Organophosphate Exposure Research Articles

Associations between prenatal organophosphate pesticide exposure and placental gene networks

BackgroundExposure to organophosphate (OP) pesticides during pregnancy has been linked to deficiencies of neurobehavioral development in childhood; however, the molecular mechanisms underlying this association remain elusive. The placenta plays a crucial role in protecting the fetus from environmental insults and safeguarding proper fetal development including neurodevelopment. The aim of our study is to evaluate changes in the placental transcriptome associated with prenatal OP exposure. MethodsPregnant farm workers from two agricultural districts in northern Thailand were recruited for the Study of Asian Women and Offspring's Development and Environmental Exposures (SAWASDEE) from 2017 to 2019. For 254 participants, we measured maternal urinary concentrations of six nonspecific dialkyl phosphates (DAP) metabolites in early, middle, and late pregnancy. In parallel, we profiled the term placental transcriptome from the same participants using RNA-Sequencing and performed Weighted Gene co-expression Network Analysis (WGCNA). Generalized linear regression modeling was used to examine associations of urinary OP metabolites and placental co-expression module eigenvalues. ResultsWe identified 21 gene co-expression modules in the placenta. From the six DAP metabolites assayed, diethylphosphate (DEP) and diethylthiophosphate (DETP) were detected in more than 70% of the urine samples. Significant associations between DEP at multiple time points and two specific placental gene modules were observed. The ‘black’ module, enriched in genes involved in epithelial-to-mesenchymal transition (EMT) and hypoxia, was negatively associated with DEP in early (p = 0.034), and late pregnancies (p = 0.016). The ‘lightgreen’ module, enriched in genes involved in myogenesis and EMT, was negatively associated with DEP in late pregnancy (p = 0.010). We observed 2 hub genes (CELSR1 and PYCR1) of the ‘black’ module to be negatively associated with DEP in early and late pregnancies. ConclusionsOur results suggest that prenatal OP exposure may disrupt placental gene networks in a time-dependent manner. Such transcriptomic effects may lead to down-stream changes in placental function that ultimately affect the developing fetus.

Rapid LC-MS/MS quantification of Organophosphate non-specific metabolites in hair using alkaline extraction approach

Assessing human exposure to commonly used, highly toxic, but non-persistent organophosphates (OPs) is challenging because these toxicants are readily biotransformed into dialkyl phosphates (DAPs) and other metabolites. Growing hair accumulates toxicants and their metabolites, which makes hair a valuable non-invasively sampled matrix that can be used to retrospectively examine chemical exposure. However, the efficient quantification of hydrophilic DAP compounds in hair is challenging due to complex hair matrix effects. To improve upon existing methods, we first examined the acid dissociation constants (pKa) of DAPs and amino acids (major components in hair) and identified the best pH conditions for minimizing matrix effects. We hypothesized that under basic pH conditions DAPs and amino acids would be negatively charged and have weak interactions favorable to DAP dissociation from the matrix. To test this, we compared the efficiency of various pH conditions of suitable solvents to extract six DAPs from hair samples, and we quantified these DAPs using liquid chromatography-tandem mass spectroscopy (LC-MS/MS). As expected, a basic extraction (methanol with 2% NH4OH) approach had the highest extraction efficiency and yielded satisfactory recoveries for all six DAPs (72%-152%) without matrix effects. Additionally, the alkaline extract can be directly injected into the LC-MS/MS. This relatively rapid and simple procedure allowed us to process up to 90 samples per week with reproducible results. To our knowledge, this is the first method to quantify all six DAPs simultaneously in hair using LC-MS/MS with electrospray ionization (ESI) in negative ion mode. Finally, we demonstrated the feasibility of measuring DAP levels in hair samples from patients affected with amyotrophic lateral sclerosis (ALS), a neurodegenerative disease potentially linked to OP exposure. Due to our optimized solvent extraction process, the method we have developed is compatible with the rapidity and sensitivity needed for hair analysis applied to population biomonitoring.

A novel RP-HPLC method for quantification of cholinesterase activity in human blood: An application for assessing organophosphate and carbamate insecticide exposure.

