In Vitro Studies in Microsomes from Rat and Human Liver, Kidney, and Intestine Suggest That Perfluorooctanoic Acid Is Not a Substrate for Microsomal UDP-Glucuronosyltransferases

Abstract

Perfluorooctanoic acid (PFOA) is a fluorinated fatty acid analogue used as a surfactant in the manufacture of fluoropolymers. Previous studies have indicated that PFOA was metabolically inert in mammals, but recent metabolism studies with related fluorochemicals suggested that PFOA might form a glucuronide conjugate. [¹⁴C₁]-PFOA was incubated with male and female human and rat liver, kidney, and small intestine microsomes. Incubations were carried out in the presence of alamethicin and β-saccharolactone to increase access of PFOA to the enzyme active site and to inhibit potential hydrolysis of PFOA-glucuronide by microsomal β-glucuronidase, respectively. Although positive control experiments using p-nitrophenol demonstrated significant UDP-glucuronosyltransferase (UDPGT) activity in all of the tested microsomal preparations, no evidence for formation of a PFOA-glucuronide was obtained, either by high-sensitivity radiochromatography or by LC/MS. These data suggest that PFOA is not a substrate for human or rodent microsomal UDPGTs.