BACKGROUND: Adolescents living in agricultural communities may be at risk for the adverse effects of pesticide exposure because they are involved in agriculture either as a career or to support their families.
OBJECTIVE: The purpose of this study was to investigate the association of farm activities related to pesticide exposure on blood cholinesterase (ChE) levels among adolescents from farming families in the north of Thailand.
METHODS: This cross-sectional study included 336 adolescents aged 12-19 years from farming families in Chiang Dao District, Chiang Mai Province. Data on pesticide exposure was collected using a questionnaire, and blood ChE activity was assessed using a ChE reactive paper test kit via fingerstick blood sampling.
RESULTS: Overall, 51.2% of participants had abnormal blood ChE levels. Univariable logistic regression analysis revealed that pesticide-related activities on farms associated with abnormal ChE levels were mixing/spraying (OR=10.54; 95%CI=4.63-23.99), assisting or working in areas with pesticide application (OR=5.54; 95%CI=3.45-8.89), and harvesting (OR=3.70; 95%CI=2.35-5.82). In a multivariable model (Nagelkerke R2=0.374), mixing/spraying (OR=4.90; 95%CI=2.03-11.83) and assisting or working in areas with pesticide application (OR=2.61; 95%CI=1.49-4.57) were significantly associated with abnormal ChE levels, but harvesting (OR=1.48; 95%CI=0.84-2.61) was not significant after adjusting for sex, age in years, and entering or walking through a farm.
CONCLUSIONS: The findings indicated that Thai adolescents living in farming families are at risk of pesticide exposure, particularly those involved in agricultural activities such as pesticide applicators. An intervention and measure to raise awareness and reduce the risk of pesticide exposure in adolescents is required.

The improper application of pesticides in cultivating vegetables has resulted in the buildup of pesticide residues on vegetables. This study evaluated organophosphate pesticide residue levels in cabbage with specific objectives of investigating the varieties of organophosphate pesticides employed by farmers and their awareness, assessing residue levels on cabbage using semi-structured questionnaires, and determining the distribution of pesticide residues within the layers of the cabbage head using 50 cabbage samples randomly collected from farmers from 14 cabbage-producing communities. The findings indicated that 98 % of the farmers applied pesticides in the morning, whereas 24 % preferred evening application. Meanwhile, 22 % applied pesticides twice in a day. Also, 18 % combined pesticides, 40 % applied 20 ml during the application, 72 % chose a particular pesticide based on the expected efficiency, 46 % applied pesticides between 1 and 5 times in a season and 66 % sprayed between 7 and 14 days. Pyrinex 48 EC and Perferthion emerged as the predominant organophosphates, with usage rates of 10 % and 12 % respectively. Also, eleven (11) organophosphate pesticide residues were identified in the cabbage samples. Profenofos and chlorpyrifos exhibited the highest concentrations of pesticide residues, with levels reaching 0.02 mg/kg, with 56.6 % of the samples containing chlorpyrifos pesticide residue. Nevertheless, all the identified pesticide residues did not exceed the maximum residue limits for cabbage. The study analysis disclosed the presence of various organophosphate pesticide residues in the first 10 layers of cabbage. However, it was noted that the innermost layers might not contain any detectable pesticide residues. The findings highlight the need for farmers to use pesticides judiciously and follow recommended application practices to minimize vegetable residues.

