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Neurotoxicology May 2024Exposure to pesticides, such as carbamates, organophosphates, organochlorines and pyrethroids, has been linked to various health problems, including neurotoxicity....
Exposure to pesticides, such as carbamates, organophosphates, organochlorines and pyrethroids, has been linked to various health problems, including neurotoxicity. Although most in vivo studies use only male rodents, some studies have shown in vivo sex-specific effects after acute exposure. Since in vivo studies are costly and require a large number of animals, in vitro assays that take sex-specific effects into account are urgently needed. We therefore assessed the acute effects of exposure to different carbamates (methomyl, aldicarb and carbaryl), organophosphates (chlorpyrifos (CPF), chlorpyrifos-oxon (CPO) and 3,5,6-trichloropyridinol), organochlorines (endosulfan, dieldrin and lindane) and pyrethroids (permethrin, alpha-cypermethrin and 3-phenoxy-benzoic acid (3-PBA)) on neuronal network function in sex-separated rat primary cortical cultures using micro-electrode array (MEA) recordings. Our results indicate that exposure to the carbamate carbaryl and the organophosphates CPF and CPO decreased neuronal activity, with CPO being the most potent. Notably, (network) burst patterns differed between CPF and CPO, with CPO inducing fewer, but more intense (network) bursts. Exposure to low micromolar levels of endosulfan induced a hyperexcitation, most likely due to the antagonistic effects on GABA receptors. Interestingly, females were more sensitive to endosulfan than males. Exposure to dieldrin and lindane also increased neuronal activity, albeit less than endosulfan and without sex-specific effects. Exposure to type I pyrethroid permethrin increased neuronal activity, while exposure to type II pyrethroid alpha-cypermethrin strongly decreased neuronal activity. The increase seen after permethrin exposure was more pronounced in males than in females. Together, these results show that acute exposure to different classes of pesticides exerts differential effects on neuronal activity. Moreover, it shows that MEA recordings are suited to detect sex-specific neurotoxic effects in vitro.
Topics: Animals; Insecticides; Neurons; Female; Male; Cerebral Cortex; Rats; Cells, Cultured; Action Potentials; Dose-Response Relationship, Drug; Microelectrodes; Rats, Wistar
PubMed: 38599286
DOI: 10.1016/j.neuro.2024.04.004 -
Materials (Basel, Switzerland) Jan 2024A formaldehyde-free reactive flame retardant, an ammonium salt of triethylenetetramine phosphoryl dimethyl ester phosphamide phosphoric acid (ATPEPDPA), was synthesized...
A formaldehyde-free reactive flame retardant, an ammonium salt of triethylenetetramine phosphoryl dimethyl ester phosphamide phosphoric acid (ATPEPDPA), was synthesized and characterized using nuclear magnetic resonance (NMR). Fourier transform infrared spectroscopy test (FT-IR), durability test and scanning electron microscopy (SEM) results suggested that ATPEPDPA was successfully grafted on cotton fabrics through a -N-P(=O)-O-C covalent bond. Moreover, the limiting oxygen index (LOI) value of 20 wt% ATPEPDPA-treated cotton was 44.6%, which met stringent washing standard after 50 laundering cycles (LCs). The high washing resistance of the ATPEPDPA-treated cotton was due to the p-π conjugation between the N atom and the P(=O) group in the flame-retardant molecule, which strengthened the stability of the -N-P(=O)-O-C bonds between ATPEPDPA and cellulose, and the -N-P(=O)-(O-CH) groups in the ATPEPDPA. The cone calorimetric test showed that the treated cotton had excellent flame retardance. In addition, the TG and TG-IR tests suggested that ATPEPDPA performed a condensed flame retardance mechanism. Furthermore, the physical properties and hand feel of the treated cotton were well maintained. These results suggested that introducing -N-P(=O)-(O-CH) and -N-P(=O)-(ONH) groups into ATPEPDPA could significantly increase the fire resistance and durability of cotton fabrics.
