Environmental toxicology and pharmacology最新文献

We evaluated levels of urinary five organophosphorus flame retardant (OPFR) diesters and their primary metabolites, serum sex hormones, and semen quality among men in southern Taiwan. Associations were evaluated using multivariable linear regression and weighted quantile sum (WQS) regression models to examine both individual and mixture effects on male reproduction. Each level of bis(1,3-dichloro-2-propyl) phosphate (BDCPP), tris(1,3-dichloro-2-propyl) phosphate (TDCPP), and sum of OPFRs (ΣOPFRs) were significantly associated with a reduced percentage of morphologically normal sperm. Di-n-butyl phosphate (DnBP) and TDCPP were positively associated with the proportion of sperm with abnormal mitochondrial membrane potential (MMP). Diphenyl phosphate (DPHP), BDCPP, tris(n-butyl) phosphate (TnBP), tris(2-butyloxyethyl) phosphate (TBEP), triphenyl phosphate (TPHP), and ΣOPFR were positively associated with the estradiol/testosterone ratio. WQS regression demonstrated positively associations between OPFR mixtures, sperm abnormal morphology and MMP. Mixture-based analyses identify TDCPP, TCEP, and DnBP as key contributors to the observed associations with reproductive outcomes in environmental risk assessment.

Polycyclic aromatic hydrocarbons (PAHs) occur in complex mixtures, yet their comparative cytogenotoxic effects remain insufficiently characterized. We investigated benzo[b]fluoranthene (BbF), benzo[ghi]perylene (BghiP), and their binary mixture in human blood-derived models, A549, and HepG2 cells. Viability was assessed using fluorescent dual staining or MTT, while genotoxicity was evaluated using alkaline comet and cytokinesis-block micronucleus assays. BbF reduced blood-cell viability across a broader concentration range than BghiP, whereas A549 cells showed minimal cytotoxic responses. HepG2 cells exhibited concentration- and time-dependent viability reductions and significant DNA damage after 24h of individual and binary exposure. Binary exposure increased nuclear buds in A549 cells and nucleoplasmic bridges in HepG2 cells; micronucleus frequencies increased without consistently reaching statistical significance. Responses varied across models and endpoints under controlled in vitro conditions. These findings support further investigation of co-occurring PAHs, although additivity, synergism, and antagonism were not evaluated.

Lipophilic persistent organic pollutants (lipPOPs) including polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) persist in human body and possess endocrine-disrupting potentials. To investigate the combined effects of real-life serum mixture of lipPOPs from 482 Greenlandic pregnant women on estrogen receptor (ER) and androgen receptor (AR) transactivity and their associations with neonatal birth size, lipPOPs mixture was extracted and xenohormone transactivities (XER and XAR) were measured using reporter gene bioassays. Around 29.7% of the serum lipPOP extracts exhibited agonistic XER and 10.8% antagonized the estradiol-induced ER transactivity. About 54.9% of extract elicited agonistic XAR, and 39.9% antagonized dihydrotestosterone -induced AR transactivity. XAR inversely associated with the serum estrogenic PCBs concentration and the principal component containing PCBs and OCPs. XAR inversely associated with birth weight, particular among female neonates. These findings indicate that serum lipPOPs mixtures can disrupt ER and AR function and may adversely affect fetal growth in a sex-specific manner.

Honey bees are particularly vulnerable to sublethal doses of plant protection products. In spring, when many crops are flowering, growers often use fungicides from the strobilurins group (e.g. Amistar 250 SC, active ingredient: azoxystrobin) and insecticides from the pyrethriods group (e.g. Karate Zeon 050 CS, active ingredient: λ-cyhalothrin). These compounds may disturb organismal responses to stress factors, among others, by modifying the rate of metabolic processes or inducing oxidative stress. We analysed the impact of sublethal doses of these two preparations acting alone and simultaneously on bees. We assessed their effect on the metabolic rate-evaluated indirectly by analyzing the rate of CO₂ emission-and on changes in oxidative stress markers in worker bees. We did not observe a significant effect of the pesticides on the rate of CO₂ emission. Following insecticide application, malondialdehyde levels increased significantly compared to both the control group and the group treated with both preparations. Glutathione peroxidase activity also increased significantly in bees treated with this preparation. At the dosage used, the fungicide significantly reduced total antioxidant capacity.

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants associated with adverse developmental and immunological effects, yet data on PFAS exposure through breast milk in Taiwan remain limited. This study measured concentrations of 15 PFAS in 40 breast milk samples collected from 37 Taiwanese mothers at different postpartum stages and evaluated cross-sectional associations with postpartum day. PFAS were analyzed using solid-phase extraction and LC-MS/MS. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) were detected in all samples, with median concentrations of 39.98 and 23.54ng/L, respectively. PFOA concentrations were significantly and inversely associated with postpartum day across participants. Log-transformed perfluorohexanesulfonic acid (PFHxS) showed a nominally significant inverse association, whereas other PFAS showed no clear temporal trends. Associations with maternal characteristics were limited and inconsistent. Overall, Taiwanese lactating mothers exhibited universal but low-level PFAS exposure, providing baseline data for early-life exposure assessment and supporting the need for continued biomonitoring.

