Abstract 35: Within-person reproducibility of urinary bisphenol A and phthalate metabolites among women in the Nurses' Health Studies.

The purpose of our study was to examine the long-term within-person reproducibility of bisphenol A (BPA) and 8 phthalate metabolites. Associations of BPA and phthalates with health are increasingly being investigated in epidemiologic studies, although existing studies are largely cross-sectional. Most previous studies of within-person variability in urinary BPA and phthalate metabolite concentrations have focused on stability over 3 months or less. Long-term reproducibility data are needed to assess the potential usefulness of these biomarkers for predicting risk of disease onset in prospective studies. We measured BPA and 8 phthalate metabolites in spot urine samples donated 1 to 3 years apart by women in the Nurses' Health Study and Nurses' Health Study II (n=80 for analyses of BPA; n=40 for phthalate metabolites); 86% of samples were first-morning urines. Specific phthalate metabolites were mono-ethyl phthalate (MEP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), mono-benzyl phthalate (MBzP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydrohexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5carboxypentyl) phthalate (MECPP). To measure within-person reproducibility, we calculated Spearman rank correlation coefficients and intraclass correlations (ICCs) for creatinine-adjusted BPA and phthalate metabolite concentrations; ICCs were estimated using natural log-transformed values. Additional analyses were restricted to first-morning urine samples. Distributions (medians [5th to 95th percentiles]) of creatinine-adjusted analyte concentrations (ng/mg creatinine) were: 3 (1-6) for BPA, 141 (21-895) for MEP, 4 (1-12) for MiBP, 37 (10-177) for MnBP, 14 (4-97) for MBzP, 5 (2-26) for MEHP, 32 (9-163) for MEHHP, 26 (7-136) for MEOHP, and 43 (16-215) for MECPP. Over 1 to 3 years, within-person variability of BPA was high relative to total variability (ICC=0.14) and rankings of BPA levels between time-points were weakly correlated (Spearman correlation=0.19). All phthalate metabolites, except MEHP, demonstrated moderate within-person stability over time (Spearman correlation or ICC=0.39-0.55). Restricting analyses to first-morning urine samples did not alter results. Overall, we found that single measurements of BPA in spot urine samples were highly variable within women over 1 to 3 years. However, the majority of urinary phthalate metabolites appeared moderately reproducible within women over time. Our results suggest that investigation of associations between a single urinary BPA measurement and disease risk likely will be challenging in epidemiologic studies, while single measurements of urinary phthalate metabolites are reasonable measures of long-term exposure. Further, reproducibility data could be used to correct for within-person variability that results in the attenuation of estimates of relative risk. Citation Format: Mary Townsend, Adrian Franke, Xingnan Li, Frank Hu, A. Heather Eliassen. Within-person reproducibility of urinary bisphenol A and phthalate metabolites among women in the Nurses' Health Studies. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 35.