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Background: Animal studies suggest that organophosphorus pesticides (OPs) may be environmental obesogens. While prenatal OP exposures have been associated with altered infant glucose metabolism, associations with pediatric adiposity remain unknown., Methods: We summed concentrations of three dimethylphosphate (∑DMP) and three diethylphosphate (∑DEP) metabolites of OPs measured in third trimester spot urine samples collected from pregnant women enrolled in New York City, 1998-2002. We measured percent fat mass using bio-electrical impedance analysis and calculated age- and sex-standardized body mass index (BMI) z-scores from anthropometric measurements collected at approximately 4, 6, and 7-9 years of age (166 children, 333 observations). We assessed covariate-adjusted associations of OPs with repeated adiposity measures using linear mixed models and evaluated effect measure modification (EMM) by sex and paroxonase (PON) 1 -108C/T and Q192R polymorphisms measured in maternal peripheral blood samples., Results: The geometric mean urinary concentration of ∑DMP metabolites (29.9 nmol/L, IQR: 105.2 nmol/L) was higher than ∑DEP metabolites (8.8 nmol/L, IQR: 31.2 nmol/L). Adjusted associations were null, with differences in fat mass per 10-fold increase in prenatal ∑DMP and ∑DEP concentrations of 0.7% (95% CI: -0.6, 2.0) and 0.8% (95% CI: -0.4, 2.0), respectively. Maternal PON1-108C/T polymorphisms modified relationships of prenatal ∑DMP with percent fat mass (EMM p-value = 0.18) and ∑DEP with BMI z-scores (EMM p-value = 0.12). For example, ∑DMP was modestly associated with increased percent fat mass among children of mothers with the at-risk CT or TT genotype (β = 1.2%, 95% CI: -0.6, 3.0) but not among those whose mothers had the CC genotype (β = -0.4%, 95% CI: -2.4, 1.5). Associations were not modified by sex or maternal PON1 Q192R polymorphisms., Conclusions: We observed little evidence of a relationship between prenatal OP exposures and child adiposity, although there was some suggestion of increased risk among offspring of mothers who were slow OP metabolizers. Larger studies are warranted to further evaluate possible associations of prenatal OP exposures with child adiposity and differences by maternal PON1 genotype, which regulates OP metabolism and may increase susceptibility to exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Much of the marked increase in incidence of non-Hodgkin lymphoma (NHL) over the past few decades remains unexplained. Organochlorines, including organochlorine pesticides (OCPs), have been implicated as possible contributors to the increase, but the evidence is inconsistent., Objectives: To investigate the relation between pre-diagnostic levels of OCPs and risk of NHL in a case-control study nested within the population-based Janus Serum Bank Cohort in Norway., Methods: Prediagnostic concentrations of 11 OCPs or OCP metabolites were measured in baseline blood samples collected between 1972 and 1978 from 190 cases and 190 controls matched on sex, county, age at blood draw, and date of blood draw. We conducted conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for each quartile of lipid-corrected OCP/metabolite relative to the lowest quartile., Results: We observed non-significantly elevated ORs across quartiles of β-hexachlorocyclohexane compared to the lowest quartile (OR range: 1.40-1.82) although with no apparent monotonic exposure-response relationship. We also found an inverse association between risk of NHL and o,p'-DDT (OR for Q 4 vs. Q 1  = 0.44, 95% CI: 0.19, 1.01; p-trend = 0.05). In analyses stratified by age at blood collection and duration of follow-up, several other analytes, primarily chlordane-related compounds, showed inverse associations among younger participants or those with longer follow-up time between blood draw and NHL diagnosis., Conclusions: We found only limited evidence of positive association between selected OCPs and development of NHL., Competing Interests: Declaration of competing interest The authors declare they have no actual or potential competing financial interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Disentangling the separate and synergistic effects of chemicals poses methodological challenges for accurate exposure assessment and for investigating epidemiologically how chemicals affect reproduction. We investigated combined exposures to ubiquitous contemporary use pesticides, specifically organophosphates (OP) and pyrethroids (PYR), and their association with germ cell abnormalities among adult men. Fluorescence in situ hybridization was used to determine disomy in sperm nuclei and urine was analyzed for concentrations of PYR metabolites (3-phenoxybenzoic acid; 3PBA) and OP dialkyl phosphate (DAP) metabolites. Incidence rate ratios using Poisson models were estimated for each disomy type by exposure quartile of DAP metabolites and 3PBA, controlling for confounders. The shape of the associations between PYRs, OPs and disomy were frequently nonmonotonic. There were consistent interactions between OP and PYR metabolite concentrations and the risk for sperm abnormalities. Taking both chemicals into account simultaneously resulted in quantitatively different associations than what was reported previously for OPs and PYRs separately, demonstrating the importance of modeling multiple concentrations simultaneously. Methods investigating interactions using Poisson models are needed to better quantify chemical interactions and their effects on count-based health outcomes, the importance of which was shown here for germ cell abnormalities., (Copyright © 2019. Published by Elsevier GmbH.)

We conducted a randomized-controlled trial of a home-based intervention to reduce pesticide exposures to farmworkers' children in Monterey County, California (n=116 families). The intervention consisted of three home-based educational sessions delivered by community health workers in Spanish. Measurements of organophosphate (OP) insecticide metabolites in child urine (n=106) and pesticides in home floor wipes (n=103) were collected before and after the intervention. Median child urinary dialkyl phosphate (DAP) metabolite levels were slightly lower among the intervention group children at follow-up compared with baseline, albeit nonsignificantly. DAP metabolite levels in the control group children were markedly higher at follow-up compared with baseline. In adjusted models, intervention participation was associated with a 51% decrease in total DAP metabolite levels. Carbaryl, chlorpyrifos, cypermethrin, dacthal, diazinon, malathion, and trans-permethrin were commonly detected in the floor wipes. In adjusted models, intervention participation was significantly associated with a 37% decrease in trans-permethrin floor wipe levels in homes, but not OP or other agricultural pesticides. In summary, intervention group children had slightly reduced pesticide exposures, whereas child exposures were higher among the control group. Additional intervention studies evaluating methods to reduce pesticide exposures to farmworker families and children are needed.

Organophosphate pesticides (OPs) are related to ill health among adults, including farmworkers who are exposed to OPs as part of their regular work. Children of both farmworkers and non-farmworkers in agricultural communities may also be affected by pesticide exposure. Study groups of 100 farmworkers with a referent child (aged 2-6 years) and 100 non-farmworkers with a referent child were recruited to participate in three data collection periods over the course of a year. At each collection, participants provided three urine samples within 5 days, and homes and vehicles were vacuumed to collect pesticide residues in dust. In thinning and harvest seasons, farmworkers and their children had higher dimethyl urinary metabolites than non-farmworkers and their children. During the non-spray season, the urinary metabolites levels decreased among farmworkers to a level comparable to that of non-farmworkers. Farmworkers consistently had higher pesticide residues in their home and vehicle dust. Differences exist between farmworkers and non-farmworkers in urinary metabolites, and the differences extended throughout the agricultural seasons.OP metabolites are seen at much higher levels for farmworkers and their children than for non-farmworkers and their children during agricultural seasons when OPs are in use. These metabolite levels were significantly higher than the nationwide NHANES IV survey and up to 10-fold higher than other rural agricultural studies.

