future regulatory needs. As a result, WP5 Hazard Assessment has updated its project portfolio to include four new projects that bridge identified regulatory gaps and strengthen the implementation phase of PARC. One project focuses on developmental and reproductive toxicity, another on developmental immunotoxicity, a third explores sexual dimorphism associated with hepatotoxicity, and a fourth transversal project, Regulatory Readiness of NAMs, aims to accelerate the regulatory uptake of promising methods developed under Work Package 5 (WP5). This article complements the previous PARC special issue by providing an overview of the updated WP5 project portfolio, illustrating the progression from prioritization to implementation, and highlighting how these new projects respond to evolving regulatory needs and contribute to the effective integration of new approach methodologies (NAMs) into chemical risk assessment.

Microplastics (MPs), plastic particles under 5 mm in diameter, represent a pervasive and persistent global environmental contaminant with cascading adverse effects on aquatic/terrestrial organisms and human health. While existing reviews have summarized isolated aspects of MP toxicity or assessment methods, this review advances the field through three integrated contributions that address critical knowledge gaps. First, it synthesizes physical, chemical, and biological toxicity mechanisms into a unified "particle-environment-organism" cascade, highlighting synergistic interactions that are often overlooked in fragmented syntheses. Second, it provides a critical evaluation of methodological advances by proposing a standardized dosing framework designed to address longstanding challenges to cross-study comparison. Third, it bridges ecological and human toxicology via an integrative conceptual model linking MP properties, environmental modifiers, biological modulating factors, key toxicological events (KTEs) and adverse outcomes, while outlining actionable research priorities and regulatory strategies. By consolidating these elements, this review synthesizes current understanding of MP toxicity and provides a structured framework to enhance comparability across studies, as well as guide future research and regulation. Crucially, it aims to narrow the gap between lab-based findings and real-world application, facilitating the translation of scientific insights into practical strategies for mitigating risks to both ecosystems and human health.

Objective: To explore the clinical characteristics and misdiagnosis causes of arsenic-induced peripheral neuropathy.

Methods: We report a case of arsenic-induced peripheral neuropathy initially misdiagnosed as Guillain-Barré syndrome, with analysis of clinical characteristics, diagnostic workup and therapeutic management, supplemented by literature review.

Results: A 58-year-old male presented with progressive peripheral neuropathy, initially diagnosed with Guillain-Barré syndrome but later suspected as chronic inflammatory demyelinating polyneuropathy. However, his symptoms progressed despite standard immunotherapy, developing generalized motor deficits, myokymia, ascending sensory loss, and facial palsy. Careful reevaluation revealed critical diagnostic clues: a history of intermittent topical application of an unidentified herbal medicine preceding symptom onset, accompanying gastrointestinal prodromal symptoms, and characteristic physical findings including Mee's lines, lower limb hyperpigmentation, and foot hyperkeratosis. Subsequent laboratory testing confirmed markedly elevated arsenic levels in nail and hair samples, ultimately establishing the diagnosis of arsenic-induced peripheral neuropathy.

Conclusion: Arsenic-induced peripheral neuropathy can clinically mimic Guillain-Barré syndrome. For immunotherapy-refractory cases, clinicians should maintain high suspicion for potential heavy metal poisoning. Careful elicitation of toxic exposure history and recognition of characteristic dermatologic findings are critical for definitive diagnosis, as early recognition significantly improves prognosis.

Introduction: 1,2-Dichloroethane (1,2-DCE) is a highly toxic industrial organic solvent that can cause acute toxic encephalopathy through occupational exposure, with underreported clinical data in English literature. To explore the clinical characteristics and patients' response to supportive treatments of toxic encephalopathy caused by 1,2-DCE.

Methods: Fifty-nine patients with acute 1,2-DCE poisoning admitted to the hospital from January 2009 to December 2022 were selected. Patients were divided into three groups based on clinical manifestations: intracranial hypertension (Group A), limb tremors (Group B), and behavioral changes (Group C).

Results: Toxicology testing found that 1,2-DCE was difficult to detect in serum after more than 24 h. Of the 59 patients, 45 (76.27%) achieved complete recovery, 10 (16.95%) achieved partial recovery, and 4 (6.78%) died. Statistical analysis showed a significant difference in recovery rates among the three groups (χ² = 10.612, P < 0.05). There were no statistically significant differences in symptom and cranial imaging recovery times between the three groups.

Conclusion: Acute 1,2-DCE poisoning can cause severe toxic encephalopathy. Early and prolonged treatment with dehydrating agents and glucocorticoids is effective in improving prognosis, and patients with intracranial hypertension are at higher risk of death due to brain herniation.

The foreign body reaction (FBR), characterized by chronic inflammation and fibrotic capsule formation around implanted medical devices, remains a major cause in device-related complications. Current preclinical risk assessment relies on in vivo testing according to ISO 10993-6:2024, which are limited by species differences, incomplete mechanistic insight, and ethical concerns. Additionally, ISO/TS 10993-20:2006 outlines immunotoxicity knowledge regarding implant-induced effects such as FBR and specifies a collection of in vitro assays. The perspective presented here, aims to explore the applicability of the Adverse Outcome Pathway (AOP) framework to FBR in order to integrate evidence and methods into a structured mechanistic context and facilitate the application of in vitro tests in preclinical risk assessment of FBR. A targeted literature review was conducted to identify and organize biological mechanisms into a putative AOP, map available new approach methodologies, and highlight critical knowledge gaps and uncertainties. This initial framework may guide early screening for low-FBR materials and support mechanistically anchored, non-animal biocompatibility assessment strategies for medical devices.

Developmental and reproductive toxicity (DART) testing has traditionally relied on animal studies, which are costly, time-consuming, and ethically constrained. To advance new approach methodologies (NAMs), we developed a mechanism-informed deep learning framework for predicting DART using in vitro bioactivity data from 23 ToxCast assays mechanistically linked to key developmental and reproductive pathways. Four state-of-the-art (SOTA) deep learning architectures (DGCL, TransFoxMol, MolPath, and MolFormer) were evaluated to address performance limitations commonly observed in traditional supervised learning approaches. Each model was fine-tuned using the curated ToxCast dataset, with the F1 score serving as the primary evaluation metric. Among these, the DGCL model consistently outperformed baseline machine learning algorithms, including random forest, XGB, GBT, decision tree, and logistic regression. Extending DGCL to a multi-task learning framework further improved model stability and performance for endpoints with limited active data. External validation with 91 reference chemicals curated and verified by the ECVAM ReProTect program demonstrated balanced predictive performance (F1 = 0.68), confirming the reliability and generalizability of the fine-tuned DGCL model. By leveraging advanced deep learning architectures, the model effectively handles mechanistically diverse and imbalanced assay data with limited active samples, resulting in improved predictive performance across DART-related effects. Overall, this study demonstrates the potential of integrating mechanistic bioassay information with deep learning to develop reliable, mechanism-based, and non-animal methods for DART prediction and potential regulatory application.