Pesticide Metabolites Research Articles

UTILIZAÇÃO DE MODELOS IN SILICO PARA AVALIAÇÃO DA TOXICIDADE DE RESÍDUOS DE AGROTÓXICOS, FÁRMACOS E METABÓLITOS EM ÁGUAS NATURAIS

WORKFLOW OF IN SILICO MODELS TO EVALUATE THE TOXICITY OF PESTICIDE RESIDUES, DRUGS AND METABOLITES IN NATURAL WATERS. Constantly we have to deal with an exponential increase in the amount of different chemical compounds that industries synthesize and manufacture, such as drugs, pesticides, persistent organic pollutants, preservatives, and personal hygiene products. Many of these chemical substances are biologically active and interact with biomolecules, such as proteins, through specific mechanisms that lead to different biological responses. Due to the inherent risk of many compounds to the environment and to humans, their toxicological activities must be evaluated. In order to evaluate the biological activity of molecules, three types of experiments can be used: in vivo (e.g., animal tests); in vitro (e.g., cell tissue culture); and in silico simulations. In vivo and in vitro experiments are time-consuming and expensive processes, in addition to causing ethical discussions and debates. An alternative to avoid these setbacks is the use of in silico models. The scientific community thus begins to use in silico models as a possible alternative, developing a large number of models and strategies capable of predicting the toxicological properties of several chemical compounds. This review discusses methods that employ in silico models to assess and predict the possible effects of contaminants found in natural waters.

Including the bioconcentration of pesticide metabolites in plant uptake modeling.

Although several models of pesticide uptake into plants are available, there are few modeling studies on the bioconcentration of metabolites in plants. Ignoring metabolites in plant uptake models can result in an underestimation of the parent compound's overall impacts on human health associated with pesticide residues in harvested food crops. To address this limitation, we offer a metabolite-based plant uptake model to predict the bioconcentration of the parent compound and its metabolites in plants. We used the uptake of glyphosate and its major metabolite (aminomethylphosphonic acid, AMPA) into potato as an example. The analysis of variability revealed that soil properties (affecting the soil sorption coefficient), dissipation half-life in soil, and metabolic half-life in the potato had a significant impact on the simulated AMPA concentration in the potato, indicating that regional variability could be generated in the plant bioconcentration process of metabolites. The proposed model was further compared using the non-metabolite model. The findings of the comparison suggested that the non-metabolite model, which is integrated with the AMPA bioconcentration process, can predict the AMPA concentration in the potato similarly to the proposed model. In conclusion, we provide insight into the bioconcentration process of metabolites in tuber plants from a modeling viewpoint, with some crucial model inputs, such as biotransformation and metabolic rate constants, requiring confirmation in future studies. The modeling demonstration emphasizes that it is relevant to consider bioaccumulation of metabolites, which can propagate further into increased overall residues of harmful compounds, especially in cases where metabolites have higher toxicity effect potency than their respective parent compounds.

Characterization of Urinary Pesticide Metabolite Concentrations of Pregnant Women in Suriname.

Prenatal exposure to pesticides and the association with adverse health outcomes have been examined in several studies. However, the characterization of pesticide exposure among Surinamese women during pregnancy has not been assessed. As part of the Caribbean Consortium of Research in Environmental and Occupational Health research program, 214 urine samples were collected from pregnant women living in three regions in Suriname with different agricultural practices: capital Paramaribo, the rice producing district Nickerie, and the tropical rainforest, the Interior. We used isotope dilution tandem mass spectrometry to quantify urinary concentrations of biomarkers of three pesticide classes, including phenoxy acid herbicides and organophosphate and pyrethroid insecticides, all of which are commonly used in agricultural and residential settings in Suriname. We observed that participants residing in Nickerie had the highest urinary metabolite concentrations of 2,4-dichlorophenoxyacetic acid and pyrethroids compared to those from Paramaribo or the Interior. Paramaribo had the highest concentrations of organophosphate metabolites, specifically dialkyl phosphate metabolites. Para-nitrophenol was detected in samples from Paramaribo and the Interior. Samples from Nickerie had higher median urinary pesticide concentrations of 2,4-dichlorophenoxyacetic acid (1.06 μg/L), and the following metabolites, 3,5,6-trichloro-2-pyridinol (1.26 μg/L), 2-isopropyl-4-methyl-6-hydroxypyrimidine (0.60 μg/L), and 3-phenoxybenzoic acid (1.34 μg/L), possibly due to residential use and heavy rice production.

