Toxics

The OECD recognizes that data on a compound’s ability to treat eye irritation are essential for the assessment of new compounds on the market. In silico models are frequently used to provide information when experimental data are lacking. Semi-correlations, as they are called, can be useful to build up categorical models for eye irritation. Semi-correlations are latent regressions that can be used when the endpoint is expressed by two values: 1 for an active molecule and 0 for an inactive molecule. The regression line is based on the descriptor values which serve to distribute the data into four classes: true positive, true negative, false positive, and false negative. These values are applied to calculate the corresponding statistical criterion for assessing the predictive potential of the categorical model. In our model, the descriptor is the sum of what are termed correlation weights. These are defined by optimization using the Monte Carlo method. The target function of the optimization is related to the determination coefficient and the mean absolute error for the training set. Our model gives results that are better than those previously reported for the same endpoint. Full article

Florfenicol (FLO) has been shown to elicit diverse toxic effects in plants, insects, and mammals. Previously, our investigations revealed that FLO induced abnormal cardiac development and early embryonic mortality in chicken embryos. However, the effect of FLO on mitochondrial responses in stem cells remains unclear. In this study, we show that FLO significantly diminishes proliferation viability and obstructs the directed differentiation of P19 stem cells (P19SCs) into cardiomyocytes. Proteomic analysis revealed 148 differentially expressed proteins in response to FLO. Functional analysis has pinpointed FLO interference with biological processes associated with oxidative phosphorylation within the mitochondria. In alignment with the results of proteomic analysis, we confirmed that FLO inhibits the expression of both nuclear DNA-encoded and mitochondrial DNA-encoded subunits of the electron transport chain. Subsequent experiments demonstrated that FLO disrupts mitochondrial dynamics and induces the mitochondrial unfolded protein response to maintain mitochondrial homeostasis. These findings collectively highlight the significance of mitochondrial dynamics and the mitochondrial unfolded protein response to mediate the decreased proliferation viability and directed differentiation potential in P19SCs treated with FLO. In conclusion, this study provides a comprehensive overview of mitochondrial responses to FLO-induced cytotoxicity and enhances our understandings of the molecular mechanisms underlying FLO-induced embryonic toxicity. Full article

Isoeugenol has recently been evaluated as possibly carcinogenic (Group 2B) by the WHO International Agency for Research on Cancer (IARC). In light of this evaluation, an updated risk assessment of this common food constituent was conducted using the benchmark dose (BMD) approach as recommended by the European Food Safety Authority (EFSA) for point of departure (POD) determination, as an alternative to the no observed adverse effect level (NOAEL). This approach was specifically chosen, as for the relevant neoplastic endpoints only lowest observed adverse effect level (LOAEL) values are available. The toxicological endpoint from the animal studies with the most conservative BMD lower confidence limit (BMDL) value was identified. Using the obtained BMDL value of 8 mg/kg body weight/day as POD, an acceptable daily intake (ADI) of 16 µg/kg body weight/day was obtained, which—despite being more conservative than previous approaches—is still clearly above the estimated daily exposure level to isoeugenol in the USA and in Europe. These results confirm a low risk of the estimated daily exposure levels of isoeugenol. Full article

Gaseous polycyclic aromatic hydrocarbons were measured in northern Thailand. No previous studies have provided data on gaseous PAHs until now, so this study determined the gaseous PAHs during two sampling periods for comparison, and then they were used to assess the correlation with meteorological conditions, other pollutants, and their sources. The total concentrations of 8-PAHs (i.e., NAP, ACY, ACE, FLU, PHE, ANT, FLA, and PYR) were 125 ± 22 ng m⁻³ and 111 ± 21 ng m⁻³, with NAP being the most pronounced at 67 ± 18 ng m⁻³ and 56 ± 17 ng m⁻³, for morning and afternoon, respectively. High temperatures increase the concentrations of four-ring PAHs, whereas humidity and pressure increase the concentrations of two- and three-ring PAHs. Moreover, gaseous PAHs were estimated to contain more toxic derivatives such as nitro-PAH, which ranged from 0.02 ng m⁻³ (8-Nitrofluoranthene) to 10.46 ng m⁻³ (1-Nitronaphthalene). Therefore, they could be one of the causes of local people’s health problems that have not been reported previously. Strong correlations of gaseous PAHs with ozone indicated that photochemical oxidation influenced four-ring PAHs. According to the Pearson correlation, diagnostic ratios, and principal component analysis, mixed sources including coal combustion, biomass burning, and vehicle emissions were the main sources of these pollutants. Full article

