Journal of Xenobiotics

Background: Micro- and nanoplastics (MNPs) are emerging contaminants increasingly detected in human tissues and biological fluids. Their presence in blood, vascular tissues, thrombi, and atherosclerotic plaques raises concern about their possible association with cardiovascular disease. This systematic review synthesized evidence on associations between MNPs and cardiovascular pathology. Methods: A systematic search was conducted in October 2025 in PubMed, Scopus, Web of Science, and Embase according to PRISMA guidelines and a PICOS-based strategy. Original human studies from the last 10 years were eligible. Fourteen studies were included. Due to methodological heterogeneity, a narrative synthesis was performed. Risk of bias was assessed using ROBINS-E, and certainty of evidence was evaluated using a GRADE-informed approach. Results: MNPs were detected in multiple cardiovascular-related matrices. Included studies suggested possible associations with major adverse cardiovascular events, acute coronary syndrome, myocardial infarction, arterial stenosis, vascular calcification, thromboembolic disease, hypertension, inflammatory markers, coagulation-related parameters, and lipid profiles. However, the certainty of evidence was very low, and most studies had a high or very high risk of bias. Conclusions: Current evidence suggests a possible association between MNPs and cardiovascular pathology, but causality remains unproven. Larger prospective studies using standardized detection protocols, rigorous contamination control, and adjustment for confounders are needed. Full article

Pollinators are essential for maintaining ecosystem stability and agricultural productivity, yet their populations are in decline due to various stressors, including parasites, pathogens, climate change and pesticide exposure. Protecting pollinators has become a priority for environmental safety and food security. Regulatory authorities, including the European Food Safety Authority (EFSA), the Environmental Protection Agency (EPA) and the Organisation for Economic Co-operation and Development (OECD), have guidelines for pesticide risk assessment, but conventional testing methods are costly and time-consuming, limiting their applicability to large chemical datasets. Computational approaches, such as Structure–Activity Relationship (SAR) models, offer efficient alternatives by enabling the rapid screening of pesticides for potential toxicity to pollinators. In this study, we used a dataset of 357 compounds to develop a classification model based on structural alerts to predict oral acute toxicity in Apis mellifera. The model showed a higher Matthews Correlation Coefficient in the training set (0.82), with a moderate decay in the test set (0.56) likely due to applicability domain limits. Despite this, high balanced accuracy (0.80) and sensitivity (0.79) in the test set confirm the model as a reliable tool for the toxicological screening of pesticides. Full article

Depression is increasingly recognized as a multifactorial disorder involving immune, metabolic, and neurobiological disturbances that extend beyond classical monoaminergic hypotheses. Among xenobiotic-based experimental approaches, lipopolysaccharide (LPS) has become a valuable tool for investigating how peripheral inflammatory stimuli are translated into central neurobiological dysfunction. This narrative review aimed to integrate current evidence regarding the mechanisms by which LPS-induced neuroimmune activation contributes to depression-related phenotypes and to discuss the translational relevance of these findings. Literature searches were performed in PubMed, ScienceDirect, and Google Scholar, focusing on studies addressing inflammatory signaling, oxidative imbalance, inflammasome activation, neurotransmitter dysfunction, and experimental modeling strategies. Current evidence suggests that LPS-induced neuroinflammation involves a dynamic interaction between peripheral immune signaling, mitochondrial dysfunction, redox imbalance, and glial activation, establishing self-amplifying mechanisms capable of sustaining chronic inflammatory states. Such alterations profoundly affect kynurenine metabolism, glutamatergic homeostasis, and reward-related neurotransmission, thereby contributing to synaptic dysfunction and behavioral impairment. Experimental findings obtained from animal, cellular, and computational platforms further support the emergence of integrated therapeutic strategies targeting multiple neuroimmune pathways. Collectively, these observations reinforce the concept that neuroinflammation represents a central biological interface linking xenobiotic exposure to depressive-like behavior. Full article