PubMed: 38591487
DOI: 10.3390/ma17030630 -
Clinical and Experimental Emergency... Apr 2024Organophosphorus agents are easily absorbed via respiratory, gastrointestinal, and dermal routes, and inhibit the acetylcholine transferase enzyme (AChE), which is...
Organophosphorus agents are easily absorbed via respiratory, gastrointestinal, and dermal routes, and inhibit the acetylcholine transferase enzyme (AChE), which is responsible for the majority of toxicity caused by organophosphates in the body. A comprehensive search was conducted across three prominent databases, namely Google Scholar, PubMed, and Science Direct, to identify relevant articles published. The search focused on the keywords "MgSO4" or "magnesium sulfate" in conjunction with "organophosphate" or "organophosphate poisoning." Inhibition of AChE results in the accumulation of acetylcholine (ACh) in synapses and stimulation of cholinergic receptors. Considering that several studies have shown the use of magnesium sulfate (MgSO4) in inhibiting the release of ACh in the central and peripheral sympathetic and parasympathetic synapses, this study was conducted to review the role of MgSO4 in the treatment of OP. The intravenous administration of MgSO4 exhibits favorable tolerability and clinical efficacy in alleviating cardiac toxicity associated with OP exposure.
PubMed: 38583865
DOI: 10.15441/ceem.23.179 -
BMC Genomics Apr 2024Insecticide resistance (IR) is one of the major threats to malaria vector control programs in endemic countries. However, the mechanisms underlying IR are poorly...
Transcriptomic analysis of Anopheles gambiae from Benin reveals overexpression of salivary and cuticular proteins associated with cross-resistance to pyrethroids and organophosphates.
BACKGROUND
Insecticide resistance (IR) is one of the major threats to malaria vector control programs in endemic countries. However, the mechanisms underlying IR are poorly understood. Thus, investigating gene expression patterns related to IR can offer important insights into the molecular basis of IR in mosquitoes. In this study, RNA-Seq was used to characterize gene expression in Anopheles gambiae surviving exposure to pyrethroids (deltamethrin, alphacypermethrin) and an organophosphate (pirimiphos-methyl).
RESULTS
Larvae of An. gambiae s.s. collected from Bassila and Djougou in Benin were reared to adulthood and phenotyped for IR using a modified CDC intensity bottle bioassay. The results showed that mosquitoes from Djougou were more resistant to pyrethroids (5X deltamethrin: 51.7% mortality; 2X alphacypermethrin: 47.4%) than Bassila (1X deltamethrin: 70.7%; 1X alphacypermethrin: 77.7%), while the latter were more resistant to pirimiphos-methyl (1.5X: 48.3% in Bassila and 1X: 21.5% in Djougou). RNA-seq was then conducted on resistant mosquitoes, non-exposed mosquitoes from the same locations and the laboratory-susceptible An. gambiae s.s. Kisumu strain. The results showed overexpression of detoxification genes, including cytochrome P450s (CYP12F2, CYP12F3, CYP4H15, CYP4H17, CYP6Z3, CYP9K1, CYP4G16, and CYP4D17), carboxylesterase genes (COEJHE5E, COE22933) and glutathione S-transferases (GSTE2 and GSTMS3) in all three resistant mosquito groups analyzed. Genes encoding cuticular proteins (CPR130, CPR10, CPR15, CPR16, CPR127, CPAP3-C, CPAP3-B, and CPR76) were also overexpressed in all the resistant groups, indicating their potential role in cross resistance in An. gambiae. Salivary gland protein genes related to 'salivary cysteine-rich peptide' and 'salivary secreted mucin 3' were also over-expressed and shared across all resistant groups.
CONCLUSION
Our results suggest that in addition to metabolic enzymes, cuticular and salivary gland proteins could play an important role in cross-resistance to multiple classes of insecticides in Benin. These genes warrant further investigation to validate their functional role in An. gambiae resistance to insecticides.
