Pesticide-Induced Alterations in Locomotor Activity, Anxiety, and Depression-like Behavior Are Mediated through Oxidative Stress-Related Autophagy: A Persistent Developmental Study in Mice.

Chlorpyrifos (CPF), dichlorvos (DDV), and cypermethrin (CP), as commonly used pesticides, have been implicated in inducing neuropsychiatric disorders, such as anxiety, depression-like behaviors, and locomotor activity impairment. However, the exact molecular mechanisms of these adverse effects, particularly in both sexes and their next-generation effects, remain unclear. In this study, we conducted behavioral analysis, along with cellular assays (monodansylcadaverine staining) and molecular investigations (qRT-PCR and western blotting of mTOR, P62, and Beclin-1) to clear the potential role of autophagy in pesticide-induced behavioral alterations. For this purpose, 42 adult female and 21 male inbred ICR mice (F0) were distributed into seven groups. Maternal mice (F0) and 112 F1 offspring were exposed to 0.5 and 1 ppm of CPF, DDV, and CP through drinking water. F1 male and female animals were studied to assess the sex-specific effects of pesticides on brain tissue. Our findings revealed pronounced anxiogenic effects and impaired locomotor activity in mice. F1 males exposed to CPF (1 ppm) exhibited significantly elevated depression-like behaviors compared to other groups. Moreover, pesticide exposure reduced mTOR and P62 levels, while enhancing the Beclin-1 gene and protein expression. These changes in autophagy signaling pathways, coupled with oxidative and neurogenic damage in the cerebral cortex and hippocampus, potentially contribute to heightened locomotor activity, anxiety, and depression-like behaviors following pesticide exposure. This study underscores the substantial impact of pesticides on both physiological and behavioral aspects, emphasizing the necessity for comprehensive assessments and regulatory considerations for pesticide use. Additionally, the identification of sex-specific responses presents a crucial dimension for pharmaceutical sciences, highlighting the need for tailored therapeutic interventions and further research in this field.

Neurogenesis and pesticides: news of no new neurons.

New hippocampal neurons are continuously generated in the adult human brain. Several studies have demonstrated that the proliferation of hippocampal cells is strongly influenced by a variety of stimuli, including pesticides exposure. These effects are particularly important because neurogenesis dysregulation could be associated with the decline of neuronal and cognitive functions and the possible development of neuropsychiatric disorders.

Novos neurônios hipocampais são gerados continuamente no cérebro humano adulto. Vários estudos têm demonstrado que a proliferação de células do hipocampo é influenciada por uma variedade de estímulos, incluindo a exposição a pesticidas. Estes efeitos são particularmente importantes porque a desregulação da neurogênese pode estar associada ao declínio das funções neuronais e cognitivas e ao possível desenvolvimento de doenças neuropsiquiátricas.

Data-Driven Characterization of Genetic Variability in Disease Pathways and Pesticide-Induced Nervous System Disease in the United States Population.

BACKGROUND: Genetic susceptibility to chemicals is incompletely characterized. However, nervous system disease development following pesticide exposure can vary in a population, implying some individuals may have higher genetic susceptibility to pesticide-induced nervous system disease. OBJECTIVES: We aimed to build a computational approach to characterize single-nucleotide polymorphisms (SNPs) implicated in chemically induced adverse outcomes and used this framework to assess the link between differential population susceptibility to pesticides and human nervous system disease. METHODS: We integrated publicly available datasets of Chemical-Gene, Gene-Pathway, and SNP-Disease associations to build Chemical-Pathway-Gene-SNP-Disease linkages for humans. As a case study, we integrated these linkages with spatialized pesticide application data for the US from 1992 to 2018 and spatialized nervous system disease rates for 2018. Through this, we characterized SNPs that may be important in states with high disease occurrence based on the pesticides used there. RESULTS: We found that the number of SNP hits per pesticide in US states positively correlated with disease incidence and prevalence for Alzheimer's disease, Parkinson disease, and multiple sclerosis. We performed frequent itemset mining to differentiate pesticides used over time in states with high and low disease occurrence and found that only 19% of pesticide sets overlapped between 10 states with high disease occurrence and 10 states with low disease occurrence rates, and more SNPs were implicated in pathways in high disease occurrence states. Through a cross-validation of subsets of five high and low disease occurrence states, we characterized SNPs, genes, pathways, and pesticides more frequently implicated in high disease occurrence states. DISCUSSION: Our findings support that pesticides contribute to nervous system disease, and we developed priority lists of SNPs, pesticides, and pathways for further study. This data-driven approach can be adapted to other chemicals, diseases, and locations to characterize differential population susceptibility to chemical exposures. https://doi.org/10.1289/EHP14108.

