Species difference of metabolic clearance of bisphenol A using cryopreserved hepatocytes from rats, monkeys and humans

In vitro metabolism of bisphenol A (BPA), an weak estrogen, was studied with cryopreserved hepatocytes from rat, monkey and human, and was compared with in vivo metabolism reported. The metabolites identified include a major metabolite, BPA glucuronide (BPAG) and BPA sulfate (BPAS). The metabolic rates of bisphenol A at 20 μM by the hepatocytes (BPAG plus BPAS, nmol/106 cells/h) followed the order of rats (48 + 12) > monkeys (18 + 4) > humans (8.6 + 0.8), respectively. The rate of BPAG formation was much higher than that of BPAS formation in all these species. For the BPAG formation, we have determined the apparent Km (μM) of rats (3), monkeys (7), and humans (5). Vmax (nmol/106 cells/h) in hepatocytes followed the order of rats (55) > monkeys (22) > humans (11). The total CLH for the hepatic formation of BPAG plus BPAS (L/h/kg BW) estimated by well-stirred model with low fB value followed the order of rats (3.0) > monkeys (0.68) > humans (0.27), correlating well with in vivo studies of BPA subcutaneously injected rats and monkeys. This study showed that the cryopreserved hepatocytes could be a useful tool for assessing BPA metabolism and predicting systemic exposure of BPA.