Several methods have been reported to estimate Acetylcholinesterase (AChE) enzyme activity in blood samples. The Ellman assay is the most important among all but with several shortcomings, and there is a need to develop a method which is accurate, sensitive and quick for analyzing AChE. Therefore, we have developed an assay utilizing RP-HPLC with UV detection for the determination of AChE activity. This method measured the conversion of 1-naphthol acetate to 1-naphthol to estimate AChE activity in blood samples. Performance was judged on the basis of reproducibility, sensitivity, accuracy, and the ability to screen enzyme activity within 20minutes. A series of experiments were performed, varying the concentration of blood and substrate, with optimal sensitivity using 50 μM substrate and 10μL blood. The validation parameters such as linearity (R2 of ≥ 0.9842 for 1-naphthol and ≥ 0.9897 for 1-naphthol acetate), precision (94.21-96.41%), accuracy (85.2%-99.6% and 82.6%-99.3% for 1-naphthol and 1-naphthol acetate respectively), and robustness were validated according to International Conference on Harmonization (ICH) guidelines. Blood samples were collected from healthy people, farmers exposed to spraying of pesticides, and suicidal patients who ingested pesticides and were hospitalized and were analyzed by the developed method. The AChE level was approximately 21 units/mL compared to 24units/mL in controls, whereas suicidal patients showed the least AChE levels of 1 unit/mL. The employment of this method is recommended for estimating AChE level on various matrices.

Organophosphate Insecticide Toxicity in Neural Development, Cognition, Behaviour and Degeneration: Insights from Zebrafish.

Organophosphate (OP) insecticides are used to eliminate agricultural threats posed by insects, through inhibition of the neurotransmitter acetylcholinesterase (AChE). These potent neurotoxins are extremely efficacious in insect elimination, and as such, are the preferred agricultural insecticides worldwide. Despite their efficacy, however, estimates indicate that only 0.1% of organophosphates reach their desired target. Moreover, multiple studies have shown that OP exposure in both humans and animals can lead to aberrations in embryonic development, defects in childhood neurocognition, and substantial contribution to neurodegenerative diseases such as Alzheimer's and Motor Neurone Disease. Here, we review the current state of knowledge pertaining to organophosphate exposure on both embryonic development and/or subsequent neurological consequences on behaviour, paying particular attention to data gleaned using an excellent animal model, the zebrafish (Danio rerio).

Organophosphate insecticides disturb neuronal network development and function via non-AChE mediated mechanisms

Exposure to organophosphate (OP) insecticides has been related to several adverse health effects, including neurotoxicity. The primary insecticidal mode of action of OP insecticides relies on (irreversible) binding to acetylcholine esterase (AChE), with –oxon metabolites having a much higher potency for AChE inhibition than the parent compounds. However, OP insecticides can also have non-AChE-mediated effects, including changes in gene expression, neuroendocrine effects, disruption of neurite outgrowth and disturbance of the intracellular calcium (Ca2+) homeostasis. Since Ca2+ is involved in neurotransmission and neuronal development, our research aimed to assess the effects of two widely used OP insecticides, chlorpyrifos (CPF) and diazinon (DZ) and their respective -oxon metabolites, on intracellular Ca2+ homeostasis in human SH-SY5Y cells and rat primary cortical cultures. Furthermore, we assessed the acute and chronic effects of exposure to these compounds on neuronal network maturation and function in rat primary cortical cultures using microelectrode array (MEA) recordings. While inhibition of AChE appears to be the primary mode of action of oxon-metabolites, our data indicate that both parent OP insecticides (CPF and DZ) inhibit depolarization-evoked Ca2+ influx and neuronal activity at concentrations far below their sensitivity for AChE inhibition, indicating that inhibition of voltage-gated calcium channels is a common mode of action of OP insecticides. Notably, parent compounds were more potent than their oxon metabolites, with exposure to diazinon-oxon (DZO) having no effect on both neuronal activity and Ca2+ influx. Human SH-SY5Y cells were more sensitive to OP-induced inhibition of depolarization-evoked Ca2+ influx than rat cortical cells. Acute exposure to OP insecticides had more potent effects on neuronal activity than on Ca2+ influx, suggesting that neuronal activity parameters are especially sensitive to OP exposure. Interestingly, the effects of DZ and chlorpyrifos-oxon (CPO) on neuronal activity lessened after 48 h of exposure, while the potency of CPF did not differ over time. This suggests that neurotoxicity after exposure to different OPs has different effects over time and occurs at levels that are close to human exposure levels. In line with these results, chronic exposure to CPF during 10 days impaired neuronal network development, illustrating the need to investigate possible links between early-life OP exposure and neurodevelopmental disorders in children and highlighting the importance of non-AChE mediated mechanisms of neurotoxicity after OP exposure.