Titanium dioxide is a compound that is used in the food, cosmetic, and paint industries; however, it is still toxic to humans and the environment. This study determined the toxicities of titanium dioxide nanoparticles (TiO₂ NPs) in a Caenorhabditis elegans (C. elegans) model. The effects of commercially available (C-TiO₂) and synthetically (S-TiO₂) prepared TiO₂ NP solutions on lethality, lifespan, growth, reproduction, locomotion, and gene expression were studied in C. elegans. Exposure to TiO₂ NPs (0.0, 0.01, 0.1, 1.0, and 10 mg/L) did not result in any change to the survival rate or body length of the nematodes, regardless of the concentration. However, there was a decrease in the reproduction (brood size) and locomotion (body bending and head thrashing) of the nematodes as the TiO₂ NP concentration increased. The longevity of the nematodes was shortened following TiO₂ NP exposure. The gene expression of sod-1, sod-3, ctl-1, ctl-2, cyp35A2, mlt-1, and mlt-2 in the nematodes showed that there was an overexpression of all genes when the worms were exposed to 1 mg/L C-TiO₂ or 10 mg/L S-TiO₂. It was therefore concluded that compared with S-TiO₂, C-TiO₂ possibly causes more toxicity or genotoxicity in the C. elegans model. Full article

This study presents the efficiency of a drinking water treatment plant from Constanța, Romania. Individual and aggregated indices are proposed and built using nine water parameters for this aim. The analysis of individual indices permits the detection of the period of malfunctioning of the water treatment plant with respect to various parameters at various sampling points. In contrast, the cumulated indices indicate the overall performance of the treatment plant during the study period, considering all water parameters. It was shown that the outliers significantly impact the values of some indices. Comparisons between the simple average and weighted average indices (built taking into account the importance of each parameter) better reflect the impact on the water quality of some chemical elements that might harm people’s health when improperly removed. Full article

Biofilms that colonize on the surface of microplastics (MPs) in freshwaters may pose a potential health risk. This study examined factors that influence MP-associated biofilm growth, including polymer type, degree of weathering, and source water quality. Weathered MPs produced in-lab were employed in biofilm trials conducted on site using a passive flow-through system with raw water at drinking water treatment facility intakes. Adenosine triphosphate (ATP) was used to quantify biofilm abundance; biofilm composition was assessed via metagenomic sequencing. Biofilm growth was observed on all polymer types examined and most prevalent on polyvinyl chloride (PVC), where ATP levels were 6 to 12 times higher when compared to other polymers. Pathogen-containing species including Salmonella enterica and Escherichia coli were present on all polymers with relative abundance up to 13.7%. S. enterica was selectively enriched on weathered MPs in specific water matrices. These findings support the need to research the potential accumulation of pathogenic organisms on microplastic surfaces. Full article

Bisphenol A (BPA) exposure has been widely linked to endocrine-disrupting effects. Recently, many substitutes for BPA have been developed as safe structural analogs. However, they have still been reported to have similar adverse effects. The current study evaluated the effects of bisphenol A and eight structural analogs on the transcription of estrogen receptor alpha (ERα). The effects of binary and ternary mixtures prepared from different combinations of BPA analogs were also evaluated for transcription activity. The measured data of the mixtures were compared to the predicted data obtained by the full logistic model, and the model deviation ratio (MDR) was calculated to determine whether the effects were synergistic, antagonistic, or additive. Overall, the results suggest that the effect of bisphenol compound are additive in binary and ternary mixtures. Full article

