Assessing cumulative organophosphate pesticide exposure and risk among pregnant women living in an agricultural community

Approximately 225,000 kilograms of organophosphate (OP) pesticides are used annually in California's Salinas Valley, which is intensively farmed for vegetables and fruit. These activities have raised concerns about pesticide exposures to area residents. As part of a prospective cohort study, we collected three spot urine samples from 462 pregnant women and analyzed them for six dialkyl phosphate metabolites. Based on these urinary metabolite concentrations, we estimated OP pesticide doses with deterministic steady-state models using two methods: the first method assumed the pesticide metabolites were attributable entirely to a single diethyl or dimethyl OP pesticide; the second method adapted 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 quantify the likely 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 36.0% of study participants' exposures exceeded the U.S. EPA oral benchmark dose10 (BMD10) divided by a 100-fold uncertainty factor, depending on the assumption made about the parent compound. These BMD10 values were derived from studies of brain cholinesterase inhibition in rats. 14.7% of the participants' average cumulative OP pesticide dose estimates (Method 2) exceeded the BMD10 of the selected index chemical divided by a 100- fold uncertainty factor, regardless of index chemical chosen. An uncertainty analysis of the pesticide mixture parameter suggests that this point estimate could range from 1%-38%. Because our reference value (BMD10/100) may not account for the special sensitivity of the developing fetus, this research points to the need for modeling approaches to estimate fetal exposures and assess risk from prenatal OP pesticide exposure.