Human per- and polyfluoroalkyl substances (PFAS) and metal exposures occur as mixtures, but most studies evaluate them independently. Using data from adults in the 2017–2018 National Health and Nutrition Examination Survey (NHANES) with directly measured PFAS and blood metals (N = 1648), we assessed joint associations of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), lead, cadmium, and mercury with prevalent diabetes via survey-weighted logistic regression, Weighted Quantile Sum (WQS) regression, quantile g-computation, and design-aware and naïve Bayesian Kernel Machine Regression (BKMR). Survey-weighted diabetes prevalence was 11.4%. Lead and PFOS emerged as the dominant contributors to the exposure mixture in the BKMR model, with posterior inclusion probabilities of 1.00 and 0.997, respectively. In the WQS model, PFOS and PFOA were the primary drivers of the positive mixture index, consistent with their proposed roles in endocrine disruption and insulin resistance. BKMR exposure-response functions were non-monotonic, indicating that lead and cadmium associations with diabetes are nonlinear rather than uniformly directional across the exposure range, a structure that conventional logistic regression cannot capture. Overall, restricting to directly measured exposures, incorporating the full NHANES design in the primary regression, and triangulating across complementary mixture frameworks provide a more rigorous platform than prior single-pollutant or design-naive approaches. Full article

Intensive vegetable production can increase the transfer of persistent toxic trace elements from agricultural soils into the food chain, particularly where agrochemical use, irrigation inputs, and local geochemical conditions are insufficiently characterized. This study was undertaken to assess toxic trace-metal contamination levels in soils and vegetables from two renowned vegetable-producing subdistricts—Shibganj and Kahaloo—in the Bogra district, Bangladesh. The study also estimated potential human health risks by evaluating the dietary intake of these elements. It measured Pb, Ni, Cd, and Cr content in six vegetables and their respective farm soils using an atomic absorption spectrophotometer (AAS). The average concentrations of Pb, Ni, Cd, and Cr in farm soils of Shibganj and Kahaloo subdistricts were 158.3 ± 8.83, 31.5 ± 5.25, 0.43 ± 0.08, and 14.1 ± 2.16 µg g⁻¹ and 164.1 ± 4.60, 35.7 ± 6.91, 0.53 ± 0.14, and 9.37 ± 2.87 µg g⁻¹, respectively. Soils collected from all locations in both subdistricts of Bogra fall under ‘moderate’ ecological risk. Regarding the pollution load index (PLI), 66.7% of Shibganj and 75.0% of Kahaloo sampling sites had a PLI > 1.0, confirming that ‘metal pollution exists.’ Based on the calculated bioconcentration factors (BCFs), Cr and Cd show a high tendency to migrate from soil to various vegetables in the study area, though the mean Cd BCF for brinjal in Shibganj exceeded 1.0 due to a single high observation. The results demonstrated that the edible parts of potatoes, onions, and chilies accumulate significant amounts of toxic trace elements. The calculated mean daily intake of Pb and Cr in all vegetables ranged from 0.33 to 1.21 mg person⁻¹ day⁻¹ and from 0.10 to 0.64 mg person⁻¹ day⁻¹, respectively, exceeding the upper tolerable intake limits. Similarly, dietary intake of potatoes showed both non-carcinogenic and carcinogenic risks, while brinjal showed only carcinogenic risks for adults. Redundancy analysis (RDA) indicates that the measured soil parameters are strong predictors of the response variables (trace element content in various vegetables). Overall, the results identified Pb-dominated soil contamination and human exposure to Pb and Cr associated with vegetables as the principal concerns. To address these issues, priority actions should be given to source apportionment and testing of various agricultural inputs. Additionally, before implementing site-specific remediation or issuing consumption advisories, these risks should be validated through metal speciation and bioaccessibility analyses. Full article