The research landscape concerning environmental factors in neurodevelopmental disorders: Endocrine disrupters and pesticides-A review.

In recent years, environmental epidemiology and toxicology have seen a growing interest in the environmental factors that contribute to the increased prevalence of neurodevelopmental disorders, with the purpose of establishing appropriate prevention strategies. A literature review was performed, and 192 articles covering the topic of endocrine disruptors and neurodevelopmental disorders were found, focusing on polychlorinated biphenyls, polybrominated diphenyl ethers, bisphenol A, and pesticides. This study contributes to analyzing their effect on the molecular mechanism in maternal and infant thyroid function, essential for infant neurodevelopment, and whose alteration has been associated with various neurodevelopmental disorders. The results provide scientific evidence of the association that exists between the environmental neurotoxins and various neurodevelopmental disorders. In addition, other possible molecular mechanisms by which pesticides and endocrine disruptors may be associated with neurodevelopmental disorders are being discussed.

Temperature influence on the sensitivity of Artemia franciscana to globally used pesticides - Oxyfluorfen and copper.

Climate change further the world's human population increase is a mainstream political issue, and it's critical to search for solutions to produce enough food to feed everyone. Pesticides and fertilizers have been used as an easy solution to prevent pests and increase food production. Nevertheless, their overuse has dangerous effects on the ecosystems and communities. Oxyfluorfen (Oxy) and copper (Cu) based formulations are used as pesticides and widely applied on agricultural fields for crop protection. However, they have shown negative effects on non-target species. So, this work proposes to: a)determine the lethal concentration of Oxy and Cu to the zooplankton, Artemia franciscana, at different temperatures (15 °C, 20 °C and 25 °C); b)understand the biochemical impacts of these chemicals at the different temperatures scenarios, on A. franciscana and c)evaluate the impact of the climate changes, particularly the temperature increase, on this species sensitivity to the tested pesticides. Acute and sub-lethal bioassays with Oxy and Cu were performed at different temperatures to determine the lethal concentration of each chemical and to understand the effects of the compounds at different temperatures on the biochemical profiles of A. franciscana. Results showed an increase in chemicals toxicity with the temperature, and Oxy was revealed to be more noxious to A. franciscana than Cu; at a biochemical level, significant differences were observed among temperatures, with the biggest differences between the organisms exposed to 15 °C and 25 °C. Overall, a decrease in fatty acids (FA) and sugars was observed with the increase in Cu and oxyfluorfen concentrations. Different trends were observed with temperature increase, with FA increase in the organisms exposed to Cu and the opposite was observed in the ones exposed to oxyfluorfen. Sugar content decreases in the organisms exposed to oxyfluorfen with temperature increase and showed a non-linear behaviour in the ones exposed to Control and Cu treatments.

Acute toxicity effects of pesticides on beneficial organisms - Dispelling myths for a more sustainable use of chemicals in agricultural environments.

Agricultural practitioners, researchers and policymakers are increasingly advocating for integrated pest management (IPM) to reduce pesticide use while preserving crop productivity and profitability. Using selective pesticides, putatively designed to act on pests while minimising impacts on off-target organisms, is one such option - yet evidence of whether these chemicals control pests without adversely affecting natural enemies and other beneficial species (henceforth beneficials) remains scarce. At present, the selection of pesticides compatible with IPM often considers a single (or a limited number of) widely distributed beneficial species, without considering undesired effects on co-occurring beneficials. In this study, we conducted standardised laboratory bioassays to assess the acute toxicity effects of 20 chemicals on 15 beneficial species at multiple exposure timepoints, with the specific aims to: (1) identify common and diverging patterns in acute toxicity responses of tested beneficials; (2) determine if the effect of pesticides on beetles, wasps and mites is consistent across species within these groups; and (3) assess the impact of mortality assessment timepoints on International Organisation for Biological Control (IOBC) toxicity classifications. Our work demonstrates that in most cases, chemical toxicities cannot be generalised across a range of beneficial insects and mites providing biological control, a finding that was found even when comparing impacts among closely related species of beetles, wasps and mites. Additionally, we show that toxicity impacts increase with exposure length, pointing to limitations of IOBC protocols. This work challenges the notion that chemical toxicities can be adequately tested on a limited number of 'representative' species; instead, it highlights the need for careful consideration and testing on a range of regionally and seasonally relevant beneficial species.

