Determinants of organophosphorus pesticide urinary metabolite levels in young children living in an agricultural community.

Organophosphorus (OP) pesticides are used in agriculture and several are registered for home use. As young children age they may experience different pesticide exposures due to varying diet, behavior, and other factors. We measured six OP dialkylphosphate (DAP) metabolites (three dimethyl alkylphosphates (DMAP) and three diethyl alkylphosphates (DEAP)) in urine samples collected from ~400 children living in an agricultural community when they were 6, 12, and 24 months old. We examined bivariate associations between DAP metabolite levels and determinants such as age, diet, season, and parent occupation. To evaluate independent impacts, we then used generalized linear mixed multivariable models including interaction terms with age. The final models indicated that DMAP metabolite levels increased with age. DMAP levels were also positively associated with daily servings of produce at 6- and 24-months. Among the 6-month olds, DMAP metabolite levels were higher when samples were collected during the summer/spring versus the winter/fall months. Among the 12-month olds, DMAP and DEAP metabolites were higher when children lived ≤ 60 meters from an agricultural field. Among the 24-month-olds, DEAP metabolite levels were higher during the summer/spring months. Our findings suggest that there are multiple determinants of OP pesticide exposures, notably dietary intake and temporal and spatial proximity to agricultural use. The impact of these determinants varied by age and class of DAP metabolite.

Pesticides in house dust from urban and farmworker households in California: an observational measurement study.

BACKGROUND: Studies report that residential use of pesticides in low-income homes is common because of poor housing conditions and pest infestations; however, exposure data on contemporary-use pesticides in low-income households is limited. We conducted a study in low-income homes from urban and agricultural communities to: characterize and compare house dust levels of agricultural and residential-use pesticides; evaluate the correlation of pesticide concentrations in samples collected several days apart; examine whether concentrations of pesticides phased-out for residential uses, but still used in agriculture (i.e., chlorpyrifos and diazinon) have declined in homes in the agricultural community; and estimate resident children's pesticide exposures via inadvertent dust ingestion. METHODS: In 2006, we collected up to two dust samples 5-8 days apart from each of 13 urban homes in Oakland, California and 15 farmworker homes in Salinas, California, an agricultural community (54 samples total). We measured 22 insecticides including organophosphates (chlorpyrifos, diazinon, diazinon-oxon, malathion, methidathion, methyl parathion, phorate, and tetrachlorvinphos) and pyrethroids (allethrin-two isomers, bifenthrin, cypermethrin-four isomers, deltamethrin, esfenvalerate, imiprothrin, permethrin-two isomers, prallethrin, and sumithrin), one phthalate herbicide (chlorthal-dimethyl), one dicarboximide fungicide (iprodione), and one pesticide synergist (piperonyl butoxide). RESULTS: More than half of the households reported applying pesticides indoors. Analytes frequently detected in both locations included chlorpyrifos, diazinon, permethrin, allethrin, cypermethrin, and piperonyl butoxide; no differences in concentrations or loadings were observed between locations for these analytes. Chlorthal-dimethyl was detected solely in farmworker homes, suggesting contamination due to regional agricultural use. Concentrations in samples collected 5-8 days apart in the same home were strongly correlated for the majority of the frequently detected analytes (Spearman ρ = 0.70-1.00, p < 0.01). Additionally, diazinon and chlorpyrifos concentrations in Salinas farmworker homes were 40-80% lower than concentrations reported in samples from Salinas farmworker homes studied between 2000-2002, suggesting a temporal reduction after their residential phase-out. Finally, estimated non-dietary pesticide intake for resident children did not exceed current U.S. Environmental Protection Agency's (U.S. EPA) recommended chronic reference doses (RfDs). CONCLUSION: Low-income children are potentially exposed to a mixture of pesticides as a result of poorer housing quality. Historical or current pesticide use indoors is likely to contribute to ongoing exposures. Agricultural pesticide use may also contribute to additional exposures to some pesticides in rural areas. Although children's non-dietary intake did not exceed U.S. EPA RfDs for select pesticides, this does not ensure that children are free of any health risks as RfDs have their own limitations, and the children may be exposed indoors via other pathways. The frequent pesticide use reported and high detection of several home-use pesticides in house dust suggests that families would benefit from integrated pest management strategies to control pests and minimize current and future exposures.

Concentrations and loadings of polybrominated diphenyl ethers in dust from low-income households in California.

