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Biological monitoring (biomonitoring) to quantify systemic exposure to the organophosphorus insecticide chlorpyrifos (CPF) has historically focused on the quantitation of major CPF metabolites in urine. Noninvasive techniques are being advocated as novel means of biomonitoring for a variety of potential toxicants, including pesticides (like CPF), and saliva has been suggested as an ideal body fluid. However, in order to be acceptable, there is a need to understand salivary pharmacokinetics of CPF metabolites in order to extrapolate saliva measurements to whole-body exposures. In this context, in vivo pharmacokinetics of 3,5,6-trichloro-2-pyridinol (TCPy), the major chemical-specific metabolite of CPF, was quantitatively evaluated in rat saliva. Experimental results suggest that TCPy partitioning from plasma to saliva in rats is relatively constant over a range of varying physiological conditions. TCPy pharmacokinetics was very similar in blood and saliva (area under the curve values were proportional and elimination rates ranged from 0.007 to 0.019 per hour), and saliva/blood TCPy concentration ratios were not affected by TCPy concentration in blood (p = 0.35) or saliva flow rate (p = 0.26). The TCPy concentration in saliva was highly correlated to the amount of unbound TCPy in plasma (r = 0.96), and the amount of TCPy protein binding in plasma was substantial (98.5%). The median saliva/blood concentration ratio (0.049) was integrated as a saliva/blood TCPy partitioning coefficient within an existing physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model for CPF. The model was capable of accurately predicting TCPy concentrations in saliva over a range of blood concentrations. These studies suggest that saliva TCPy concentration can be utilized to ascertain CPF exposure. It is envisioned that the PBPK/PD can likewise be used to estimate CPF dosimetry based on the quantitation of TCPy in spot saliva samples obtained from biomonitoring studies. [ABSTRACT FROM PUBLISHER]

The organophosphate pesticide chlorpyrifos was widely used in the European Union before its ban in 2020 and was associated with neurodevelopmental disorders. However, within the concept of Developmental Origins of Health and Disease, in utero exposure to chlorpyrifos can lead to neurodevelopmental effects in developing children. The aim of this study was to estimate fetal exposure to chlorpyrifos using biomonitoring data measured in Elfe pregnant women and a physiologically based pharmacokinetic (PBPK) approach and compare exposure to toxicological reference values. A pregnancy-PBPK model was developed based on an existing adult chlorpyrifos model and a new toxicological reference value was proposed for neurodevelopmental effects. The pregnant women exposure was estimated based on dialkylphosphate (DAP) levels in urine assuming constant exposure to chlorpyrifos and compared to both the existing toxicological reference value and the new proposed draft toxicological reference value. Fetal internal concentrations in target tissues were then predicted using the developed pregnancy-PBPK model. Urinary concentrations of the chlorpyrifos-specific metabolite (TCPy) were also predicted for comparison with other biomonitoring data. The median daily exposure to chlorpyrifos for the French pregnant women from the Elfe cohort was estimated at 6.3x10−4 μg/kg body weight/day. The predicted urinary excretion of TCPy, the chlorpyrifos-specific metabolite, is in the same range as observed in other European cohorts (mean: 2.13 μg/L). Predicted brain chlorpyrifos levels were similar in pregnant women and their fetus and were 10-fold higher than the predicted blood chlorpyrifos levels. It was estimated that 6% and 20% of the pregnant women population had been exposed to levels exceeding the general population and draft toxicological reference values, respectively. Prenatal exposure to chlorpyrifos was estimated for the French population based on data from the Elfe cohort. Internal chlorpyrifos concentrations in target tissues (brain and blood) were predicted for fetuses at the end of the pregnancy. Under a conservative assumption, a small percentage of the population was identified as being exposed to levels exceeding the toxicological reference values. • A pregnancy-PBPK model specific to chlorpyrifos was developed. • The current model was applied to the longitudinal French Elfe cohort. • External exposure to chlorpyrifos was estimated based on urinary biomonitoring data. • Fetal chlorpyrifos internal concentrations were predicted at the end of pregnancy. • 20% of the cohort exceeds the proposed chlorpyrifos toxicological reference value. [ABSTRACT FROM AUTHOR]

