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Rosemary Castorina,¹ Asa Bradman,¹ Thomas E. McKone,^1,2 Dana B. Barr,³ Martha E. Harnly,⁴ and Brenda Eskenazi¹

¹Center for Children's Environmental Health Research, School of Public Health, University of California, and ²Lawrence Berkeley National Laboratory and University of California, Berkeley, California, USA; ³National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA; ⁴Environmental Health Investigations Branch, California Department of Health Services, Oakland, California, USA

Abstract
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 dose₁₀ (BMD₁₀) , depending on the assumption made about the parent compound. These BMD₁₀ 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 BMD₁₀ 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. Key words: cumulative dose, exposure, mixtures, organophosphate pesticides, pregnancy, prenatal, risk, urinary metabolites, women. Environ Health Perspect 111:1640-1648 (2003) . doi:10.1289/ehp.5887 available via http://dx.doi.org/ [Online 16 June 2003]