Childhood exposure to non-persistent pesticides and pubertal development in Spanish girls and boys: Evidence from the INMA (Environment and Childhood) cohort

This study assessed cross-sectional associations between urinary metabolites of non-persistent pesticides and pubertal development in boys and girls from urban and rural areas in Spain and examined effect modification by body mass index (BMI). Four metabolites of insecticides (TCPy, metabolite of chlorpyrifos; IMPy, metabolite of diazinon; DETP, non-specific metabolite of organophosphates; 3-PBA, metabolite of pyrethroids) and the metabolite of ethylene-bis-dithiocarbamate fungicides (ETU) were quantified in urine collected in 2010–2016 from 7 to 11-year-old children (606 girls, 933 boys) participating in the INMA Project. Pubertal development was ascertained by Tanner stages and/or parent-reported Pubertal Development Scale (PDS). Associations between pesticide metabolites and odds of being in stage 2+ for breast development (girls), genital development (boys), pubic hair growth (girls and boys), and/or overall puberty onset, gonadarche, and adrenarche (PDS for girls and boys) were examined by mixed-effect logistic regression. Effect modification by BMI was explored by interaction terms and stratified analysis. In girls, DETP and ETU concentrations>75th percentile (P75) were associated with higher odds of overall puberty development (OR [95%CI] = 1.86 [1.07–3.24] and 1.71 [1.03–2.83], respectively, for > P75 vs. undetected concentrations), while ETU > P75 was also associated with higher odds of breast development (OR [95%CI] = 5.55 [2.83–12.91]), particularly in girls with underweight/normal weight (OR [95%CI] = 10.08 [2.62–38.76]). In boys, detection of TCPy (40%) and 3-PBA (34%) was associated with higher odds of genital development (OR [95%CI] = 1.97 [1.08–3.57] and 2.08 [1.15–3.81], respectively), and the association with 3-PBA was observed in boys with overweight/obesity alone. In addition, ETU > P75 was associated with higher odds of genital development in boys with underweight/normal weight (OR [95%CI] = 2.89 [1.08–7.74]) but higher DETP with lower odds of puberty in boys with overweight/obesity (OR [95%CI] = 0.94 [0.89–0.99] per log-unit increase in concentration). Results suggest an association of childhood exposure to ETU and certain insecticides with earlier puberty in girls and boys that may be modified by child BMI.

Targeted and non-targeted analysis for the investigation of pesticides influence on wheat cultivated under field conditions

A comprehensive approach was applied to evaluate the effects of pesticides on the metabolism of wheat (Triticum aestivum L). The application of commercially available pesticide formulations under field cultivation conditions provided a source of metabolic data unlimited by model conditions, representing a novel approach to study the effects of pesticides on edible plants. Gas and liquid chromatography coupled to tandem mass spectrometry were employed for targeted and non-targeted analysis of wheat roots and shoots sampled six times during the six-week experiment. The applied pesticides: prothioconazole, tebuconazole, fluoxastrobin, diflufenican, florasulam, and penoxulam were found at concentrations ranging 0.0070–25.20 mg/kg and 0.0020–2.2 mg/kg in the wheat roots and shoots, respectively. The following pesticide metabolites were identified in shoots: prothioconazole-desthio (prothioconazole metabolite), 5-(4-chlorophenyl)-2,2-dimethyl-3-(1,2,4-triazol-1-ylmethyl)pentane-1,3-diol (tebuconazole metabolite), and N-(5,8-dimethoxy[1,2,4]triazolo[1,5-c]pyrimidin-2-yl)-2,4-dihydroxy-6-(trifluoromethyl)benzene sulphonamide (penoxulam metabolite). The metabolic fingerprints and profiles changed during the experiment, reflecting the cumulative response of wheat to both its growth environment and pesticides, as well as their metabolites. Approximately 15 days after the herbicide treatment no further changes in the plant metabolic profiles were observed, despite the presence of pesticide and their metabolites in both roots and shoots. This is the first study to combine the determination of pesticides and their metabolites plant tissues with the evaluation of plant metabolic responses under field conditions. This exhaustive approach contributes to broadening the knowledge of pesticide effects on edible plants, relevant to food safety.