Many studies have investigated the neurodevelopmental effects of prenatal and early childhood exposures to organophosphate (OP) pesticides among children, but they have not been collectively evaluated. The aim of the present article is to synthesize reported evidence over the last decade on OP exposure and neurodevelopmental effects in children. The Data Sources were PubMed, Web of Science, EBSCO, SciVerse Scopus, SpringerLink, SciELO and DOAJ. The eligibility criteria considered were studies assessing exposure to OP pesticides and neurodevelopmental effects in children from birth to 18 years of age, published between 2002 and 2012 in English or Spanish. Twenty-seven articles met the eligibility criteria. Studies were rated for evidential consideration as high, intermediate, or low based upon the study design, number of participants, exposure measurement, and neurodevelopmental measures. All but one of the 27 studies evaluated showed some negative effects of pesticides on neurobehavioral development. A positive dose-response relationship between OP exposure and neurodevelopmental outcomes was found in all but one of the 12 studies that assessed dose-response. In the ten longitudinal studies that assessed prenatal exposure to OPs, cognitive deficits (related to working memory) were found in children at age 7 years, behavioral deficits (related to attention) seen mainly in toddlers, and motor deficits (abnormal reflexes) seen mainly in neonates. No meta-analysis was possible due to different measurements of exposure assessment and outcomes. Eleven studies (all longitudinal) were rated high, 14 studies were rated intermediate, and two studies were rated low. Evidence of neurological deficits associated with exposure to OP pesticides in children is growing. The studies reviewed collectively support the hypothesis that exposure to OP pesticides induces neurotoxic effects. Further research is needed to understand effects associated with exposure in critical windows of development., (Copyright © 2013 Elsevier Inc. All rights reserved.)

An estimated 200,000 children born in Thailand each year are at risk of prenatal exposure to pesticides and associated neurodevelopmental outcomes because of their mothers' agricultural occupations. Children born to non-agricultural workers may also be at risk of exposure from other pathways of maternal pesticide exposure, including exposure through home use, diet, and other environmental media. Pesticide exposure in Thailand has been linked to unsafe practices and beliefs about pesticides. However, limited information exists on pesticide knowledge, attitudes, and practices among pregnant women in Thailand or elsewhere. Obtaining this information is essential to understand the factors associated with prenatal pesticide exposure, identify populations potentially at risk, and ultimately protect pregnant women and their children. We administered surveys to 76 pregnant women in northern Thailand and used multivariable logistic regression to evaluate associations among pesticide-related knowledge, pregnancy trimester, and pesticide use behavior. In this pilot study, lower knowledge score and earliest trimester of pregnancy were marginally (p < 0.1) associated with unsafe practices in the home, but not at work. Women who worked in agriculture or applied pesticides before becoming pregnant, or who had a previous child were significantly (p < 0.05) more likely to engage in unsafe behaviors in the home during their current pregnancy. We preliminarily conclude that increasing pesticide-related knowledge among pregnant women may help promote safe practices and reduce prenatal exposure. Knowledge-based interventions may be most effective when implemented early in pregnancy and targeted to agricultural workers and other sub-populations at risk of pesticide exposure.

Background: In a longitudinal birth cohort study of inner-city mothers and children (Columbia Center for Children's Environmental Health), we have previously reported that prenatal exposure to chlorpyrifos (CPF) was associated with neurodevelopmental problems at 3 years of age., Objective: The goal of the study was to estimate the relationship between prenatal CPF exposure and neurodevelopment among cohort children at 7 years of age., Methods: In a sample of 265 children, participants in a prospective study of air pollution, we measured prenatal CPF exposure using umbilical cord blood plasma (picograms/gram plasma) and 7-year neurodevelopment using the Wechsler Intelligence Scale for Children, 4th edition (WISC-IV). Linear regression models were used to estimate associations, with covariate selection based on two alternate approaches., Results: On average, for each standard deviation increase in CPF exposure (4.61 pg/g), Full-Scale intelligence quotient (IQ) declined by 1.4% and Working Memory declined by 2.8%. Final covariates included maternal educational level, maternal IQ, and quality of the home environment. We found no significant interactions between CPF and any covariates, including the other chemical exposures measured during the prenatal period (environmental tobacco smoke and polycyclic aromatic hydrocarbons)., Conclusions: We report evidence of deficits in Working Memory Index and Full-Scale IQ as a function of prenatal CPF exposure at 7 years of age. These findings are important in light of continued widespread use of CPF in agricultural settings and possible longer-term educational implications of early cognitive deficits.

Background: Limited data document the multiple and repeated pesticide absorption experienced by farmworkers in an agricultural season or their risk factors., Methods: Data were collected from 196 farmworkers four times at monthly intervals in 2007. Urine samples were tested for 12 pesticide urinary metabolites. Questionnaire data provided measures of exposure risks., Results: Farmworkers had at least one detection for many pesticide urinary metabolites; for example, 84.2% had at least one detection for acephate, 88.8% for 3,5,6-trichloro-2-pyridinol. Most farmworkers had multiple detections for specific metabolites; for example, 64.8% had two or more detections for acephate, 64.8% for 3,5,6-trichloro-2-pyridinol, 79.1% for 3-phenoxybenzoic acid, and 86.7% for 2,4-dichlorophenoxyacetic acid. Housing type had a consistent significant association with metabolite detections., Conclusions: Farmworkers are exposed to multiple pesticides across an agricultural season, and they experience repeated exposures to the same pesticides. Reducing farmworker pesticide exposure and delineating the health outcomes of this exposure require more detailed data. Am. J. Ind. Med. 53:802-813, 2010. (c) 2010 Wiley-Liss, Inc., (Copyright 2010 Wiley-Liss, Inc.)

The goal of this study was to understand the potential threat of job stressors to farmworker health. To accomplish this goal we studied pesticide exposure, an issue with immediate and long-term health consequences, and predictions from the Demands-Control model of occupational stress. Longitudinal, self-report data and urine samples were collected at monthly intervals from a cohort of Latino farmworkers (N = 287) during the 2007 agricultural season. The primary hypothesis was that greater exposure to psychological demands, physical exertion, and hazardous work conditions are associated with greater odds of detecting dialkylphosphate (DAP) urinary pesticide metabolites, biomarkers indicating exposure to pesticides. Contrary to this hypothesis, results indicated that none of the elements of the Demands-Control model were independently associated with detection of DAP urinary pesticide metabolites. However, analyses produced several interaction effects, including evidence that high levels of control may buffer the effects of physical job demands on detection of DAP urinary pesticide metabolites.

We used a multiresidue, gas chromatography/mass spectrometry-based method to measure seven pyrethroid, five organophosphorus (OP), and six organochlorine pesticides in soil collected from 11 Atlanta homes in 2006. Our objective was to collect preliminary data for a larger study of pesticide exposures among Atlanta children. The pyrethroid insecticides (cis- and trans-permethrin, bioallethrin) were the most commonly detected analytes, giving evidence of widespread outdoor use among our study homes. Our pyrethroid insecticide detection frequencies were higher than those reported in a recent study of Ohio and North Carolina homes; however, our maximum values were approximately half of those reported. We detected the target OP pesticides in only a few samples, but we found two restricted-use OP pesticides--methyl parathion and terbufos--and thus possible evidence of illegal residential use or environmental persistence in soil. We also detected dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethane (DDE) in samples from six homes. Although our small sample size limits comparison to other studies, our results provide evidence that residential soil is a potential source of human exposure to both current and historically used pesticides.

Urine samples were collected from 51 participants in a study investigating pesticide exposure among farm families in Iowa. Aliquots from the samples were sent to two different labs and analyzed for metabolites of atrazine (atrazine mercapturate), metolachlor (metolachlor mercapturate) and chlorpyrifos (TCP) by two different analytical methods: immunoassay and high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). HPLC-MS/MS methods tend to be highly specific, but are costly and time consuming. Immunoassay methods are cheaper and faster, but can be less sensitive due to cross reactivity and matrix effects. Three statistical methods were employed to compare the two analytical methods. Each statistical method differed in how the samples that had results below the limit of detection (LOD) were treated. The first two methods involved an imputation procedure and the third method used maximum likelihood estimation (MLE). A fourth statistical method that modeled each lab separately using MLE was used for comparison. The immunoassay and HPLC-MS/MS methods were moderately correlated (correlation 0.40-0.49), but the immunoassay methods consistently had significantly higher geometric mean (GM) estimates for each pesticide metabolite. The GM estimates for atrazine mercapturate, metolachlor mercapturate, and TCP by immunoassay ranged from 0.16-0.98 microg l(-1), 0.24-0.45 microg l(-1) and 14-14 microg l(-1), respectively and by HPLC-MS/MS ranged from 0.0015-0.0039 microg l(-1), 0.12-0.16 microg l(-1), and 2.9-3.0 microg l(-1), respectively. Immunoassays tend to be cheaper and faster than HPLC-MS/MS, however, they may result in an upward bias of urinary pesticide metabolite levels.

