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

Glyphosate-based herbicides (GBHs) are among the most widely used chemical agents in modern agriculture, raising environmental and health concerns due to their persistence in the environment. The aim of this study was to examine the toxicological effects attributed to exposure to two GBHs: a newly released sales-restricted commercial formulation (XEQUE MATE HT IHARA® - GBHn) and a publicly available gardening formulation (CITROMAX MAX 20 - GBHg), using immobilization bioassays with Artemia salina, a saltwater filter-feeding invertebrate, and Panagrellus redivivus, a free-living nematode. Organisms were exposed to increasing concentrations of each herbicide, and immobilization was assessed after 24 hr. Both GBHs initiated dose-dependent toxicity, with immobilization reaching 100% for GBHg in A. salina and 73.4% for GBHn in P. redivivus at the highest concentration tested. The Sensitivity Index (SI) indicated that A. salina appeared to be more sensitive to GBHg, while P. redivivus was more susceptible to GBHn. Despite these differences, both herbicides exhibited similar Overall Sensitivity Index (OSI) values-0.73 for GBHg and 0.75 for GBHn - indicating comparable overall toxicity profiles. These findings suggest that GBHn does not present a markedly higher environmental risk than existing formulations. However, the results emphasize the importance of continuous ecotoxicological monitoring of new glyphosate formulations.

Blood lead (Pb) monitoring plays an important role in identifying children experiencing increased Pb exposure based upon their elevated blood Pb levels (PbB). Following actions to decrease Pb exposure, it is important to understand whether a slow decline in PbB is due to the slow reduction in bone Pb following prolonged exposure or due to continued exposure from an unknown source. The goal of this study was to examine the ability of the All Ages Lead Model (AALM) version 3.0 to predict long-term clearance kinetics of PbB in children. Data for six children exhibiting increased Pb exposure during home renovations lasting 4-20 months were obtained from a published study. The AALM was used to simulate PbB kinetics in children following removal of this residential renovation exposure. Quantitative analyses showed reliable agreement between predicted and observed PbB data as well as halftimes for PbB clearance, which ranged from 7.8 to 38 months. The AALM can predict long-term PbB clearance in children who were exposed to Pb for months to years during home renovations. Short-term (1 week or less) PbB clearance was most affected by exposure duration with minimal effects attributed to exposure magnitude. Long-term (months to years) PbB clearance was affected by both the magnitude and duration of renovation exposure. In addition to PbB monitoring, AALM simulations might improve understanding of probable causes for changes in and contributors to children's PbB.

Prior studies have investigated individual single nucleotide polymorphisms (SNPs) as risk factors for the development of lung disease in swine operation workers. The aim of this study was to determine the collective effects of multiple SNPs and a polygenic risk score (PRS) in swine operation workers and identify workers at a higher risk of airway disease. This study included 374 full-time swine operation workers and 411 non-farming rural residents. Least absolute shrinkage and selection operator (LASSO) with 10-fold cross-validation was used to identify SNPs, which were used to calculate a PRS score for airway obstruction. Decision tree was applied to dichotomize the PRS score into two genetic susceptible groups (high vs. low). Logistic regression was employed to examine the association between dichotomous PRS score and airway obstruction. All workers were divided into two PRS genetic susceptible groups (high vs. low) by a cutoff value of 4.196. Logistic regression showed that workers in the high PRS group were 5.5-fold more likely to be associated with airway obstruction compared to workers in the low PRS group after controlling for potential confounders. A PRS score was identified as a useful tool in identifying workers at increased risk of airway obstruction in swine operations.

Engineered stone (ES) fabrication workers face risks from exposure to respirable crystalline silica (RCS), leading to accelerated silicosis. Toxicological data to elucidate pulmonary effects attributed to ES dusts, particularly those with varying compositions, are lacking. This study aimed to determine pulmonary effects following intratracheal instillation (IT) of ES dust in rats. Male Sprague-Dawley rats received a single 10 mg IT dose of dust from one of three ES types containing varying amounts of crystalline silica (CS) (ES A [high CS], ES B [mid CS], ES C [low CS]), or granite, MIN-U-SIL 5 (MS 5, positive control), or saline. Pulmonary inflammation and fibrosis were assessed via bronchoalveolar lavage fluid (BALF) analysis and lung histology at 1-, 21-, and 84-days post-exposure. Early BALF inflammation as evidenced by increased levels of neutrophils and lymphocytes, and cytotoxicity by elevated LDH activity was found in all exposure groups. Neutrophils primarily correlated with higher CS content (MS 5, ES A, ES B). Persistent inflammation comparable with pure silica was noted by increased levels of neutrophils and macrophages and cytotoxicity by elevated LDH activity at 21- and 84-days post-exposure was most pronounced in MS 5 and high-CS ES A groups. By 84-day post-exposure, granulomatous inflammation in lung, BALF and lymph node, was associated with alveolar lipoproteinosis, type II epithelial changes, lymph node and alveolar fibrosis. Toxicity appeared to be driven by complex interactions between silica and trace metal content of dust. These findings warrant further research to assess combined effects of particle characteristics and chemical co-exposures.