Chemometrics-driven prediction and prioritization of diverse pesticides on chickens for addressing hazardous effects on public health.

The extensive use of various pesticides in the agriculture field badly affects both chickens and humans, primarily through residues in food products and environmental exposure. This study offers the first quantitative structure-toxicity relationship (QSTR) and quantitative read-across-structure toxicity relationship (q-RASTR) models encompassing the LOEL and NOEL endpoints for acute toxicity in chicken, a widely consumed protein. The study's significance lies in the direct link between chemical toxicity in chicken, human intake, and environmental damage. Both the QSTR and the similarity-based read-across algorithms are applied concurrently to improve the predictability of the models. The q-RASTR models were generated by combining read-across derived similarity and error-based parameters, alongside structural and physicochemical descriptors. Machine Learning approaches (SVM and RR) were also employed with the optimization of relevant hyperparameters based on the cross-validation approach, and the final test set prediction results were compared. The PLS-based q-RASTR models for NOEL and LOEL endpoints showed good statistical performance, as traced from the external validation metrics Q2F1: 0.762-0.844; Q2F2: 0.759-0.831 and MAEtest: 0.195-0.214. The developed models were further used to screen the Pesticide Properties DataBase (PPDB) for potential toxicants in chickens. Thus, established models can address eco-toxicological data gaps and development of novel and safe eco-friendly pesticides.

A prospective cohort study of exposure to household pesticide with cardiovascular diseases mortality in older adults.

OBJECTIVES: We examined the associations of self-reported exposures, and urinary metabolites related to household pesticide with cardiovascular disease (CVD) mortality in older adults based on the 2007 to 2014 waves of National Health and Nutrition Examination Survey (NHANES). METHODS: Information on application and urinary metabolites related to household pesticide exposure were collected. We estimated the risks of household pesticide exposure, urinary metabolites with subsequent incident CVD death using Cox proportional hazards regression models. The indirect effects of urinary metabolites and effect modifications were examined. RESULTS: The participants who reported exposure to household pesticide had a higher risk of incident CVD death (adjusted HR 1.40, 95% CI 1.08 to 1.81). Per 1-log10 increase in urinary N, N-diethyl-3-methylbenzamide (DEET) related to household insect repellents was associated with a higher risk of incident CVD death (adjusted HR 1.97, 95% CI 1.14 to 3.40). Urinary DEET explained 4.21% of the total association between household pesticide exposure and CVD death risk. The participants who persisted a low level of health diet exhibited pronounced CVD death risks with household pesticide exposures. CONCLUSIONS: Exposure to household pesticide, especially household insect repellents, was consistently associated with an elevated CVD death risk in older adults. A heatlhy diet could partly attenuate the associations.

Synergistic interactions between the emerging contaminant ivermectin and the ubiquitous pesticide glyphosate at an environmentally relevant ratio on Rhinella arenarum larvae.

Glyphosate (GLY) is a widely used broad-spectrum herbicide, and ivermectin (IVM) is a commonly used antiparasitic in livestock farming. Both substances can be found in water bodies from agricultural areas and can have negative impacts on ecosystems. The aim of this study was to evaluate the lethal and sublethal toxicity individually and in combination of a glyphosate-based herbicide (GBH) and an ivermectin commercial formulation (ICF). Groups of 10 larvae were exposed for 504 h, in triplicate to a concentration gradient of the commercial formulation of glyphosate and ivermectin, individually, and to a series of dilutions of a non-equitoxic mixture of both compounds based on environmental concentrations. Additionally, biomarkers of oxidative stress (catalase, glutathione S-transferase, and reduced glutathione) and neurotoxicity (acetylcholinesterase and butyrylcholinesterase) were evaluated at sublethal and environmental concentrations of ivermectin (0.00125 mg/L) and glyphosate (0.7 mg/L) individually and in mixture. The ICF (LC50-504h: 0.047 mg ai IVM/L) was more toxic to larvae than the GBH (LC50-504h: 24.73 mg ae GLY/L). In terms of lethality, exposure to the mixture was synergistic at all exposure times. Both compounds separately caused alterations in the biomarkers of oxidative stress and neurotoxicity. Regarding sublethal effects in organisms exposed to the mixture, potentiation was observed in acetylcholinesterase. The simultaneous exposure to both substances in water bodies can have synergistic and negative effects on aquatic organisms.

