Methods for assessing risk from pesticide exposure in pregnant women living in an agricultural community using biomarkers and benchmark dose modeling

This dissertation presents methods to assess cumulative organophosphate (OP) pesticide exposure among pregnant women, and identifies research needed to fill data and methodological gaps. It begins with an overview of the challenges posed by using the results of benchmark dose modeling and biological monitoring data to assess the cumulative risk of toxicant exposure. Two case studies are presented that estimate pregnant women's cumulative OP pesticide dose equivalents based on urinary OP metabolite levels obtained from the Center for the Health Assessment of Women and Children of Salinas (CHAMACOS).;All women assessed had detectable levels of urinary OP metabolites at some point during pregnancy. In the first case study, the average cumulative dose equivalents for 66 of 445 (14.8%) women failed to attain the margin of exposure (MOE) of 100 or more relative to the index chemical's U.S. Environmental Protection Agency (U.S. EPA) oral benchmark dose. Because this case study was based on non-specific urinary dialkyl phosphate metabolite data, pesticide use reporting data for the Salinas Valley was used to quantify the likely mixture of OP pesticides to which the women were exposed. The second case study addresses this issue by basing cumulative OP pesticide dose equivalents on four chemical-specific urinary metabolites. This case study reports estimated cumulative dose equivalents of four OP pesticides based on samples collected from 430 pregnant women, all of which attained an MOE greater than 100. These exposures may be underestimated because methods do not currently exist to analyze the metabolites of several OP compounds heavily used in the Salinas Valley. To put these results in context, currently available risk assessment information for the 23 chemicals with U.S. EPA reference values based on benchmark dose modeling were analyzed to determine the potential risks from exposure at the established reference doses (RfDs) and reference concentrations (RfCs). Twenty-four percent of the reference values corresponded to estimated risk levels greater than 1 in 1,000, calling into question the assumption that noncancer RfD and RfC values represent "acceptable levels" of exposure.;These results suggest that a small portion of women participating in the CHAMACOS study may have cumulative OP pesticide exposures exceeding a health-protective reference value, and that current regulatory reference values may not be adequately protective of sensitive populations.