Few population studies have measured urinary levels of pesticides in individuals with vegan, vegetarian, or organic diets. The objectives of this study were to evaluate whether a vegan/vegetarian diet was associated with increased exposure to organophosphate and carbamate pesticides, and to evaluate the impact of organic consumption on pesticide exposure in vegans and vegetarians. In the current pilot study conducted in 2013–2014, we collected spot urine samples and detailed 24 h recall dietary data in 42 adult residents of Amirim, a vegetarian community in Northern Israel. We measured urinary levels of non-specific organophosphate pesticide metabolites (dialkylphosphates, (DAPs)) and specific metabolites of the current-use pesticides chlorpyrifos (3,5,6-trichloro-2-pyridinol (TCPy)), propoxur (-isopropoxyphenol (IPPX)), and carbaryl (1-naphthol). Six DAP metabolites were detected in between 67 and 100% of urine samples, with highest geometric mean concentrations for dimethylphosphate (19.2 μg/g). Creatinine-adjusted median concentrations of total DAPs and of TCPy were significantly higher in Amirim residents compared to the general Jewish population in Israel (0.29 μmol/g compared to 0.16, p < 0.05 for DAPs and 4.32 μg/g compared to 2.34 μg/g, p < 0.05 for TCPy). Within Amirim residents, we observed a positive association between vegetable intake and urinary TCPy levels (rho = 0.47, p < 0.05) and lower median total dimethyl phosphate levels in individuals reporting that > 25% of the produce they consume is organic (0.065 μmol/L compared to 0.22, p < 0.05). Results from this pilot study indicate relatively high levels of urinary organophosphate pesticide metabolite concentrations in residents of a vegetarian community, a positive association between vegetable intake and urinary levels of a chlorpyrifos specific metabolite, and lower levels of total dimethyl phosphate in individuals reporting higher intake of organic produce. Results suggest that consumption of organic produce may offer some protection from increased exposure to organophosphate pesticide residues in vegetarians. [ABSTRACT FROM AUTHOR]

A number of biomonitoring surveys have been performed for chlorpyrifos (CPF) and its metabolite (3,5,6-trichloro-2-pyridinol, TCPy); however, there is no available guidance on how to interpret these data in a health risk assessment context. To address this gap, Biomonitoring Guidance Values (BGVs) are developed using a physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model. The PBPK/PD model is used to predict the impact of age and human variability on the relationship between an early marker of cholinesterase (ChE) inhibition in the peripheral and central nervous systems [10% red blood cell (RBC) ChE inhibition] and levels of systemic biomarkers. Since the PBPK/PD model characterizes variation of sensitivity to CPF in humans, interspecies and intraspecies uncertainty factors are not needed. Derived BGVs represent the concentration of blood CPF and urinary TCPy associated with 95% of the population having less than or equal to 10% RBC ChE inhibition. Blood BGV values for CPF in adults and infants are 6100 ng/L and 4200 ng/L, respectively. Urinary TCPy BGVs for adults and infants are 2100 μg/L and 520 μg/L, respectively. The reported biomonitoring data are more than 150-fold lower than the BGVs suggesting that current US population exposures to CPF are well below levels associated with any adverse health effect. [ABSTRACT FROM AUTHOR]

Analytical methods to quantify pesticide biomarkers in human population studies are critical for exposure assessment given the widespread use of pesticides for pest and weed control and their potential for affecting human health. We developed a method to quantify, in 0.2 mL of urine, concentrations of 10 pesticide biomarkers: four organophosphate insecticide metabolites (3,5,6-trichloro-2-pyridinol (TCPy), 2-isopropyl-6-methyl-4-pyrimidinol, para -nitrophenol, malathion dicarboxylic acid); five synthetic pyrethroid insecticide metabolites (4-fluoro-3-phenoxybenzoic acid, 3-phenoxybenzoic acid, cis and trans -3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (DCCA), cis -3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid); and the herbicide 2,4-dichlorophenoxyacetic acid. he method is based on enzymatic hydrolysis of conjugated urinary metabolites, extraction and pre-concentration of the deconjugated metabolites using automated online solid-phase extraction, and separation and quantification using liquid chromatography-isotope dilution tandem mass spectrometry. Depending on the analyte, method detection limits were 0.1–0.6 ng/mL; mean accuracy, calculated as spike recoveries, was 91–102%, and total precision, given as percent variation coefficient, was 5.9–11.5%. Percent differences associated with three freeze-thaw cycles, 24-h benchtop storage, and short-term processed sample stability were <14%. Method suitability was assessed by recurring successful participation in external quality assessment schemes and by analyzing samples from subjects with suspected exposure to pesticides (n = 40) or who self-reported consuming an organic diet (n = 50). Interquartile ranges were considerably lower for people consuming an organic diet than for those potentially exposed for cis -DCCA (0.37 ng/mL vs 0.75 ng/mL), trans -DCCA (0.88 ng/mL vs 1.78 ng/mL) and TCPy (1.81 ng/mL vs 2.48 ng/mL). This method requires one-fifth of the sample used in our previous method and is suitable for assessing background exposures to select pesticides in large human populations and for studies with limited sample volumes. [Display omitted] • Novel LC-MS/MS method for quantifying pesticide biomarkers in urine • Online sample cleanup and isotope dilution LC-MS/MS pesticide exposure method • Method uses 0.2 mL urine and is sensitive, reproducible, and accurate • Suitable to assess background exposures in large-scale population studies [ABSTRACT FROM AUTHOR]