Heavy metals (HMs) such as copper (Cu), lead (Pb), cadmium (Cd), chromium (Cr) and zinc (Zn) from industrial activities are discharged into nearby water resources after treatment. In the present study, the potential of utilizing chemically activated carbon derived from water hyacinths as a sustainable and low-cost adsorbent for heavy metal removal from industrial wastewater from the Nakawa industrial area, Uganda was investigated. The measured physicochemical parameters of wastewater (temperature, pH, electrical conductivity, total dissolved solids, turbidity, dissolved oxygen, chlorides and total hardness) varied significantly among the three sampled sites (p < 0.05), except for pH. Similarly, the concentration of the HMs in the samples (0.54 ± 0.04 mg L⁻¹ for Cr to 93.54 ± 0.07 mg L⁻¹ for Pb) varied significantly between sites (p < 0.05), exceeding the maximum permissible limits of Cd, Pb, Cr, Cu and Zn specified in the National Environment Standards for Discharge of Effluent into Water or Land. The water hyacinth biomass was activated using eggshell powder and phosphoric acid, followed by thermal treatment. Characterization using Fourier-transform infrared spectroscopy and scanning electron microscopy confirmed that there was improvement in its surface functionality and porosity post activation. Batch adsorption experiments indicated that optimal removal of the HMs was achieved at pH 4–5, contact time of 90 min, and 1.0 g of adsorbent. Maximum adsorption capacities of Pb, Cd, Cu, Cr and Zn were in the range of 1.04–8.36 mg g⁻¹. Under the optimized conditions, the eggshell-activated carbon derived from water hyacinths had removal efficiencies of 91.2 ± 9.1% (range: 71.3–100%). Adsorption occurred through both monolayer and multilayer coverage, as indicated by the experimental data which fitted well to the Freundlich isotherm (Cd²⁺, Pb²⁺, Zn²⁺ and Cu²⁺ ions) and Langmuir isotherm model (Cr³⁺ ions). These results support the potential of water hyacinth-derived activated carbon as an ecofriendly alternative for treating low concentrations of these HMs in industrial wastewater. Full article

Drug repurposing represents a rational and resource-efficient strategy to expand the oncological armamentarium by leveraging the established pharmacology, clinical experience, and safety-monitoring frameworks of approved non-oncological agents. Clozapine (CZP), an atypical antipsychotic characterized by broad receptor pharmacology, complex biotransformation, and clinically relevant toxicological liabilities, has emerged as a candidate of interest following preclinical evidence of context-dependent anticancer activity across multiple tumor types. As such, CZP provides an informative case study at the interface between therapeutic drug action and xenobiotic behavior. This review provides a critical and integrated synthesis of the current evidence supporting the repurposing of CZP in oncology, with particular emphasis on the relationship between its molecular mechanisms, dose–exposure requirements, pharmacological complexity, and potential toxicity. Analysis of in vitro and in vivo studies across glioblastoma, non-small cell lung cancer, breast cancer, and melanoma brain metastasis models indicates that CZP can impair tumor cell proliferation and survival through a form of mechanistic plasticity. Rather than acting through a single conserved pathway, CZP appears to disrupt shared upstream processes related to pro-survival signaling, cellular stress tolerance, and metabolic homeostasis, while engaging tumor-specific downstream responses, including autophagic cell death, mitochondria-dependent apoptosis, oxidative stress, and coordinated modulation of survival and angiogenic pathways. Despite this mechanistic rationale, translation remains substantially constrained, most notably by the order of magnitude gap between anticancer-effective concentrations in vitro and clinically achievable plasma exposures, requiring careful distinction between potentially useful anticancer pharmacology and nonspecific xenobiotic-induced cellular stress and clinically unacceptable toxicity. Key limitations include the discrepancy between anticancer-effective concentrations observed in vitro and exposures achievable during standard psychiatric dosing, the limited understanding of how CZP metabolism and metabolite formation may influence efficacy and toxicity, the absence of integrated pharmacokinetic–pharmacodynamic and toxicokinetic modeling, and the lack of dedicated clinical trial evidence. To address these challenges, this review examines complementary translational strategies, including patient-derived organoids, co-culture systems, microphysiological platforms, pharmacokinetic and toxicological modeling, and computational digital twin frameworks. Together, these approaches may support a biologically informed and risk-aware evaluation of CZP, helping to identify responsive tumor contexts, anticipate exposure-related liabilities, and prioritize rational combination strategies. By integrating therapeutic potential with xenobiotic pharmacology and toxicology, this review positions CZP within the evolving landscape of precision oncology and evidence-driven drug repurposing. Full article