The aim of this study was to investigate the association between benzene and toluene, and the ratio of triglycerides to high-density lipoprotein cholesterol (TG/HDL-C). This cross-sectional study analyzed 1928 adults using nationally representative data from the Korean National Environmental Health Survey (KoNEHS) Cycle 4 (2018–2020). Urinary trans, trans-muconic acid (t,t-MA) and benzylmercapturic acid (BMA) were measured by high-performance liquid chromatography–mass spectrometry (HPLC–MS/MS), and high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) were analyzed by colorimetry. Survey logistic regression analysis was applied to examine the association between urinary t,t-MA and BMA and the TG/HDL-C ratio. Urinary t,t-MA is significantly associated with an elevated TG/HDL-C ratio in both men and women (for men, OR [95% (CI)]: 2nd quartile: 2.10 [1.04, 4.22]; 3rd quartile: 2.13 [0.98, 4.62]; 4th quartile: 2.39 [1.05, 5.45]; for women, OR [95% (CI)]: 2nd quartile: 1.21 [0.71, 2.06]; 3rd quartile: 1.65 [0.94, 2.90]; 4th quartile: 1.78 [1.01, 3.11]), with significant dose–response relationships (P for trend: for men, 0.029; women, 0.024). This study shows that environmental exposure to benzene is associated with the TG/HDL-C ratio in the Korean general population. This suggests that more stringent environmental health policies are needed to reduce benzene exposure. Full article

Arecoline is a pyridine alkaloid derived from areca nut in the Arecaceae family. It has extensive medicinal activity, such as analgesic, anti-inflammatory, and anti-allergic. However, the toxicity of Arecoline limits its application. Most current studies on its toxicity mainly focus on immunotoxicity, carcinogenesis, and cancer promotion. However, there are few systematic studies on its hepatotoxicity and mechanisms. Therefore, this research explored the mechanism of hepatotoxicity induced by Arecoline in rats and analyzed endogenous metabolite changes in rat plasma by combining network toxicology with metabolomics. The differential metabolites after Arecoline exposure, such as D-Lysine, N4-Acetylaminobutanal, and L-Arginine, were obtained by metabolomics study, and these differential metabolites were involved in the regulation of lipid metabolism, amino acid metabolism, and vitamin metabolism. Based on the strategy of network toxicology, Arecoline can affect the HIF-1 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, and other concerning pathways by regulating critical targets, such as ALB, CASP3, EGFR, and MMP9. Integration of metabolomics and network toxicology results were further analyzed, and it was concluded that Arecoline may induce hepatotoxicity by mediating oxidative stress, inflammatory response, energy and lipid metabolism, and cell apoptosis. Full article

The environmental pollution that occurs in direct response to the widespread use of man-made/conventional pesticides results from many chemicals that require a long period of time, often decades, to degrade. The synthetic nature of pesticides also harms animals, beneficial insects, microorganisms, and plants, as well as humans. Fortunately, however, there are many natural pesticides, the so-called biopesticides, that are also effective against pests and more importantly, do not interfere with the well-being of ecosystems. Consequently, most biopesticides are safer for use around people and pets than man-made pesticides because, for example, they can be easily washed away from fruits and vegetables. The natural habitat is a rich resource with a wide selection of plants, many of which are also used to treat diseases in humans, animals, and plants. Out of concern for public health, environmental safety, and the stringent regulation of pesticide residues in agricultural commodities, the use of biopesticides is becoming increasingly important, but questions regarding potential pest resistance to these products may arise, just as is the case with conventional pesticides. Therefore, the performance and potential role of biopesticides in the management of plant pests should be prioritized due to their sustainability and importance to human and environmental welfare. In this review, we propose to highlight a scenario in which we discuss in detail the main constraints posed by the use of pesticides compared to biopesticides, starting with issues regarding their definition and continuing on to issues related to their toxicity and their impact on the environment and human health. Full article