Sensors have been developed for noninvasive biomonitoring of the organophosphate pesticide chlorpyrifos (CPF), and previous studies have suggested consistent partitioning of 3,5,6-trichloro-2-pyridinol (TCPy), a metabolite of CPF, into saliva after exposure to TCPy. The objective of this study was to quantitatively evaluate in vivo pharmacokinetics and pharmacodynamics of CPF and TCPy in saliva after CPF administration. Rats were coadministered CPF (0.5–5mg/kg) and pilocarpine (~13mg/kg) iv. Saliva and blood were collected, and levels of CPF, TCPy, and cholinesterase (ChE) activity were quantified. Experimental results suggest that CPF is rapidly metabolized after iv administration. Formation of TCPy from administered CPF at the low dose (0.5mg/kg) was slower than from higher CPF doses, potentially due to differences in plasma protein binding to CPF. CPF was measured in saliva only at the first time point sampled (0–15min), indicating low partitioning and rapid metabolism. After formation, TCPy pharmacokinetics were very similar in blood and saliva. Saliva/blood TCPy concentration ratios were not affected by TCPy concentration in blood, saliva flow rate, or salivary pH and were consistent with previous studies. ChE activity in plasma demonstrated a dose-dependent decrease, and ChE activity in saliva was extremely variable and demonstrated no dose relationship. A physiologically based pharmacokinetic and pharmacodynamic model for CPF was modified and predicted the data reasonably well. It is envisioned that a combination of biomonitoring compounds like TCPy in saliva coupled with computational modeling will form an approach to measure pesticide exposure to susceptible human populations such as agricultural workers. [ABSTRACT FROM PUBLISHER]

Chlorpyrifos (CPF) is an organophosphourus insecticide applied to cotton fields by adolescents employed by the Egyptian Ministry of Agriculture. Urinary 3,5,6-trichloro-2-pyridinol (TCPy) is a biomarker of CPF exposure that has substantial variability among these applicators. In order to identify predictors of CPF exposure, we conducted a longitudinal study of 43 adolescent pesticide applicators in Egypt from April 2010 to January 2011 in Egypt. Urinary TCPy was quantified at 25 time-points, prior to, during, and following application. We used log-linear regression and a best subset selection approach to identify the exposure determinants that were most predictive of cumulative TCPy and participants' highest TCPy values (peak exposure). Applicators had cumulative urinary TCPy levels ranging from 167 to 49,8208μg/g creatinine. Total hours applying CPF (semi-partial r2=0.32), and total hours in the field applying other pesticides (semi-partial r2=0.08) were the strongest predictors of cumulative TCPy. Applicators had peak urinary TCPy levels ranging from 4 to 5715μg/g creatinine. The amount of time applying pesticides prior to blood draw was the strongest predictor of peak TCPy (semi-partial r2=0.30). We also observed evidence that wearing clean clothes to work was associated with lower longitudinal TCPy. Our results suggest there is an opportunity for targeted interventions, particularly related to hygiene or implementation of personal protective equipment usage to reduce CPF exposure among adolescent pesticide workers. [ABSTRACT FROM AUTHOR]