This analysis describes the detection of urinary pesticide metabolites for Latino farmworkers across the agricultural season. Two hundred and eighty four farmworkers were recruited from 44 camps in eastern North Carolina in 2007. Data were collected at one month intervals for a total of 939 data points. The OP insecticide metabolites 3,5,6-trichloropyridinol (46.2%), malathion dicarboxylic acid (27.7%), and para-nitrophenol (97.4%); the pyrethroid metabolite 3-phenoxybenzoic acid (56.4%); and the herbicides 2,4-D (68.1%), acetochlor (29.2%), and metolachlor (16.9%) were found in sizable percentages of the samples. The percentage of farmworkers for whom metabolites were detected varied across the agricultural season. None of the farmworker characteristics were significantly associated with the detection of any pesticide metabolite. Seasonality overrides the effects of other farmworker characteristics in predicting detection of pesticide urinary metabolites. Future research needs to collect multiple exposure measures at frequent intervals over an extended period to characterize factors associated with exposure.

The aim was to develop quantitative estimates of farmers' pesticide exposure to atrazine and to provide an overview of background levels of selected non-persistent pesticides among corn farmers in a longitudinal molecular epidemiologic study. The study population consisted of 30 Agricultural Health Study farmers from Iowa and 10 non-farming controls. Farmers completed daily and weekly diaries from March to November in 2002 and 2003 on pesticide use and other exposure determinants. Urine samples were collected at 10 time points relative to atrazine application and other farming activities. Pesticide exposure was assessed using urinary metabolites and diaries. The analytical limit of detection (LOD) ranged between 0.1 and 0.2 microg/l for all pesticide analytes except for isazaphos (1.5 microg/l) and diazinon (0.7 microg/l). Farmers had higher geometric mean urinary atrazine mercapturate (AZM) values than controls during planting (1.1 vs

Organophosphates are pesticides ubiquitous in the environment and have been hypothesized as one of the risk factors for acute lymphoblastic leukemia (ALL). In this study, we evaluated the associations of pesticide exposure in a residential environment with the risk for pediatric ALL. This is a case-control study of children newly diagnosed with ALL, and their mothers (n = 41 child-mother pairs) recruited from Georgetown University Medical Center and Children's National Medical Center in Washington, DC, between January 2005 and January 2008. Cases and controls were matched for age, sex, and county of residence. Environmental exposures were determined by questionnaire and by urinalysis of pesticide metabolites using isotope dilution gas chromatography-high-resolution mass spectrometry. We found that more case mothers (33%) than controls (14%) reported using insecticides in the home (P < 0.02). Other environmental exposures to toxic substances were not significantly associated with the risk of ALL. Pesticide levels were higher in cases than in controls (P < 0.05). Statistically significant differences were found between children with ALL and controls for the organophosphate metabolites diethylthiophosphate (P < 0.03) and diethyldithiophosphate (P < 0.05). The association of ALL risk with pesticide exposure merits further studies to confirm the association.

We evaluated exposure to pesticides among secondary school students aged 12-13 years old in Chiang Mai Province, Thailand. Pesticide-specific urinary metabolites were used as biomarkers of exposure for a variety of pesticides, including organophosphorus insecticides, synthetic pyrethroid insecticides and selected herbicides. We employed a simple solid-phase extraction with analysis using isotope dilution high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). A total of 207 urine samples from Thai students were analyzed for 18 specific pesticide metabolites. We found 14 metabolites in the urine samples tested; seven of them were detected with a frequency > or=17%. The most frequently detected metabolites were 2-[(dimethoxyphosphorothioyl) sulfanyl] succinic acid (malathion dicarboxylic acid), para-nitrophenol (PNP), 3,5,6-trichloro-2-pyridinol (TPCY; metabolite of chlorpyrifos), 2,4-dichlorophenoxyacetic acid (2,4-D), cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acids (c-DCCA and t-DCCA; metabolite of permethrin) and 3-phenoxybenzoic acid (3-PBA; metabolite of pyrethroids). The students were classified into 4 groups according to their parental occupations: farmers (N=60), merchants and traders (N=39), government and company employees (N=52), and laborers (N=56). Children of farmers had significantly higher urinary concentrations of pyrethroid insecticide metabolites than did other children (p<0.05). Similarly, children of agricultural families had significantly higher pyrethroid metabolite concentrations. Males had significantly higher values of PNP (Mann-Whitney test, p=0.009); however, no other sex-related differences were observed. Because parental occupation and agricultural activities seemed to have little influence on pesticide levels, dietary sources were the likely contributors to the metabolite levels observed.

Objective: The objective of this study was to assess pesticide exposures in children being treated for head lice with either lindane or permethrin (exposed group) and children who did not have a lice infestation and thus were not being treated with chemicals for head lice or scabies (unexposed group)., Methods: In 2001, we enrolled 78 children aged 6-10 years old and collected baseline urine samples and demographic information from all the children. We subsequently collected post-exposure urine samples and questionnaire information about lice treatment from the 29 (37%) children (exposed children) who had been diagnosed and were being treated for head lice. Metabolites of the pesticides lindane and permethrin were measured in the samples., Results: The mean age of exposed and unexposed children in the study population was 9.3 years and 8.5 years, respectively. Fourteen of the 29 exposed children used prescription lice treatments (i.e., lindane or malathion); 25 of the 29 exposed children used at least one over-the-counter permethrin treatment, either alone or in addition to prescription treatments. Exposed children in both counties had higher urinary pyrethroid metabolite levels in their post-exposure samples compared with their baseline samples. However this difference was only significant in Forsyth County children., Conclusions: The significantly increased post-exposure pyrethroid metabolite levels in the urine of Forsyth County children suggest that the children are exposed to pyrethroid insecticides through the use of lice shampoos.

The US EPA Worker Protection Standard requires pesticide safety training for farmworkers. Combined with re-entry intervals, these regulations are designed to reduce pesticide exposure. Little research has been conducted on whether additional steps may reduce farmworker exposure and the potential for take-home exposure to their families. We conducted an intervention with 44 strawberry harvesters (15 control and 29 intervention group members) to determine whether education, encouragement of handwashing, and the use of gloves and removable coveralls reduced exposure. Post-intervention, we collected foliage and urine samples, as well as hand rinse, lower-leg skin patch, and clothing patch samples. Post-intervention loading of malathion on hands was lower among workers who wore gloves compared to those who did not (median=8.2 vs. 777.2 microg per pair, respectively (P<0.001)); similarly, median MDA levels in urine were lower among workers who wore gloves (45.3 vs. 131.2 microg/g creatinine, P<0.05). Malathion was detected on clothing (median=0.13 microg/cm(2)), but not on skin. Workers who ate strawberries had higher malathion dicarboxylic acid levels in urine (median=114.5 vs. 39.4 microg/g creatinine, P<0.01). These findings suggest that wearing gloves reduces pesticide exposure to workers contacting strawberry foliage containing dislodgeable residues. Additionally, wearing gloves and removing work clothes before returning home could reduce transport of pesticides to worker homes. Behavioral interventions are needed to reduce consumption of strawberries in the field.

Our research goal was to assess exposure to currently used pesticides among small-scale male farmers residing in two topographically different areas in Chiang Mai Province, Thailand. Farmers (N=136) were recruited from Pong Yaeng subdistrict (N=67) and Inthakhin subdistrict (N=69). Each farmer provided a morning urine void for the analysis of 30 urinary metabolites of insecticides, herbicides, and fungicides. Farmers in Pong Yaeng had significantly higher urinary concentrations of metabolites of organophosphorus insecticides and ethylene bisdithiocarbamates, while farmers from Inthakhin had significantly higher concentrations of malathion, 2,4-D, alachlor, and parathion or EPN metabolites. Based upon the metabolites measured in the urine of the farmers, chlorpyrifos and pyrethroid insecticides seemed to be commonly used across both communities; no significant differences in metabolite concentrations of these insecticides were observed between the two farmer groups. The presence of methamidaphos in the urine of farmers suggests that, despite a ban on its use, methamidaphos continues to be used in the communities. A similar finding with metabolites of methyl parathion must be further investigated. Overall, our results suggest that while each community may use different pesticides, Thai farmers are exposed to a wide variety of pesticides with a broad range in exposure magnitude. Furthermore, age, field size, crop production type, and the use of protective equipment were found to be potential factors influencing the degree of exposure.

