Urinary levels of bisphenol A, F and S and markers of oxidative stress among healthy adult men: Variability and association analysis

Background: Bisphenol F (BPF) and bisphenol S (BPS) are increasingly used as alternatives to endocrine disrupting chemical bisphenol A (BPA). Evidence from in vitro and animal studies demonstrates that BPA, BPF and BPS induce oxidative stress, a proposed mechanism that is relevant to various adverse health effects. Evaluation in humans is hampered by the potentially high within-subject variability of urinary measurements. Objective: To evaluate the variability and associations of levels of BPA, BPS, BPF and 3 oxidative stress markers [i.e., 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F-2 alpha (8-isoPGF(2 alpha)) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)] in urine collected on multiple occasions over 3 months. Method: A total of 529 spot urine samples, including 88 first morning voids (FMVs) and 24-h specimens, were gathered from 11 adult men on days 0, 1, 2, 3, 4, 30, 60 and 90 and analyzed for BPA, BPF, BPS, 8-OHdG, 8-isoPGF(2 alpha) and HNE-MA. Intraclass correlation coefficients (ICCs) were estimated to characterize the reproducibility of urinary bisphenols and oxidative stress markers, and linear mixed models were applied to assess the associations between markers of exposure and response. Results: BPA and BPF were detected in >= 85% of the spot samples, while BPS in 13% of the samples. High degrees of within-subject variability were found for BPA, BPF, 8-OHdG, 8-isoPGF(2 alpha) and HNE-MA in spot samples, FMVs and 24-h specimens (creatinine-corrected ICCs <= 0.37). The sensitivities were low-to-moderate (0.30-0.63) when using single spot samples or FMVs to predict high (> 27th, or 36th percentile) 3-month average urinary levels of BPA, BPF, 8-OHdG, 8-isoPGF(2 alpha) and HNE-MA. Collecting repeated specimens at different time points improved the accuracy of classification for markers of exposure and response. Elevated urinary BPA and BPF were associated with significantly higher levels of oxidative stress markers. Conclusions: Repeated urinary specimens are required to characterize bisphenol exposure levels and the oxidative stress status of individuals. Exposure to BPA and BPF may partly contribute to the elevated urinary levels of oxidative stress makers in adult men.