The first report on the assessment of maximum acceptable daily intake (MADI) of pesticides for humans using intelligent consensus predictions.

Direct or indirect consumption of pesticides and their related products by humans and other living organisms without safe dosing may pose a health risk. The risk may arise after a short/long time which depends on the nature and amount of chemicals consumed. Therefore, the maximum acceptable daily intake of chemicals must be calculated to prevent these risks. In the present work, regression-based quantitative structure-activity relationship (QSAR) models were developed using 39 pesticides with maximum acceptable daily intake (MADI) for humans as the endpoint. From the statistical results (R2 = 0.674-0.712, QLOO2 = 0.553-0.580, Q(F1)2 = 0.544-0.611, and Q(F2)2 = 0.531-0.599), it can be inferred that the developed models were robust, reliable, reproducible, accurate, and predictive. Intelligent Consensus Prediction (ICP) was employed to improve the external predictivity (Q(F1)2 =0.579-0.657 and Q(F2)2 = 0.563-0.647) of the models. Some of the chemical markers responsible for toxicity enhancement are the presence of unsaturated bonds, lipophilicity, presence of C< (double bond-single bond-single bonded carbon), and the presence of sulphur and phosphate bonds at the topological distances 1 and 6, while the presence of hydrophilic groups and short chain fragments reduces the toxicity. The Pesticide Properties Database (PPDB) (1694 pesticides) was also screened with the developed models. Hence, this research work will be helpful for the toxicity assessment of pesticides before their synthesis, the development of eco-friendly and safer pesticides, and data-gap filling reducing the time, cost, and animal experimentation. Thus, this study might hold promise for future potential MADI assessment of pesticides and provide a meaningful contribution to the field of risk assessment.

Assessing the negative impact of chlorantraniliprole, isoxaflutole, and simazine pesticides on phospholipid membrane models and tilapia gill tissues.

The indiscriminate and, very often, incorrect use of pesticides in Brazil, as well as in other countries, results in severe levels of environmental pollution and intoxication of human life. Herein, we studied plasma membrane models (monolayer and bilayer) of the phospholipid Dioleoyl-sn-glycerol-3-phosphocholine (DOPC) using Langmuir films, and large (LUVs) and giant (GUVs) unilamellar vesicles, to determine the effect of the pesticides chlorantraniliprole (CLTP), isoxaflutole (ISF), and simazine (SMZ), used in sugarcane. CLTP affects the lipid organization of the bioinspired models of DOPC π-A isotherms, while ISF and SMZ pesticides significantly affect the LUVs and GUVs. Furthermore, the in vivo study of the gill tissue in fish in the presence of pesticides (2.0 × 10-10 mol/L for CLTP, 8.3 × 10-9 mol/L for ISF, and SMZ at 9.9 × 10-9 mol/L) was performed using optical and fluorescence images. This investigation was motivated by the gill lipid membranes, which are vital for regulating transporter activity through transmembrane proteins, crucial for maintaining ionic balance in fish gills. In this way, the presence of phospholipids in gills offers a model for understanding their effects on fish health. Histological results show that exposure to CLTP, ISF, and SMZ may interfere with vital gill functions, leading to respiratory disorders and osmoregulation dysfunction. The results indicate that exposure to pesticides caused severe morphological alterations in fish, which could be correlated with their impact on the bioinspired membrane models. Moreover, the effect does not depend on the exposure period (24h and 96h), showing that animals exposed to pesticides for a short period suffer irreparable damage to gill tissue. In summary, we can conclude that the harm caused by pesticides, both in membrane models and in fish gills, occurs due to contamination of the aquatic system with pesticides. Therefore, water quality is vital for the preservation of ecosystems.

Evaluation of in silico model predictions for mammalian acute oral toxicity and regulatory application in pesticide hazard and risk assessment.