Background: Widespread residential pesticide use throughout the United States has resulted in ubiquitous, low-level pesticide exposure. The mix of active pesticide ingredients is changing in response to 2000-2001 regulations restricting use of the organophosphorus insecticides chlorpyrifos and diazinon., Objectives: We aimed to determine the impact of U.S. Environmental Protection Agency regulations on pest infestation levels, pesticide use, and pesticides measured in indoor air samples., Methodology: 511 pregnant women from inner-city New York were enrolled between 2000 and 2006. Permethrin, a pyrethroid insecticide; piperonyl butoxide (PBO), a pyrethroid synergist; chlorpyrifos; and diazinon were measured in 48-hr prenatal personal air samples. Data on pest infestation and pesticide use were collected via questionnaire., Results: Eighty-eight percent of women reported using pesticides during pregnancy; 55% reported using higher-exposure pesticide applications (spray cans, pest bombs and/or professional pesticide applicators). Self-reported pest sightings and use of higher-exposure applications increased significantly after the regulations were implemented (p < 0.001). PBO, cis-, and trans-permethrin were detected in 75, 19, and 18% of personal air samples, respectively. Detection frequencies of PBO and cis- and trans-permethrin increased significantly over time (p < 0.05 controlling for potential confounders). Levels and/or detection frequencies of these compounds were significantly higher among mothers reporting use of high exposure pesticide applications (p < or = 0.05). Chlorpyrifos and diazinon levels decreased significantly over time (p < 0.001)., Conclusion: In this cohort, pest infestations, use of pesticides, and use of permethrin appear to increase after the residential restriction of organophosphorus insecticides. This is one of the first studies to document widespread residential exposure to PBO.

Objective: This study examined whether exposure to pesticides, including dichlorodiphenyltrichloroethane (DDT), was associated with longer time to pregnancy (TTP)., Methods: Pregnant women (N = 402) living in a migrant farmworker community were asked how many months they took to conceive. Women reported their and their partners' occupational and home pesticide exposure preceding conception. In a subset (N = 289), levels of DDT and dichlorodiphenyldichloroethylene (DDE), were measured in maternal serum., Results: No associations were seen with p, p'-DDT, o, p'-DDT, or p, p'-DDE. Maternal occupational pesticide exposure (fecundability odds ratios [fOR] = 0.8, 95% CI: 0.6 to 1.0), home pesticide use (fOR = 0.6, 95% CI: 0.4 to 0.9), and residence within 200 ft of an agricultural field (fOR = 0.7, 95% CI: 0.5 to 1.0) were associated with reduced fecundability (ie, longer TTP)., Conclusions: Longer TTP was seen among women, but not men, reporting exposure to agricultural and home pesticides.

Background: We studied the relationship between behaviors promoted through the US Environmental Protection Agency Worker Protection Standard (WPS) and other programs and agricultural pesticide exposures in 73 strawberry fieldworkers employed in Monterey County, California., Methods: Farmworkers' behaviors were assessed via self-report and organophosphorus (OP) pesticide exposure was measured using dimethyl alkylphosphate (DMAP) and malathion dicarboxylic acid (MDA) urinary metabolite levels., Results: Wearing WPS-recommended clothing, wearing clean work clothes, and the combination of handwashing with soap and wearing gloves were associated with decreases in DMAP and MDA metabolite levels. Despite these protective behaviors, however, participants had significantly higher levels of exposure as compared with a national reference sample., Conclusions: Interventions that facilitate compliance with these behaviors may be effective in decreasing fieldworkers' pesticide exposures. However, further efforts are needed to reduce the exposure disparities experienced by farmworkers and decrease the potential for "take home" exposures to farmworkers' families., (Published 2008 Wiley-Liss, Inc.)

Background: 3-Phenoxybenzoic acid (3PBA), a pyrethroid metabolite, was detected in 75% of urine samples analyzed for pesticides in the U.S. National Health and Nutrition Examination Survey (NHANES) 1999-2002. NHANES also includes 24-hr diet data and information on household pesticide use, activities, occupation, demographics, and other exposure factors., Objectives: The objective of our study was to explore the relative importance of diet versus nondiet predictors in explaining variability in urinary 3PBA. A secondary objective was to explore whether the NHANES data could be used to identify particular foods driving 3PBA levels., Methods: We divided subjects into child (6-10 years of age), teen (11-18 years), and adult (> or = 19 years) age groups and restricted our analyses to subjects in the morning sampling session who fasted for > or = 8 hr beforehand. Regression modeling consisted of several model-building steps and a final Tobit regression on the left-censored log 3PBA measurements. We also conducted bootstrap analyses to evaluate the stability of the regression parameters., Results: Reported household pesticide use was not significantly associated with urinary 3PBA in any age group. Diet was significant for all three groups, and certain foods appeared to contribute more than others. Among adults, tobacco use was positively associated with 3PBA (p = 0.0326), and positive associations were suggested with the number of cytochrome p450-inhibiting medications taken (p = 0.0652) and minutes spent gardening (p = 0.0613) in the past month., Conclusions: Although exploratory, our findings underline the importance of collecting accurate data on household pesticide use and dietary intake when evaluating pyrethroid exposure-biomarker relationships.

Testicular germ cell carcinoma (TGCC) is the most common malignancy among men ages 20 to 34 years. Although the pathogenesis of TGCC is poorly understood, suboptimal androgen levels or impaired androgen signaling may play a role. Some persistent organochlorine pesticides commonly found in human tissue possess antiandrogenic properties. We examined whether the risk of TGCC is associated with serum levels of 11 organochlorine pesticides, including p,p'-DDE, and whether the p,p'-DDE-TGCC association is modified by CAG or GGN repeat polymorphisms in the androgen receptor gene. We conducted a population-based case-control study among 18- to 44-year-old male residents of three Washington State counties. Cases (n = 246) were diagnosed during 1999 to 2003 with a first, primary TGCC. Controls (n = 630) were men of similar age with no history of TGCC from the same population identified through random-digit telephone dialing. Questionnaires elicited information on demographic, medical, and lifestyle factors. A blood specimen provided serum for gas chromatography-high-resolution mass spectrometry analysis of organochlorine pesticide residues and DNA for genotyping. We observed no clear patterns between TGCC risk and concentrations of any of the organochlorines measured, nor did we observe that the risk associated with p,p'-DDE was modified by androgen receptor CAG (<23 versus > or =23 repeats) or GGN (<17 versus > or =17 repeats) genotype. This study does not provide support for the hypothesis that adult exposure to organochlorine pesticides is associated with risk of TGCC. Due to uncertainty regarding how well organochlorine levels measured in adulthood reflect exposures during early life, further research is needed using exposure measurements collected in utero or during infancy.

Background: The widespread use of organophosphorus (OP) pesticides has led to frequent exposure in adults and children. Because such exposure may cause adverse health effects, particularly in children, the sources and patterns of exposure need to be studied further., Objectives: We assessed young urban/suburban children's longitudinal exposure to OP pesticides in the Children's Pesticide Exposure Study (CPES) conducted in the greater Seattle, Washington, area, and used a novel study design that allowed us to determine the contribution of dietary intake to the overall OP pesticide exposure., Methods: Twenty-three children 3-11 years of age who consumed only conventional diets were recruited for this 1-year study conducted in 2003-2004. Children switched to organic diets for 5 consecutive days in the summer and fall sampling seasons. We measured specific urinary metabolites for malathion, chlorpyrifos, and other OP pesticides in urine samples collected twice daily for a period of 7, 12, or 15 consecutive days during each of the four seasons., Results: By substituting organic fresh fruits and vegetables for corresponding conventional food items, the median urinary metabolite concentrations were reduced to nondetected or close to non-detected levels for malathion and chlorpyrifos at the end of the 5-day organic diet intervention period in both summer and fall seasons. We also observed a seasonal effect on the OP urinary metabolite concentrations, and this seasonality corresponds to the consumption of fresh produce throughout the year., Conclusions: The findings from this study demonstrate that dietary intake of OP pesticides represents the major source of exposure in young children.

