Reconstructing Organophosphorus Pesticide Doses Using the Reversed Dosimetry Approach in a Simple Physiologically-Based Pharmacokinetic Model

We illustrated the development of a simple pharmacokinetic (SPK) model aiming to estimate the absorbed chlorpyrifos doses using urinary biomarker data, 3,5,6-trichlorpyridinol as the model input. The effectiveness of the SPK model in the pesticide risk assessment was evaluated by comparing dose estimates using different urinary composite data. The dose estimates resulting from the first morning voids appeared to be lower than but not significantly different to those using before bedtime, lunch or dinner voids. We found similar trend for dose estimates using three different urinary composite data. However, the dose estimates using the SPK model for individual children were significantly higher than those from the conventional physiologically based pharmacokinetic (PBPK) modeling using aggregate environmental measurements of chlorpyrifos as the model inputs. The use of urinary data in the SPK model intuitively provided a plausible alternative to the conventional PBPK model in reconstructing the absorbed chlorpyrifos dose

Within- and Between-Child Variation in Repeated Urinary Pesticide Metabolite Measurements over a 1-Year Period

Background: Children are exposed to pesticides from many sources and routes, including dietary and incidental ingestion, dermal absorption, and inhalation. Linking health outcomes to these exposures using urinary metabolites requires understanding temporal variability within subjects to avoid exposure misclassification. Objectives: We characterized the within- and between-child variability of urinary organophosphorus and pyrethroid metabolites in 23 participants of the Children’s Pesticide Exposure Study–Washington over 1 year and examined the ability of one to four spot urine samples to categorize mean exposures. Methods: Each child provided urine samples twice daily over 7- to 16-day sessions in four seasons in 2003 and 2004. Samples were analyzed for five pyrethroid and five organophosphorus (OP) metabolites. After adjusting for specific gravity, we used a customized maximum likelihood estimation linear mixed-effects model that accounted for values below the limit of detection to calculate intraclass correlation coefficients (ICC) and conducted surrogate category analyses. Results: Within-child variability was 2–11 times greater than between-child variability. When restricted to samples collected during a single season, ICCs were higher in the fall, winter, and spring than in summer for OPs, and higher in summer and winter for pyrethroids, indicating an increase in between-person variability relative to within-person variability during these seasons. Surrogate category analyses demonstrated that a single spot urine sample did not categorize metabolite concentrations well, and that four or more samples would be needed to categorize children into quartiles consistently. Conclusions: Urinary biomarkers of these short half-life pesticides exhibited substantial within-person variability in children observed over four seasons. Researchers investigating pesticides and health outcomes in children may need repeated biomarker measurements to derive accurate estimates of exposure and relative risks. Citation: Attfield KR, Hughes MD, Spengler JD, Lu C. 2014. Within- and between-child variation in repeated urinary pesticide metabolite measurements over a 1-year period. Environ Health Perspect 122:201–206; http://dx.doi.org/10.1289/ehp.130673

Biologic Monitoring to Characterize Organophosphorus Pesticide Exposure among Children and Workers: An Analysis of Recent Studies in Washington State

We examined findings from five organophosphorus pesticide biomonitoring studies conducted in Washington State between 1994 and 1999. We compared urinary dimethylthiophosphate (DMTP) concentrations for all study groups and composite dimethyl alkylphosphate (DMAP) concentrations for selected groups. Children of pesticide applicators had substantially higher metabolite levels than did Seattle children and farmworker children (median DMTP, 25 μg/L; p < 0.0001). Metabolite levels of children living in agricultural communities were elevated during periods of crop spraying. Median DMTP concentrations for Seattle children and farmworker children did not differ significantly (6.1 and 5.8 μg/L DMTP, respectively; p = 0.73); however, the DMAP concentrations were higher for Seattle children than for farmworker children (117 and 87 nmol/L DMAP, respectively; p = 0.007). DMTP concentrations of U.S. children 6–11 years of age (1999–2000 National Health and Nutrition Examination Survey population) were higher than those of Seattle children and farmworker children at the 75th, 90th, and 95th percentiles. DMTP concentrations for workers actively engaged in apple thinning were 50 times higher than DMTP concentrations for farmworkers sampled outside of peak exposure periods. We conclude that workers who have direct contact with pesticides should continue to be the focus of public health interventions and that elevated child exposures in agricultural communities may occur during active crop-spraying periods and from living with a pesticide applicator. Timing of sample collection is critical for the proper interpretation of pesticide biomarkers excreted relatively soon after exposure. We surmise that differences in dietary exposure can explain the similar exposures observed among farmworker children, children living in the Seattle metropolitan area, and children sampled nationally

The Implications of Using a Physiologically Based Pharmacokinetic (PBPK) Model for Pesticide Risk Assessment

Background: A physiologically based pharmacokinetic (PBPK) model would make it possible to simulate the dynamics of chemical absorption, distribution, metabolism, and elimination (ADME) from different routes of exposures and, in theory, could be used to evaluate associations between exposures and biomarker measurements in blood or urine. Objective: We used a PBPK model to predict urinary excretion of 3,5,6-trichloro-2-pyridinol (TCPY), the specific metabolite of chlorpyrifos (CPF), in young children.Methods We developed a child-specific PBPK model for CPF using PBPK models previously developed for rats and adult humans. Data used in the model simulation were collected from 13 children 3–6 years of age who participated in a cross-sectional pesticide exposure assessment study with repeated environmental and biological sampling. Results: The model-predicted urinary TCPY excretion estimates were consistent with measured levels for 2 children with two 24-hr duplicate food samples that contained 350 and 12 ng/g of CPF, respectively. However, we found that the majority of model outputs underpredicted the measured urinary TCPY excretion. Conclusions: We concluded that the potential measurement errors associated with the aggregate exposure measurements will probably limit the applicability of PBPK model estimates for interpreting urinary TCPY excretion and absorbed CPF dose from multiple sources of exposure. However, recent changes in organophosphorus (OP) use have shifted exposures from multipathways to dietary ingestion only. Thus, we concluded that the PBPK model is still a valuable tool for converting dietary pesticide exposures to absorbed dose estimates when the model input data are accurate estimates of dietary pesticide exposures

Organic Diets Significantly Lower Children’s Dietary Exposure to Organophosphorus Pesticides

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

Quantitative Analysis of Neonicotinoid Insecticide Residues in Foods: Implication for Dietary Exposures

This study quantitatively measured neonicotinoids in various foods that are common to human consumption. All fruit and vegetable samples (except nectarine and tomato) and 90% of honey samples were detected positive for at least one neonicotinoid; 72% of fruits, 45% of vegetables, and 50% of honey samples contained at least two different neonicotinoids in one sample, with imidacloprid having the highest detection rate among all samples. All pollen samples from New Zealand contained multiple neonicotinoids, and five of seven pollens from Massachusetts detected positive for imidacloprid. These results show the prevalence of low-level neonicotinoid residues in fruits, vegetables, and honey that are readily available in the market for human consumption and in the environment where honeybees forage. In light of new reports of toxicological effects in mammals, the results strengthen the importance of assessing dietary neonicotinoid intakes and the potential human health effects