Exposure to disinfection by-products and hypospadias risk: An evaluation of exposure assessment techniques

Epidemiologic studies have illustrated an association between disinfection by-products (DBPs) and increased risks of birth defects. Many of these studies use community water system (CWS) monitoring data to estimate exposure. Use of such data requires linkage of residence location to a specific CWS and associated monitoring data during a given exposure period. This dissertation presents the validation of an approach to link study participants to exposure data in such epidemiologic studies, evaluates and compares five techniques that have been proposed for reducing exposure misclassification in epidemiologic studies of DBPs, and presents the results of two population-based case-control studies of a genitourinary tract birth defect and DBP exposure during a critical period of gestation.;We successfully geocoded 97.2% of study participant addresses and validated 81.4% addresses as being correctly linked to a CWS. We evaluated five metrics that have been proposed to decrease exposure misclassification and compared them to the commonly utilized method of linking quarterly sampling data collected at multiple sampling sites to meet regulatory requirements. While the approaches employed to account for spatial and temporal variability of DBPs within a distribution system produced results different from those yielded by using exposure window concentrations alone, they were not associated with a risk of hypospadias. The results of analyses that incorporated water use and behavior data were also different from those yielded by using exposure window concentrations alone, and were associated with an increasing risk of hypospadias as exposure to DBPs increased between gestational weeks six and sixteen of pregnancy.;We evaluated the risk of hypospadias associated with exposure to two groups of DBPs as well as individual species of DBPs during a specific period of gestation. We did not find any statistically significant ORs for the association between hypospadias and any species of DBP concentration alone. We found a suggestion of a weak association with bromochloroacetic acid and total trihalomethanes when personal water consumption was taken into account and a statistically significant association with TTHM when water-use behaviors (consumption, bathing and showering) were taken into account.