Organochlorine pesticides are used in some countries for malaria control and organophosphate pesticides are widely used in agriculture and in homes. Previous literature documents children's exposure to these chemicals both in utero and during development. Animal studies suggest that many of these chemicals are neurodevelopmental toxicants even in moderate doses, but there are few studies in human beings. Associations of children's pesticide exposure with neurodevelopment from studies being conducted worldwide are summarized. In addition, we present the work of the CHAMACOS study, a longitudinal birth cohort study of Mexican-American children living in the Salinas Valley of California. In this study, we investigated the relationship of children's neurodevelopment with maternal dichlorodiphenyltrichloroethane and dichlorodiphenyldichloroethylene serum levels, as well as prenatal and child organophosphate urinary metabolite levels. We have examined the association with children's performance on the Brazelton Neonatal Assessment Scales and at 6, 12 and 24 months on the Bayley Scales of Infant Development (mental development and psychomotor development) and mothers report on the Child Behaviour Checklist. We observed a negative association of prenatal dichlorodiphenyltrichloroethane exposure and child mental development. We also observed adverse associations of prenatal but not postnatal organophosphate pesticide exposure with mental development and pervasive developmental disorder at 24 months.

Organophosphorus (OP) pesticides are used as insecticides in agriculture and pest control and are often called "junior strength" nerve agents because they share the same mechanism of toxicity. OP pesticides are metabolized to dialkylphosphates and other metabolites, which are excreted in urine. In case of a terrorism incident involving widely available OP pesticides, an occurrence that may be likely given their widespread availability, a rapid, accurate, and cost-effective method for detecting exposure is required. We have evaluated several analytical methods to determine the most reliable and cost-effective methods for incident response. Our comparisons have included different internal standards (isotopically labeled standards versus chemically similar surrogate standards), different isolation techniques (some of which are automatable), and different analysis platforms. We found that isotopically labeled standards were a necessity to provide accurate quantification; the chemically similar surrogate was not suitable as an internal standard. The most sensitive and precise method uses isotopically labeled standards with gas chromatography-tandem mass spectrometry analysis. However, the most cost-effective method employed isotopically labeled standards with gas chromatography-single quadrupole-mass spectrometry using a less expensive mass selective detector. Because this method is lower in cost, it may be a more viable option for equipping multiple laboratories with chemical-terrorism response capabilities.

In support of planning efforts for the National Children's Study, we conducted a study to test field methods for characterizing pesticide exposures to 20 farmworker children aged 5-27 months old living in the Salinas Valley of Monterey County, California. We tested methods for collecting house dust, indoor and outdoor air, dislodgeable residues from surfaces and toys, residues on clothing (sock and union suits), food, as well as spot and overnight diaper urine samples. We measured 29 common agricultural and home use pesticides in multiple exposure media samples. A subset of organophosphorus (OP), organochlorine (OC) and pyrethroid pesticides were measured in food. We also analyzed urine samples for OP pesticide metabolites. Finally, we administered four field-based exposure assessment instruments: a questionnaire; food diary; home inspection; and a self-administered child activity timeline. Pesticides were detected more frequently in house dust, surface wipes, and clothing than other media, with chlorpyrifos, diazinon, chlorthal-dimethyl, and cis- and trans-permethrin detected in 90% to 100% of samples. Levels of four of these five pesticides were positively correlated among the house dust, sock, and union suit samples (Spearman's rho=0.18-0.76). Pesticide loading on socks and union suits was higher for the group of 10 toddlers compared to the 10 younger crawling children. Several OP pesticides, as well as 4,4'-DDE, atrazine, and dieldrin were detected in the food samples. The child activity timeline, a novel, low-literacy instrument based on pictures, was successfully used by our participants. Future uses of these data include the development of pesticide exposure models and risk assessment.

Organochlorine (OC) pesticide use was restricted starting in the 1970s in developed countries and the 1980s and 1990s in developing countries. Current exposure to OC pesticides - dichlorodiphenyltrichloroethane (DDT), lindane (99% pure gamma-hexachlorocyclohexane (gamma-HCH)), hexachlorobenzene (HCB) - occurs on a limited basis. We measured para, para' (p,p')-DDE, p,p'-DDT, ortho, para' (o,p')-DDT, HCB, beta (beta)-HCH (the most persistent isomer of technical-grade HCH) and gamma-HCH in serum from 426 low-income pregnant Latina women living in an agricultural community in California. Detection frequencies were 94% to 100%. Median levels (ng/g lipid) of p,p'-DDE (1,052), p,p'-DDT (13), beta-HCH (37) and HCB (65) were significantly higher than United States population levels. Multivariate analyses of p,p'-DDE, p,p'-DDT, o,p'-DDT, beta-HCH and HCB indicate that time spent living outside the United States and birthplace in an area of Mexico with recent use of OC pesticides were significant predictors of exposure. Time spent living in the United States was associated with increased serum levels of p,p'-DDE and beta-HCH, but the increase for each year lived in the United States was lower than for each year lived outside the United States. There was no difference between the increase of HCB levels over time spent in or outside the United States, suggesting current and thus preventable exposure routes. However, we observed no associations between serum levels of any OC compound and current intake of saturated fat or agricultural take-home exposure risk factors. Lactation history and recent weight gain were negatively associated with serum levels of some, but not all OC compounds studied. Smoking history was borderline associated with elevated HCB levels. We observed no significant associations with body mass index. Although the weight of evidence from this study indicates that most exposure occurred before moving to the United States, the results for HCB indicate the possibility of ongoing exposure in this country.

Prenatal exposures to organophosphate pesticides and polychlorinated biphenyls have been associated with abnormal neonatal behavior and/or primitive reflexes. In 1998-2002, the Mount Sinai Children's Environmental Health Center (New York City) investigated the effects of indoor pesticide use and exposure to polychlorinated biphenyls on pregnancy outcome and child neurodevelopment in an inner-city multiethnic cohort. The Brazelton Neonatal Behavioral Assessment Scale was administered before hospital discharge (n = 311). Maternal urine samples were analyzed for six dialkylphosphate metabolites and malathion dicarboxylic acid. A random subset of maternal peripheral blood samples from the entire cohort (n = 194) was analyzed for polychlorinated biphenyls and 1,1'-dichloro-2,2'-bis(4-chlorophenyl)ethylene. Malathion dicarboxylic acid levels above the limit of detection were associated with a 2.24-fold increase in the number of abnormal reflexes (95% confidence interval: 1.55, 3.24). Likewise, higher levels of total diethylphosphates and total dialkylphosphates were associated with an increase in abnormal reflexes, as was total dimethylphosphates after paraoxonase expression was considered. No adverse associations were found with polychlorinated biphenyl or 1,1'-dichloro-2,2'-bis(4-chlorophenyl)ethylene levels and any behavior. The authors uncovered additional evidence that prenatal levels of organophosphate pesticide metabolites are associated with anomalies in primitive reflexes, which are a critical marker of neurologic integrity.

