Journal of Toxicology and Environmental Health-Part A-Current Issues最新文献

The demand for mineral resources is increasing mining activities worldwide. In Norway, marine tailing disposal (MTD) is practiced, introducing mineral particles into fjord ecosystems. We investigated the effects of two concentrations (high and low) of fine tailings from a CaCO₃ processing plant on early life stages of the marine copepod Calanus finmarchicus. Results show that the exposure did not significantly impact hatching success or development in non- and early feeding life stages. However, feeding stage nauplii ingested tailings, which caused a significantly slower development in later nauplii stages in high exposure groups, with most individuals being two stages behind the control group. Further, high mortality occurred in late nauplii and early copepodite stages in low exposure groups, which could be caused by insufficient energy accumulation and depleted energy reserves during development. Individuals exposed to high exposure concentrations seemed to survive by arresting development and potentially by reduced activity, thereby conserving energy reserves. In nature, slower development could affect lipid storage buildup and reproduction.

Fish early life stages are well known for their sensitivity to crude oil exposure. However, the effect of crude oil exposure on adults and their gametes during their spawning period is not well studied. Polar cod, a key arctic fish, may be at risk for crude oil exposure during this potentially sensitive life stage. Additionally, this species experiences lower food availability during their spawning season, with unknown combined consequences. In the present study, wild-caught polar cod were exposed to decreasing levels of a water-soluble fraction (WSF) of crude oil or control conditions and fed either at a low or high feed ration to assess the combined effect of both stressors. Samples were taken during late gonadal development, during active spawning (spawning window), and in the post-spawning period. Histology analysis of gonads from fish sampled during the spawning window showed that oil-exposed polar cod were more likely to have spawned compared to controls. Oil-exposed females had 947 differentially regulated hepatic genes, and their eggs had a higher polycyclic aromatic hydrocarbon body burden compared to controls. Feed ration did not consistently affect polar cod's response to oil exposure for the endpoints measured, however, did alone result in decreases in some sperm motility parameters. These results suggest that polar cod's spawning period is a sensitive life event to crude oil exposure, while feed limitation may play a minor role for this supposedly capital breeder. The effects of adult exposure to crude oil on gamete quality and the next generation warrant further investigation.

Designing ideal human biomonitoring studies involves the selection of reliable markers of exposure in adequate biological matrix. Besides conventional matrices such as blood or urine, hair has been increasingly investigated as a promising noninvasive alternative. However, understanding the pollutant distribution between differing biological compartments is essential for reliable interpretation of data collected. Therefore, the contamination levels and the distribution of some persistent (8 perfluoroalkyl substances - PFAS - and 6 polychlorobiphenyls - PCBs) and non-persistent pollutants (2 bisphenols and 3 parabens) were investigated in paired serum and hair samples, or paired spot urine and hair samples obtained from 30 Belgian non-occupationally exposed individuals. The levels measured were close to those reported in recent larger-scale studies. PFAS, PCB and bisphenol distributions largely differed depending upon the matrix and within the same chemical family depending upon the congener. The correlation and agreement between pollutant levels in differing matrices demonstrated that the information provided is comparable only for highly chlorinated PCBs and parabens, while the classification of exposure for bisphenols was substantially different according to the matrix. The selection of the human matrix thus remains complex and might markedly bias the results obtained, especially when assessing the health risk related to chemical exposure.

The chemotherapeutic drug doxorubicin (DOX) has been widely used for treating solid tumors attributed to its antiproliferative effectiveness; however, its clinical use is limited due to side effects, including cardiotoxicity, myelosuppression, and drug resistance. Combining DOX with buthionine sulfoximine (BSO), a glutathione (GSH) synthesis inhibitor, showed promising results in overcoming these adverse effects, potentially reducing the required DOX dose while maintaining efficacy. The aim of the present study was to examine the effects of different concentrations of BSO and DOX, both individually and in combination, utilizing B16/F10 (murine melanoma), SNB-19 (human glioblastoma), S180 (murine sarcoma), and SVEC4-10 (murine endothelial) cell lines. Cell viability, migration, and clonogenicity were assessed using the following assays MTT, scratch, and colony formation. Antioxidant levels of GSH, as well as activities catalase (CAT), and superoxide dismutase (SOD) were measured. BSO alone exhibited minimal cytotoxic effects, while DOX alone reduced cell viability significantly. The combination of BSO+DOX decreased IC₅₀ values for most cell lines, demonstrating a synergistic effect, especially in B16/F10, S180, and SVEC4-10 cells. BSO+DOX combination significantly inhibited cell migration and clonogenicity compared to DOX alone. While GSH levels were decreased with BSO+DOX treatment activities of CAT and SOD increased following DOX administration but remained unchanged by BSO. These results suggest that BSO may be considered a valuable tool to improve DOX therapeutic efficacy, particularly in cases of chemotherapy-resistant tumors, as BSO enhances DOX activity while potentially reducing systemic chemotherapeutic drug toxicity.