Maternal exposure to polycyclic aromatic hydrocarbons (PAHs) during pregnancy has been associated with adverse obstetric and perinatal outcomes, including miscarriage, low birth weight, intrauterine growth restriction, and spontaneous abortion. Exposure occurs through multiple pathways, including dietary intake and inhalation, which ultimately determine the final body burden. PAHs may reach relevant levels in the blood, representing the initial step in their internal distribution to the placenta, umbilical cord, and breast milk, thereby compromising maternal–fetal health. In this exploratory study, maternal blood samples were collected from pregnant women residing in different regions of Antioquia, Colombia. Serum was isolated from whole blood, subsequently extracted using freezing-assisted liquid–liquid extraction, purified by solid-phase extraction, and analyzed by GC–MS. Method performance showed PAH recoveries between 60 and 120%, limits of detection (LOD) ranging from 0.5 to 3.3 ng·mL⁻¹, and limits of quantification (LOQ) ranging from 1.4 to 9.9 ng·mL⁻¹. Airborne PAH concentrations were measured using a photoelectric aerosol sensor, and higher levels were observed in municipalities intersected by major highways, indicating a strong vehicular contribution, with an average concentration of 72.6 ± 39.2 ng·m⁻³. Low and medium-molecular weight PAHs were detected in serum samples at an average concentration of 43.8 ± 8.8 ng·g⁻¹ of lipid (mean of ∑ individual congeners). In contrast, a high-molecular-weight PAH, benzo[a]pyrene (BaP), was detected in one participant. Pyrene (PYR) and fluoranthene (FLU) were the predominant congeners, suggesting combustion-related sources, primarily vehicular emissions. Serum PAH levels showed a correlation with the frequency of consumption of canned fish and meat, but not with short-term airborne PAH measurements. These exploratory findings suggest that dietary intake is a primary pathway of bioaccumulation during acute exposure and plays a key role in determining the parental PAHs burden during pregnancy in polluted environments. However, additional data on parent PAHs and their metabolites are needed to provide a more comprehensive assessment of cumulative exposure arising from dietary sources and chronic inhalation of airborne PAHs. Full article

Selenium is a trace element of vital importance for ecosystem functioning and human health mainly due to its antioxidant and protective properties. Since both selenium deficiency and excess can have harmful effects on living organisms, monitoring its distribution in biological systems and the environment is of significant scientific and public health interest. This study systematically assessed selenium concentrations in biological (urine, serum, and hair) and environmental (soil and dandelion) samples in eastern Croatia. Selenium concentrations were determined using the inductively coupled plasma mass spectrometry method. In biological samples, median selenium concentrations were from 15.02 to 37.15 μg·L⁻¹ in urine, from 80.76 to 114.05 μg·L⁻¹ in serum, and from 0.21 to 0.46 µg·g⁻¹ in hair. In environmental samples, median selenium concentrations varied depending on location, ranging from 0.32 to 0.51 mg·kg⁻¹ in soil and from 6.55 to 84.41 µg·kg⁻¹ in dandelion. PCA was applied to identify overall patterns and groupings among biological and environmental samples, showing that dandelion samples from urban locations exhibited the highest selenium concentrations, indicating the influences of urban environmental conditions on selenium accumulation. Full article

Tetracyclines (TCs) are antibiotics widely used in human and veterinary medicine as well as in agricultural practices. They may be retained in soil or drift into freshwater, thereby exerting effects on non-target organisms and deteriorating ecological quality. In this study, tetracycline (T), oxytetracycline (OT), chlortetracycline (CT), and their binary and ternary mixtures were evaluated using a battery of bioassays including terrestrial plants, aquatic crustaceans, a ciliate protist and a bacterial species. Results showed a concentration-dependent effect for parameter immobilization in Daphnia magna and Artemia salina, seed germination in the terrestrial plants, and bioluminescence inhibition and growth inhibition in Aliivibrio fischeri and Tetrahymena thermophila, respectively. For A. fischeri, statistically significant interactions were observed between dose and exposure time. A. salina demonstrated greater sensitivity than D. magna in all cases. Both A. salina and A. fischeri showed increased toxicity to OT and the ternary mixture. Dicots presented greater sensitivity than the monocot species in all cases. In the combined exposures, there was a deviation from the concentration addition (CA) model, with possible synergism for CT + T and the ternary mixture for A. fischeri. The concurrent environmental exposure of non-target organisms to TCs should be investigated further. Full article