A large scale multi-laboratory suspect screening of pesticide metabolites in human biomonitoring: From tentative annotations to verified occurrences.

Within the Human Biomonitoring for Europe initiative (HBM4EU), a study to determine new biomarkers of exposure to pesticides and to assess exposure patterns was conducted. Human urine samples (N=2,088) were collected from five European regions in two different seasons. The objective of the study was to identify pesticides and their metabolites in collected urine samples with a harmonized suspect screening approach based on liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) applied in five laboratories. A combined data processing workflow included comprehensive data reduction, correction of mass error and retention time (RT) drifts, isotopic pattern analysis, adduct and elemental composition annotation, finalized by a mining of the elemental compositions for possible annotations of pesticide metabolites. The obtained tentative annotations (n=498) were used for acquiring representative data-dependent tandem mass spectra (MS2) and verified by spectral comparison to reference spectra generated from commercially available reference standards or produced through human liver S9 in vitro incubation experiments. 14 parent pesticides and 71 metabolites (including 16 glucuronide and 11 sulfate conjugates) were detected. Collectively these related to 46 unique pesticides. For the remaining tentative annotations either (i) no data-dependent MS2 spectra could be acquired, (ii) the spectral purity was too low for sufficient matching, or (iii) RTs indicated a wrong annotation, leaving potential for more pesticides and/or their metabolites being confirmed in further studies. Thus, the reported results are reflecting only a part of the possible pesticide exposure.

The challenge of assessing exposure to fast-elimination endocrine disruptors: When collecting? Which matrix? How many samples?

Background and Aim The assessment of human exposure to fast-elimination endocrine disruptors (FEED) such as phthalates, bisphenols or pesticides is usually based on urinary biomarkers. The variability of biomarkers concentration, due to rapid elimination from the body combined with frequent exposure is however pointed out as a major limitation to obtain reliable information. Collecting samples at specific times of the day, or increasing the number of samples have been suggested to improve the quality of exposure assessment. In parallel, the use of hair, less sensitive to short-term variations in the exposure, have also been proposed as a possible alternative. No consensus has however been reached yet on these points and providing a reliable information on exposure to FEED remains highly challenging. Methods Urine and hair samples were repeatedly collected from 16 volunteers over a 6 months follow-up. 92 hair samples and 805 urines samples were collected and analyzed for 16 phthalate metabolites, 4 bisphenols and 8 pesticides metabolites. Results 21 biomarkers were more frequently detected in urine, 6 in hair, and 1 was equivalent. Biomarkers were much more variable in urine, with intraclass correlation coefficients (ICC) ranging from 0.09 to 0.51, compared to 0.1 to 0.8 in hair. No preferred moment between first urine of the day, morning, afternoon and evening could be identified for urine collection. Algorithms demonstrated that between 10 (for monobenzyl phthalate) and 31 (for bisphenol S) samples were necessary to correctly classify 87.5% of the subjects into quartiles according to their level of exposure. Conclusions The study illustrates the complexity of assessing exposure to FEED and documents the respective advantages and limitations of urine and hair. These results provide new insights in exposure assessment based on biological matrices and will help to better design future biomonitoring strategies. Keywords: Exposure Biomarkers, Endocrine disruptors, Exposure assessment, Phthalates, Pesticides