Dichlorvos is an organophosphate pesticide that is commonly used for agricultural and domestic control of pests and insects. Despite its usefulness, it exerts reproductive toxicity and induces male sexual dysfunction. On the other hand, curcumin has been reported to improve sexual dysfunction. However, till date, no study has reported the impact of curcumin on dichlorvos-induced sexual dysfunction. This study investigated the effect and associated mechanism of curcumin on dichlorvos-induced sexual dysfunction. Thirty-two male Wistar rats were randomized into four groups; the control (1 mL of olive oil), curcumin-treated (100 mg/kg), DDVP-treated (98.54 g/m3 of dichlorvos by inhalation), and DDVP + Curcumin-treated. Dichlorvos induced sexual dysfunction as depicted by reduced motivation to mate (8.38 ± 0.18 vs. 4.00 ± 0.33, P < 0.0001), prolonged latencies (46.63 ± 1.30 vs. 98.75 ± 1.32, P < 0.0001) and reduced frequencies of mount (14.88 ± 0.52 vs. 8.63 ± 0.38), intromission (9.38 ± 0.50 vs. 3.75 ± 0.31, P < 0.0001), and ejaculation (7.63 ± 0.38 vs. 1.50 ± 0.19, P < 0.0001). These findings were accompanied by suppression of hypothalamic-pituitary-testicular axis, evidenced by marked reductions in circulating FSH (60.00 ± 1.04 vs. 21.13 ± 0.52, P < 0.0001), LH (46.38 ± 1.38 vs. 19.00 ± 0.46, P < 0.0001), and testosterone (6.01 ± 0.50 vs. 0.74 ± 0.05, P < 0.0001). Nonetheless, the administration of curcumin in dichlorvos-exposed rats significantly attenuated dichlorvos-induced sexual dysfunction by improving the assessed indices of male sexual act. Also, curcumin significantly increased serum levels of FSH (21.13 ± 0.52 vs. 47.25 ± 0.10, P < 0.0001), LH (19.00 ± 0.46 vs. 43.00 ± 1.49), and testosterone (0.74 ± 0.05 vs. 3.98 ± 0.08, P < 0.0001). This study revealed that curcumin attenuated dichlorvos-induced sexual dysfunction by activating the hypothalamic-pituitary-testicular axis and upregulating circulating testosterone.

Amitraz poisoning is being increasingly seen in clinical practice, presenting physicians with challenges due to its rapidity of onset of severe clinical features, its similarity with organophosphate poisoning and the absence of specific antidotes. Early initiation and appropriate treatment are vital for favourable outcomes. Our case report is of a 40-year-old male who presented to us with grave clinical features following deliberate ingestion of Amitraz in a suicidal attempt. On arrival, he had bradycardia, hypotension, respiratory depression, and altered sensorium. Immediate administration of atropine stabilised his vital signs. Laboratory investigations revealed uncommon electrolyte imbalances, which were promptly corrected. The patient received supportive care in the intensive care unit (ICU), regained consciousness within three days, and was discharged after a week of hospitalisation. Despite the rapid onset and severity of symptoms caused by Amitraz poisoning, early intervention and supportive care can lead to a full recovery. This case underscores the importance of promptly recognising Amitraz poisoning and initiating treatment, its similarity with organophosphate poisoning and the role of atropine. Further research is needed to establish comprehensive management guidelines for tackling this emerging poisoning hazard.

Due to their inhibition of acetylcholinesterase, organophosphates are among the most toxic of chemicals. Pralidoxime (a.k.a 2-PAM) is the only acetylcholinesterase reactivator approved in the U.S., but 2-PAM only poorly traverses the blood-brain barrier. Previously, we have demonstrated that scL-2PAM, a nanoformulation designed to enter the brain via receptor-mediated transcytosis, is superior to unencapsulated 2-PAM for reactivating brain acetylcholinesterase, ameliorating cholinergic crisis, and improving survival rates for paraoxon-exposed mice. Here, we employ histology and transcriptome analyses to assess the ability of scL-2PAM to prevent neurological sequelae including microglial activation, expression of inflammatory cytokines, and ultimately loss of neurons in mice surviving paraoxon exposures. Levels of the mRNA encoding chemokine ligand 2 (CCL2) were significantly upregulated after paraoxon exposures, with CCL2 mRNA levels in the brain correlating well with the intensity and duration of cholinergic symptoms. Our nanoformulation of 2-PAM was found to be superior to unencapsulated 2-PAM in reducing the levels of the CCL2 transcript. Moreover, brain histology revealed that scL-2PAM was more effective than unencapsulated 2-PAM in preventing microglial activation and the subsequent loss of neurons. Thus, scL-2PAM appears to be a new and improved countermeasure for reducing neuroinflammation and mitigating brain damage in survivors of organophosphate exposures.