Background: Organophosphate (OP) pesticides are widely used in agriculture and homes. Animal studies suggest that even moderate doses are neurodevelopmental toxicants, but there are few studies in humans., Objectives: We investigated the relationship of prenatal and child OP urinary metabolite levels with children's neurodevelopment., Methods: Participating children were from a longitudinal birth cohort of primarily Latino farm-worker families in California. We measured six nonspecific dialkylphosphate (DAP) metabolites in maternal and child urine as well as metabolites specific to malathion (MDA) and chlorpyrifos (TCPy) in maternal urine. We examined their association with children's performance at 6 (n = 396), 12 (n = 395), and 24 (n = 372) months of age on the Bayley Scales of Infant Development [Mental Development (MDI) and Psychomotor Development (PDI) Indices] and mother's report on the Child Behavior Checklist (CBCL) (n = 356)., Results: Generally, pregnancy DAP levels were negatively associated with MDI, but child measures were positively associated. At 24 months of age, these associations reached statistical significance [per 10-fold increase in prenatal DAPs: beta = -3.5 points; 95% confidence interval (CI), -6.6 to -0.5; child DAPs: beta = 2.4 points; 95% CI, 0.5 to 4.2]. Neither prenatal nor child DAPs were associated with PDI or CBCL attention problems, but both prenatal and postnatal DAPs were associated with risk of pervasive developmental disorder [per 10-fold increase in prenatal DAPs: odds ratio (OR) = 2.3, p = 0.05; child DAPs OR = 1.7, p = 0.04]. MDA and TCPy were not associated with any outcome., Conclusions: We report adverse associations of prenatal DAPs with mental development and pervasive developmental problems at 24 months of age. Results should be interpreted with caution given the observed positive relationship with postnatal DAPs.

Evidence is inconsistent or poorly understood for links between polychlorinated biphenyls (PCBs), 1,1'-dichloro-2,2'-bis(4-chlorophenyl)ethylene (DDE), and organophosphate (OP) pesticides and adverse pregnancy outcomes, although they are known developmental toxicants. We measured biomarkers of maternal exposure to DDE, PCB, and OP metabolites in the third trimester of pregnancy among 404 mothers in a multiethnic cohort in New York City. We also determined maternal paraoxonase (PON1), butyrylcholinesterase (BuChe), and PON1Q192R gene variant. Higher multivariate-adjusted DDE levels (but not PCB) were associated with lower birth weight (-98 g/log10 DDE, p = 0.096) and head circumference (-0.54 cm/log10 DDE, p = 0.030). DDE and PCB levels were not related to birth length, Ponderal index, or gestational age. Birth length was shorter for mothers with PON192RR slow genotype compared with PON192QQ (p = 0.026), and head circumference was inversely associated with maternal PON1 activity (p = 0.004). With slow-activity PON1 or PON192, urinary diethylphosphates (SigmaDEPs) were associated with lower birth weight and dimethylphosphates (SigmaDMPs) with shorter birth length. No associations were found between birth outcomes and BuChe. In summary, we found suggestive relationships between prenatal environmental biomarkers and birth outcomes in this population. Maternal susceptibility factors including PON1 and maternal weight contributed to the observed effects.

Organophosphorus (OP) pesticides are among the most widely used pesticides in the United States. Human exposure to these pesticides may occur from their use on crops in agriculture and for pest control in residential settings. Most of the OP pesticides used in the United States are metabolized to up to three of six common urinary dialkyl phosphate metabolites. Quantification of these metabolites provides information on cumulative exposure to most OP pesticides. To accurately quantify OP pesticide metabolites in human urine, we developed a simple, highly sensitive, analytic method involving automated solid-phase extraction (SPE) of human urine, followed by post-extraction derivatization of the organophosphorus metabolites with 1-chloro-3-iodopropane, and analysis by isotope dilution gas-chromatography-tandem mass spectrometry. The styrene-divinyl benzene polymer-based SPE cartridges yielded good SPE recoveries of the metabolites because of their enhanced non-polar interactions. This method is less labor-intensive, more time-efficient, and reproducible than previously reported methods. Automation of the SPE allowed unattended extraction of urine samples, and hence, increased the sample throughput and reduced the inter- and intra-day variations. The method limits of detection were excellent for all analytes ranging from 50 pg/ml to 170 pg/ml. Relative standard deviations ranged from 2% to 12%.

Exposures were assessed for seven small-scale farmers using chlorpyrifos on corn and ten banana plantation employees applying diazinon, and for one child of each worker. Metabolites (TCPYand IMPY) were measured in urine before and after applications. TCPY concentrations peaked at 27 and 8.5 hours post-application for applicators and children, respectively (geometric means, 26 and 3.0 microg/L). Proximity to spraying and spray mixture preparation in homes were important exposure factors. IMPY concentrations differed substantially across workers at two plantations (geometric means, 1.3 and 168 mirog/L); however, their children had little or no diazinon exposure. These workers and children were also exposed to chlorpyrifos, most likely through contact with chlorpyrifos-impregnated bags used in banana production. Several recommendations are offered: (1) monitor children's activities during applications; (2) do not store or prepare pesticides in homes; (3) institute sound occupational hygiene practices at banana plantations; (4) dispose of plastic insecticide bags properly at the worksite.

We conducted a longitudinal study to assess the exposure of 23 elementary school-age children to pyrethroid pesticides, using urinary pyrethroid metabolites as exposure biomarkers. We substituted most of the children's conventional diets with organic food items for 5 consecutive days and collected two daily spot urine samples, first morning and before bedtime voids, throughout the 15-day study period. We analyzed urine samples for five common pyrethroid metabolites. We found an association between the parents' self-reported pyrethroid use in the residential environment and elevated pyrethroid metabolite levels found in their children's urine. Children were also exposed to pyrethroids through their conventional diets, although the magnitude was smaller than for the residential exposure. Children's ages appear to be significantly associated with pyrethroids exposure, which is likely attributed to the use of pyrethroids around the premises or in the facilities where older children engaged in the outdoor activities. We conclude that residential pesticide use represents the most important risk factor for children's exposure to pyrethroid insecticides. Because of the wide use of pyrethroids in the United States, the findings of this study are important for both children's pesticide exposure assessment and environmental public health.

Background: Organophosphorus (OP) pesticide urinary metabolite levels in a sample of farmworker children in North Carolina are documented and compared to national reference data. The relative importance of para-occupational, residential, and environment risk factors are delineated., Methods: Urine samples were collected from 60 farmworker children 1-6 years of age, and interviews were completed by their mothers. Urine samples were analyzed for the dialkylphosphate (DAP) metabolites of OP pesticides. Summed molar concentrations of the diethyl and dimethyl DAP metabolites provided summary measures., Results: The farmworker children had relatively high levels of OP pesticide urinary metabolites compared to national reference data; for example, participating children had higher geometric means for diethylphosphate (DEP), diethylthiophosphate (DETP), and the summed diethyl metabolites. However, analyses found no pattern of significant associations between predictors and metabolite levels., Conclusions: Future research requires greater precision in sampling and measurement to determine the risk factors for pesticide exposure among farmworker children.

The exposure of migrant and seasonal farmworkers and their families to agricultural and residential pesticides is a continuing public health concern. Pesticide exposure research has been spurred on by the development of sensitive and reliable laboratory techniques that allow the detection of minute amounts of pesticides or pesticide metabolites. The power of research on farmworker pesticide exposure has been limited because of variability in the collection of exposure data, the predictors of exposure considered, the laboratory procedures used in analyzing the exposure, and the measurement of exposure. The Farmworker Pesticide Exposure Comparable Data Conference assembled 25 scientists from diverse disciplinary and organizational backgrounds to develop methodologic consensus in four areas of farmworker pesticide exposure research: environmental exposure assessment, biomarkers, personal and occupational predictors of exposure, and health outcomes of exposure. In this introduction to this mini-monograph, first, we present the rationale for the conference and its organization. Second, we discuss some of the important challenges in conducting farmworker pesticide research, including the definition and size of the farmworker population, problems in communication and access, and the organization of agricultural work. Third, we summarize major findings from each of the conference's four foci-environmental exposure assessment, biomonitoring, predictors of exposure, and health outcomes of exposure-as well as important laboratory and statistical analysis issues that cross-cut the four foci.

Although biomonitoring has been used in many occupational and environmental health and exposure studies, we are only beginning to understand the complexities and uncertainties involved with the biomonitoring process--from study design, to sample collection, to chemical analysis--and with interpreting the resulting data. We present an overview of concepts that should be considered when using biomonitoring or biomonitoring data, assess the current status of biomonitoring, and detail potential advancements in the field that may improve our ability to both collect and interpret biomonitoring data. We discuss issues such as the appropriateness of biomonitoring for a given study, the sampling time frame, temporal variability in biological measurements to nonpersistent chemicals, and the complex issues surrounding data interpretation. In addition, we provide recommendations to improve the utility of biomonitoring in farmworker studies.