Geospatial determinants of urinary insecticide concentrations and internalizing disorders in Ecuadorian adolescents

Background: Depression and anxiety are top 5 contributors of increased disability-adjusted life years. Pesticide exposure has been linked to increased depression and anxiety; evidence in adolescents is limited. This study assesses clustering patterns of mental health symptoms and urinary pesticide metabolites, and their relationships with home proximity to floricultural crops in an Ecuadorean agricultural county. Methods: We assessed 514 adolescents (11-17 years) who lived in the 5 parishes of Pedro Moncayo County, Ecuador. We measured 8 urinary metabolites for neonicotinoid, pyrethroid and organophosphate pesticides, and assessed depression and anxiety symptoms using standardized questionnaires. Getis-Ord Gi* evaluated spatial clustering to identify hot and cold spots of pesticide metabolites, depression symptoms and anxiety symptoms. The association between home distance to floricultural greenhouses and anxiety/depression scores were tested using generalized estimating equations, adjusting for confounders. Results: The floricultural surface areas (% of total land) across parishes were: Tocachi: 0.12 km2 (0.001%), La Esperanza: 0.43 km2 (0.01%), Malchingui: 0.04 km2 (0.05%), Tupigachi: 5.36 km2 (12.5%), and Tabacundo: 9.36 km2 (13.2%). The average scores for anxiety (53.0 [SD=9.31]) and depression (58.8 [SD=9.61]) were in the anticipated range. We observed hotspots for anxiety and depression symptoms in Tupigachi (95-99%C [confidence]) and Tabacundo (90-95%C). There were hotpots for organophosphate and pyrethroid metabolites in Tupigachi, coinciding with anxiety and depression hotspots (malathion dicarboxylic acid [90%-99%C], para-nitrophenol [95%], 2-isopropyl-4-methyl-6-hydroxypyrimidine, trans-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid [90%C], and 3-phenoxybenzoic acid [95%C]). Additionally, greater proximity to greenhouses was associated with greater depression (βper100m=0.94 [95%CI: 0.53, 1.36]) and anxiety (βper100m= 0.32 [95%CI: 0.11, 0.54]) scores. Conclusions: We observed hotspots in Tupigachi for both anxiety, depression, and multiple organophosphate/pyrethroid metabolites. Throughout the county, residential proximity to floricultural crops was associated with higher anxiety and depression symptoms. This suggests that off-target pesticide drift from crops may be a contributor to increased internalizing behaviors. Keywords: Pesticides

Oxidative stress of glyphosate, AMPA and metabolites of pyrethroids and chlorpyrifos pesticides among primary school children in Cyprus

Oxidative stress of glyphosate, AMPA and metabolites of pyrethroids and chlorpyrifos pesticides among primary school children in Cyprus

Organophosphorus Pesticides Promote Protein Cross-Linking.

Exposure to organophosphorus pesticides (OP) can have chronic adverse effects that are independent of inhibition of acetylcholinesterase, the classic target for acute OP toxicity. In pure proteins, the organophosphorus pesticide chlorpyrifos oxon induces a cross-link between lysine and glutamate (or aspartate) with loss of water. Tubulin is particularly sensitive to OP-induced cross-linking. Our goal was to explore OP-induced cross-linking in a complex protein sample, MAP-rich tubulin from Sus scrofa and to test 8 OP for their capacity to promote isopeptide cross-linking. We treated 100 μg of MAP-rich tubulin with 100 μM chlorpyrifos, chlorpyrifos oxon, methamidophos, paraoxon, diazinon, diazoxon, monocrotophos, or dichlorvos. Each sample was separated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and stained with Coomassie blue. Five gel slices (at about 30, 50, 150, and 300 kDa, and the top of the separating gel) were removed from the lanes for each of the eight OP samples and from untreated control lanes. These gel slices were subjected to in-gel trypsin digestion. MSMS fragmentation spectra of the tryptic peptides were examined for isopeptide cross-links. Sixteen spectra yielded convincing evidence for isopeptide cross-linked peptides. Ten were from the chlorpyrifos oxon reaction, 1 from dichlorvos, 1 from paraoxon, 1 from diazinon, and 3 from diazoxon. It was concluded that catalysis of protein cross-linking is a general property of organophosphorus pesticides and pesticide metabolites. Data are available via ProteomeXchange with identifier PXD034529.

