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 20micro 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) (microf 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.
Kurebayashi
Hideo
H
Division of Pharmacology, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo 158-8501, Japan. kurebaya@nihs.go.jp
Okudaira
Kazuho
K
Ohno
Yasuo
Y
D000818:Animals; D001559:Benzhydryl Compounds; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D015925:Cryopreservation; D020719:Glucuronides / Q000737:chemistry / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D008657:Metabolic Clearance Rate; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D020719:Glucuronides; D010636:Phenols; C512161:bisphenol A glucuronide; D000098826:Bisphenol A Compounds; C006780:bisphenol A