A combination experimental and computational approach was developed to predict chemical transport into saliva. A serous-acinar chemical transport assay was established to measure chemical transport with nonphysiological (standard cell culture medium) and physiological (using surrogate plasma and salivamedium) conditions using 3,5,6-trichloro-2-pyridinol (TCPy) ametabolite of the pesticide chlorpyrifos. High levels of TCPy protein binding were observed in cell culture medium and rat plasma resulting in different TCPy transport behaviors in the 2 experimental conditions. In the nonphysiological transport experiment, TCPy reached equilibrium at equivalent concentrations in apical and basolateral chambers. At higher TCPy doses, increased unbound TCPy was observed, and TCPy concentrations in apical and basolateral chambers reached equilibrium faster than lower doses, suggesting only unbound TCPy is able to cross the cellularmonolayer. In the physiological experiment, TCPy transport was slower than nonphysiological conditions, and equilibriumwas achieved at different concentrations in apical and basolateral chambers at a comparable ratio (0.034) to what was previouslymeasured in rats dosed with TCPy (saliva:blood ratio: 0.049). A cellular transport computationalmodel was developed based on TCPy protein binding kinetics and simulated all transport experiments reasonably well using different permeability coefficients for the 2 experimental conditions (1.14 vs 0.4 cm/h for nonphysiological and physiological experiments, respectively). The computationalmodel was integrated into a physiologically based pharmacokinetic model and accurately predicted TCPy concentrations in saliva of rats dosed with TCPy. Overall, this study demonstrates an approach to predict chemical transport in saliva, potentially increasing the utility of salivary biomonitoring in the future. [ABSTRACT FROM AUTHOR]

We developed an isotopic dilution high-performance liquid chromatography (HPLC)/tandem mass spectrometer (MS/MS) method to rapidly and accurately quantify nine metabolites of several classes of pesticide in 1 mL human urine specimens. The analytes covered in the method are two organophosphate (OP) pesticide metabolites: 3,5,6-trichloro-2-pyridinol (TCPy), 2-isopropyl-6-methyl-4-pyrimidinol (IMPY); three synthetic pyrethroid metabolites: 3-phenoxy benzoic acid (3-PBA), 4-fluoro-3-phenoxybenzoic acid (4-F-3-PBA) andtrans-3-(2,2-dichlorovinyl)-2,2-dimethyl-1(1-cyclopropane) carboxylic acid (t-DCCA); three herbicide metabolites: 2,4-dichlorophenoxyacetic acid (DCPAA), 2,4,5-trichlorophenoxyacetic acid (TCPAA) and atrazine mercapturate; and one insect repellent:N,N-diethyl-meta-toluamide (DEET). The analytes are first deconjugated by incubating with acetate/β-glucuronidase buffer at 37°C for 17 h. The deconjugated analytes are extracted and concentrated from the urine matrix using solid-phase extraction cartridges, separated through C18 reversed phase HPLC, and analysed on MS/MS. The MS/MS was operated in positive and negative electrospray ionisation switch mode. Two ions from each analyte and one from each labelled internal standard are monitored for quantification and confirmation. The limit of detections (LODs) for all the analytes are in the low parts-per-trillion (0.05 ng/mL) except TCPy where it was 0.5 ng/mL) with a wide linear range (0.05 up to 40 ng/mL) and provides high accuracy (recoveries: 90–118%) and high precision (coefficient of variation <15%). The method accuracy was also verified by the analysis of proficiency testing urine samples. We analysed 101 urine samples for a recent California study cohort, and detection frequencies ranged from ~100% to 0%: 3-PBA (98%), IMPY (91%), TCPy, (89%), DCPAA (66%), 4-F-3-PBA (11%), TCPAA (0%). [ABSTRACT FROM AUTHOR]

