Toxics

Finding new marketable mosquito repellents is a complex and time-consuming process that can be optimized via modelling. In this context, a SAR (Structure–Activity Relationship) model was designed from a set of 2171 molecules whose actual repellent activity against Aedes aegypti was available. Information-rich descriptors were used as input neurons of a three-layer perceptron (TLP) to compute the models. The most interesting classification model was a 20/6/2 TLP showing 94% and 89% accuracy on the training set and test set, respectively. A total of 57 other artificial neural network models based on the same architecture were also computed. This allowed us to consider all chemicals both as training and test set members in order to better interpret the results obtained with the selected model. Most of the wrong predictions were explainable. The 20/6/2 TLP model was then used for predicting the potential repellent activity of new molecules. Among them, two were successfully evaluated in vivo. Full article

Introduction: Health effects after long-term exposure to subway particulate matter (PM) remain unknown due to the lack of individual PM exposure data. This study aimed to apply the job exposure matrix (JEM) approach to retrospectively assess occupational exposure to PM in the Parisian subway. Methods: Job, the line and sector of the transport network, as well as calendar period were four JEM dimensions. For each combination of these dimensions, we generated statistical models to estimate the annual average PM₁₀ concentration using data from an exhaustive inventory of the PM measurement campaigns conducted between 2004 and 2020 in the Parisian subway and historical data from the Parisian air pollution monitoring network. The resulting JEM and its exposure estimates were critically examined by experts using the uncertainty analysis framework. Results: The resulting JEM allows for the assignment of the estimated annual PM₁₀ concentration to three types of professionals working in the subway: locomotive operators, station agents, and security guards. The estimates’ precision and validity depend on the amount and quality of PM₁₀ measurement data used in the job-, line-, and sector-specific models. Models using large amounts of personal exposure measurement data produced rather robust exposure estimates compared to models with lacunary data (i.e., in security guards). The analysis of uncertainty around the exposure estimates allows for the identification of the sources of uncertainty and parameters to be addressed in the future in order to refine and/or improve the JEM. Conclusions: The JEM approach seems relevant for the retrospective exposure assessment of subway workers. When applied to available data on PM₁₀, it allows for the estimation of this exposure in locomotive operators and station agents with an acceptable validity. Conversely, for security guards, the current estimates have insufficient validity to recommend their use in an epidemiological study. Therefore, the current JEM should be considered as a valid prototype, which shall be further improved using more robust measurements for some jobs. This JEM can also be further refined by considering additional exposure determinants. Full article

This study aimed to investigate the levels of 12 sulfonamide antibiotics in freshwater fish species obtained from three cities in northeastern China (Harbin, Changchun, and Shenyang). The analysis was conducted using HPLC–MS/MS to accurately quantify the antibiotic concentrations in the fish samples. The results showed that the average levels of sulfonamide antibiotics in fish samples from Harbin, Changchun, and Shenyang were 1.83 ng/g ww, 0.98 ng/g ww, and 1.60 ng/g ww, respectively. Sulfamethoxazole displayed the highest levels and detection rates in all three cities, whereas sulphapyridine exhibited the lowest concentrations in all the fish samples. The levels of sulfonamide antibiotic residues in the different fish species varied widely among the cities, and the highest level of antibiotic residues was found in the muscle of carnivorous fish. The results from a health risk evaluation on the consumption of these fish indicated that the risk from long-term antibiotic exposure to local residents from the intake of the sampled fish was small and not sufficient to pose a significant health risk to consumers. Full article

Objective: This study aimed to compare the resistance rates of Blattella germanica to beta-cypermethrin nanoemulsion and conventional emulsion and establish reference values via biochemical detection for conventional emulsion. Methods: We conducted experiments using subcultured Blattella germanica and applied the micro-drop method for treatment. Subsequently, the activity of metabolic enzymes was measured using spectrophotometry. Profile analysis was employed to study the resistance rates of beta-cypermethrin nanoemulsion and beta-cypermethrin emulsion. Results: The regression equation for the relationship between generation and resistance factor in Blattella germanica treated with beta-cypermethrin nanoemulsion was as follows: y₁ = 0.091x₁ + 0.991, with an r-value of 0.990 (F = 95.184, p = 0.01 < 0.05). Similarly, the regression equation for Blattella germanica treated with emulsion was y₂ = 0.376x₂ + 1.051, with an r-value of 0.993 (F = 141.094, p = 0.007 < 0.05). The comparison of slopes between these two regression equations yielded an F-value of 8.61, indicating a significant difference (p = 0.001 < 0.05). Conclusion: Our findings suggest that the resistance factor in Blattella germanica treated with beta-cypermethrin nanoemulsion differs from that treated with beta-cypermethrin emulsion. Specifically, the resistance factor of beta-cypermethrin nanoemulsion increased at a slower rate compared to beta-cypermethrin emulsion. Full article