Weeds are a concern in agriculture and the use of herbicides constitutes an effective, efficient, and economical way to control their growth. Recent discoveries of herbicides are promising for the management of resistant weeds. However, there is a gap in the knowledge of the toxic effects of some herbicides previously reported on immune cells. The present study aimed to examine cellular immunotoxicity of three herbicides (clomazone, glyphosate, and sulfentrazone) after 96 hr incubation utilizing RAW 264.7 BALB/c mouse monocyte/macrophage-like cell line to elucidate the role of some toxicological pathways. Data demonstrated the herbicides clomazone, glyphosate, and sulfentrazone initiated a cytotoxic effect as evidenced by EC₅₀ values of 429.2; 53.7; 866.6 mg/L, respectively. Clomazone and sulfentrazone, at all concentrations, induced excess production of reactive oxygen (ROS) and reactive nitrogen (RNS) free radicals. An immunosuppression was observed in RAW 264.7 cells after incubation with 50 or 100 mg/L glyphosate and 500 or 1000 mg/L sulfentrazone. In addition, all herbicides produced mitochondrial depolarization and decreased tumor necrosis factor-α (TNF-α) levels. This constitutes the first report of the effects of clomazone and sulfentrazone on RAW 264.7 cells, including reduced TNF-α levels, indicating the adverse influence of herbicides on the immune system.

The global phenomenon of cyanobacterial bloom pollution is spreading globally due to climate change and eutrophication. It is well established that harmful cyanobacteria produce a wide range of toxins including microcystin-LR (MC-LR), a cyclic heptapeptide toxin known to damage various organs. The intestinal tract is the main site of MC-LR absorption and one of the targets susceptible to toxicity. Currently, studies on the enterotoxic effects of MC-LR predominantly focused on the colorectum, with limited investigations addressing the impact of microcystins on the small intestine. Therefore, the aim of our study was to examine the impact of chronic 9-month exposure of mice to low-dose 120 μg/L MC-LR in drinking water on ileal inflammation and potential mechanisms underlying these effects. Our findings showed that in mice chronically administered with low-dose MC-LR disorganized intestinal epithelial cells, lymphocytic infiltration and disturbed crypt arrangement were detected. The results of qPCR and Western blot demonstrated that, in comparison to control, the mRNA expression levels of pro-inflammatory factors IL-6, IL-17, IL-18, and IFN-γ were markedly elevated in the ileal tissue of mice treated with MC-LR, associated with significant increases in protein expression levels of p-PI3K, p-AKT, and p-mTOR. Taken together, evidence indicates that MC-LR induces ileal inflammation and histopathological damage involved activation of the PI3K/AKT/mTOR signaling pathway.

Microcystin-LR (MC-LR) a cyclic toxin produced by cyanobacterial species is known to exert detrimental effects on various organs, including lung. Several investigators demonstrated that MC-LR exerts pulmonary toxicity, but the underlying mechanisms remain unclear. This study aimed to investigate whether exposure to MC-LR-induced lung inflammation and examine the underlying mechanisms. Thirty specific pathogen-free (SPF) male mice were allocated into control and MC-LR treatment groups. Mice were intraperitoneally injected with physiological saline or MC-LR (20 μg/kg) daily for a total of 21 days. Our findings indicated that exposure to MC-LR-produced histopathological changes in lung tissue, including thickening of alveolar walls and inflammatory infiltration. MC-LR was found to upregulate mRNA expression levels of pro-inflammatory cytokines TNFα, IL-6, IL-1β, and IL-18. Further, MC-LR significantly elevated the expression levels of proteins associated with the NF-κB/NLRP3 pathway p-NF-κB, NLRP3, Caspase-1, ASC. The activation of NF-κB/NLRP3 pathway further promoted the release of inflammatory cytokine IL-1β and cleavage of pyroptosis-associated GSDMD protein. These findings indicate that MC-LR may induce lung inflammation by promoting cell pyroptosis via the activation of the NF-κB/NLRP3 pathway.

