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Toxics

Toxics is an international, peer-reviewed, open access journal on all aspects of the toxic chemicals and materials, published monthly online by MDPI.

Indexed in PubMed | Quartile Ranking JCR - Q1 (Toxicology)

All Articles (4,582)

  • Feature Paper
  • Article
  • Open Access

The development of new approach methodologies that include human cells differentiated into organotypic formats is of high interest due to their structural and functional similarities to tissues in vivo, enabling mechanistic understanding and translation to adverse health outcomes in humans. However, these systems often fail to capture complex intercellular signaling required for processes such as pulmonary inflammation induced by polycyclic aromatic hydrocarbons (PAHs). To investigate airway epithelial–macrophage interactions in response to benzo[a]pyrene and a PAH mixture (Tox Mix), co-culture models utilizing primary human bronchial epithelial cells (HBECs) differentiated at the air–liquid interface were cultured with THP-1 macrophages either directly or indirectly, alongside HBECs alone. After 24 h of exposure, cytokine expression (IL1B, IL6, CXCL8, TNF) as well as PAH biomarkers previously identified for chemical metabolism (CYP1A1, CYP1B1), oxidative stress (ALDH3A1, HMOX1, NQO1), and barrier integrity (TJP2) were evaluated. Cytotoxicity and barrier integrity were also assessed. HBECs alone and direct co-cultures exhibited similar responses after PAH treatment, while indirect co-cultures showed lower sensitivity to induction of inflammatory cytokines and CYP1A1 and CYP1B1 biomarker expression following exposure to PAHs. The expression of other biomarkers, including ALDH3A1, HMOX1, and NQO1, remained largely consistent across all models after treatment. Overall, these findings suggest that direct co-culture systems may provide a more physiologically relevant platform for studies of PAH-induced toxicity and demonstrate that the configuration of co-culture systems can influence cellular responses to chemical exposure.

9 December 2025

Suspended THP-1 cell counts and viability. (A) THP-1 cells were treated with PMA (0–250 nM) for 48 h before culture media was removed and THP-1 cells in suspension were counted. (B) Fresh RPMI-1640 was added after the 48 h incubation with PMA and THP-1 cells had a ‘rest’ period for 24 h before THP-1 cells in suspension were counted again. (C) Viability of suspended THP-1 cells after 48 h PMA incubation was determined by trypan blue exclusion. Statistical significance is indicated by asterisks. For cell counts, data was analyzed by one-way ANOVA followed by Dunnett’s post hoc test (* p-adj < 0.05, **** p-adj < 0.0001). For viability, data was analyzed by one-way ANOVA followed by Tukey’s post hoc test (* p < 0.05, **** p < 0.0001).

This study investigated the relationship between maternal barium (Ba) exposure and the risk of miscarriage using metabolomics and machine learning. Analyses were performed on samples from 183 pregnant women from Nanjing: the concentration of Ba in whole blood was measured using inductively coupled plasma mass spectrometry (ICP-MS), and untargeted metabolomics was performed on decidual tissue using high-resolution accurate mass spectrometry (UHPLC-QExactive HF-X). A metabolome-wide association study (MWAS) and mediation interaction effect analysis (MITM) identified metabolites and pathways linked to Ba exposure and miscarriage risk. Among 523 detected metabolites, 19 metabolites and 5 pathways were significantly associated with both Ba exposure and miscarriage, particularly glycerophospholipid metabolism. The effect of Ba exposure on miscarriage risk was mediated by five metabolites, with cuminaldehyde showing the highest share of the total mediating effect (54.74%). These metabolites, including N-acetyl-L-methionine, 4-hydroxynonenal, DG(18:0/18:3(9Z,12Z,15Z)/0:0), 10-formyldihydrofolate, and eicosadienoic acid, were used as biomarkers in a predictive model. The XGBoost model achieved an optimal AUC of 0.90 (95%CI: 0.83–0.96). This study suggests that maternal Ba exposure increases miscarriage risk, potentially through disruptions in amino acid metabolism, oxidative stress, and lipid peroxidation, and highlights the potential of metabolite biomarkers for predicting adverse birth outcomes.

10 December 2025

  • Feature Paper
  • Article
  • Open Access

Oxylipins are specialized lipid mediators that can have dual functions, either promoting inflammation or supporting resolution. Exposure to air pollution is associated with systemic inflammation that may be modified by oxylipins derived from polyunsaturated fatty acids (FA). In this study, we examined whether short-term air pollution exposure is associated with changes in circulating oxylipins in healthy adults, who were on high- or low-dietary omega-3 fatty acid (n-3 FA) intakes. We measured 56 oxylipin species from participants’ plasma samples and employed mixed-effects models to assess the associations, stratified by n-3 FA groups. Plasma concentrations of oxylipins derived from n-3 FA [e.g., 14-hydroxydocosahexaenoic acid (14-HDHA) & 11-hydroxydocosahexaenoic acid (11-HDoHE), and 12-hydroxyeicosapentaenoic acid (12-HEPE)] were significantly higher in the high n-3 FA group compared to the low group. Conversely, selected oxylipins derived from n-6 FA [e.g., 15-hydroxyeicosatetraenoic acid (15-HETE) and 14,15-Dihydroxyeicosatrienoic acid (14,15-DiHETrE)] were significantly lower in the high n-3 group. Exposure to PM2.5, O3, and NO2 was associated with reductions in pro-inflammatory oxylipins produced by lipoxygenase in the high n-3 FA group, but not in the low group; for example, 12-HETE. Furthermore, participants in the high n-3 group exposed to PM2.5, O3, and NO2 had elevated levels of n-3 FA-derived pro-resolving oxylipins compared to those in the low n-3 group; for instance, 12-HEPE and 14-HDHA & 11-HDoHE. In conclusion, short-term air pollution exposure was associated with lower pro-inflammatory and higher pro-resolving oxylipin levels in the high n-3 FA group. These findings suggest n-3-derived lipid metabolites may promote inflammation resolution induced by air pollution.

9 December 2025

Environmental contamination with heavy metals, resulting from industrialization, urbanization, and agricultural intensification, poses serious ecological and health risks. Horses, due to their grazing behavior and close association with human environments, serve as reliable sentinel species for assessing environmental pollution. This study aimed to evaluate the bioaccumulation of heavy metals and trace elements in different biological matrices of horses—blood, hair, hooves, and synovial fluid—and to investigate their relationship with hematological biomarkers as indicators of physiological stress. Samples were collected from horses raised in anthropogenically influenced areas and analyzed using inductively coupled plasma mass spectrometry (ICP–MS). Hematological parameters were determined with an automated analyzer to assess systemic effects. The results revealed significant variations in metal concentrations among matrices, with keratinized tissues reflecting long-term exposure, while blood and synovial fluid indicated recent contamination. Correlations between elevated metal levels and altered hematological values suggested oxidative stress and adaptive physiological responses. These findings demonstrate the value of multi-matrix biomonitoring in evaluating both environmental quality and animal health. Horses effectively reflect the cumulative impact of heavy metal exposure, supporting their role as bioindicators within a One Health framework that links environmental, animal, and human well-being.

9 December 2025

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Toxics - ISSN 2305-6304