California residents may experience the highest polybrominated diphenyl ether (PBDE) flame retardant exposures in the United States, the nation with the highest body burdens worldwide. It is hypothesized that Californians' high exposures are due to the state's strict furniture flammability standards. Ingestion of PBDE-contaminated dust, to which children may be particularly susceptible, is a dominant exposure pathway. Low-income populations may also face disparately high exposures due to the presence of older, deteriorated or poorly manufactured furniture treated with PBDEs. We collected up to two dust samples per home (54 samples total), several days apart, from low-income California households in the urban community of Oakland (n=13 homes) and the agricultural community of Salinas (n=15 homes). We measured BDE-47, BDE-99 and BDE-100, the major constituents of the penta-PBDE flame retardant formulation commonly used in furniture. All three PBDE congeners were detected in every sample with concentrations (loadings) ranging from 185 to 126,000ng/g (621-264,000ng/m(2)), 367-220,000ng/g (1550-457,000ng/m(2)), and 84-41,100ng/g (257-85,700ng/m(2)) for BDE-47, BDE-99 and BDE-100, respectively. Median concentrations (loadings) observed in Salinas homes for BDE-47, BDE-99 and BDE-100 were 3100ng/g (10,800ng/m(2)), 5480ng/g (19,500ng/m(2)), and 1060ng/g (3810ng/m(2)), respectively, and in Oakland homes 2780ng/g (10,700ng/m(2)), 4450ng/g (19,100ng/m(2)), and 1050ng/g (4000ng/m(2)), respectively. Maximum concentrations for BDE-47 and BDE-99 are the highest reported to date. Indoor concentrations and loadings did not significantly differ between communities; concentrations and loadings were strongly correlated between collections for all three congeners (Spearman rho=0.79-0.97, p<0.002). We estimated non-dietary ingestion of each congener for one child in each home (n=28 children) and found that estimated intake for BDE-47 and BDE-99 exceeded the U.S. Environmental Protection Agency's recommended chronic reference dose for three and five children, respectively. Children's estimated intake via dust ranged from 1.0 to 599ng/kg/day, 2.0-1065ng/kg/day and 0.5-196ng/kg/day for BDE-47, BDE-99 and BDE-100, respectively. In order to mitigate these exposures, future research must address the factors that contribute to PBDE exposures in low-income homes.

Comparison of current-use pesticide and other toxicant urinary metabolite levels among pregnant women in the CHAMACOS cohort and NHANES.

BACKGROUND: We measured 34 metabolites of current-use pesticides and other precursor compounds in urine samples collected twice during pregnancy from 538 women living in the Salinas Valley of California, a highly agricultural area (1999-2001). Precursors of these metabolites included fungicides, carbamate, organochlorine, organophosphorus (OP), and pyrethroid insecticides, and triazine and chloroacetanilide herbicides. We also measured ethylenethiourea, a metabolite of the ethylene-bisdithiocarbamate fungicides. Repeat measurements of the compounds presented here have not been reported in pregnant women previously. To understand the impact of the women's regional environment on these findings, we compared metabolite concentrations from the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) cohort with U.S. national reference data for 342 pregnant women sampled by the National Health and Nutrition Examination Survey (1999-2002). RESULTS: The eight metabolites detected in > 50% of samples [2,4-dichlorophenol (2,4-DCP); 2,5-dichlorophenol (2,5-DCP); 1- and 2-naphthol; ortho-phenylphenol (ORTH); para-nitrophenol (PNP); 2,4,6-trichlorophenol (2,4,6-TCP); and 3,4,6-trichloro-2-pyridinol (TCPy)] may be related to home or agricultural pesticide use in the Salinas Valley, household products, and other sources of chlorinated phenols. More than 78% of women in this study had detectable levels of at least one of the OP pesticide-specific metabolites that we measured, and > 30% had two or more. The 95th percentile values of six of the most commonly detected (> 50%) compounds were significantly higher among the CHAMACOS women after controlling for age, race, socioeconomic status, and smoking [(2,4-DCP; 2,5-DCP; ORTH; PNP; 2,4,6-TCP; and TCPy); quantile regression p < 0.05]. CONCLUSIONS: Findings suggest that the CHAMACOS cohort has an additional burden of precursor pesticide exposure compared with the national sample, possibly from living and/or working in an agricultural area.

Pesticides in dust from homes in an agricultural area.

We collected indoor dust samples from homes in the Salinas Valley of California. Of 22 pesticides measured in 504 samples, permethrins and the organophosphate chlorpyrifos were present in highest amounts. In multivariate Tobit regression models among samples from 197 separate residences, reported agricultural uses of chlorpyrifos, a herbicide (2,3,5,6-tetrachloroterephthalate (DCPA)), and a fungicide (iprodione) on agricultural fields were significantly (p < 0.01) associated, with 83%, 19%, and 49% increases, respectively, in dust concentrations for each kg applied per day, near participant homes, in the month or season prior to sample collection. However, agricultural use of diazinon, which was 2.2 times that of chlorpyrifos, and of permethrin were not significantly associated with dust levels. Other variables independently associated with dust levels included temperature and rainfall, farmworkers storing work shoes in the home, storing a diazinon product in the home, housing density, having a home less clean, and having an air conditioner. Permethrins, chlorpyrifos, DCPA, and iprodione have either a log octanol-water partition coefficient (K(ow)) greater than 4.0, a very low vapor pressure, or both. Health risk assessments for pesticides that have these properties may need to include evaluation of exposures to house dust.