Higher coil temperature in e-cigarette devices increases the formation of aerosols and toxicants, such as carbonyls. At present, the health implications of vaping at higher temperatures, including exacerbation of pulmonary inflammation, are largely unknown when aerosol dose is considered. To isolate the pulmonary effects of coil temperature, C57BL/6 mice were exposed to e-cigarette aerosols generated at lower (190°C) or higher (250°C) temperature for 3 days, while maintaining a similar chamber aerosol concentration. Increasing coil temperature did not markedly alter aerosol mass-normalized emissions of select carbonyls formed from thermal degradation pathways including formaldehyde, acetaldehyde, propionaldehyde, and acetone under the tested environment. Total bronchoalveolar cells, primarily macrophages, were significantly decreased in mice exposed to aerosols generated with higher coil temperatures compared to lower temperature exposures. The gene expression of IFNβ, IL-1β, TNFα, and IL-10 in mouse lung tissue was significantly reduced following e-cigarette exposure under both conditions, compared to filtered air exposure. Higher temperature exposures further exacerbated downregulation of IFNβ and IL-1β. Data suggest that higher temperature vaping might modulate acute pulmonary immune responses, potentially inducing immune suppression, even when normalized for aerosol dose exposure. Coil temperature thus appears to be an important parameter that needs to be regulated to ensure harm reduction for e-cigarette users.

The International Agency for Research on Cancer (IARC) classifies exposure to fine particulate matter (PM_2.5) air pollution as carcinogenic to humans (Group I), most frequently associated with lung cancer. Airborne air pollutants may be associated with other sites of cancer, although few studies have examined this avenue of research. Esophageal cancer mortality rates vary substantially across townships in Taiwan, a fact that suggests environment influence. Therefore, the aim of this study was to investigate the association between long-term exposure to ambient PM_2.5 and deaths attributed to esophageal cancer in 66 municipal areas across Taiwan. To conduct this study, annual PM_2.5 levels were determined taking into account age-standardized esophageal cancer mortality rates in male and female residents of these municipalities from 2012 to 2021. The annual PM_2.5 levels of each municipality were divided into tertiles and computed adjusted risk ratio (RR) using weighted-multiple regression analyses controlling for municipal lung cancer deaths, urbanization level, and physician density. Men residing in those areas with intermediate PM_2.5 tertile levels (18.96-25.19 ug/m³) were found to have an adjusted RR of 1.22 (1.15-1.30) and those of residing areas with the highest tertiles levels (25.20-29.48 ug/m³) exhibited an RR of 1.11 (1.051.18). However, in women in the same municipalities, a significant inverse association was found between PM_2.5 levels and mortality attributed to esophageal cancer, 0.82 (95% CI = 0.65-1.04) and 0.61 (95% CI = 0.47-0.79), respectively. These findings suggest that long-term exposure to PM_2.5 increases the risk of developing esophageal cancer in men in Taiwan.

There is a need to assess whether ecological resources are being protected on large, federal lands. The aim of this study was to present a methodology which consistently and transparently determines whether two large Department of Energy (U.S. DOE) facilities have protected valuable ecological lands on their sites compared to the surrounding region. The National Land Cover Database (2019) was used to examine the % shrub-scrub (shrub-steppe) and other habitats on the DOE's Hanford Site (HS, Washington) and on the Idaho National Laboratory (INL), compared to a 10-km and 30-km diameter band of land surrounding each site. On both sites, over 95% is in shrub-scrub or grassland, compared to the surrounding region. Approximately 70% of 10 km and 30-km bands around INL, and less than 50% of land surrounding HS is located in these two habitat types. INL has preserved a significantly higher % shrub/scrub habitat than HS, but INL allows grazing on 60% of its land. HS has preserved a significantly higher % grassland than INL but no grazing on site is present. The methodology presented may be used to compare key ecological habitat types such as grasslands, forest, and desert among sites in different parts of the country. This methodology enables managers, resource trustees, and the public to (1) make remediation decisions that protect resources, (2) assess whether landowners and managers have adequately characterized and protected environmental resources on their sites, and (3) whether landowners and managers have protected the integrity of that land as well as its climax vegetation.