LP-11 (Q)SAR and Read Across Analyses in Regulatory Assessment of Pesticide Metabolites and Impurities in the Light of Current Insights and Demands

LP-11 (Q)SAR and Read Across Analyses in Regulatory Assessment of Pesticide Metabolites and Impurities in the Light of Current Insights and Demands

Occupational and residential exposures to organophosphate and pyrethroid pesticides in a rural setting

Organophosphate (OP) and pyrethroid pesticides (PYR) are extensively used in agriculture, resulting in higher exposures among farmworkers. The present study reports the occurrence of 8 urinary OP and PYR metabolites in a sample of farmworkers and residents from Sucs (n = 87), a rural township in North West Catalonia (Spain). The aim of the present study was to examine differences in urinary pesticide metabolite concentrations between occupationally-exposed (farmworkers; n = 45) and environmentally-exposed subjects (n = 42) and to assess the relationship between pesticide's exposures and occupational activities in a real-case scenario.Six OP and two PYR metabolites have been investigated, urine samples were extracted using SPE extraction and analyzed by UPLC-MS/MS. Three OP metabolites were commonly detectable in urine, namely TCPY (metabolite of chlorpyrifos), PNP (parathion) and DEAMPY (pirimiphos). Regarding pyrethroids, the two analyzed metabolites, 3-PBA and 4F-3-PBA, were detected in a high proportion of urine samples. Differences in concentrations between both groups were statistically significant for TCPY and 4F-3-PBA (Mann-Whitney U Test for independent groups, p < 0.05). In the case of TCPY, the concentrations were higher among the farmworkers, which is consistent with their occupational activity. The small differences found in DEAMPY, PNP, 3-PBA or even the significant higher concentrations of 4F-3-PBA among rural population suggest a general exposure to these compounds, even in those who do not carry an occupational activity.Specific personal protective equipment (PPE) among farmworkers, such as the use of gloves and mask during mixing, showed a decrease in the exposure levels, although the differences were not statistically significant. However, a positive association was found between the use of a cap during mixing (for PNP and 3-PBA) and during application (only for 3-PBA). However, this piece of cloth is mainly used for sun protection, and when not cleaned after the handling of pesticides, it might represent a continuous source of exposure through dermal contact. Farmworkers using tractors with cabin had statistically significant lower concentrations of DEAMPY than those using a tractor without cabin. The previous results suggest that occupational protections should be encouraged among farmworkers and other potential workers handling with pesticides.

Analysis of environmental chemical mixtures and nonalcoholic fatty liver disease: NHANES 1999–2014

We aimed to investigate the associations between chemical mixtures and the risk of nonalcoholic fatty liver disease (NAFLD) in this study. A total of 127 exposure analytes within 13 chemical mixture groups were included in the current analysis. Associations between chemical mixture exposure and prevalence of NAFLD were examined using weighted quantile sum (WQS) regressions. NAFLD was diagnosed by hepatic steatosis index (HSI) and US fatty liver index (USFLI). In USFLI-NAFLD cohort, chemical mixtures positively associated with NAFLD development included urinary metals (OR: 1.10, 95% CI: 1.04–1.16), urinary perchlorate, nitrate and thiocyanate (OR: 1.06, 95% CI: 1.02–1.11), urinary pesticides (OR: 1.24, 95% CI: 1.09–1.40), urinary phthalates (OR: 1.18, 95% CI: 1.09–1.28), urinary polyaromatic hydrocarbons (PAHs) (OR: 1.08, 95% CI: 1.03–1.14), and urinary pyrethroids, herbicides, and organophosphate pesticides metabolites (OR: 1.32, 95% CI: 1.15–1.51). All of the above mixtures were also statistically significant in WQS regressions in the HSI-NAFLD cohort. Besides, some chemical mixtures were only significant in HSI-NAFLD cohort including urinary arsenics (OR: 1.07, 95% CI: 1.02–1.12), urinary phenols (OR: 1.10, 95% CI: 1.02–1.19) and blood polychlorinated dibenzo-p-dioxins (OR: 1.10, 95% CI: 1.03–1.17). Three types of chemical mixtures only showed significant associations in the healthy lifestyle score (HLS) of 3–4 subgroup, including urinary perchlorate, nitrate and thiocyanate, urinary PAHs and blood polychlorinated dibenzo-p-dioxins. In conclusion, the exposure of specific types of chemical mixtures were associated with elevated NAFLD risk, and the effects of some chemical mixtures on NAFLD development exhibited differences in participants with different lifestyles.