The recalcitrant nature of emerging contaminants (ECs) in aquatic environments necessitates the development of effective strategies for their remediation, given the considerable impacts they pose on both human health and the delicate balance of the ecosystem. Semiconductor-based photocatalytic technology is recognized for its dual benefits in effectively addressing both ECs and energy-related challenges simultaneously. Among the plethora of photocatalysts, black phosphorus (BP) stands as a promising nonmetallic candidate, offering a host of advantages including its tunable direct band gap, broad-spectrum light absorption capabilities, and exceptional charge mobility. Nevertheless, pristine BP frequently underperforms, primarily due to issues related to its limited ambient stability and the rapid recombination of photogenerated electron–hole pairs. To overcome these challenges, substantial research efforts have been devoted to the creation of BP-based photocatalysts in recent years. However, there is a noticeable absence of reviews regarding the advancement of BP-based materials for the degradation of ECs in aqueous solutions. Therefore, to fill this gap, a comprehensive review is undertaken. In this review, we first present an in-depth examination of the fabrication processes for bulk BP and BP nanosheets (BPNS). The review conducts a thorough analysis and comparison of the merits and limitations inherent in each method, thereby delineating the most auspicious avenues for future research. Then, in line with the pathways followed by photogenerated electron–hole pairs at the interface, BP-based photocatalysts are systematically categorized into heterojunctions (Type I, Type II, Z-scheme, and S-scheme) and hybrids, and their photocatalytic performances against various ECs and the corresponding degradation mechanisms are comprehensively summarized. Finally, this review presents personal insights into the prospective avenues for advancing the field of BP-based photocatalysts for ECs remediation. Full article

Objective: To investigate the role of miR-212-5p-targeted ARAF during the apoptosis of rat alveolar macrophages induced by cowshed PM_2.5. Methods: miRNA and related target genes and pathways were predicted using the KEGG, TargetScan, and other prediction websites. NR8383 macrophages were treated with cowshed PM_2.5 to establish an in vitro lung injury model in rats; meanwhile, for the assessment of cell viability, apoptosis, intracellular calcium ions, and mitochondrial membrane potential in NR8383 cells, RT-qPCR was used to detect the expression of miR-212-5p and the target gene ARAF. Result: The bioinformatic analyses showed that miR-212-5p and ARAF were involved in PM_2.5-associated cellular damage. Exposure to different concentrations (0 μg/mL, 60 μg/mL, 180 μg/mL, 300 μg/mL) with different durations (0 h, 12 h, 24 h, 48 h) of cowshed PM_2.5 resulted in apoptosis, increased intracellular calcium ions, and decreased mitochondrial membrane potential. The miR-212-5p mimic group showed an up-regulation of Bax and cleaved Caspase 3 expression but decreased Bcl2 expression compared to the NC group, and overexpression of ARAF up-regulated the expression of p-MEK1/2 and p-ERK1/2 and simultaneously reversed the above phenomena. Conclusion: miR-212-5p targets ARAF to affect the cowshed PM_2.5-induced apoptosis through the MEK/ERK signaling pathway, providing a potential target for relevant farming industry and pathology studies. Full article