The United States Environmental Protection Agency (USEPA) uses the lethal dose 50% (LD50) value from in vivo rat acute oral toxicity studies for pesticide product label precautionary statements and environmental risk assessment (RA). The Collaborative Acute Toxicity Modeling Suite (CATMoS) is a quantitative structure-activity relationship (QSAR)-based in silico approach to predict rat acute oral toxicity that has the potential to reduce animal use when registering a new pesticide technical grade active ingredient (TGAI). This analysis compared LD50 values predicted by CATMoS to empirical values from in vivo studies for the TGAIs of 177 conventional pesticides. The accuracy and reliability of the model predictions were assessed relative to the empirical data in terms of USEPA acute oral toxicity categories and discrete LD50 values for each chemical. CATMoS was most reliable at placing pesticide TGAIs in acute toxicity categories III (>500-5000 mg/kg) and IV (>5000 mg/kg), with 88% categorical concordance for 165 chemicals with empirical in vivo LD50 values ≥ 500 mg/kg. When considering an LD50 for RA, CATMoS predictions of 2000 mg/kg and higher were found to agree with empirical values from limit tests (i.e., single, high-dose tests) or definitive results over 2000 mg/kg with few exceptions.

Mixture of pesticides based on dimethylamine and imidacloprid affects locomotion of adult zebrafish.

Numerous chemical compounds are found in aquatic environments; among them are pesticides. Pesticides are widely used worldwide, and this use has progressively increased in recent decades, resulting in the accumulation of potentially toxic compounds in surface waters. Dimethylamine-based herbicides (DBH) and imidacloprid-based insecticides (IBI) have low soil absorption and high water solubility, facilitating the arrival of these compounds in aquatic environments. In this study, our objective was to analyze whether two pesticides, DBH and IBI at environmentally relevant concentrations of 320 µg/L for each compound, and their mixtures impact the behavioral and endocrine parameters of adult zebrafish, verifying the effect of pesticides on exploratory behavior and social and analyzing hormonal parameters related to stress. Acute exposure to the mixture of pesticides reduced fish locomotion. Pesticides alone and in combination did not affect cortisol levels in exposed animals. Pesticides, when tested together, can cause different effects on non-target organisms, and the evaluation of mixtures of these compounds is extremely important.

[Pesticide exposure and chronic respiratory diseases]. / Exposition aux pesticides et maladies respiratoires chroniques.

INTRODUCTION: Pesticides are used worldwide, mainly in agriculture as a means of controlling pests and protecting crops. That said, the entire world population is ultimately subject to pesticide exposure (consumption of fruits and vegetables, living near treated fields…), with varying degrees of toxicity involved. STATE OF THE ART: In recent decades, epidemiological studies have contributed to the identification of chemical pesticide families with detrimental effects on human health: cognitive disorders, Parkinson's disease, prostate cancer… and impairment in respiratory functioning. Current scientific evidence points to the implication of the active substances in insecticides, herbicides and fungicides in chronic respiratory diseases, two examples being chronic obstructive pulmonary disease (COPD) in exposed workers, and asthmatic wheezing in children during prenatal or postnatal exposure. PERSPECTIVES: The safety of individuals exposed to pesticides is of key importance in public health. Further epidemiological investigations are needed to identify the chemical families affecting certain populations. CONCLUSIONS: The scientific literature suggests strong links between pesticide exposure and respiratory health. Whether it be environmental or occupational, pesticide exposure can lead to respiratory disorders and symptoms of varying severity.

Chromosomal Damage, Chromosome Instability, and Polymorphisms in GSTP1 and XRCC1 as Biomarkers of Effect and Susceptibility in Farmers Exposed to Pesticides.

In the department of Boyacá, Colombia, agriculture stands as one of the primary economic activities. However, the escalating utilization of pesticides within this sector has sparked concern regarding its potential correlation with elevated risks of genotoxicity, chromosomal alterations, and carcinogenesis. Furthermore, pesticides have been associated with a broad spectrum of genetic polymorphisms that impact pivotal genes involved in pesticide metabolism and DNA repair, among other processes. Nonetheless, our understanding of the genotoxic effects of pesticides on the chromosomes (as biomarkers of effect) in exposed farmers and the impact of genetic polymorphisms (as susceptibility biomarkers) on the increased risk of chromosomal damage is still limited. The aim of our study was to evaluate chromosomal alterations, chromosomal instability, and clonal heterogeneity, as well as the presence of polymorphic variants in the GSTP1 and XRCC1 genes, in peripheral blood samples of farmers occupationally exposed to pesticides in Aquitania, Colombia, and in an unexposed control group. Our results showed statistically significant differences in the frequency of numerical chromosomal alterations, chromosomal instability, and clonal heterogeneity levels between the exposed and unexposed groups. In addition, we also found a higher frequency of chromosomal instability and clonal heterogeneity in exposed individuals carrying the heterozygous GSTP1 AG and XRCC1 (exon 10) GA genotypes. The evaluation of chromosomal alterations and chromosomal instability resulting from pesticide exposure, combined with the identification of polymorphic variants in the GSTP1 and XRCC1 genes, and further research involving a larger group of individuals exposed to pesticides could enable the identification of effect and susceptibility biomarkers. Such markers could prove valuable for monitoring individuals occupationally exposed to pesticides.