Chlorpyrifos is a widely used organophosphorus pesticide that efficiently protects crops against pests. However, recent studies suggest that severe exposure to chlorpyrifos may present adverse health effects in human. To analyze the exposure level and metabolic characteristics of chlorpyrifos pesticide in urban adults and farmers with/without occupation pesticide contact, the occurrence of urinary chlorpyrifos and methyl chlorpyrifos (CP-me), as well as their metabolite, 3,5,6-trichloro-2-pyridinol (TCPy), was determined in farmers of an agricultural village in China, and in urban adults of a nearby town. The geometric mean (GM) concentrations of TCPy, which is the major marker of chlorpyrifos exposure, were 4.29 and 7.57 μg/g-creatinine in urban adults and farmers before pesticide application, respectively. Chlorpyrifos spraying significantly increased the concentrations of urinary TCPy. In the first day after spraying, a GM concentration of 43.7 μg/g-creatinine was detected in the urine specimens from farmers, which decreased to 38.1 and 22.8 μg/g-creatinine in the second and third day after chlorpyrifos spraying. The ratio of TCPy and its parent compounds, i.e. chlorpyrifos and CP-me, was positively associated with the sum concentration of urinary chlorpyrifos, CP-me, and TCPy, suggesting the increasing metabolic efficiency of chlorpyrifos to TCPy at higher chlorpyrifos exposure levels. To estimate the farmers’ occupational exposure to chlorpyrifos pesticide, a new model based on the fitted first-order elimination kinetics of TCPy was established. Occupational chlorpyrifos exposure in a farmer was estimated to be 3.70 μg/kg-bw/day (GM), which is an exposure level that is higher than the recommended guideline levels. Significant increase of urinary 8-hydroxydeoxyguanosine (8-OHdG) was observed on the first day after chlorpyrifos spraying, which indicates a potential oxidative damage in farmers. However, urinary 8-OHdG returned to its baseline level within two days. [ABSTRACT FROM AUTHOR]

Purpose: Chlorpyrifos (CPF) is one of the most widely used organophosphorous pesticides in China. However, few reports on CPF pesticide exposure and body burden of infants at 2 years of age in China are available. The aim of this study was to assess the exposure level and the absorbed daily dose (ADD) of CPF among infants from an agricultural area of Jiangsu, China, and determine whether the infants' estimated dose exceeds the recommended reference dose (RfD) and the population adjusted dose (PAD) set by U.S. Environmental Protection Agency (EPA). Methods: In our study, 364 infants at 2 years of age who lived in the agricultural area of Jiangsu Province (China) were enrolled into the biomonitoring study from June 2011 to January 2012. CPF exposure was estimated based on both questionnaire survey and measured results of urinary metabolite 3,5,6-trichloro-2-pyridinol (TCPy) of CPF by high-performance liquid chromatography. Furthermore, the ADD of CPF among infants was also evaluated and compared with the RfD and the PAD values issued by EPA. Results: Urinary TCPy was detected in more than 70 % of the urine samples among 364 infants. The unadjusted and creatinine-adjusted geometric means in these subjects for TCPy were 1.33 μg/L and 6.73 μg/g Cre., respectively. Infants lived nearby (100 m distance) plantations or green parks present significantly higher levels of urinary TCPy than those lived far away ( p = 0.045). Urinary TCPy levels were also significantly higher in infants who had frequent hand-to-mouth activities than those with less frequency ( p = 0.037). Urinary TCPy concentrations in the infants at 2 years of age in Jiangsu were lower than those in the children at 2-6 years of age in the USA. The median estimated ADD of CPF in this study (0.07 μg/kg/day) was much lower than the acute and chronic RfDs (5 and 0.3 μg/kg/day, respectively) announced by EPA, but higher than the chronic PAD (cPAD) (0.03 μg/kg/day) for children. Additionally, the 75th percentile of the estimated ADD in our study was 2.5 times as much as the cPAD from EPA, even assuming only half of the TCPy amount from CPF exposure. Conclusions: Our findings revealed that infants at 2 years of age in Jiangsu of China were widely exposed to CPF pesticide. The estimated ADD probably suggested that about 25 % of the enrolled infants were at potential risk of pesticide exposure, which warned of urgency to eliminate the potential exposure risk to infants living in agricultural areas of China. [ABSTRACT FROM AUTHOR]