Environmental behaviour of a pesticide metabolite, the AMPA. Sequestration of Ca2+, Mg2+, Cu2+, Zn2+ and Al3+

The chelating and sequestering ability of a glyphosate metabolite, the aminomethylphosphonic acid (AMPA) towards bi- and trivalent metal cations, such as Ca2+, Mg2+, Zn2+, Cu2+ and Al3+, were investigated in aqueous solutions of NaCl, in an ionic strength range of 0.1 ≤ I/mol dm−3 ≤ 1.0 and at constant temperature of T = 298.15 ± 0.15 K. The investigations on the acid-base properties and complexing ability were performed, by means of potentiometry, in conditions of different cM:cAMPA molar ratios and pH values. The formation of insoluble species was experimentally observed in the Mn+/AMPA2− systems, and the solid phases were characterized by means of X-Ray Diffractometry (XRD), Scanning Electron Microscopy (SEM) and InfraRed Attenuated Total Reflection spectroscopy (IR-ATR). The dependence on ionic strength of the stability constants of the Mn+/AMPA2− complexes species, determined at different ionic strengths, was modelled by the Debye-Hückel type equation. The sequestering ability of AMPA toward the investigated metal cations was evaluated by pL0.5 parameter.

Risk Behavior for Pesticide Exposure in Children living in Agricultural Area

Chemical pesticides are mixtures of chemicals used to control or kill pests. Pesticides are often used in agriculture to maintain and increase agricultural production, but have a negative impact on the environment and public health. Children who live in agricultural areas are a group at risk of exposure to pesticides due to activities such as playing and participating in agricultural activities. The purpose of this study was to identify the behavior at risk of exposure to pesticides in children in the agricultural area of ​​Bulakamba District. This type of research is descriptive with a cross-sectional study design. The research variable is the identification of behavior at risk of exposure to pesticides in children. The subjects of the study were elementary school students in the Bulakamba district as many as 48 students. Data were collected by interview, observation, and examination of pesticide metabolites in students' urine. . The results showed that of the 48 students exposed to pesticides, 17 students were positive for pesticide metabolites and 31 students were negative. Risk behavior is the work of parents as farmers from 19 students there are 10 students who are positively exposed to pesticides, the habit of playing in agricultural areas from 18 students there are 11 students who are exposed to pesticides, the habit of helping with agricultural activities from 15 students there are 10 students positive for pesticides and the habit of storing pesticides in the home environment of 21 students there are 11 students positively exposed to pesticides.&#x0D;

Diethyl phosphate disrupts hypothalamus-pituitary-adrenal axis endocrine hormones via nuclear receptors GR and Nur77: Integration of evidences from in vivo, in vitro and in silico approaches