Heavy hemolysis after organophosphate poisoning by chlorpyrifos ethyl

Organophosphates (OPs) inactivate the acetylcholinesterase enzyme, thus increasing the cholinergic effect. In a clinical setting, patients with OP poisoning may experience nausea and vomiting, diarrhea, and abdominal pain, or in severe cases respiratory failure, seizures, and death. Rarely, acute hemolysis has also been observed. The existing literature contains few descriptions of several delayed diseases associated with OP poisoning. This article presents the case of a patient who experienced severe hemolysis approximately one week after OP exposure. Only a small number of similar cases have been previously examined.

Cognitive Impairment and Neurodegenerative Diseases Development Associated with Organophosphate Pesticides Exposure: a Review Study.

A significant body of literature emphasizes the role of insecticide, particularly organophosphates (OPs), as the major environmental factor in the etiology of neurodegenerative diseases. This review aims to study the relationship between OP insecticide exposure, cognitive impairment, and neurodegenerative disease development. Human populations, especially in developing countries, are frequently exposed to OPs due to their extensive applications. The involvement of various signaling pathways in OP neurotoxicity are reported, but the OP-induced cognitive impairment and link between OP exposure and the pathophysiology of neurodegenerative diseases are not clearly understood. In the present review, we have therefore aimed to come to new conclusions which may help to find protective and preventive strategies against OP neurotoxicity and may establish a possible link between organophosphate exposure, cognitive impairment, and OP-induced neurotoxicity. Moreover, we discuss the findings obtained from animal and human research providing some support for OP-induced cognitive impairment and neurodegenerative disorders.

Toxic-Induced Nonthyroidal Illness Syndrome Induced by Acute Low-Dose Pesticides Exposure-Preliminary In Vivo Study.

Background and Objectives: Conditions such as trauma, burns, sepsis, or acute intoxications have considerable consequences on the endocrine status, causing “sick euthyroid syndrome”. Organophosphate exposure may induce an increase in acetylcholine levels, thus altering the thyroid’s hormonal status. The present study aims to identify the effects of acetylcholinesterase inhibition on thyroid hormones. Material and methods: A prospective experimental study was conducted on twenty Wistar rats. Blood samples were drawn to set baseline values for thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4). Chlorpyrifos 0.1 mg/kg was administered by oral gavage to induce acetyl-cholinesterase inhibition. After exhibiting cholinergic symptoms, blood samples were collected to assess levels of cholinesterase and thyroid hormones using ELISA. Results: Butyrylcholinesterase levels confirmed major inhibition immediately after intoxication compared to the baseline, certifying the intoxication. A significant increase in T4 levels was noted (p = 0.01) both at 2 h and 48 h after administration of organophosphate in sample rats. Similarly, T3 almost doubled its value 2 h after poisoning (4.2 ng/mL versus 2.5 ng/mL at baseline). Surprisingly, TSH displayed acute elevation with an afterward slow descending trend at 48 h (p = 0.1), reaching baseline value. Conclusions: This study demonstrated that cholinesterase inhibition caused major alterations in thyroid hormone levels, which may be characterized by a transient hypothyroidism status with an impact on survival prognosis.