Inorganic arsenic in drinking water is prioritized as a top environmental contaminant by the World Health Organization, with over 230 million people potentially being exposed. Arsenic toxicity has been well documented and is associated with a plethora of human diseases, including diabetes, as established in numerous animal and epidemiological studies. Our previous study revealed that arsenic exposure leads to the inhibition of nuclear receptors, including LXR/RXR. To this end, FXR is a nuclear receptor central to glucose and lipid metabolism. However, limited studies are available for understanding arsenic exposure-FXR interactions. Herein, we report that FXR knockout mice developed more profound glucose intolerance than wild-type mice upon arsenic exposure, supporting the regulatory role of FXR in arsenic-induced glucose intolerance. We further exposed mice to arsenic and tested if GW4064, a FXR agonist, could improve glucose intolerance and dysregulation of hepatic proteins and serum metabolites. Our data showed arsenic-induced glucose intolerance was remarkably diminished by GW4064, accompanied by a significant ratio of alleviation of dysregulation in hepatic proteins (83%) and annotated serum metabolites (58%). In particular, hepatic proteins “rescued” from arsenic toxicity by GW4064 featured members of glucose and lipid utilization. For instance, the expression of PCK1, a candidate gene for diabetes and obesity that facilitates gluconeogenesis, was repressed under arsenic exposure in the liver, but revived with the GW4064 supplement. Together, our comprehensive dataset indicates FXR plays a key role and may serve as a potential therapeutic for arsenic-induced metabolic disorders. Full article

In recent times, there has been a concerning and noteworthy rise in the global use of sodium nitrite for suicidal purposes. This is facilitated either through the employment of specialized “suicide kits” or by acquiring sodium nitrite through alternative means. Additionally, another occurrence contributing to nitrite poisoning is the recreational utilization of nitrites in the form of volatile aliphatic esters of nitrous acid, commonly referred to as “poppers”. Based on current available papers and reports on the subject of nitrates, nitrites, and poppers intoxications, an epidemiological analysis and evaluation of analytical methods were performed. A total of 128 papers, documenting a collective count of 492 intoxication cases, were identified. Additionally, in order to complete the epidemiological profile of nitrite poisoning, the authors briefly examined six cases of nitrite intoxication that were under investigation in our laboratory. Furthermore, a review of nitrite poisoning cases over the past 100 years shows that the old poison is still in use and poses a substantial risk to society. Full article

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants, with perfluorooctanoic acid (PFOA) being a prominent member. PFOA poses a risk to aquatic ecosystems and human health due to its presence in water, environmental persistence, and bioaccumulation. Since rodlet cells (RCs) have emerged as potential biomarkers for chemical stressors, this study aimed to investigate the effects of sub-chronic PFOA exposure on RCs in the renal hematopoietic tissue of common carp. Three groups of fish were used: an unexposed control group and two groups exposed to environmentally relevant (200 ng L⁻¹) and elevated (2 mg L⁻¹) PFOA concentrations. Light and transmission electron microscopy were employed to assess RCs’ distribution patterns and exocytosis, while biometry quantified RCs in the hematopoietic tissue. The results showed that, even at environmentally relevant concentrations, PFOA significantly influenced RCs’ distribution patterns, leading to increased occurrence and cluster formation, as well as heightened exocytosis activity. This research highlights PFOA’s immunotoxicity in fish and suggests the potential of RCs as sentinel cells in the immunological response to environmental contaminants. These findings enhance our understanding of PFAS toxicity and emphasise the importance of monitoring their impact on fish as representative vertebrates and reliable animal models. Full article