Plenty of population epidemiology and cohort studies have found dialkyl phosphates (DAPs) in the urine were related to endocrine hormone disorders. However, we did not know whether these effects were caused by parent organophosphorus pesticides (OPs) or metabolite DAPs, especially the non-specific metabolite diethyl phosphate (DEP), which was the metabolic end product of most widely used diethyl OPs. In this study, animal experiments (in vivo), cell experiments (in vitro), small molecule-protein binding interaction experiments and computer molecular simulations (in silico) were used to explore the disturbing effects and molecular mechanisms of DEP on the hypothalamic-pituitary-adrenal (HPA) axis endocrine hormones. The animal experiments showed that chronic DEP exposure significantly disturbed the serum contents of HPA axis hormones in adult male rats. The target genes of glucocorticoid receptor (GR) in rat liver, including 11β-hsd1 and Pepck1 and PEPCK protein expressions, were down-regulated. Moreover, the gluconeogenic abilities of rats were impaired. However, it did not affect the expression of GR in the rat hypothalamus. These results indicated that the physiological functions of glucocorticoids and GR were damaged. Furthermore, spectroscopy experiments, cell experiments, molecular docking and molecular dynamics simulations also suggested that DEP can bind to nuclear receptors GR and Nur77, affecting their transcription factor functions, and the transcriptional expression levels of their downstream target genes were reduced. The biosynthesis and secretion of adrenocorticotropic hormone and glucocorticoids were blocked. Therefore, DEP can inhibit the production and physiological functions of HPA axis endocrine hormones by disrupting these related proteins and antagonizing nuclear receptors. These results were considered to provide a theoretical basis for strictly controlling the residue limits of OPs and their metabolites in foods, agricultural products and the environment. They also revealed new targets for evaluating the toxicities and risks of pesticide metabolites.

Current Role of Mass Spectrometry in the Determination of Pesticide Residues in Food

The extensive use of pesticides represents a risk to human health. Consequently, legal frameworks have been established to ensure food safety, including control programs for pesticide residues. In this context, the performance of analytical methods acquires special relevance. Such methods are expected to be able to determine the largest number of compounds at trace concentration levels in complex food matrices, which represents a great analytical challenge. Technical advances in mass spectrometry (MS) have led to the development of more efficient analytical methods for the determination of pesticides. This review provides an overview of current analytical strategies applied in pesticide analysis, with a special focus on MS methods. Current targeted MS methods allow the simultaneous determination of hundreds of pesticides, whereas non-targeted MS methods are now applicable to the identification of pesticide metabolites and transformation products. New trends in pesticide analysis are also presented, including approaches for the simultaneous determination of pesticide residues and other food contaminants (i.e., mega-methods), or the recent application of techniques such as ion mobility–mass spectrometry (IM–MS) for this purpose.

Dissipative behavior, residual pattern, and risk assessment of four pesticides and their metabolites during tea cultivation, processing and infusion.

In recent years, metabolic products of pesticides have gained much attention due to their substantial characteristics as organic pollutants. So far, the behavior and metabolite levels of pesticide metabolites in crops have not been characterized well. In the present study, four registered pesticides (imidacloprid, diafenthiuron, malathion and chlorothalonil) were applied on tea plants in Fujian and Sichuan to characterize their metabolites residue pattern and dietary risk. Four pesticides dissipated first-order kinetics in the fresh tea leaves with the half-lives of 1.4-3.8 days. Nine metabolites were detected in the fresh tea leaves and green tea after processing. The metabolites residues showed an increasing trend first and then declined after treatment, and reached the maximum near the half-lives of pesticide. Compared with the parent pesticide, the total residue and acute risk (included the metabolites) increased by 1.7-105.2 times. Some metabolites, especially those whose parent pesticides have high water solubility and low Log Kow, will be more easily transferred to tea infusion. Pesticides were metabolized rapidly on tea plants after application, but the production of metabolites increased the health risk of tea consumption. These results could provide insights to use the pesticides in tea gardens and risk monitoring after application. © 2022 Society of Chemical Industry.

