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

Abstract 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/10 6 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 K m (μM) of rats (3), monkeys (7), and humans (5). V max (nmol/10 6 cells/h) in hepatocytes followed the order of rats (55) > monkeys (22) > humans (11). The total CL H for the hepatic formation of BPAG plus BPAS (L/h/kg BW) estimated by well-stirred model with low f B 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.