Mycotoxins are produced by more than one hundred fungi and produce secondary metabolites that contaminate various agricultural commodities, especially rice and corn. Their presence in the food chain is considered a serious problem worldwide. In recent years, a link between exposure to mycotoxins and impaired fertility has been suggested. Consequently, it has become vital to investigate the interactive effects of these mycotoxins on ovarian function. In this study, we investigated the intergenerational effects of the mycotoxin fumonisin B1 (FB1) on ovarian structure and function. Virgin Wistar albino female rats were separated into control and FB1 treatment groups and examined from day 6 of pregnancy until delivery (20 and 50 mg/kg b.w./day). The obtained female rats of the first (F1) and second generations (F2) were euthanized at 4 weeks of age, and ovary samples were collected. We found that the ovary weight index increased with the high dose of the treatment (50 mg/kg b.w./day) among both F1 and F2, in a manner similar to that observed in polycystic ovary syndrome. As expected, FB1 at a high dose (50 mg/kg b.w.) reduced the number of primordial follicles in F1 and F2, leading to an accelerated age-related decline in reproductive capacity. Moreover, it reduced the fertility rate among the F1 female rats by affecting follicle growth and development, as the number of secondary and tertiary follicles decreased. Histopathological changes were evidenced by the altered structures of most of the growing follicle oocytes, as revealed by a thinning irregular zona pellucida and pyknosis in granulosa cells. These findings are concomitant with steroidogenesis- and folliculogenesis-related gene expression, as evidenced by the decrease in CYP19 activity and estrogen receptor beta (ESR2) gene expression. Additionally, GDF-9 mRNA levels were significantly decreased, and IGF-1 mRNA levels were significantly increased. However, the results from the ovaries of the F2 treatment groups were different and unexpected. While there was no significant variation in CYP19 activity compared to the control, the ESR2 significantly increased, leading to stereological and histopathological changes similar to those of the control, except for some altered follicles. The hallmark histological feature was the appearance of vacuolar structures within the oocyte and between granulosa cell layers. Interestingly, the autophagic marker LC3 was significantly increased in the F2 offspring, whereas this protein was significantly decreased in the F1 offspring. Therefore, we suggest that the promotion of autophagy in the ovaries of the F2 offspring may be considered a recovery mechanism from the effect of prenatal FB1 exposure. Thus, autophagy corrected the effect of FB1 during the early life of the F1 female rats, leading to F2 offspring with ovarian structure and function similar to those of the control. However, the offspring, treated female rats may experience early ovarian aging because their ovarian pool was affected. Full article

This study sought to investigate the impact of exposure to metals and per- and polyfluoroalkyl substances (PFASs) on cardiovascular disease (CVD)-related risk. PFASs, including PFOA, PFOS, PFNA, and PFHxS, as well as metals such as lead (Pb), cadmium (Cd), and mercury (Hg), were analyzed to elucidate their combined effects on CVD risk. Methods: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2014, this investigation explored the effects of PFASs and metals on CVD risk. A spectrum of individual CVD markers, encompassing systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and triglycerides, was examined. Additionally, comprehensive CVD risk indices were evaluated, namely the Overall Cardiovascular Biomarkers Index (OCBI), including the Framingham Risk Score and an Overall Cardiovascular Index. Linear regression analysis was employed to probe the relationships between these variables. Furthermore, to assess dose–response relationships between exposure mixtures and CVD while mitigating the influence of multicollinearity and potential interaction effects, Bayesian Kernel Machine Regression (BKMR) was employed. Results: Our findings indicated that exposure to PFAS and metals in combination increased CVD risk, with combinations occurring with lead bringing forth the largest impact among many CVD-related markers. Conclusions: This study finds that combined exposure to metals and PFASs significantly elevates the likelihood of CVD risk. These results highlight the importance of understanding the complex interplay between multipollutant exposures and their potential implications for cardiovascular health. Full article

Long-term exposure to arsenic has been linked to a variety of cancers, among which skin cancer is the most prevalent form. However, the mechanism underlying arsenic carcinogenesis is unclear, and there is still limited information on the role of miRNAs in arsenic-induced skin cancer. This study aims to explore the role of miR-96-5p in the arsenite-induced proliferation and malignant transformation of human HaCaT keratinocytes. The GEO database (accession numbers GSE97303, GSE97305, and GSE97306) was used to extract mRNA and miRNA expression profiles of HaCaT cells treated with or without 0.1 μmol/L sodium arsenite for 3 and 7 weeks. In this paper, according to the CCK8 assay result, HaCaT cells exposed to 0.1 μmol/L sodium arsenite for 48 h were finalized. CCK8, MTT, EdU incorporation, and colony formation assays were used to determine the viability and proliferation of HaCaT cells and transformed HaCaT (T-HaCaT) cells. The subcellular localization and relative expression levels of DTL, as well as miR-96-5p in HaCaT cells induced by arsenite, were determined via immunofluorescence, RT-qPCR, and Western blot. Dual-luciferase reporter assay was performed to identify miR-96-5p bound directly to DTL. Transfection of miR-96-5p mimics or DTL siRNA was conducted to verify the arsenite-induced viability of HaCaT cells and T-HaCaT cells. T-HaCaT cells and nude mice were used to construct arsenite-induced malignant transformation and an in vivo xenograft model to demonstrate the over-expressed effect of miR-96-5p. The results showed that DTL was the target gene of miR-96-5p. Meanwhile, we also found that 0.1 μmol/L sodium arsenite upregulated DTL by decreasing the miR-96-5p level, leading to the proliferation and malignant transformation of HaCaT cells. MiR-96-5p agomir treatment slowed the growth of transplanted HaCaT cells transformed by arsenite in a manner associated with DTL downregulation in the nude mice xenograft model. Taken together, we confirmed that miR-96-5p, as a potent regulator of DTL, suppressed arsenite-induced HaCaT cell proliferation and malignant transformation, which might provide a novel therapeutic target for the treatment of arsenic-induced skin cancer. Full article