Exposure to heavy metals exerts toxic effects on female reproduction and embryo development. This study examined the exposure of patients with unexplained recurrent miscarriage (uRM) to multiple metals and the correlations among exposures to different metals. A total of 275 participants were enrolled, including 43 healthy women without previous miscarriage (the control group) and 232 uRM women (the case group); among these uRM women, 159 had two miscarriages (2M), 42 had three miscarriages (3M) and 31 had four or more miscarriages (≥4M). A total of 22 elements were measured in serum samples via inductively coupled plasma–mass spectrometry. The levels of calcium (104.37 mg/L vs. 92.65/93.02/92.61/92.47 mg/L) and selenium (131.85 µg/L vs. 117.80/118.04/115.88/124.35 µg/L) were higher in the controls than in the total uRM group and the 2M, 3M and ≥4M subgroups. The level of vanadium was significantly lower in the controls than in the total uRM group (0.15 µg/L vs. 0.23 µg/L), and the level of lead was lower in the controls than that in the total uRM group and the 2M, 3M and ≥4M subgroups (0.01 µg/L vs. 0.28/0.18/0.63/0.34 µg/L). After adjusting for age, body mass index and education level, calcium and selenium exposure were consistently negatively associated with miscarriage, while lead exposure was positively associated with miscarriage. In addition, the correlations among exposures to different metals slightly differed between the control and uRM groups. Therefore, changes in some metal elements in the blood might be related to the risk of uRM. Full article

Sustained-release materials are increasingly being used in the delivery of oxidants for in situ chemical oxidation (ISCO) for groundwater remediation. Successful implementation of sustained-release materials depends on a clear understanding of the mechanism and kinetics of sustained release. In this research, a columnar sustained-release material (PS@PW) was prepared with paraffin wax and sodium persulfate (PS), and column experiments were performed to investigate the impacts of the PS@PW diameter and PS/PW mass ratio on PS release. The results demonstrated that a reduction in diameter led to an increase in both the rate and proportion of PS release, as well as a diminished lifespan of release. The release process followed the second-order kinetics, and the release rate constant was positively correlated with the PS@PW diameter. A matrix boundary diffusion model was utilized to determine the PS@PW diffusion coefficient of the PS release process, and the release lifespan of a material with a length of 500 mm and a diameter of 80 mm was predicted to be more than 280 days. In general, this research provided a better understanding of the release characteristics and kinetics of persulfate from a sustained-release system and could lead to the development of columnar PS@PW as a practical oxidant for in situ chemical oxidation of contaminated aquifers. Full article

Water quality depends on its physicochemical and biological parameters. Changes in parameters such as pH, temperature, and essential and non-essential trace metals in water can render it unfit for human use. Moreover, the characteristics of the local environment, geological processes, geochemistry, and hydrological properties of water sources also affect water quality. Generally, groundwater is utilized for drinking purposes all over the globe. The surface is also utilized for human use and industrial purposes. There are several natural and anthropogenic activities responsible for the heavy metal contamination of water. Industrial sources, including coal washery, steel industry, food processing industry, plastic processing, metallic work, leather tanning, etc., are responsible for heavy metal contamination in water. Domestic and agricultural waste is also responsible for hazardous metallic contamination in water. Contaminated water with heavy metal ions like Cr (VI), Cd (II), Pb (II), As (V and III), Hg (II), Ni (II), and Cu (II) is responsible for several health issues in humans, like liver failure, kidney damage, gastric and skin cancer, mental disorders and harmful effects on the reproductive system. Hence, the evaluation of heavy metal contamination in water and its removal is needed. There are several physicochemical methods that are available for the removal of heavy metals from water, but these methods are expensive and generate large amounts of secondary pollutants. Biological methods are considered cost-effective and eco-friendly methods for the remediation of metallic contaminants from water. In this review, we focused on water contamination with toxic heavy metals and their toxicity and eco-friendly bioremediation approaches. Full article