Background/Objectives: Glucocorticoid therapy remains clinically indispensable, yet its long-term use is profoundly constrained by insulin resistance (IR), hepatic steatosis, and progressive metabolic dysfunction. Methylsulfonylmethane (MSM), a naturally occurring sulfur-containing nutraceutical with established antioxidant and anti-inflammatory activities, has emerged as a promising metabolic modulator; however, its therapeutic relevance in glucocorticoid-induced hepatic IR has not previously been explored. Methods: Male Wistar rats received MSM (200 or 400 mg/kg/day, p.o.) for 14 days, while dexamethasone (DEX) (8 mg/kg/day, i.p.) was administered during the final 7 days to induce severe metabolic dysfunction. Results: DEX provoked profound IR, dyslipidemia, oxidative stress, hepatocellular injury, and steatotic degeneration accompanied by marked ultrastructural abnormalities. Remarkably, MSM conferred dose-dependent metabolic and hepatoprotective effects, significantly restoring glucose homeostasis, insulin responsiveness, lipid metabolism, and hepatic structural integrity. Mechanistically, MSM exerted a pleiotropic regulatory effect through suppression of the glucocorticoid-responsive kinase SGK1, restoration of AMPK/mTOR signaling balance, and normalization of insulin signaling pathways and metabolic transcriptional regulators. Furthermore, MSM effectively attenuated oxidative stress and inflammatory amplification consistent with modulation of the NLRP3/NF-κB/IL-6 axis. Importantly, the current work identifies angiogenic remodeling demonstrated by DEX-induced upregulation of VEGF and CD34, both of which were substantially suppressed by MSM treatment. Conclusions: This study provides novel evidence that MSM mitigates glucocorticoid-induced hepatic IR through coordinated modulation of glucocorticoid-responsive kinases, metabolic signaling networks, redox–inflammatory cascades, and pathological angiogenesis. Consequently, MSM may represent a promising candidate for further preclinical and clinical evaluation regarding its capacity to limit glucocorticoid-associated metabolic burdens. Full article

Although praziquantel (PZQ) is the main antischistosomal drug currently in use, concerns remain regarding incomplete reversal of schistosomiasis-induced pathology and the emergence of drug resistance. This study evaluates the combined effect of PZQ with safranal, a bioactive saffron constituent, on Schistosoma mansoni-induced pathology in mice. Male CD1 Swiss albino mice were exposed to 60 S. mansoni cercariae and, at week 9 post-infection, were treated with PZQ (500 mg/kg orally for two consecutive days), safranal (50 mg/kg/day), or both, for three weeks. The animals were sacrificed at week 11 post-infection. Worm and egg burdens, liver histopathology, fibrotic markers, oxidative stress, and inflammatory cytokines were assessed. Combined PZQ + safranal therapy significantly reduced adult worm counts and hepatic and intestinal egg loads compared to PZQ alone. All treatments decreased liver index (hepatomegaly), with the combination treatment providing the best intervention. Histological analyses revealed significantly reduced granuloma size and hepatic necrosis post-treatment, particularly in the combination group. The levels of proinflammatory cytokines (TNF-α, IL-1β) and Th2 cytokines (IL-4, IL-5, IL-6, IL-10) were significantly lowered in treated mice, most notably with the combination treatment. Oxidative stress was also markedly attenuated, and infected mice exhibited elevated malondialdehyde and depleted antioxidant enzymes (SOD, CAT, GSH). Interestingly, PZQ and/or safranal restored antioxidant status and reduced lipid peroxidation, with the combination being most effective. Furthermore, collagen deposition and expression of hepatic fibrotic markers α-smooth muscle actin (α-SMA), TGF-β1, and matrix metalloproteinase-9 were most effectively suppressed by combined therapy. To conclude, safranal enhances PZQ’s antischistosomal efficacy and confers additive protection against Schistosoma-induced liver fibrosis. Full article

Most airline passengers and crew assume that the air in the cabin is free from harmful or hazardous substances, as is mandated by airworthiness regulations. While fresh air entering the cabin is sterile (and if recirculated is usually efficiently filtered to remove microorganisms), if the fresh air is bled off the turbine compressors (as is the case in about 95% of airliners currently in service), it may be contaminated with traces of engine oil and ultrafine particles abraded from the turbine blades, and possibly traces of hydraulic fluid leaking from servo systems. Engine oil contains tricresyl phosphate (TCP) as an essential antiwear agent, but it is also a well-known neurotoxin, and it has been suggested that there may be no safe lower limit of exposure, not least because of considerable variation among individuals in sensitivity to tri-ortho-cresyl phosphate (ToCP) and other isomers with at least one ortho constituent. This paper reviews current knowledge about these hazards and discusses the medical and economic motivations for diminishing them. A calculation based on maintaining the life quality index shows that eliminating xenobiotic hazards in aircraft cabin air is likely to be affordable. Full article