Organophosphate Insecticide Exposure Impacts Reproductive Success in Insensitive Acetylcholinesterase Anopheles gambiae Mosquitoes

Extensive use of insecticides has led to the selection of resistance alleles in malaria vectors threatening the control programs. Even if mosquitoes are not killed directly in the contact of insecticide-treated bed nets, their capacity to transmit malaria parasite could be decreased because of the consequences on their life-history traits after repeated exposure. The current work investigated the effects of organochlorine, carbamate, organophosphate, and pyrethroid insecticide exposure on the reproductive success in Anopheles gambiae s.s. Two Anopheles gambiae strains, AcerKis, KisKdr, were used. According to WHO recommendations, female mosquitoes of these resistant strains were exposed to discriminant doses of DDT, chlorpyriphos-methyl, bendiocarb, and permethrin insecticides. Surviving mosquitoes were then fed and allowed to lay eggs. Fecundity was assessed by examining the number of eggs per mosquito, the number of larvae per egg batch and larval hatching rates were used to evaluate the fertility. The data showed that AcerKis females surviving chlorpyriphos-methyl exposure significantly laid few eggs. No significant difference in the hatching rate was noticed in AcerKis females exposed to bendiocarb compared to their control. No significant effect on the fecundity and fertility was observed in KisKdr females exposed to permethrin. Our finding showed that organophosphate insecticides represented here by chlorpyriphos-methyl could hamper egg-laying in insensitive acetylcholinesterase An. gambiae female mosquitoes. This knowledge could help design alternative vector control strategies targeting fecundity and fertility in resistant malaria vectors.

Organophosphate Poisoning in a Paediatric Intensive Care Unit: A Retrospective Analysis Based on Ten Years of Experience.

BackgroundOrganophosphate (OP) poisoning is one of the most common etiologies of poisoning in the pediatric age group.ObjectiveThis study aimed to evaluate the demographic characteristics, clinical features, clinical course, and outcomes of children with toxicity from organophosphates admitted to the pediatric intensive care unit.MethodsA retrospective review of hospital medical records of all children aged 14 years and younger who were admitted to the PICU with a provisional diagnosis of organophosphate poisoning at King Fahad Hospital of the University (KFHU), Alkhobar, Saudi Arabia, between January 1, 2008, and December 31, 2018, was conducted. Patients with incomplete medical record information or with suspicion or evidence of one or more agents other than organophosphate were excluded from the study.ResultsThirty-one patients were enrolled in the study. The median age of the study population was 2 years, and 19 (61%) were males. The majority of patients (68%) had more than one route of organophosphate exposure. Skin exposure was reported in 26 patients (84%). Only three patients (10%) had suicidal organophosphate exposure from organophosphates, while the majority (28 patients; 90%) had accidental poisoning. Bronchorrhea was the most prevalent presenting feature, reported in 28 patients (90%). 17 patients (55%) were treated with intravenous atropine and (45%) were used a combination of pralidoxime with atropine for treatment. Five patients (16%) developed acute respiratory distress syndrome. Twelve patients (39%) needed endotracheal intubation and mechanical ventilation secondary to respiratory failure.ConclusionThe presenting features of organophosphate poisoning differ widely in children. Risk factors for mortality for PICU patients with organophosphate poisoning include delayed hospital arrival by more than 1 hour, inhalational route of exposure, need for mechanical ventilation, and high lactate levels in the first 24 hours post-exposure.

Comparing impact of pesticide exposure on cognitive abilities of Latinx children from rural farmworker and urban non-farmworker families in North Carolina.

Pesticide exposure remains a health hazard despite extensive study into adverse effects. Children in vulnerable populations, such as Latinx children in farmworker families, are particularly at risk for exposure. Several studies have demonstrated the detrimental cognitive effects of prenatal exposure to pesticides, particularly organophosphates (OPs) within this high-risk group. However, results from studies investigating the cognitive effects of early childhood pesticide exposure are equivocal. Most studies examining the effects of pesticide exposure have used correlative analyses rather than examining populations with expected high and low exposure. The current study compares 8-year-old children from rural families of farmworkers and urban, non-farmworker families. We used the Weschler Intelligence Scale for Children – Fifth Edition (WISC-V) to assess cognitive performance in these children. We designed this study with the expectation that children from farmworker families would have greater exposure to agricultural pesticides than urban, non-farmworker children. This assumption of exposure to agricultural pesticides was confirmed in a recent report that assessed exposure probabilities using life history calendars. However, data from passive wristband sampling of acute (1-week) pesticide exposure from these same children indicate that both study populations have considerable pesticide exposure but to different chemicals. As expected the children of farmworkers had greater OP exposure than non-farmworker children, but the non-farmworker children had greater exposure to two other classes of insecticides (organochlorines [OCs] and pyrethroids). Our analyses considered these findings. A comparison of the cognitive scores between groups revealed that children from farmworker families had slightly higher performance on the Visual-Spatial Index (VSI) and Verbal Comprehension Index (VCI) when compared to children from non-farmworker families. Regression analyses where pesticide exposure was included as covariates revealed that OC exposure accounted for the largest portion of the group differences for both VSI and VCI. However, a post-hoc moderation analysis did not find significant interactions. The main study outcome was that the non-farmworker children exhibited lower WISC-V scores than the children from farmworker families, and the analyses incorporating pesticide exposure measures raise the hypothesis the that pervasive and persistent nature of a variety of pesticides may have adverse effects on the neurodevelopment of young Latinx children whether living in rural or non-farmworker environments.