From 1940 through the 1970s, organochlorine compounds were widely used as insecticides in the United States. Thereafter, their use was severely restricted after recognition of their persistence in the environment, their toxicity in animals, and their potential for endocrine disruption. Although substantial evidence exists for the fetal toxicity of organochlorines in animals, information on human reproductive effects is conflicting. We investigated whether infants' length of gestation, birth weight, and crown-heel length were associated with maternal serum levels of 11 different organochlorine pesticides: p,p -dichlorodiphenyltrichloroethane (p,p -DDT), p,p -dichlorodiphenyldichloroethylene (p,p -DDE), o,p -dichlorodiphenyltrichloroethane (o,p -DDT), hexachlorobenzene (HCB), gamma-hexachlorocyclohexane (gamma-HCCH), gamma-hexachlorocyclohexane (gamma-HCCH), dieldrin, heptachlor epoxide, oxychlordane, trans-nonachlor, and mirex. Our subjects were a birth cohort of 385 low-income Latinas living in the Salinas Valley, an agricultural community in California. We observed no adverse associations between maternal serum organochlorine levels and birth weight or crown-heel length. We found decreased length of gestation with increasing levels of lipid-adjusted HCB (adjusted gamma = -0.47 weeks; p = 0.05). We did not find reductions in gestational duration associated with any of the other organochlorine pesticides. Our finding of decreased length of gestation related to HCB does not seem to have had clinical implications for this population, given its relatively low rate of preterm delivery (6.5%).

Objectives: To examine possible effects on blood pressure, neurological function, and neurobehavioral tests in school-aged children with and without prenatal pesticide exposure in an area where stunting is common., Methods: In a community of Northern Ecuador with intensive floriculture and a high female employment rate, we invited 79 children attending the 2 lowest grades of a public school for clinical examinations. In addition to a thorough physical examination, we administered simple reaction time, Santa Ana dexterity test, Stanford-Binet copying, and Wechsler Intelligence Scale for Children-Revised Digit Spans forward. Maternal interview included detailed assessment of occupational history to determine pesticide exposure during pregnancy. Recent and current pesticide exposure was assessed by erythrocyte acetylcholine esterase activity and urinary excretion of organophosphate metabolites., Results: All eligible children participated in the study, but 7 children were excluded from data analysis due to other disease or age >9 years. A total of 31 of the remaining 72 children were classified as stunted based on their height for age. Maternal occupational history revealed that 37 children had been exposed to pesticides during development. After confounder adjustment, prenatal pesticide exposure was associated with a higher systolic blood pressure than in the controls. On neurological examination, 14 exposed children and 9 controls showed > or =1 abnormalities. Of 5 neurobehavioral tests, the Stanford-Binet copying test showed a lower drawing score for copying designs in exposed children than in controls. Stunting was associated with a lower score on this test only, and both risk factors remained statistically significant in a multiple regression analysis with adjustment for demographic and social confounders. Increased excretion of dimethyl and diethyl metabolites of organophosphates was associated with increased reaction time and no other outcomes., Conclusion: Prenatal pesticide exposure may cause lasting neurotoxic damage and add to the adverse effects of malnutrition in developing countries. The effects differ from those due to acute pesticide exposure.

We used a novel study design to measure dietary organophosphorus pesticide exposure in a group of 23 elementary school-age children through urinary biomonitoring. We substituted most of children's conventional diets with organic food items for 5 consecutive days and collected two spot daily urine samples, first-morning and before-bedtime voids, throughout the 15-day study period. We found that the median urinary concentrations of the specific metabolites for malathion and chlorpyrifos decreased to the nondetect levels immediately after the introduction of organic diets and remained nondetectable until the conventional diets were reintroduced. The median concentrations for other organophosphorus pesticide metabolites were also lower in the organic diet consumption days; however, the detection of those metabolites was not frequent enough to show any statistical significance. In conclusion, we were able to demonstrate that an organic diet provides a dramatic and immediate protective effect against exposures to organophosphorus pesticides that are commonly used in agricultural production. We also concluded that these children were most likely exposed to these organophosphorus pesticides exclusively through their diet. To our knowledge, this is the first study to employ a longitudinal design with a dietary intervention to assess children's exposure to pesticides. It provides new and persuasive evidence of the effectiveness of this intervention.

Little information has been published about pesticide exposures experienced by pregnant women. We measured six dialkyl phosphate (DAP) urinary metabolites of organophosphate (OP) pesticides in 600 pregnant, low-income women living in the Salinas Valley, California, an agricultural area. A total of 28% were employed as farm fieldworkers during pregnancy, and 81% had at least one household member who worked in agriculture. Samples were collected twice during pregnancy (mean = 13 and 26 weeks' gestation, respectively) and just after delivery (mean = 9 days). As in other studies, dimethyldithiophosphate levels were higher than those of other urinary OP metabolites. Total DAP metabolite levels in samples collected after delivery were higher than in samples collected during pregnancy. Median metabolite levels at the first and second prenatal sampling points and at the postpartum collection were 102.8, 106.8, and 227.2 nmol/L, respectively. Both prenatal and postpartum metabolite levels were higher in these Salinas Valley women than in a sample of women of childbearing age in the general U.S. population (National Health and Nutrition Examination Survey), although the deviation from U.S. reference levels was most pronounced after delivery. Higher DAP metabolite levels in the immediate postpartum period may have implications for estimating dose during pregnancy and for exposure during lactation.

We report population-based concentrations (stratified by age, sex, and composite race/ethnicity variables) of selective metabolites of chlorpyrifos (3,5,6-trichloro-2-pyridinol; TCPY), chlorpyrifos methyl (TCPY), malathion (malathion dicarboxylic acid; MDA), diazinon (2-isopropyl-4-methyl-6-hydroxypyrimidine; IMPY), methyl parathion (para-nitrophenol; PNP), and parathion (PNP). We measured the concentrations of TCPY, MDA, IMPY, and PNP in 1997 urine samples from participants, aged 6-59 years, of the National Health and Nutrition Examination Survey, 1999-2000. We detected TCPY in more than 96% of the samples tested. Other organophosphorus pesticide metabolites were detected less frequently: MDA, 52%; IMPY, 29%; and PNP, 22%. The geometric means for TCPY were 1.77 microg/L and 1.58 microg/g creatinine. The 95th percentiles for TCPY were 9.9 microg/L and 8.42 microg/g creatinine. The 95th percentiles for MDA were 1.6 microg/L and 1.8 microg/g creatinine. The 95th percentiles for IMPY and PNP were 3.7 microg/L (3.4 microg/g creatinine) and 5.0 microg/L (4.2 microg/g creatinine), respectively. Multivariate analyses showed that children aged 6-11 years had significantly higher concentrations of TCPY than adults and adolescents. Similarly, adolescents had significantly higher TCPY concentrations than adults. Although the concentrations between sexes and among composite racial/ethnic groups varied, no significant differences were observed.

In the spring and summer of 2001, as part of a larger study investigating farm family pesticide exposure and home contamination in Iowa, urine and hand wipe samples were collected from 24 male farmers and 23 male nonfarmer controls. On two occasions approximately 1 month apart, one hand wipe sample and an evening and morning urine sample were collected from each participant. The samples were analyzed for the parent compound or metabolites of six commonly used agricultural pesticides: alachlor, atrazine, acetochlor, metolachlor, 2,4-dichlorophenoxyacetic acid (2,4-D) and chlorpyrifos. For atrazine, acetochlor, metolachlor and 2,4-D, farmers who reported applying the pesticide had significantly higher urinary metabolite levels than nonfarmers, farmers who did not apply the pesticide, and farmers who had the pesticide commercially applied (P-value <0.05). Generally, there were no differences in urinary pesticide metabolite levels between nonfarmers, farmers who did not apply the pesticide, and farmers who had the pesticide commercially applied. Among farmers who reported applying 2,4-D themselves, time since application, amount of pesticide applied, and the number of acres to which the pesticide was applied were marginally associated with 2,4-D urine levels. Among farmers who reported applying atrazine themselves, time since application and farm size were marginally associated with atrazine mercapturate urine levels. Farmers who reported using a closed cab to apply these pesticides had higher urinary pesticide metabolite levels, although the difference was not statistically significant. Farmers who reported using closed cabs tended to use more pesticides. The majority of the hand wipe samples were nondetectable. However, detection of atrazine in the hand wipes was significantly associated with urinary levels of atrazine above the median (P-value <0.01).