Topics: Animals; Insecticides; Anopheles; Benin; Organophosphates; Mosquito Vectors; Malaria; Pyrethrins; Insecticide Resistance; Gene Expression Profiling; Nitriles
PubMed: 38582836
DOI: 10.1186/s12864-024-10261-x -
Chemosphere May 2024Climate change complicates ecotoxicology studies because species responses to pesticides depend on temperature. Classically illustrated by the effect of constant...
Climate change complicates ecotoxicology studies because species responses to pesticides depend on temperature. Classically illustrated by the effect of constant laboratory temperatures, a recent review revealed that the toxicity of pesticides is also often increased by daily temperature fluctuations. Here, we investigated the combined effects of daily temperature fluctuation and mean temperature on the toxicity of two insecticides in the moth Spodoptera littoralis. Our study tested the toxicity of chlorpyrifos and deltamethrin on larvae of six experimental groups that crossed three treatments of daily temperature fluctuations (0, 5 or 10 °C) and two treatments of mean temperatures (25 or 33 °C). We showed that daily temperature fluctuation increased larval mortality induced by chlorpyrifos and deltamethrin. However, the response differed between the organophosphorus insecticide chlorpyrifos and the pyrethroid insecticide deltamethrin. The increase in chlorpyrifos toxicity by daily temperature fluctuation did not differ between mean temperatures of 25 and 33 °C. Remarkably, the increase in deltamethrin toxicity by daily temperature fluctuation was dependent on the crossed effects of the amplitude of daily fluctuation and mean temperature. This increase in deltamethrin toxicity occurred with a daily fluctuation of only 5 °C for larvae reared at 25 °C and a daily fluctuation of 10 °C in larvae reared at 33 °C. To confidently quantify the responses of insecticide toxicity to temperature, future ecotoxicology studies will have to evaluate the generality of the interaction between the effects of daily temperature fluctuation and mean temperature.
Topics: Animals; Insecticides; Pyrethrins; Larva; Temperature; Nitriles; Chlorpyrifos; Climate Change; Spodoptera; Moths
PubMed: 38582169
DOI: 10.1016/j.chemosphere.2024.141888 -
Scientific Reports Apr 2024Glyphosate, the most widely used herbicide, is linked with environmental harm and there is a drive to replace it in agricultural systems. We model the impacts of...
Glyphosate, the most widely used herbicide, is linked with environmental harm and there is a drive to replace it in agricultural systems. We model the impacts of discontinuing glyphosate use and replacing it with cultural control methods. We simulate winter wheat arable systems reliant on glyphosate and typical in northwest Europe. Removing glyphosate was projected to increase weed abundance, herbicide risk to the environment, and arable plant diversity and decrease food production. Weed communities with evolved resistance to non-glyphosate herbicides were not projected to be disproportionately affected by removing glyphosate, despite the lack of alternative herbicidal control options. Crop rotations with more spring cereals or grass leys for weed control increased arable plant diversity. Stale seedbed techniques such as delayed drilling and choosing ploughing instead of minimum tillage had varying effects on weed abundance, food production, and profitability. Ploughing was the most effective alternative to glyphosate for long-term weed control while maintaining production and profit. Our findings emphasize the need for careful consideration of trade-offs arising in scenarios where glyphosate is removed. Integrated Weed Management (IWM) with more use of cultural control methods offers the potential to reduce chemical use but is sensitive to seasonal variability and can incur negative environmental and economic impacts.
Topics: Glyphosate; Crops, Agricultural; Plants, Genetically Modified; Herbicide Resistance; Weed Control; Herbicides; Plant Weeds
PubMed: 38580796
DOI: 10.1038/s41598-024-58183-8 -
Environmental Research Jul 2024Significant levels of glyphosate, the world's most widely used herbicide, and its primary metabolites, AMPA and MPA, are detected in various human organs and body...
The impact of the herbicide glyphosate and its metabolites AMPA and MPA on the metabolism and functions of human blood neutrophils and their sex-dependent effects on reactive oxygen species and CXCL8/IL-8 production.