Organophosphorus compounds (OPs) are widely used and have the potential to be harmful environmental toxicants to humans. Long non-coding RNA (lncRNA) plays a crucial regulatory role in cytotoxicity. This study aimed to investigate the effects of OPs on the expression of lncRNAs in cells. The effects of the industrial OPs TNPP and TCPP on both CYTOR and cellular viability were examined in the following human renal cell lines: HEK293T and HK-2. Both TCPP and TNPP downregulated CYTOR expression, increased reactive oxygen species levels, and induced apoptosis; the upregulated expression of CYTOR resulted in a reduction in apoptosis. The results of the luciferase reporter assay and the knock-down assay indicate that CEBPA binds to the upstream promoter region of CYTOR and regulates its transcription. Furthermore, TCPP and TNPP were found to downregulate the phosphorylation of ERK in the signaling pathway that is upstream of CEBPA. These results indicate that TCPP and TNPP can decrease the level of CEBPA by reducing ERK phosphorylation; this leads to a decrease in CYTOR expression, which further promotes cellular reactive oxygen species and apoptosis. Therefore, the ERK/CEBPA/CYTOR axis is one of the pathways by which organophosphates produce cytotoxicity, leading to renal cell injury. This study presents evidence for both the abnormal expression of lncRNA that is caused by organophosphates and the regulatory function of lncRNA regarding downstream cellular viability.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) bottle bioassay is a commonly used susceptibility test for measuring insect response to insecticide exposure. However, inconsistencies and high variability in insect response when conducting CDC bottle bioassays have been reported in previous publications. We hypothesized that the CDC bottle bioassay results may be compromised when expected and actual insecticide concentrations in the bottles are not equivalent and that inadequate bottle cleaning and/or loss during insecticide introduction and bottle storage steps could be responsible. We explored this hypothesis by quantifying insecticides using gas chromatography tandem mass spectrometry (GC-MS/MS) in bottles that had been cleaned, prepared, and stored according to the CDC guidelines.
METHODS: We investigated the bottle cleaning, preparation, and storage methods outlined in the CDC bottle bioassay procedure to identify sources of irreproducibility. We also investigated the effectiveness of cleaning bottles by autoclaving because this method is commonly used in insecticide assessment laboratories. The two insecticides used in this study were chlorpyrifos and lambda-cyhalothrin (λ-cyhalothrin). Insecticides were removed from glass bioassay bottles by rinsing with ethyl-acetate and n-hexane and then quantified using GC-MS/MS.
RESULTS: The CDC bottle bioassay cleaning methods did not sufficiently remove both insecticides from the glass bottles. The cleaning methods removed chlorpyrifos, which has higher water solubility, more effectively than λ-cyhalothrin. Chlorpyrifos experienced significant loss during the bottle-coating process whereas λ-cyhalothrin did not. As for bottle storage, no significant decreases in insecticide concentrations were observed for 6 h following the initial drying period for either insecticide.
CONCLUSIONS: The CDC bottle bioassay protocol is susceptible to producing inaccurate results since its recommended bottle cleaning method is not sufficient and semi-volatile insecticides can volatilize from the bottle during the coating process. This can lead to the CDC bottle bioassay producing erroneous LC50 values. High levels of random variation were also observed in our experiments, as others have previously reported. We have outlined several steps that CDC bottle bioassay users could consider that would lead to improved accuracy and reproducibility when acquiring toxicity data.