Benzophenone-3 (BP-3) is a lipophilic organic compound that occurs naturally in flower pigments. Since it adsorbs ultraviolet (UV) radiation in the UVA and UVB regions, it is one of the most common UV filters found in sunscreen and cosmetic products. We explored by in vivo micronuclei (MNi) assay the genotoxic effects of BP-3 on hemocytes from the freshwater gastropod Lymnaea stagnalis. We also studied its possible toxic effects on life-history traits: body growth in L. stagnalis and egg production of both L. stagnalis and the marine polychaete worm Ophryotrocha diadema. Adult individuals were exposed to increasing concentrations of BP-3 (0.025, 0.050, 0.100, and 0.200 mg/L) once a week for 4 weeks. In L. stagnalis, exposure to BP-3 at concentrations of both 0.2 and 0.1 mg/L produced genotoxic effects on the micronuclei frequencies, but only concentrations of 0.2 mg/L affected the NBUDs frequencies. Similarly, negative effects on body growth were observed at the concentrations of 0.2 and 0.1 mg/L and a significant reduction of egg production at 0.2 mg/L. In O. diadema, a negative correlation between egg production and increasing BP-3 concentrations was observed. Our findings suggest the need for more stringent measures to reduce the presence of BP-3 in the environment. Full article

This study investigated the effect of Rosmarinus officinalis L. (RO) extract on neurobehavioral and neurobiological changes in male rats with pentylenetetrazol (PTZ)-induced epilepsy. Rats were assigned into five groups: (1) control rats, (2) RO-treated rats, (3) PTZ-treated rats, (4) PTZ + RO-treated rats, and (5) PTZ + valproic acid (VA)-treated rats. The PTZ-treated rats required a significantly longer time and distance to find the platform in the Morris water maze test than the control and RO-treated rats. Additionally, PTZ-treated rats showed a decrease in tendency to cross over the platform compared to PTZ group. PTZ + RO-treated rats showed decreased swimming time and distance to find the platform compared to PTZ group. PTZ + RO-treated rats showed a significant decrease in seizure score, a reduced number of myoclonic jerks, and an increased onset of the first myoclonic jerk compared to PTZ group. PTZ reduced the time required to enter the dark room in the passive avoidance learning test, which was reversed by RO treatment. Biochemical results revealed that PTZ-treated rats had higher levels of oxidative stress markers. RO significantly increased the antioxidant markers levels and maintained normal rat brain histology. This study revealed that RO can shield the brain and neural tissues from PTZ. Full article

Shiyang River Watershed is an important ecological barrier and agricultural production area in Northwest China, and the study of soil heavy metal content, distribution, and sources is important for agricultural product safety, pollution control, and ecosystem health. In this paper, 140 soil samples were collected from 28 stations to assess the level of heavy metal (Arsenic (As), Copper (Cu), Lead (Pb), Cadmium (Cd), Chromium (Cr), Mercury (Hg), Nickel (Ni), Zinc (Zn)) contamination, pollutant sources and influencing factors of soil in Shiyang River Watershed through determination of the metal contents and statistical analysis. The results indicated that the soils in the study area are typical saline soils in arid zones. The enrichment factors (EF) of As, Cr, Cu, Ni, Zn, and Pb indicate no contamination, and the EFs of Cd and Hg suggested minor contamination. Although the concentrations of Cd and Hg in soil are lower than others, they are more biotoxic and exhibit a moderate–high ecological risk. The index of geoaccumulation (I_geo) values reflect that most of the stations, especially the three groups of samples from depths of 10–20 cm, 20–40 cm, and 40–80 cm, are below the contamination threshold for all heavy metals. The chemical speciation of heavy metals, principal component analysis, and correlation analysis showed that Cr, Cu, Pb, Cd, Ni, and Zn mainly come from the natural accumulation upon weathering of soil-forming matrices. Hg and As mainly come from anthropogenic contributions. The effect of agricultural crop cultivation on soil heavy metal contamination is mainly through farm irrigation and crop–soil interactions, which accelerate the release of heavy metals through the weathering of soil-forming parent material and irrigation, which transports the heavy metals below the surface. The results of this study can provide a scientific basis for the involved authorities to formulate reasonable policies on environmental protection and pollution control. Full article