Significant levels of glyphosate, the world's most widely used herbicide, and its primary metabolites, AMPA and MPA, are detected in various human organs and body fluids, including blood. Several studies have associated the presence of glyphosate in humans with health problems, and effects on immune cells and their functions have been reported. However, the impact of this molecule and its metabolites on neutrophils, the most abundant leukocytes in the human bloodstream, is still poorly documented. We isolated neutrophils from human donor blood and investigated the effects of exposure to glyphosate, AMPA, and MPA on viability, energy metabolism, and essential antimicrobial functions in vitro. We observed that neutrophil viability was unaffected at the blood-relevant average concentrations of the general population and exposed workers, as well as at higher intoxication concentrations. Neutrophil energy metabolism was also not altered following exposure to the chemicals. However, while phagocytosis was unaffected, reactive oxygen species generation and CXCL8/IL-8 production were altered by exposure to the molecules. Alterations in function following exposure to glyphosate and metabolites differed according to the sex of the donors, which could be linked to glyphosate's known role as an endocrine disruptor. While ROS generation was increased in both sexes, male neutrophils exposed to glyphosate had increased intracellular production of CXCL8/IL-8, with no effect on female neutrophils. Conversely, exposure to the metabolites AMPA and MPA decreased extracellular production of this chemokine only in female neutrophils, with MPA also increasing intracellular production in male cells exposed to the chemoattractant N-formyl-methionine-leucyl-phenylalanine. Our study highlights the effects of glyphosate and its metabolites on the antimicrobial functions of neutrophils, which could be associated with health problems as future studies provide a better understanding of the risks associated with glyphosate use. Advances in knowledge will enable better and potentially stricter regulations to protect the public.
Topics: Humans; Glyphosate; Glycine; Neutrophils; Herbicides; Reactive Oxygen Species; Female; Male; Interleukin-8; Adult; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Tetrazoles; Sex Factors; Isoxazoles; Organophosphonates
PubMed: 38580005
DOI: 10.1016/j.envres.2024.118831 -
Ecotoxicology and Environmental Safety Apr 2024Triocresyl phosphate (TOCP) was commonly used as flame retardant, plasticizer, lubricant, and jet fuel additive. Studies have shown adverse effects of TOCP on the...
Triocresyl phosphate (TOCP) was commonly used as flame retardant, plasticizer, lubricant, and jet fuel additive. Studies have shown adverse effects of TOCP on the reproductive system. However, the potential harm brought by TOCP, especially to mammalian female reproductive cells, remains a mystery. In this study, we employed an in vitro model for the first time to investigate the effects of TOCP on the maturation process of mouse oocytes. TOCP exposure hampered the meiotic division process, as evidenced by a reduction in the extrusion of the first polar body from oocytes. Subsequent research revealed the disruption of the oocyte cell cytoskeleton induced by TOCP, resulting in abnormalities in spindle organization, chromosome alignment, and actin filament distribution. This disturbance further extended to the rearrangement of organelles within oocytes, particularly affecting the mitochondria. Importantly, after TOCP treatment, mitochondrial function in oocytes was impaired, leading to oxidative stress, DNA damage, cell apoptosis, and subsequent changes of epigenetic modifications. Supplementation with nicotinamide mononucleotide (NMN) alleviated the harmful effects of TOCP. NMN exerted its mitigating effects through two fundamental mechanisms. On one hand, NMN conferred stability to the cell cytoskeleton, thereby supporting nuclear maturation. On the other hand, NMN enhanced mitochondrial function within oocytes, reducing the excess reactive oxygen species (ROS), restoring meiotic division abnormalities caused by TOCP, preventing oocyte DNA damage, and suppressing epigenetic changes. These findings not only enhance our understanding of the molecular basis of TOCP induced oocyte damage but also offer a promising avenue for the potential application of NMN in optimizing reproductive treatment strategies.