Oxidative stress of glyphosate, AMPA and metabolites of pyrethroids and chlorpyrifos pesticides among primary school children in Cyprus

BackgroundExposure to various pesticides, such as pyrethroids and chlorpyrifos, has been previously associated with adverse effects on children's health. Scientific evidence on the human toxicity of glyphosate (GLY) and its primary metabolite, aminomethylphosphonic acid (AMPA) is limited, particularly for children. This study aimed to i) assess the exposure determinants of the studied pesticides measured in children in Cyprus, and ii) determine the association between the urinary pesticides and the biomarkers of DNA and lipid oxidative damage. MethodsA children's health study was set up in Cyprus (ORGANIKO study) by aligning it with the methodology and tools used in the European Human Biomonitoring Initiative (HBM4EU). Urinary GLY and AMPA, pyrethroid metabolites and the chlorpyrifos metabolite TCPy were measured in 177 children aged 10–11 years old, using mass spectrometry. Oxidative stress was assessed with 8-iso-prostaglandin F2a (8-iso-PGF2α) as a marker of lipid damage and 8-hydroxy-2′-deoxyguanosine (8-OHdG) as a DNA oxidative damage marker, both measured with immunoassays. Questionnaires about demographic characteristics, pesticide usage, and dietary habits were filled out by the parents. Μultivariable regression models examined associations between pesticides and biomarkers of effect using two creatinine adjustments (cr1: adding it as covariate and cr2: biomarkers of exposure and effect were creatinine-adjusted). ResultsParental educational level was a significant predictor of urinary pyrethroids but not for GLY/AMPA. Median [interquartile range, IQR] values for GLY and AMPA were <LOQ [<LOQ, 0.19] μg/L and 0.18 [0.10, 0.29] μg/L, respectively, while a moderate correlation was shown between GLY and AMPA (r = 0.45). 8-OHdG was positively associated with AMPA (beta = 0.17; 95% CI: 0.02, 0.31, p = 0.03 cr2, and beta = 0.12; 95% CI: 0.0,0.24, p = 0.06, cr1), albeit not with GLY (p > 0.05). Similar significant associations with 8-OHdG were shown for a pyrethroid metabolite (3-PBA) and the chlorpyrifos metabolite (TCPy). No associations were observed between the aforementioned pesticides and 8-iso-PGF2α (p > 0.05). ConclusionsThis is the first children's health dataset demonstrating the association between AMPA and DNA oxidative damage, globally. More data is needed to replicate the observed trends in other children's populations around the globe.

Simultaneous determination of 16 urinary metabolites of organophosphate flame retardants and organophosphate pesticides by solid phase extraction and ultra performance liquid chromatography coupled to tandem mass spectrometry

Organophosphate flame retardants (OPFRs) and organophosphate pesticides (OPPs), pertaining to organophosphate esters, are ubiquitous in environment and have been verified to pose noticeable risks to human health. To evaluate human exposures to OPFRs and OPPs, a fast and sensitive approach based on a solid phase extraction (SPE) followed by the ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) detection has been developed for the simultaneous analysis of multiple organophosphorus metabolites in urine. The method allows the identification and quantification of ten metabolites of the most common OPFRs and all six dialkylphosphates (DAPs) of OPPs concerning the population exposure characteristics. The method provided good linearities (R2 = 0.998–0.999), satisfactory method detection limits (MDLs) (0.030–1.129 ng/mL) and only needed a small volume (200 μL) of urine. Recovery rates ranged 73.4–127.1% at three spiking levels (2, 10 and 25 ng/mL urine), with both intra- and inter-day precision less than 14%. The good correlations for DAPs in a cross-validation test with a previous gas chromatography-mass spectrometry (GC-MS) method and a good inter-laboratory agreement for several OPFR metabolites in a standard reference material (SRM 3673) re-enforced the precision and validity of our method. Finally, the established method was successfully applied to analyze 16 organophosphorus metabolites in 35 Chinese children's urine samples. Overall, by validating the method's sensitivity, accuracy, precision, reproducibility, etc., data reliability and robustness were ensured; and the satisfactory pilot application on real urine samples demonstrated feasibility and acceptability of this method for being implemented in large population-based studies.