African soils face increasing levels of metal pollution due to industrialization, artisanal mining activities, improper waste management, and enhanced agricultural productivity. However, unlike many organic pollutants, heavy metals do not degrade naturally and therefore persist in environmental systems for prolonged periods. Heavy metals accumulate over many decades in the soil and bioaccumulate through the food chain causing severe health complications such as cancer, kidney problems, and neurological impairment. This paper reviews the current literature on the origin, prevalence, and behavior of the main pollutants Pb, Cd, Cr, As, Hg, and Cu. The major phytoremediation methods including phytoextraction, rhizofiltration, phytostabilization, and phytovolatilization are highlighted alongside in planta screening methods for hyperaccumulating plants including Berkheya coddii (Ni) and Haumaniastrum robertii (Co). The paper evaluates various enhancement techniques such as the use of chelators, Rhizobium inoculations, and genetic modifications. The significance of these approaches in tropical and subtropical climates is discussed. The paper suggests a holistic framework involving empirical kinetic modeling, geospatial machine learning (random forest, kriging), and molecular omics in prediction modeling. Major hurdles in such predictions include lack of field-based verification of the models, biotechnology safety of genetically modified (GM) organisms, and inadequate regulations. Future perspectives emphasize community-driven phytomining, biomass recycling, and resilient phytoremediation solutions. Full article

This study analyzes the determinants of self-reported behaviours and perceptions associated with pesticide toxicity risk in children using the Social Practice Theory framework, linking individual factors and agricultural practices to understand vulnerability and prevention opportunities. This research was conducted in Pattapang Village, Tinggimoncong District, Gowa Regency, South Sulawesi Province, Indonesia. To examine the relationship between pesticide use patterns, social norms, competence, material, and individual aspects and the risk of sensitive toxicity in children, data were analyzed using structural equation modeling-partial least squares (SEM-PLS) with bootstrapping resampling. Pesticide use patterns had a significant negative effect on toxicity risk. Competence was the strongest predictor of pesticide use patterns, followed by materials and short-term goals. Personal values dominate personal norms and long-term goals, while social norms only influence personal norms. Self-efficacy, personal norms, and long-term goals showed no significant effects. The novelty of this research lies in the integration of a socio-ecological approach with individual psychological factors in a comprehensive structural model that explains the complex mechanisms of children’s protective behavior formation from pesticide toxicity, identifying that personal values—not personal norms or self-efficacy—are the most effective leverage points for farmer behavior change interventions. Full article

Atmospheric wet deposition represents a major pathway for the transfer of organic micropollutants into terrestrial and aquatic ecosystems. This study investigates the occurrence and spatial distribution of polycyclic aromatic hydrocarbons (PAHs), phthalate esters (PAEs), and BTEX compounds in rainwater across Northern Serbia (Vojvodina region). Rainwater samples were collected during the 2025–2026 heating season at three locations: a petrochemical site in Kikinda, a traffic- and residentially influenced site in Sremska Mitrovica, and an urban background site in Sombor. Total concentrations showed pronounced spatial variability, with the highest ΣBTEX and ΣPAE levels recorded in Kikinda (∑BTEX = 2.818 μg L^∑1; ∑PAE = 0.930 μg L^∑1). Diagnostic ratios identified a dominant petrogenic signature in Kikinda (LMW/HMW > 1), while pyrogenic sources prevailed in Sremska Mitrovica and Sombor ((Fla/Fla + Pyr) > 0.5). BTEX profiles across all sites were characterised by the absence of benzene and elevated toluene and xylene levels (B/T ≈ 0; T/X > 1). Health risk assessment indicated an acceptable but non-negligible carcinogenic risk from PAHs, particularly for children in industrial areas. These findings highlight the role of precipitation as an efficient scavenger of organic pollutants and emphasise the need for integrated atmospheric–hydrological monitoring frameworks in industrialised regions. Full article