Topics: Female; Mice; Animals; Nicotinamide Mononucleotide; Phosphates; Oocytes; Cytoskeleton; Mitochondria; Reactive Oxygen Species; Mammals; Tritolyl Phosphates
PubMed: 38564869
DOI: 10.1016/j.ecoenv.2024.116264 -
Ecotoxicology and Environmental Safety Apr 2024Glyphosate, ranked as one of the most widely used herbicides in the world, has raised concerns about its potential disruptive effects on sex hormones. However, limited...
Glyphosate, ranked as one of the most widely used herbicides in the world, has raised concerns about its potential disruptive effects on sex hormones. However, limited human evidence was available, especially for children and adolescents. The present study aimed to examine the associations between exposure to glyphosate and sex hormones among participants aged 6-19 years, utilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2016. Children and adolescents who had available data on urinary glyphosate, serum sex steroid hormones, including testosterone (TT), estradiol (E) and sex hormone binding globulin (SHBG), and covariates were selected. Additionally, the ratio of TT to E (TT/E) and the free androgen index (FAI), which was calculated using TT/SHBG, were also included as sex hormone indicators. Survey regression statistical modeling was used to examine the associations between urinary glyphosate concentration and sex hormone indicators by age and sex group. Among the 964 participants, 83.71% had been exposed to glyphosate (>lower limit of detection). The survey regression revealed a marginally negative association between urinary glyphosate and E in the overall population, while this association was more pronounced in adolescents with a significant trend. In further sex-stratified analyses among adolescents, a significant decrease in E, FAI, and TT (p trend <0.05) was observed in female adolescents for the highest quartile of urinary glyphosate compared to the lowest quartile. However, no similar association was observed among male adolescents. Our findings suggest that exposure to glyphosate at the current level may decrease the levels of sex steroids in adolescents, particularly female adolescents. Considering the cross-sectional study design, further research is needed to confirm our findings.
Topics: Child; Humans; Male; Adolescent; Female; Young Adult; Adult; Glyphosate; Nutrition Surveys; Cross-Sectional Studies; Gonadal Steroid Hormones; Testosterone; Estradiol; Sex Hormone-Binding Globulin
PubMed: 38564862
DOI: 10.1016/j.ecoenv.2024.116266 -
Yakugaku Zasshi : Journal of the... 2024In Japan, the use of frame retardants [tris(2,3-dibromopropyl)phosphate: TDBPP and bis(2,3-dibromopropyl)phosphate: BDBPP] in several household textile products is...
[Examination of Analytical Method for Tris(2,3-dibromopropyl)phosphate and Bis(2,3-dibromopropyl)phosphate to Revise the Official Methods Based on "Act on the Control of Household Products Containing Harmful Substances"].
In Japan, the use of frame retardants [tris(2,3-dibromopropyl)phosphate: TDBPP and bis(2,3-dibromopropyl)phosphate: BDBPP] in several household textile products is banned under the "Act on the Control of Household Products Containing Harmful Substances." As the official analytical methods for testing these substances have not been revised for over 42 years, several issues such as the using of harmful reagents, have been pointed out. Therefore, we developed a new method to revise the official method in our previous study. In this study, the validity of the developed test method is evaluated at six laboratories using two types of textile samples spiked with TDBPP and BDBPP at three concentrations (4, 8, and 20 µg/g). TDBPP and BDBPP are extracted under reflux using methanol containing hydrochloric acid. TDBPP is analyzed using GC-MS, and BDBPP is also analyzed using GC-MS after methylation with trimethylsilyl diazomethane. Although the accuracy (70-120%), repeatability (<10%), and reproducibility (<15%) of a few samples, mainly low concentration samples, are out of range, overall, the concentration level of detection limits of TDBPP and BDBPP (8 and 10 µg/g) in official analytical methods are quantifiable with sufficient precision using the proposed method. Furthermore, harmful reagents are not used in this method. Thus, the method validated in this study is effective as a revised method for the testing of TDBPP and BDBPP in household textile products.
Topics: Phosphates; Reproducibility of Results; Organophosphates; Household Products
PubMed: 38556319
DOI: 10.1248/yakushi.23-00188