Abstract Background Previous diet intervention studies indicate that an organic diet can reduce urinary pesticide metabolite excretion; however, they have largely focused on organophosphate (OP) pesticides. Knowledge gaps exist regarding the impact of an organic diet on exposure to other pesticides, including pyrethroids and neonicotinoids, which are increasing in use in the United States and globally. Objective To investigate the impact of an organic diet intervention on levels of insecticides, herbicides, and fungicides or their metabolites in urine collected from adults and children. Methods We collected urine samples from four racially and geographically diverse families in the United States before and after an organic diet intervention (n = 16 participants and a total of 158 urine samples). Results We observed significant reductions in urinary levels of thirteen pesticide metabolites and parent compounds representing OP, neonicotinoid, and pyrethroid insecticides and the herbicide 2,4-D following the introduction of an organic diet. The greatest reductions were observed for clothianidin (− 82.7%; 95% confidence interval [95% CI]: − 86.6%, − 77.6%; p < 0.01), malathion dicarboxylic acid (MDA), a metabolite of malathion (− 95.0%; 95% CI: − 97.0%, − 91.8%; p < 0.01), and 3,5,6-trichlor-2-pyridinol (TCPy), a metabolite of chlorpyrifos (− 60.7%; 95% CI: − 69.6%, − 49.2%; p < 0.01). Metabolites or parent compounds of the fungicides boscalid, iprodione, and thiabendazole and the neonicotinoid insecticide imidacloprid were not detected among participants in our study. Conclusion An organic diet was associated with significant reductions in urinary excretion of several pesticide metabolites and parent compounds. This study adds to a growing body of literature indicating that an organic diet may reduce exposure to a range of pesticides in children and adults. Additional research is needed to evaluate dietary exposure to neonicotinoids, which are now the most widely used class of insecticides in the world. Highlights • Diet is a primary source of pesticide exposure. • Organic diet reduced neonicotinoid, OP, pyrethroid, 2,4-D exposure in U.S. families. • Greatest reduction observed for malathion, clothianidin, and chlorpyrifos. [ABSTRACT FROM AUTHOR]

Pesticide handlers and pet owners who use products such as shampoos and dips and insecticide-impregnated collars to treat and control fleas on companion animals are exposed to a variety of active ingredients. Chlorpyrifos exposures of adults and children were measured using urine biomonitoring following use of over-the-counter products on dogs. Age and gender-specific measurements of urinary 3, 5, 6-trichloro-2-pyridinol (TCPy) revealed modest elevations of biomarker excretion following shampoo/dips. Smaller TCPy increments were measured following application of impregnated dog collars. The extent of indoor activity and potential pet contact were important determinants of urine biomarker level. Children without direct pet contact excreted more TCPy following collar application. Pet collars may be a source of indoor surface contamination and human exposure. Children excreted up to 4 times more TCPy than adults when urine volumes were adjusted using age-specific creatinine excretion levels. Although chlorpyrifos is no longer used in the United States in pet care products, results of this research provide perspective on the extent of human exposure from similar pet care products. These pilot studies demonstrated that pet care products such as insecticidal shampoos and dips and impregnated collars may expose family members to low levels of insecticide relative to toxic levels of concern. [ABSTRACT FROM AUTHOR]

Abstract: Neurobehavioral deficits have been reported in Egyptian pesticide application teams using organophosphorus (OP) pesticides, but whether these effects are related to OP pesticide exposures has yet to be established. In preparation for a comprehensive study of the relationship between OP pesticide dose and neurobehavioral deficits, we assessed exposure within this population. We conducted occupational surveys and workplace observations, and collected air, dermal patch and biological samples from applicators, technicians and engineers involved in chlorpyrifos applications during cotton production to test the hypotheses that: (1) dermal exposure was an important contributor to internal dose and varied across body regions; and (2) substantial differences would be seen across the three job categories. Applicators were substantially younger and had shorter exposure histories than did technicians and engineers. Applicators and technicians were observed to have relatively high levels of skin or clothing contact with pesticide-treated foliage as they walked through the fields. Both dermal patch loadings of chlorpyrifos and measurements of a chlorpyrifos-specific metabolite (TCPy) in urine confirmed substantial exposure to and skin absorption of chlorpyrifos that varied according to job category; and dermal patch loading was significantly higher on the thighs than on the forearms. These findings support our hypotheses and support the need for research to examine neurobehavioral performance and exposures in this population. More importantly, the exposures reported here are sufficiently high to recommend urgent changes in work practices amongst these workers. [Copyright &y& Elsevier]