Exposures to pollutants rarely occur in isolation, often coexisting with other environmental stressors such as diet and may be particularly insidious in early life. The aim of this study was to examine effects of maternal exposure to cadmium (Cd) and consumption of a high-fructose diet (HFrD) on development of mouse offspring. Female CD-1 mice were administered either 0.5 or 5 ppm Cd in drinking water with or without an approximate 60% fructose diet for 3 weeks prior to mating. Dams were maintained on the same treatment until postnatal day (PND) 16. Cadmium concentrations in maternal, fetal, and neonatal liver increased in a concentration-dependent manner irrespective of diet. Endpoints known to be associated with Cd or HFrD adverse effects were assessed longitudinally in offspring from birth to young adulthood, including growth trajectory, pubertal development, body composition, glycemic tolerance and hepatic lipid accumulation. Maternal exposure to either Cd or HFrD alone significantly advanced onset of puberty, hypoglycemia, and reduced adiposity in adulthood. HFrD rarely exacerbated metal-initiated effects in most of the endpoints examined outside of pubertal timing. Because of chronic effects attributed to Cd or HFrD on metabolic function (e.g. glucose tolerance), transcriptomics and gene methylation analyses were performed on livers from neonatal and adult offspring. Data were largely consistent with phenotypic findings. In summary, maternal exposure to Cd or HFrD alone perturbed growth and development, producing long-lasting changes in metabolic function in adult offspring. HFrD did not appear to significantly exaggerate adverse outcomes attributed to metal exposure in the endpoints examined.

Flumioxazin-based herbicides are frequently used in agriculture to control broadleaf weeds attributed to their high efficacy, rapid action, and residual soil activity, making these compounds a preferred choice over other herbicides in pre-emergence weed control. Due to their beneficial properties, use of these herbicides has significantly increased in recent years, raising concerns regarding potential environmental risks. This study aimed to examine the effects of a commercial flumioxazin-based formulation on different plant models. The species Lactuca sativa L. Raphanus sativus L. Pennisetum glaucum L. and Triticum aestivum L. were used to assess the herbicide's impact on seed germination and early seedling development. In addition, the genotoxic effects of the herbicide on Allium cepa L. root tip cells were analyzed, including determination of mitotic index, chromosomal aberrations, and the presence of micronuclei. Data demonstrated that flumioxazin-based herbicide produced significant effects on seedling development in all 4 plant models, particularly at concentrations higher than those recommended for agricultural use ( > 0.05 g/L). Differential sensitivity was observed amongst the species, with T. aestivum being the most sensitive, emphasizing the importance of determining effects across a variety of plant organisms. Genotoxicity responses in A. cepa showed effects at a dose 6-fold higher than the recommended field application amount. However, at doses within the recommended range, flumioxazin-based herbicide was considered low-risk in the terrestrial environment. Evidence indicates the need for caution in agrochemical use and emphasizes the importance of plant models in ecotoxicological studies to promote more sustainable agriculture.

Pediatric high-grade gliomas remain a significant therapeutic challenge due to their resistance to conventional treatments. The aim of this study was to investigate the cytotoxic potential of solamargine (SM), a natural glycoalkaloid, alone and in combination with the chemotherapeutic agent temozolomide (TMZ) against the human KNS-42 glioma cell line. Solamargine significantly reduced cell viability and proliferation in a concentration-, time-, and hypoxia-dependent manner, while selectively sparing non-tumor human astrocytes (NHA). Morphological changes indicative of cell stress and death were observed, although SM did not markedly impair the migratory capacity of KNS-42 cells. In contrast, TMZ exhibited limited cytotoxicity against KNS-42 cells but demonstrated off-target effects on NHA cells. Combination therapy resulted in significant antagonism, with TMZ diminishing the cytotoxic effects of SM. These findings indicate the potential of SM to serve as a selective therapeutic agent for gliomas. Data obtained emphasize (1) the need for further research to optimize combination strategies and (2) to elucidate the underlying mechanisms of drug interactions.