Merging models and biomonitoring data to characterize sources and pathways of human exposure to organophosphorus pesticides in the Salinas Valley of California.

We characterize cumulative intakes of organophosphorus (OP) pesticides in an agricultural region of California by drawing on human biomonitoring data, California pesticide use reporting (PUR) data, and limited environmental samples together with outputs from the CalTOX multimedia, multipathway, source-to-dose model. The study population is the CHAMACOS cohort of almost 600 pregnant Latina women in the Salinas Valley region. We use model estimates of OP intake and urinary dialkylphosphate (DAP) metabolite excretion to develop premises about relative contributions from different exposure sources and pathways. We evaluate these premises by comparing the magnitude and variation of DAPs in the CHAMACOS cohort with those of the whole U.S. population using data from the National Health and Nutrition Examination Survey (NHANES). This comparison supports the premise that diet is the common and dominant exposure pathway in both populations. Biomarker comparisons and model results support the observation that, relative to NHANES, the CHAMACOS population has a statistically significant (p < 0.001) added intake of OP pesticides with low inter-individual variability. We attribute the magnitude and small variance of this intake to residential nondietary exposures from local agricultural OP uses. These results show that mass-balance models can estimate exposures for OP pesticides within the range measured by biological monitoring.

Organophosphate urinary metabolite levels during pregnancy and after delivery in women living in an agricultural community.

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.

Cumulative organophosphate pesticide exposure and risk assessment among pregnant women living in an agricultural community: a case study from the CHAMACOS cohort.

Approximately 230,000 kg of organophosphate (OP) pesticides are applied annually in California's Salinas Valley. These activities have raised concerns about exposures to area residents. We collected three spot urine samples from pregnant women (between 1999 and 2001) enrolled in CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas), a longitudinal birth cohort study, and analyzed them for six dialkyl phosphate metabolites. We used urine from 446 pregnant women to estimate OP pesticide doses with two deterministic steady-state modeling methods: method 1, which assumed the metabolites were attributable entirely to a single diethyl or dimethyl OP pesticide; and method 2, which adapted U.S. Environmental Protection Agency (U.S. EPA) draft guidelines for cumulative risk assessment to estimate dose from a mixture of OP pesticides that share a common mechanism of toxicity. We used pesticide use reporting data for the Salinas Valley to approximate the mixture to which the women were exposed. Based on average OP pesticide dose estimates that assumed exposure to a single OP pesticide (method 1), between 0% and 36.1% of study participants' doses failed to attain a margin of exposure (MOE) of 100 relative to the U.S. EPA oral benchmark dose(10) (BMD(10)), depending on the assumption made about the parent compound. These BMD(10) values are doses expected to produce a 10% reduction in brain cholinesterase activity compared with background response in rats. Given the participants' average cumulative OP pesticide dose estimates (method 2) and regardless of the index chemical selected, we found that 14.8% of the doses failed to attain an MOE of 100 relative to the BMD(10) of the selected index. An uncertainty analysis of the pesticide mixture parameter, which is extrapolated from pesticide application data for the study area and not directly quantified for each individual, suggests that this point estimate could range from 1 to 34%. In future analyses, we will use pesticide-specific urinary metabolites, when available, to evaluate cumulative OP pesticide exposures.

Childhood cancer and agricultural pesticide use: an ecologic study in California.

We analyzed population-based childhood cancer incidence rates throughout California in relation to agricultural pesticide use. During 1988-1994, a total of 7,143 cases of invasive cancer were diagnosed among children under 15 years of age in California. Building on the availability of high-quality population-based cancer incidence information from the California Cancer Registry, population data from the U.S. Census, and uniquely comprehensive agricultural pesticide use information from California's Department of Pesticide Regulation, we used a geographic information system to assign summary population, exposure, and outcome attributes at the block group level. We used Poisson regression to estimate rate ratios (RRs) by pesticide use density adjusted for race/ethnicity, age, and sex for all types of childhood cancer combined and separately for the leukemias and central nervous system cancers. We generally found no association between pesticide use density and childhood cancer incidence rates. The RR for all cancers was 0.95 [95% confidence interval (CI), 0.80-1.13] for block groups in the 90th percentile and above for use of pesticides classified as probable carcinogens, compared to the block groups with use of < 1 lb/mi(2). The RRs were similar for leukemia and central nervous system cancers. Childhood leukemia rates were significantly elevated (RR = 1.48; 95% CI, 1.03-2.13) in block groups with the highest use of propargite, although we saw no dose-response trend with increasing exposure categories. Results were unchanged by further adjustment for socioeconomic status and urbanization.