Widespread application of contemporary-use insecticides results in low-level exposure for a majority of the population through a variety of pathways. Urinary insecticide biomarkers account for all exposure pathways, but failure to account for temporal within-subject variability of urinary levels can lead to exposure misclassification. To examine temporal variability in urinary markers of contemporary-use insecticides, nine repeated urine samples were collected over 3 months from 10 men participating in an ongoing study of male reproductive health. These 90 samples were analyzed for urinary metabolites of chlorpyrifos (3,5,6-trichloro-2-pyridinol (TCPY)) and carbaryl (1-naphthol (1N)). Volume- based (unadjusted), as well as creatinine (CRE)- and specific gravity (SG)-adjusted concentrations were measured. TCPY had low reliability with an intraclass correlation coefficient between 0.15 and 0.21, while 1N was moderately reliable with an intraclass correlation coefficient between 0.55 and 0.61. When the 10 men were divided into tertiles based on 3-month geometric mean TCPY and 1N levels, a single urine sample performed adequately in classifying a subject into the highest or lowest exposure tertiles. Sensitivity and specificity ranged from 0.44 to 0.84 for TCPY and from 0.56 to 0.89 for 1N. Some differences in the results between unadjusted metabolite concentrations and concentrations adjusted for CRE and SG were observed. Questionnaires were used to assess diet in the 24?h preceding the collection of each urine sample. In mixed-effects models, TCPY was significantly associated with season as well as with consuming grapes and cheese, while 1N levels were associated with consuming strawberries. In conclusion, although a single sample adequately predicted longer-term average exposure, a second sample collected at least 1 month following the first sample would reduce exposure measurement error.Journal of Exposure Analysis and Environmental Epidemiology (2005) 15, 271-281. doi:10.1038/sj.jea.7500402 Published online 1 September 2004 [ABSTRACT FROM AUTHOR]

Human exposure to pesticides is widespread and has received much attention in recent years because of its link to adverse health outcomes. Measurement of urinary concentrations of pesticides and their metabolites is often used in the assessment of body burdens of these chemicals. However, pesticides and their metabolites can be present in blood circulatory system, although little is known on serum levels of pesticides. In this study, we aimed to examine the occurrence and profile of four organophosphate (OP), five pyrethroid (PYR) insecticides, two phenoxy acid (PA) herbicides, 14 neonicotinoid (neonic) insecticides and six dialkylphosphate metabolites in serum from 25 individuals diagnosed with osteoarthritis in Jeddah, Saudi Arabia. 2-Isopropyl-4-methyl-6-hydroxypyrimidine (IMPY), 3,5,6-trichloro-2-pyridinol (TCPY), 2,4-dichlorophenoxyacetic acid, 2,4,5-trichlorophenoxyacetic acid, 3-phenoxybenzoic acid, N -desmethyl acetamiprid, dimethylphosphate (DMP) and dimethylthiophosphate (DMTP) were detected in ≥80% of the serum samples analyzed. Metabolites of OPs, DMTP (median concentration: 2.14 ng/mL), DMP (1.04 ng/mL) and TCPY (0.84 ng/mL), collectively accounted for 67–83% of the total serum pesticide concentrations. Serum concentrations of pesticides were similar to or lower than those reported in urine. Our preliminary evidence suggests that serum can be used as a matrix for the assessment of exposure to OPs, PYRs, PAs and neonics. Unlabelled Image • Thirty-one pesticides and their metabolites were measured in human serum. • Eight out of 31 pesticides were detected in ≥80% of the serum samples. • Metabolites of organophosphates, DMP, DMTP and TCPY, were dominant in serum. • Serum can be used as a matrix to assess pesticide exposures. [ABSTRACT FROM AUTHOR]

Human serum and urine samples were analyzed for a suite of nitrosatable pesticides and potentially carcinogenic pesticide-associated N –nitroso (PA N N) compounds. Formation of PA N N compounds may occur in vivo after consumption of food or water containing trace amounts of nitrosatable pesticide residues and nitrate. Using a modified version of the Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) method, nine nitrosatable pesticides and byproducts were extracted from serum and urine from 64 individuals from two different sample populations in Atlantic Canada: (i) Prince Edward Island, a region where nitrate and trace amounts of nitrosatable pesticides have been detected in groundwater; and (ii) Halifax, Nova Scotia, a non-agricultural urban area. Samples were then analyzed using ultra-high pressure liquid chromatography (UHPLC) coupled with high-resolution accurate mass (HRAM) single-stage orbitrap mass spectrometry (MS), which allows for semi-targeted analysis and tentative identification of a virtually limitless number of exposure biomarkers. Two nitrosatable target analytes, ethylenethiourea (ETU) and 3,5,6-trichloro-2-pyridinol (TCPy) were found in serum, while atrazine (ATR) and ETU were detected in urine. Five and six PA N N compounds were tentatively identified in serum and urine, respectively. The two PA N N compounds that were most frequently tentatively identified in serum were N -nitroso dimethoate (N -DIM) and N -nitroso omethoate (N -OME) with detection frequencies of 78% and 95%, respectively. This is the first biomonitoring study of its kind to investigate PA N N compounds in human serum and urine. [ABSTRACT FROM AUTHOR]