Developing a Prenatal Acute Exposure and Medical Countermeasure Evaluation Model for Organophosphate Compounds in a Genetically Modified Mouse

Organophosphate (OPs) compounds make up the most common class of pesticides as well as chemical warfare nerve agents (CWNA), all of which covalently inhibit the active site of acetylcholinesterase (AChE), resulting in intoxication via a cholinergic crisis. While the biochemical mechanism of action resulting in acute intoxication of an exposed individual is well understood, less is known about the mechanism of OP intoxication via other exposure routes, particularly prenatal exposure. The clinical effects of non‐acute prenatal OP exposure have been previously studied primarily in cases involving diet and agricultural labor, while case studies documenting the effects on conception of acute exposure during chemical warfare attacks (Japan 1995, Syria 2013 and 2017) have also been published. Such exposure events were linked to a range of serious neurodevelopmental anomalies in children, but the underlying mechanism of action as well as the potential benefits of medical countermeasures have not been clearly elucidated. A robust human‐relevant animal model to test both is therefore essential for evaluating current and future OP countermeasures. The present study used a novel humanized mouse strain expressing human AChE and an inactivated native serum carboxylesterase to create a prenatal acute exposure and emergency medical countermeasure evaluation model. Pregnant mice were acutely exposed to an OP at a critical point in cholinergic development, generally equivalent to the first trimester in humans. Dams were challenged with either sarin or the pesticide paraoxon, followed by either a saline vehicle control or 2‐PAM and an atropine/midazolam cocktail, the currently fielded emergency treatment for OP intoxication. Mice were allowed to carry pups to term, and upon reaching maturity, cortex, cerebellum, bone marrow and gonads were collected from offspring in each exposure group. Phenotypical and histopathological evaluation of tissues and other factors in dams and offspring were evaluated. Gene expression analyses conducted for each tissue generated a detailed profile associated with each OP exposure/treatment group, providing robust criteria for model development. The resulting data demonstrated a significant beneficial impact of medical countermeasures for both sarin and paraoxon exposures, significantly reducing the amount and the scope of gene expression changes induced by OP exposure. This model provides insight into the developmental pathologies resulting from prenatal acute OP exposure as well as serves as an evaluation model for future treatments.

DNA damage in a Chilean population exposed to pesticides and its association with PON1 (Q192R and L55M) susceptibility biomarker.

The active ingredients in pesticides are known to be genotoxic that can cause mutations, chromosomal aberrations, or other types of DNA damage. Early detection of genotoxicity reduces the risk of developing diseases such as cancer or suffering from reproductive disorders. In turn, the genotoxic risk depends on the intrinsic capability of the individual to metabolize and eliminate the xenobiotic from the organism. This study aimed to determine if two polymorphisms of paraoxonase-1 (PON1), which is involved in the metabolism of several organophosphate (OP) pesticides, are predictors of susceptibility to DNA damage in agricultural workers and inhabitants of rural areas chronically exposed to pesticides. A cross-sectional study was made considering three groups: agricultural workers (occupational exposure, OE, n= 85), rural inhabitants (environmental exposure, EE, n= 60), and an unexposed group conformed by people living far from agricultural areas (U, n= 33). The level of individual DNA damage was measured using the comet assay, and genotyping was done to determine the PON1 Q192R and L55M polymorphisms. Acetylcholinesterase and butyrilcholinesterase activities were also measured to determine exposure to OP. Individuals belonging to EE and OE groups displayed higher levels of DNA damage compared with U group (p< .001). OP exposure was the main predictor of genotoxicity (β=16.19; 95% CI: 1.85, 30.52), instead of PON1 polymorphisms (β=-12.20; 95% CI: -27.87, 3.48). These results confirm the genotoxic effects of pesticide exposure and suggest that the catalytic efficiency of PON1 to metabolize OP pesticides becomes negligible in individuals with a history of long-term environmental or occupational exposure to these substances.