Methylparaben (MeP) has a wide application in several industries including cosmetics, pharmaceuticals, and personal care products (PCP), thus accounting for its ubiquity in the environment. The aim of this study was to investigate the effects of exposure to sub-lethal concentrations of MeP on cytotoxicity, immunotoxicity, and antioxidant defense mechanisms utilizing juvenile African catfish, Clarias gariepinus as a model. Juvenile C. gariepinus were exposed to 0.74 or 1.48 mg/L MeP for 28 days after which the liver was excised for determination of cytotoxicity and oxidative stress parameters. The head kidney was extracted for histopathological analysis. Control fish were maintained in water spiked with 10 μL/L ethanol. The levels of respiratory burst, lipid peroxidation, and activities of superoxide dismutase and lactate dehydrogenase increased significantly in MeP-exposed fish especially at 1.48 mg/L compared to control. The % of DNA fragmentation also significantly increased across the treatments. Exposure to MeP resulted in various histological lesions including vacuolation of epithelial cells, infiltration of renal tubules with inflammatory cells, and thickening of the glomerular membrane in the head kidney. Data demonstrated that MeP exerted various adverse effects including cytotoxicity, immunotoxicity, and oxidative stress in the fish, C. gariepinus, attributed to possible activation of cellular stress inflammatory pathways.

Diet and living conditions are modifiers of behavioral and cardiovascular health, yet the combined effect is understudied, and their potential to alter responses to environmental stressors like wildfire smoke (WS) requires characterization. The purpose of this study was to determine whether housing enrichment (1) mitigates adverse cardiometabolic and neurobehavioral effects following a high fructose diet and (2) decreases responses to WS. Male Wistar-Kyoto (WKY) rats were divided into either depleted (DH) or enriched housing (EH) and fed a normal (ND) or high-fructose (HF) diet. Body composition, metabolism, and behavior were assessed over 30-weeks and cardiac function tested after a single exposure to either filtered air (FA) or flaming eucalyptus WS. EH rats exhibited significantly lower % body fat and higher % lean mass, no difference in weight, and significantly lower respiratory exchange ratio (RER) during the light phase, indicating a shift in basal metabolism after 13 weeks. EH rats habituated faster to acoustic startle and displayed less prepulse inhibition than DH, associated with improved learning and locomotor activity. In general, the effect of housing on behavior was greater than diet, while HF worsened within-group responses. WS increased blood and left ventricular pressure and contractility in EH rats, which was blunted by HF. Thus, housing enrichment appears to (1) improve certain systemic functions and behaviors and (2) enhance cardiovascular responses following WS, but partially blunting the effect of HF. These results indicate a complex interaction between housing and diet over the long-term and potentially altered adverse health risks from environmental smoke exposures.

Although long-term exposure to fine particulate matter (PM_2.5) has been linked to lung cancer, its association with non-lung cancers remains underexplored. The aim of this study was to examine the association between PM_2.5 exposure and development of gastric cancer (GC), which ranks as the eighth leading cause of cancer-related deaths in Taiwanese men and sixth in women. The mortality rates of GC vary considerably across townships in Taiwan, suggesting potential environmental influence. Thus, whether there was an association between long-term exposure to PM_2.5 and deaths attributed to GC was investigated across 66 municipalities in Taiwan. To determine this relationship, age-standardized GC mortality data were collected for the years 2012-2021 and correlated with PM_2.5 levels divided into tertiles. Adjusted risk ratio (RR) attributed to GC death was calculated by multiple regression analyses. For men, adjusted RRs were 1.04 (95% CI = 0.97-1.11) and 0.89 (95% CI = 0.82-0.95) in municipalities in the middle tertile (18.96-25.19 μg/m³) and highest (25.2-29.46 μg/m³), respectively, compared to the lowest (9.44-18.95 μg/m³). For women, the corresponding adjusted RRs were 1.04 (95% CI = 0.94-1.13) and 0.85 (95% CI = 0.77-0.94), respectively. Surprisingly, trend analyses noted a significant inverse association between PM_2.5 levels and GC-related mortality in both men and women. This counterintuitive finding may be a chance finding. Further investigation is needed to study the possible adverse effects of long-term exposure to PM_2.5 on GC-associated mortality.