Although Spain does not have a regular national human biomonitoring program yet, different research groups are active in evaluating the exposure of children and adults to chemicals. In the last seven years, several studies in Spain have evaluated the internal exposure of the population to currently used pesticides. The present review analyzes the scope of these studies, the employed analytical methods and the main results of the exposure and risk, mainly for children and mothers. The frequency of exposure to biomarkers of exposure to organophosphate pesticides is high. Some non-specific dialkyl phosphate metabolites (DAPs), such as the diethyl phosphate (DEP), present Detection Frequencies (DFs) in the range of 65–92% in various studies. Also, the specific biomarker of the chlorpyrifos (3,5,6-trichloro-2-pyridinol, TCPy), achieves Detection Frequencies between 74% and 100% in many studies. For pyrethroids, the metabolite 3-phenoxybenzoic acid (PBA) is present, in general, in more than the 65% of the studied samples. Highly polar herbicides were only assessed in one study and both glyphosate and its metabolite aminomethylphosphonic acid showed Detection Frequencies around 60%. However, putting the biomonitoring data in a risk assessment context, the mean Hazard Quotient (HQ), used as a metric for the individual risk, ranges from 0.0006 (glyphosate) to 0.93 in farm workers (parathion), which means that is unlike that the exposure poses a health concern (HQ < 1). [ABSTRACT FROM AUTHOR]

• Among first studies to evaluate pesticide exposures in pregnant women in Bangladesh. • Levels of urinary metabolites of chlorpyrifos and parathion were notably high. • Higher exposure to parathion was associated with increased risk of preterm birth. • Exposure to parathion was also associated with increased risk of small for gestational age. • Exposure to diazinon was associated with increased risk of low birth weight. Pesticide exposure during pregnancy is thought to adversely affect fetal growth, which in turn may impact child growth, but results have been inconsistent across studies and few have explored these effects in developing countries. To quantify urinary concentrations of pesticide biomarkers in early pregnancy (<16 weeks' gestation), and to estimate the association of these concentrations with preterm birth, low birth weight, small for gestational age, and stunting at ~1 and 2 years of age. Eight pesticide biomarkers were quantified in urine collected from 289 pregnant women (aged 18–40 years) participating in a birth cohort study in Bangladesh. Anthropometry measurements were conducted on the index child at birth and approximately 1 and 2 years of age. A directed acyclic graph was used to identify minimal sufficient adjustment sets. Log-binomial regression was used to estimate the relative risk (RR) with 95% confidence intervals (CI). 3,5,6-trichloro-2-pyridinol (TCPY), a metabolite of chlorpyrifos and chlorpyrifos methyl, and 4-nitrophenol, a metabolite of parathion and methyl parathion, were detected in nearly all women with geometric mean (95% CI) values of 3.17 (2.82–3.56) and 18.66 (17.03–20.46) µg/g creatinine, respectively. 3-phenoxybenzoic acid (3-PBA), a non-specific metabolite of several pyrethroids, and 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMPY), a diazinon metabolite, were detected in 19.8% and 16.1% of women, respectively. The remaining four pesticide biomarkers were detected in <10% of women. Women in the highest quartile of 4-nitrophenol were more than 3 times more likely to deliver preterm than women in the lowest quartile: unadjusted RR (95% CI), 3.57 (1.65, 7.73). Women in the highest quartile of 4-nitrophenol were also at increased risk of having a child born small for gestational age: RR (95% CI) adjusted for household income, maternal education, and maternal total energy and meat intake, 3.81 (1.10, 13.21). Women with detectable concentrations of IMPY were at increased risk of having a child born with low birth weight compared to women with non-detectable concentrations: adjusted RR (95% CI), 2.13 (1.12, 4.08). We observed no association between any of the pesticide biomarkers and stunting at 1 or 2 years of age. Exposure to the insecticides parathion and diazinon during early pregnancy may increase the risk of adverse birth outcomes. [ABSTRACT FROM AUTHOR]

Highlights: [•] Developed and validated a method for the measurement of these analytes in urine. [•] The method is highly efficient using automation for preparation and analysis. [•] High mass resolution analysis reduces chemical noise and increases sensitivity. [•] Smaller diameter, smaller pore size chromatography column improves chromatography. [Copyright &y& Elsevier]