Manganese (Mn) exclusion in the Mn hyperaccumulator pokeweed (Phytolacca americana L.) was investigated. Hydroponic experiments were carried out to observe the responses of pokeweeds continually exposed to high levels of Mn. In this study, crystals were observed to appear firstly on the root hair, and soon after, more crystals appeared on the root surface, and crystals of Mn phosphate were observed to appear on the root surface in a time sequence negatively correlated with the number of leaves treated with 5 mM Mn. Crystals were identified via phase analysis of X-ray diffraction and element analysis, and these white insoluble crystals were identified using XRD to be Mn phosphate, with the molecular formula (Mn,Fe)₃(PO₄)₂·4H₂O. The nutrient solution pH increased from 4.5 to about 5.6 before the crystals appeared. Mn phosphate crystals appeared in all solutions except those without phosphate and emerged earlier in the solutions containing no Fe. Compared with control group, pokeweed accumulated much more Mn in the leaves when treated without phosphate or Fe. The present study suggests that pokeweed can exclude Mn by means of rhizosphere precipitation by phosphate to form Mn phosphate crystals that accumulate on the root surface. Although the detailed mechanism requires further investigation, this study provides the first direct evidence of a novel strategy to inhibit Mn uptake in the roots of a hyperaccumulator in a P-enriched environment. Full article

The use of genetically modified, glyphosate-resistant crops has led to the widespread application of glyphosate-based herbicides (GBHs), making them one of the most widely used herbicide formulations on the market. To enhance the efficacy of the active ingredient, GBHs used in practice often contain other ingredients marked as inert “adjuvants” or “co-formulants”, the toxic properties of which are poorly understood. The objective of this study was to compare the cytotoxic effects of pure glyphosate, three GBHs (Roundup Mega, Fozat 480 and Glyfos) and two co-formulants commonly used in GBHs as assessed via CCK-8 assay, and the extent of their potential oxidative damage as assessed via superoxide dismutase (SOD) assay, in order to reveal the role of adjuvants in the toxicity of the formulations. Our results showed that glyphosate alone did not significantly affect cell viability. In contrast, GBHs and adjuvants induced a pronounced cytotoxic effect from a concentration of 100 μM. SOD activity of cells treated with GBHs or adjuvants was significantly lower compared to cells treated with glyphosate alone. This suggests that the adjuvants in GBHs are responsible for the cytotoxic effects of the formulations through the induction of oxidative stress. Full article

Black Carbon (BC), the second-largest contributor to global warming, has detrimental effects on human health and the environment. However, the accurate quantification of BC poses a significant challenge, impeding the comprehensive assessment of its impacts. Therefore, this paper aims to critically review three quantitative methods for measuring BC: Thermal Optical Analysis (TOA), the Optical Method, and Laser-Induced Incandescence (LII). The determination principles, available commercial instruments, sources of deviation, and correction approaches associated with these techniques are systematically discussed. By synthesizing and comparing the quantitative results reported in previous studies, this paper aims to elucidate the underlying relationships and fundamental disparities among Elemental Carbon (EC), Equivalent Black Carbon (eBC), and Refractory Black Carbon (rBC). Finally, based on the current advancements in BC quantification, recommendations are proposed to guide future research directions. Full article