Per- and polyfluoroalkyl substances (PFAS) are persistent, chemically stable compounds widely used in daily life. Perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexanesulfonic acid (PFHxS), and perfluorooctanesulfonic acid (PFOS) were identified as the most relevant PFAS due to their prevalence and toxicity. This study aimed to investigate the immunotoxic mechanisms of a mixture of these PFAS using an in silico approach. Comparative Toxicogenomic Database (CTD), GeneMANIA, CytoHubba (Cytoscape), ToppGene Suite, and Metascape were used for the analysis. A total of 65 immune-related genes were identified as common to all four PFAS, with IFNG, TNF, IL1B, IL6, TYK2, CD3E, CASP8, VAV1, ARHGAP4, and CARD11 emerging as key hub genes. CTD phenotype analysis indicated immune dysregulation, with decreased humoral and adaptive immune responses in humans and tissue-specific modulation of B- and T-cell activity in mice, while no immune-related phenotypes were observed for PFNA. Network analysis identified functional modules associated with apoptotic and immune signaling, endothelial cell migration and angiogenesis, and shared inflammatory and viral response pathways. Disease enrichment analysis associated PFAS with autoimmune disorders (rheumatoid arthritis, asthma), metabolic conditions, and cardiovascular diseases (experimental diabetes, hypertensive disease). These results highlight PFAS involvement in immune modulation, cytokine signaling, and disease susceptibility. Full article

Air pollution is a major environmental determinant of premature mortality and population health burden. Liguria represents a vulnerable Mediterranean region due to intense urbanisation, port-related emissions, complex topography and an ageing population. This study quantified the mortality burden and Years of Life Lost (YLL) attributable to long-term exposure to PM_2.5, NO₂ and O₃ in Liguria (Italy), and estimated the potentially avoidable burden under WHO guideline scenarios. A Health Impact Assessment (HIA) was conducted using ARPAL air quality data and ISTAT mortality data for the population aged ≥30 years during 2022–2024. Relative risks were derived from the European ELAPSE project and WHO meta-analyses. Attributable mortality was estimated using a log-linear Health Impact Function, while YLL were calculated using regional life tables and normalised per 100,000 inhabitants. PM_2.5 was the main contributor to air pollution-related mortality, accounting for 1333 attributable deaths in 2022. Corresponding YLL ranged from 755 to 1012 per 100,000 inhabitants over the study period. NO₂ showed a relevant but secondary contribution, while O₃ effects were smaller and more uncertain. WHO guideline scenarios indicated a substantial potentially avoidable burden of deaths and YLL. These findings support targeted environmental and public health interventions in highly urbanised coastal regions. Full article

M8OI is a cytotoxic methylimidazolium ionic liquid solvent through its binding to the ubiquinone binding site on complex I of the mitochondrial electron transport chain. Given the overlap in terms of toxic mechanism of action with the pesticide rotenone, the potential neurotoxic effects of M8OI were examined. In vitro, cytotoxicity and mitochondrial function were assessed in SH-SY5Y cells by measuring MTT reduction and oxygen consumption/extracellular acidification using a Seahorse analyser. SH-SY5Y cells were sensitised to M8OI toxicity by replacing medium glucose with galactose. Glucose protected the cells from M8OI toxicity, whereas galactose showed no clear dose–response protection. M8OI induced a dose-dependent reduction in oxygen consumption rate with a compensatory increase in extracellular acidification rate, consistent with inhibition of mitochondrial oxidative phosphorylation and a shift toward glycolysis. In vivo, rats were orally exposed via drinking water for 20 weeks and assessed using behavioural tests. In addition, the concentrations of M8OI and its metabolites were quantified by LC–MS in rat brain and other tissues. In rats, M8OI concentrations were ~30-fold higher in kidney than brain, and brain levels were at least 100-fold lower than the concentrations that affected SH-SY5Y cell viability in vitro. However, based on open field tests, M8OI exposure suppressed motor activity without any anxious behaviours. The cytotoxicity of M8OI in SH-SY5Y neuroblastoma cells was associated with metabolic mitochondrial dysfunction. However, the neurobehavioural changes observed in orally exposed rats occurred at significantly lower brain concentrations than would be predicted to lead to neural cell death. Nevertheless, direct comparisons between acute in vitro exposures and chronic in vivo outcomes should be interpreted cautiously. Full article