In this article we examine sampling strategies and analytical methods used in a series of recent studies of children's exposure to pesticides that may prove useful in the design and implementation of the National Children's Study. We focus primarily on the experiences of four of the National Institute of Environmental Health Sciences/U.S. Environmental Protection Agency/ Children's Centers and include University of Washington studies that predated these centers. These studies have measured maternal exposures, perinatal exposures, infant and toddler exposures, and exposure among young children through biologic monitoring, personal sampling, and environmental monitoring. Biologic monitoring appears to be the best available method for assessment of children's exposure to pesticides, with some limitations. It is likely that a combination of biomarkers, environmental measurements, and questionnaires will be needed after careful consideration of the specific hypotheses posed by investigators and the limitations of each exposure metric. The value of environmental measurements, such as surface and toy wipes and indoor air or house dust samples, deserves further investigation. Emphasis on personal rather than environmental sampling in conjunction with urine or blood sampling is likely to be most effective at classifying exposure. For infants and young children, ease of urine collection (possible for extended periods of time) may make these samples the best available approach to capturing exposure variability of nonpersistent pesticides; additional validation studies are needed. Saliva measurements of pesticides, if feasible, would overcome the limitations of urinary metabolite-based exposure analysis. Global positioning system technology appears promising in the delineation of children's time-location patterns.

The detrimental effects of organophosphate pesticide (OP) exposure on neurodevelopment have been shown in animals. The present study aimed to assess the relationship between in utero and early postnatal OP exposure and neonatal neurobehavior in humans, as measured by seven clusters (habituation, orientation, motor performance, range of state, regulation of state, autonomic stability, and reflex) on the Brazelton Neonatal Behavioral Assessment Scale (BNBAS). We assessed 381 infants < or = 2 months old and born to women participating in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a longitudinal, birth cohort study of low-income, Latina women living in the agricultural community of the Salinas Valley, California. Exposure to OP pesticides was determined by urinary levels of dialkylphosphate (DAP) metabolites, including dimethyl and diethylphosphate metabolites, measured twice during pregnancy (M = 14 and 26 weeks gestation) and once post-delivery (M = 7 days postpartum). The relationship between exposure and BNBAS performance was examined for the entire sample and stratified by the median age at assessment, 3 days. We observed a significant association between exposure and the reflex cluster for the entire sample and for infants >3 days old (n = 184). Among the >3 day old infants, increasing average prenatal urinary metabolite levels were associated with both an increase in number of abnormal reflexes (total DAP: adjusted beta = 0.53, 95% CI = 0.23, 0.82; dimethyls: adjusted beta = 0.41, 95% CI = 0.12, 0.69; diethyls: adjusted beta = 0.37, 95% CI = 0.09, 0.64), and the proportion of infants with more than three abnormal reflexes (total DAP: adjusted OR = 4.9, 95% CI = 1.5, 16.1; dimethyls: adjusted OR = 3.2, 95% CI = 1.1, 9.8; diethyls: adjusted OR = 3.4, 95% CI = 1.2, 9.9). No detrimental associations were found between postnatal urinary metabolite levels and any of the BNBAS clusters for infants < or = 3 or >3 days old at assessment. Whether neonatal reflex functioning is predictive of neuropsychological functioning as the child matures will continue to be evaluated in this birth cohort.

A total organophosphorus pesticide exposure study was conducted in Washington State in 1998 in a sample population of 13 children aged 2.5-5.5 years. The children were roughly split between rural and suburban populations and had been previously identified as having potentially elevated organophosphorus pesticide exposures. One component of the study was urine collection and analysis. Urine samples were collected from each subject up to four times in 24 h in two different seasons. Samples were collected at specific time points: before bed, first morning void, after lunch, and before dinner. Urine samples were analyzed initially for the six nonspecific dialkylphosphate (DAP) metabolites and subsequently for eight specific metabolites including malathion dicarboxylic acid (MDA), 3,5,6-trichloro-2-pyridinol (TCPy), and paranitrophenol (PNP). Relatively large percentages of the urine samples contained quantifiable amounts of two of the nonspecific DAP metabolites (DMTP-97%; DETP-67%), and three of the specific metabolites (MDA (71%), TCPy (79%), and PNP (96%)). A percent deviation analysis was employed to determine which of the spot sample time points was the best predictor of the estimated volume-weighted daily average. Of the four spot samples collected, first morning void samples were consistently found to be the best predictors of weighted-average daily metabolite concentration. This finding also held when the data were creatinine-adjusted. The results of this analysis suggest that if spot sampling is to be conducted as part of a biological monitoring study, first morning void samples should be preferentially collected.

The Third National Health and Nutrition Examination Survey (NHANES-III) of the Centers for Disease Control and Prevention (CDC) recorded data on the urinary concentrations of 12 chemicals (analytes), which were either pesticides or their metabolites, that represent exposure to certain pesticides, in urine samples collected from 1988 to 1994 from a cohort of 978 volunteer subjects, aged 20-59 years. We have used each subject's urinary creatinine concentration and their individual daily creatinine excretion rate (g/day) computed from their age, gender, height and weight, to estimate their daily excretion rate in microg analyte/kg/day. We discuss the mechanisms of excretion of the analytes and certain assumptions needed to compute the equivalent daily dietary intake (microg/kg/day) of the most likely parent pesticide compounds for each excreted analyte. We used literature data on the average amount of parent compound ingested per unit amount of the analyte excreted in the urine, and compared these estimated daily intakes to the US EPA's reference dose (RfD) values for each of those parent pesticides. A Johnson S(B) distribution (four-parameter lognormal) was fit to these data to estimate the national distribution of exclusive exposures to these 12 parent compounds. Only three such pesticides had a few predicted values above their RfD (lindane 1.6%; 2,4-dichlorophenol 1.3%; chlorpyrifos 0.02%). Given the possibility of a subject's dietary intake of a pesticide's metabolites incorporated into treated food, our results show that few, if any, individuals in the general US population aged 20-59 years and not employed in pesticide application were likely to have exceeded the USEPA RfD for these parent compounds during the years studied.

Prenatal pesticide exposures may adversely affect children's health. However, exposure and health research is hampered by the lack of reliable fetal exposure data. No studies have been published that report measurements of commonly used nonpersistent pesticides in human amniotic fluid, although recent studies of pesticides in urine from pregnant women and in meconium indicate that fetuses are exposed to these chemicals. Amniotic fluid collected during amniocentesis is the only medium available to characterize direct fetal exposures early in pregnancy (approximately 18 weeks of gestation). As a first step in validating this exposure biomarker, we collected 100 amniotic fluid samples slated for disposal and evaluated analytical methods to measure organophosphate and carbamate pesticides and metabolites, synthetic pyrethroid metabolites, herbicides, and chlorinated phenolic compounds. The following six phenols were detected (detection frequency): 1- and 2-naphthol (70%), 2,5-dichlorophenol (55%), carbofuranphenol (5%), ortho-phenylphenol (30%), and pentachlorophenol (15%), with geometric mean concentrations of 0.72, 0.39, 0.12, 0.13, and 0.23 microg/L, respectively, for positive values. The organophosphate metabolites diethylphosphate and dimethylphosphate were detected in two (10%) samples, and dimethylthiophosphate was detected in one (5%) sample, with geometric mean concentrations of 0.31, 0.32, and 0.43 microg/L, respectively, for positive values. These levels are low compared with levels reported in urine, blood, and meconium in other studies, but indicate direct exposures to the young fetus, possibly during critical periods of development. Results of this pilot study suggest that amniotic fluid offers a unique opportunity to investigate fetal exposures and health risks.