An economical and effective method is still lacking for cadmium (Cd) toxicity reduction and food product safety improvement in soil–vegetable systems. Therefore, this study aimed to reduce the Cd toxicity to pak choi (Brassica campestris L.) by jointly using passivators and organic fertilizer, highlighting food products’ safety based on pot experiments. The results showed that compared with the control, organic fertilizer decreased the Cd content in edible parts and the soil’s available Cd by 48.4% and 20.9% on average, respectively, due to the 0.15-unit increases in soil pH. Once jointly applied with passivators, the decrements increased by 52.3–72.6% and 32.5–52.6% for the Cd content in edible parts and for the soil’s available Cd, respectively, while the pH increment increased by 0.15–0.46 units. Compared with the control, the transport factor of Cd was reduced by 61.9% and 50.9–55.0% when applying organic fertilizer alone and together with the passivators, respectively. The combination treatment of biochar and organic fertilizer performed the best in decreasing the Cd content in the edible parts and the soil’s available Cd. The combination treatment of fish bone meal and organic fertilizer induced the greatest increases in soil pH. The grey relational analysis results showed that the combination treatment of biochar and organic fertilizer performed the best in reducing the potential Cd pollution risk, thereby highlighting the vegetable food safety. This study provides a potential economical and effective technology for toxicity reduction and food safety in Cd-polluted soil. Full article

Air pollution is an important public health problem that endangers human health. However, the casual association and pathogenesis between particles < 2.5 μm (PM_2.5) and hyperlipidemia remains incompletely unknown. Mendelian randomization (MR) and transcriptomic data analysis were performed, and an air pollution model using mice was constructed to investigate the association between PM_2.5 and hyperlipidemia. MR analysis demonstrated that PM_2.5 is associated with hyperlipidemia and the triglyceride (TG) level in the European population (IVW method of hyperlipidemia: OR: 1.0063, 95%CI: 1.0010–1.0118, p = 0.0210; IVW method of TG level: OR: 1.1004, 95%CI: 1.0067–1.2028, p = 0.0350). Mest, Adipoq, Ccl2, and Pcsk9 emerged in the differentially expressed genes of the liver and plasma of PM_2.5 model mice, which might mediate atherosclerosis accelerated by PM_2.5. The studied animal model shows that the Paigen Diet (PD)-fed male LDLR^−/− mice had higher total cholesterol (TC), TG, and CM/VLDL cholesterol levels than the control group did after 10 times 5 mg/kg PM_2.5 intranasal instillation once every three days. Our study revealed that PM_2.5 had causality with hyperlipidemia, and PM_2.5 might affect liver secretion, which could further regulate atherosclerosis. The lipid profile of PD-fed Familial Hypercholesterolemia (FH) model mice is more likely to be jeopardized by PM_2.5 exposure. Full article

Since July 2022, the Yangtze River basin has experienced the most severe hydro-meteorological drought since record collection started in 1961, which has greatly affected the ecological environment of the Dongting Lake (DTL) basin. To investigate the effects of drought events on the eutrophication and phytoplankton community structure of DTL, the lake was sampled twice in August and September 2022 based on the water level fluctuations resulting in 47 samples. Furthermore, we combined the comprehensive trophic level index (TLI) and phytoplankton Shannon–Wiener diversity index (H) to characterize and evaluate the eutrophication status. The key influencing factors of the phytoplankton community were identified using redundancy analysis (RDA), hierarchical partitioning, and the Jaccard similarity index (J). Our results showed that the TLI of DTL changed from light–moderate eutrophication status (August) to mesotrophic status (September), whereas the H changed from light or no pollution to medium pollution. The phytoplankton abundance in August (122.06 × 10⁴ cells/L) was less than that in September (351.18 × 10⁴ cells/L) in DTL. A trend in phytoplankton community succession from Bacillariophyta to Chlorophyta and Cyanophyta was shown. The combination of physiochemical and ecological assessment more accurately characterized the true eutrophic status of the aquatic ecosystem. The RDA showed that the key influencing factors in the phytoplankton community were water temperature (WT), pH, nitrogen and phosphorus nutrients, and the permanganate index (COD_Mn) in August, while dissolved oxygen (DO) and redox potential (ORP) were the key factors in September. Hierarchical partitioning further indicated that temporal and spatial variations had a greater impact on the phytoplankton community. And the J of each region was slightly similar and very dissimilar, from August to September, which indicated a decreased hydrological connectivity of DTL during drought. These analyses indicated that the risk to the water ecology of DTL intensified during the summer–autumn drought in 2022. Safeguarding hydrological connectivity in the DTL region is a prerequisite for promoting energy flow, material cycle, and water ecosystem health. Full article