Rethinking our chemical legacy and reclaiming our planet

Rethinking our chemical legacy and reclaiming our planet

Repeated exposure to chlorpyrifos is associated with a dose-dependent chronic neurobehavioral deficit in adult rats

Organophosphate (OP) chemicals include commonly used pesticides and chemical warfare agents, and mechanistically they are potent inhibitors of the cholinesterase (ChE) enzyme. Epidemiological studies report long-term neuropsychiatric issues, including depression and cognitive impairments in OP-exposed individuals. Chlorpyrifos (CPF) is one of the most widely used pesticides worldwide. Multiple laboratory studies have reported on either the long-term behavioral effect of an acute high-dose CPF (30–250 mg/kg) or studied sub-chronic behavioral effects, particularly the motor and cognitive effects of repeated low-dose CPF. However, studies are lacking on chronic mood and depression-related morbidities following repeated CPF doses that would mimic occupationally relevant OP exposures during adulthood. In this study, adult male rats were injected with CPF (1, 3, 5, or 10 mg/kg/d, s.c.) for 21 consecutive days. Dependent on the CPF dose, ChE activity was inhibited approximately 60–80% in the blood and about 20–50% in the hippocampus at 2-days after the end of CPF exposures. Following a 12-week washout period, a complete recovery of ChE activity was noted. However, CPF-treated rats exhibited a dose-dependent increase in signs related to anhedonia (sucrose preference test), anxiety (open-field and elevated plus-maze), and despair (forced swim test) at this stage. To the best of our knowledge, this could be the first laboratory study that demonstrates a cause-effect relationship between occupational-like CPF exposures in adult rats and the development of long-term depression-related outcomes and could provide an experimental system to study molecular mechanisms underlying environmental OP exposures and the elevated risk for chronic behavioral deficits.

Association between Organophosphate Exposure and Mental Health among Rural Residents from Two Towns in China

Association between Organophosphate Exposure and Mental Health among Rural Residents from Two Towns in China

Effects of chlorpyrifos on non-cholinergic toxicity endpoints in immortalized and primary rat hepatocytes under normal and hepatosteatotic conditions

Chlorpyrifos (CPS) is the most widely used organophosphate (OP) insecticide. Non-cholinergic targets of OPs include enzymes belonging to the serine hydrolase family. Carboxylesterases (Ces) are involved in detoxication of xenobiotics as well as lipid metabolism in the liver. Monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH) are responsible for hydrolyzing endocannabinoids and can also be inhibited by OP compounds. However, there are no in vitro studies examining the sensitivities of these non-cholinergic endpoints following CPS exposure in the steatotic liver. Therefore, we determined the effects of CPS on these endpoints in immortalized McArdle-RH7777 (MCA) hepatoma cells and primary rat hepatocytes under normal and steatotic conditions. Ces activity was more sensitive to inhibition than MAGL or FAAH activity following exposure to the lowest CPS concentration. Additionally, Ces and MAGL activities in steatotic primary hepatocytes were less sensitive to CPS mediated inhibition than those in normal primary hepatocytes, whereas Ces inhibition was more pronounced in steatotic MCA cells. These findings suggest that steatotic conditions enhance the inhibition of hepatic serine hydrolases following exposure to CPS in an enzyme- and cell type-specific manner. CPS-mediated inhibition of these enzymes may play a part in the alterations of hepatic lipid metabolism following OP exposures.