Enantioselective bioaccumulation and toxicological effects of chiral neonicotinoid sulfoxaflor in rats.

Sulfoxaflor is a widely used fourth-generation neonicotinoid pesticide, which has been detected in biological and environmental samples. Sulfoxaflor can potentially be exposed to humans via the food chain, thus understanding its toxic effects and enantioselective bioaccumulation is crucial. In this study, toxicokinetics, bioaccumulation, tissue distribution and enantiomeric profiles of sulfoxaflor in rats were investigated through single oral exposure and 28-days continuous exposure experiment. Sulfoxaflor mainly accumulated in liver and kidney, and the (-)-2R,3R-sulfoxaflor and (-)-2S,3R-sulfoxaflor had higher enrichment than their enantiomers in rats. The toxicological effects were evaluated after 28-days exposure. Slight inflammation in liver and kidney were observed by histopathology. Sphingolipid, amino acid, and vitamin B6 metabolism pathways were significantly disturbed in metabonomics analysis. These toxicities were in compliance with dose-dependent effects. These results improve understanding of enantioselective bioaccumulation and the potential health risk of sulfoxaflor.

Combined effects of azoxystrobin and oxytetracycline on rhizosphere microbiota of Arabidopsis thaliana.

The rhizosphere is one of the key determinants of plant health and productivity. Mixtures of pesticides are commonly used in intensified agriculture. However, the combined mechanisms underlying their impacts on soil microbiota remain unknown. The present study revealed that the rhizosphere microbiota was more sensitive to azoxystrobin and oxytetracycline, two commonly used pesticides, than was the microbiota present in bulk soil. Moreover, the rhizosphere microbiota enhanced network complexity and stability and increased carbohydrate metabolism and xenobiotic biodegradation as well as the expression of metabolic genes involved in defence against pesticide stress. Co-exposure to azoxystrobin and oxytetracycline had antagonistic effects on Arabidopsis thaliana growth and soil microbial variation by recruiting organic-degrading bacteria and regulating ABC transporters to reduce pesticide uptake. Our study explored the composition and function of soil microorganisms through amplicon sequencing and metagenomic approaches, providing comprehensive insights into the synergistic effect of plants and rhizosphere microbiota on pesticides and contributing to our understanding of the ecological risks associated with pesticide use.

The use of amino acids and their derivates to mitigate against pesticide-induced toxicity.

Exposure to pesticides induces oxidative stress and deleterious effects on various tissues in non-target organisms. Numerous models investigating pesticide exposure have demonstrated metabolic disturbances such as imbalances in amino acid levels within the organism. One potentially effective strategy to mitigate pesticide toxicity involves dietary intervention by supplementing exogenous amino acids and their derivates to augment the body's antioxidant capacity and mitigate pesticide-induced oxidative harm, whose mechanism including bolstering glutathione synthesis, regulating arginine-NO metabolism, mitochondria-related oxidative stress, and the open of ion channels, as well as enhancing intestinal microecology. Enhancing glutathione synthesis through supplementation of substrates N-acetylcysteine and glycine is regarded as a potent mechanism to achieve this. Selection of appropriate amino acids or their derivates for supplementation, and determining an appropriate dosage, are of the utmost importance for effective mitigation of pesticide-induced oxidative harm. More experimentation is required that involves large population samples to validate the efficacy of dietary intervention strategies, as well as to determine the effects of amino acids and their derivates on long-term and low-dose pesticide exposure. This review provides insights to guide future research aimed at preventing and alleviating pesticide toxicity through dietary intervention of amino acids and their derivates.