Organophosphates constitute a major class of pesticides widely employed in agriculture to manage insect pests. Their toxicity is attributed to their ability to inhibit the functioning of acetylcholinesterase (AChE), an essential enzyme for normal nerve transmission. Organophosphates, especially chlorpyrifos, have been a key component of the integrated pest management (IPM) in onions, effectively controlling onion maggot Delia antiqua, a severe pest of onions. However, the growing concerns over the use of this insecticide on human health and the environment compelled the need for an alternative organophosphate and a potential microbial agent for bioremediation to mitigate organophosphate pesticide pollution. In the present study, chloropyrifos along with five other organophosphate insecticides, phosmet, primiphos-methyl, isofenphos, iodofenphos and tribuphos, were screened against the target protein AChE of D. antiqua using molecular modeling and docking techniques. The results revealed that iodofenphos showed the best interaction, while tribuphos had the lowest interaction with the AChE based on comparative binding energy values. Further, protein-protein interaction analysis conducted using the STRING database and Cytoscap software revealed that AChE is linked with a network of 10 different proteins, suggesting that the function of AChE is disrupted through interaction with insecticides, potentially leading to disruption within the network of associated proteins. Additionally, an in silico study was conducted to predict the binding efficiency of two organophosphate degrading enzymes, organophosphohydrolase (OpdA) from Agrobacterium radiobacter and Trichoderma harzianum paraoxonase 1 like (ThPON1-like) protein from Trichoderma harzianum, with the selected insecticides. The analysis revealed their potential to degrade the pesticides, offering a promising alternative before going for cumbersome onsite remediation.

Dimethoate (DMT) is one of the most harmful and commonly used organophosphate pesticides in agricultural lands to control different groups of parasitic insects. However, this pesticide is considered a dangerous pollutant for aquatic organisms following its infiltration in coastal ecosystems through leaching. Yet, our investigation aimed to gain new insights into the toxicity mechanism of DMT in the muscles of the green crab Carcinus aestuarii, regarding oxidative stress, neurotransmission impairment, histological aspects, and changes in lipid composition, assessed for the first time on the green crab\'s muscle. Specimens of C. aestuarii were exposed to 50, 100, and 200 µg DMT L-1 for 24 h. Compared to the negative control group, the higher the DMT concentration, the lower the saturated fatty acids (SFA), and the higher the monounsaturated fatty acids (MUFA). The significant increase in polyunsaturated fatty acid n-6 (PUFA n-6) was related to the high release, mainly, of linoleic acid (LA, C18: 2n6) and arachidonic acid (ARA, C20: 4n6) levels. Biochemical biomarkers showed that DMT exposure promoted oxidative stress, highlighted by increased levels of hydrogen peroxide (H2O2), malondialdehyde (MDA), advanced oxidation protein product levels (AOPP), and protein carbonyl (PCO). Furthermore, the antioxidant defense system was activated, as demonstrated by the significant changes in the enzymatic activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) levels associated with an adaptation process of C. aestuarii to cope with the DMT exposure. This pesticide significantly impairs the neurotransmission process, as evidenced by the inhibition of acetylcholinesterase (AChE) activity. Finally, several histopathological changes were revealed in DMT-treated crabs, including vacuolation, and muscle bundle loss.This research offered new insights into the toxic mechanism of DMT, pointing to the usefulness of fatty acid (FA) composition as a sensitive biomarker in littoral crabs.

Most organophosphates (OPs) are hydrophobic, and after exposure, can sequester into lipophilic regions within the body, such as adipose tissue, resulting in long term chronic effects. Consequently, there is an urgent need for therapeutic agents that can decontaminate OPs in these hydrophobic regions. Accordingly, an enzyme-polymer surfactant nanocomplex is designed and tested comprising chemically supercharged phosphotriesterase (Agrobacterium radiobacter; arPTE) electrostatically conjugated to amphiphilic polymer surfactant chains ([cat.arPTE][S-]). Experimentally-derived structural data are combined with molecular dynamics (MD) simulations to provide atomic level detail on conformational ensembles of the nanocomplex using dielectric constants relevant to aqueous and lipidic microenvironments. These show the formation of a compact admicelle pseudophase surfactant corona under aqueous conditions, which reconfigures to yield an extended conformation at a low dielectric constant, providing insight into the mechanism underpinning cell membrane binding. Significantly, it demonstrated that [cat.arPTE][S-] spontaneously binds to human mesenchymal stem cell membranes (hMSCs), resulting in on-cell OP hydrolysis. Moreover, the nanoconstruct can endocytose and partition into the intracellular fatty vacuoles of adipocytes and hydrolyze sequestered OP.