The contexts where there are mining and agriculture activities are potential sources of risk to human health due to contamination by chemical mixtures. These contexts are frequent in several Colombian regions. This study explored the potential association between the frequency of micronuclei and pesticides and elements in regions with ferronickel (Montelibano, Córdoba) and gold (Nechí, Antioquia) mining, and a closed native mercury mine (Aranzazu, Caldas), with an emphasis in the potential effect of selenium as a potential chelator. A cross-sectional study was carried out with 247 individuals. Sociodemographic, occupational, and toxicological variables were ascertained. Blood and urine samples were taken for pesticide analysis (5 organophosphates, 4 organochlorines, and 3 carbamates), 68 elements were quantified in hair, and micronuclei were quantified in lymphocytes. The mixtures of elements were grouped through principal component analysis. Prevalence ratios were estimated with robust variance Poisson regressions to explore associations. Interactions of selenium with toxic elements were explored. The highest concentrations of elements were in the active mines. The potentially most toxic chemical mixture was observed in the ferronickel mine. Pesticides were detected in a low proportion of participants (<2.5%), except paraoxon-methyl in blood (27.55%) in Montelibano and paraoxon-ethyl in blood (18.81%) in Aranzazu. The frequency of micronuclei was similar in the three mining contexts, with means between 4 to 7 (p = 0.1298). There was great heterogeneity in the exposure to pesticides and elements. The “hormetic effect” of selenium was described, in which, at low doses, it acts as a chelator in Montelibano and Aranzazu, and at high doses, it can enhance the toxic effects of other elements, maybe as in Nechí. Selenium can serve as a protective agent, but it requires adaptation to the available concentrations in each region to avoid its toxic effects. Full article

New approach methods (NAMs) can reduce the need for chronic animal studies. Here, we apply benchmark dose (concentration) (BMD(C))–response modeling to transcriptomic changes in the liver of mice and in fathead minnow larvae after short-term exposures (7 days and 1 day, respectively) to several dose/concentrations of three organophosphate pesticides (OPPs): fenthion, methidathion, and parathion. The mouse liver transcriptional points of departure (TPODs) for fenthion, methidathion, and parathion were 0.009, 0.093, and 0.046 mg/Kg-bw/day, while the fathead minnow larva TPODs were 0.007, 0.115, and 0.046 mg/L, respectively. The TPODs were consistent across both species and reflected the relative potencies from traditional chronic toxicity studies with fenthion identified as the most potent. Moreover, the mouse liver TPODs were more sensitive than or within a 10-fold difference from the chronic apical points of departure (APODs) for mammals, while the fathead minnow larva TPODs were within an 18-fold difference from the chronic APODs for fish species. Short-term exposure to OPPs significantly impacted acetylcholinesterase mRNA abundance (FDR p-value <0.05, |fold change| ≥2) and canonical pathways (IPA, p-value <0.05) associated with organism death and neurological/immune dysfunctions, indicating the conservation of key events related to OPP toxicity. Together, these results build confidence in using short-term, molecular-based assays for the characterization of chemical toxicity and risk, thereby reducing reliance on chronic animal studies. Full article

Human biomonitoring (HBM) data in Europe are often fragmented and collected in different EU countries and sampling periods. Exposure levels for children and adult women in Europe were evaluated over time. For the period 2000–2010, literature and aggregated data were collected in a harmonized way across studies. Between 2011–2012, biobanked samples from the DEMOCOPHES project were used. For 2014–2021, HBM data were generated within the HBM4EU Aligned Studies. Time patterns on internal exposure were evaluated visually and statistically using the 50th and 90th percentiles (P50/P90) for phthalates/DINCH and organophosphorus flame retardants (OPFRs) in children (5–12 years), and cadmium, bisphenols and polycyclic aromatic hydrocarbons (PAHs) in women (24–52 years). Restricted phthalate metabolites show decreasing patterns for children. Phthalate substitute, DINCH, shows a non-significant increasing pattern. For OPFRs, no trends were statistically significant. For women, BPA shows a clear decreasing pattern, while substitutes BPF and BPS show an increasing pattern coinciding with the BPA restrictions introduced. No clear patterns are observed for PAHs or cadmium. Although the causal relations were not studied as such, exposure levels to chemicals restricted at EU level visually decreased, while the levels for some of their substitutes increased. The results support policy efficacy monitoring and the policy-supportive role played by HBM. Full article