Diet and food type affect urinary pesticide residue excretion profiles in healthy individuals: results of a randomized controlled dietary intervention trial

Observational studies have linked pesticide exposure to various diseases, whereas organic food consumption has been associated with positive health outcomes. Organic farming standards prohibit the use of most pesticides, and organic food consumption may therefore reduce pesticide exposure. To determine the effects of diet (Western compared with Mediterranean) and food type (conventional compared with organic) and sex on urinary pesticide residue excretion (UPRE), as well as associations between specific diet components and UPRE. In this 2-wk, randomized dietary intervention trial, healthy adults were randomly allocated to an intervention (n=13) or conventional (n=14) group. Whereas participants in the intervention group consumed a Mediterranean diet (MedDiet) made entirely from organic foods, the conventional group consumed a MedDiet made entirely from conventional foods. Both groups consumed habitual Western diets made from conventional foods before and after the 2-wk intervention period. The primary outcome was UPRE. In addition, we assessed diet composition and pesticide residue profiles in foods eaten. Participants were aware of group assignment, but the study assessors were not. During the intervention period, total UPRE was 91% lower with organic (mean 17μg/d; 95% CI: 15, 19) than with conventional (mean 180μg/d; 95% CI: 153, 208) food consumption (P<0.0001). In the conventional group, switching from the habitual Western diet to the MedDiet increased insecticide excretion from 7 to 25μg/d (P<0.0001), organophosphate excretion from 5 to 19μg/d (P<0.0001), and pyrethroid residue excretion from 2.0 to 4.5μg/d (P<0.0001). Small but significant effects of sex were detected for chlormequat, herbicide, and total pesticide residue excretion. Changing from a habitual Western diet to a MedDiet was associated with increased insecticide, organophosphate, and pyrethroid exposure, whereas organic food consumption reduced exposure to all groups of synthetic chemical pesticides. This may explain the positive health outcomes linked to organic food consumption in observational studies. This trial was registered at www.clinicaltrials.gov as NCT03254537.

Increased Thyroid Hormone Levels in Pesticide Sprayer at Agricultural Area

Pesticides still used massively in the agricultural sector would cause many poisoning and serious health problems. Organophosphate pesticides have been identified as endocrine-disrupting chemicals. This study aimed to analyze the comparison of thyroid hormone levels between the sprayers chronically exposed to pesticides and the control respondents who had never been exposed to pesticides. This study was an analytical observational with a cross-sectional design. The total number of respondents was 150, 50 as sprayers and 100 as control respondents. The venous blood samples were examined using the Enzyme-Linked Immunosorbent Assay (ELISA). The findings significantly showed that the sprayer had a higher level of thyroid-stimulating hormone (TSH) (4.776 ± 1.1166), lower triiodothyronine (T3) (108.822 ± 18.810), and lower thyroxine (T4) (7.808 ± 1.067). Determinant factors among sprayers that significantly correlated to TSH levels was (age = 0.006; work duration = 0.000; PPE = 0.045; body position = 0.014; type of pesticides = 0.004), correlated with T3 levels was (age = 0.037; body position = 0.045), correlated with T4 levels was (age = 0.000; PPE = 0.045). It could be concluded that chronic organophosphate exposure would increase TSH and decrease T3 and T4.

An insight into neurotoxicity effects associated with Organophosphate exposure

Organophosphates comprise several groups of chemicals derived from phosphonic, phosphinic and phosphoric acids. The chemicals cause four major neurotoxic disorders: cholinergic syndrome, chronic organophosphate-induced neuropsychiatric disorder (COPIND), intermediate syndrome and organophosphate-induced delayed polyneuropathy (OPIDP). In the cholinergic syndrome, organophosphates exert their toxic effect through the inhibition of acetylcholinesterase. Patients with cholinergic syndrome experience several symptoms including sweating, lacrimation, salivation and rhinorrhea and respiratory difficulties. The primary symptoms in the intermediate syndrome are respiratory and proximal limb muscle weakness. In contrast, psychiatric conditions, such as depression and anxiety, have been reported in patients with COPIND. In OPIDP, patients experience acute cramping pain inside their calves and itchiness in the hands and feet, paresthesia and distal unresponsiveness.