We assessed cytogenetic damage in 50 jewelry workers and 50 controls (25 smokers and 25 non-smokers/group) using the buccal micronucleus cytome assay. We scored 2,000 cells each for micronuclei (MN), nuclear buds (BE), binucleated cells (BN), karyorrhexis (KR), and karyolysis (KL), deriving total nuclear changes (TNC) and repair index (RI). MN and TNC were higher in exposed workers (5.35 ± 1.26‰ vs. 1.80 ± 0.73‰; 17.09 ± 3.09‰ vs. 7.49 ± 2.27‰; p<0.001). Adjusted rate ratios (95% CI) were 2.84 (2.38-3.40) for MN, 2.75 (2.26-3.36) for BE, 2.22 (1.87-2.64) for BN, 2.27 (2.08-2.49) for TNC, 1.80 (1.51-2.15) for KR, and 1.92 (1.60-2.31) for KL. RI was 41% lower (adjusted ratio 0.59; 95% CI 0.52-0.67; p<0.001). Smoking independently increased MN, KL, BE, and TNC; combined effects were sub-additive. Employment duration correlated with MN and BN, but age-adjusted associations disappeared. Findings support protection, ventilation, biomonitoring.

Exposure to trichloroethylene (TCE) can cause occupational medicamentose-like dermatitis and severe immune-related kidney damage. Existing treatments focusing on TNF-α and complement pathways show limited effectiveness against TCE-induced kidney injury, with unclear molecular mechanisms. This study explores the involvement of mitochondrial double-stranded RNA (mt-dsRNA) in TCE-related kidney damage and its regulatory pathways. Patients with occupational medicamentose-like dermatitis due to TCE (OMDT) showed higher serum lipopolysaccharide (LPS) levels, especially in severe cases. Both in vivo and in vitro studies indicated that LPS reduced PNPT1 expression, leading to mt-dsRNA release, triggering the PKR/eIF2α/ATF4/CHOP pathway, causing endoplasmic reticulum (ER) stress and apoptosis. By boosting PNPT1 or inhibiting mitochondrial RNA polymerase with inhibitor of mitochondrial transcription 1(IMT1) decreased mt-dsRNA production and reduced cell damage. These findings suggest that TCE exposure increases systemic LPS, which suppresses PNPT1, causing pathological mt-dsRNA buildup. This activates PKR-dependent ER stress, leading to tubular injury.

Nanoplastics (NPs) are emerging environmental contaminants able to cross biological barriers, disrupt cellular and organelle homeostasis, and alter the brain microenvironment. This study investigated whether NPs affect microglia-neuron communication, a key mechanism underlying neuronal resilience, via the nuclear factor erythroid 2-like 2 (NFE2L2) pathway. Using an in vitro model, we evaluated the effects of polystyrene nanoplastics on microglial metabolic fitness and microglia-mediated neuronal stress responses. Increasing NP concentrations induced a dose-dependent biphasic effect. Low- to intermediate-concentration treatments increased intracellular adenosine triphosphate (ATP) levels in microglia and enhanced microglia-mediated activation of neuronal NFE2L2. In contrast, high NP concentrations impaired microglial metabolism, reduced ATP availability, and decreased microglial-neuronal communication. These findings indicate that NPs alter microglial energetic status and modulate neuroprotective signaling, potentially contributing to impaired neuron-microglia interactions and increased susceptibility to neurotoxicity.

Titanium dioxide nanoparticles (TiO₂ NPs) are widely used, raising concerns about neurotoxicity. This review summarizes their pathways into the central nervous system, brain distribution, and neurotoxic mechanisms. Evidence indicates TiO₂ NPs may reach the brain via the blood-brain barrier, olfactory nerve pathways, and systemic circulation. While titanium is detected in regions like the hippocampus, cortex, and cerebellum, total Ti measurements do not confirm intact nanoparticle translocation. Mechanisms primarily involve oxidative stress, neuroinflammation, mitochondrial dysfunction, neurotransmitter disruption, and protein aggregation, modulated by particle size, phase, coating, and exposure route. Crystal-phase effects are highly cell-type-specific, precluding a fixed anatase/rutile toxicity ranking, and mixed-phase materials may show enhanced photocatalytic ROS generation under specific conditions. We also address current research limitations and risk assessment challenges to support the safe application of TiO₂ NPs.

A commercial Glyphosate-based-herbicide (GBH) containing 450g/L of glyphosate (R450) was shown to affect the soil filamentous fungus Aspergillus nidulans, with multiple cytotoxic effects. Recently, R450 proved to exert also mutagenic effects on A. nidulans but only on dividing cells with active metabolism. The present study investigated further the R450 genotoxic potential by studying its putative recombinogenic effects on this fungus, which is a relevant model for such studies since the G2 phase represents the main period of its cell cycle. While R450 had no impact on sexual and meiotic processes, herbicide exposure resulted in a higher mitotic segregation frequency due to crossing-over and/or gene conversion stimulation. Sexual cycle induction being associated with a slowed metabolism, our results again suggest the prerequisite of active metabolism for the herbicide to exert these recombinogenic effects. The significance of such genotoxic damage in the context of human and animal exposure to GBH is discussed.