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.
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. [(14)C(1)]-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 beta-saccharolactone to increase access of PFOA to the enzyme active site and to inhibit potential hydrolysis of PFOA-glucuronide by microsomal beta-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.
Kemper
Raymond A
RA
Discovery Toxicology Group, Haskell Laboratory for Health and Environmental Sciences, E. I. DuPont de Nemours & Company, Newark, Delaware 19714, USA. Raymond.a.kemper@usa.dupont.com
Nabb
Diane L
DL
D000818:Animals; D002210:Caprylates / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005466:Fluorocarbons / Q000378:metabolism*; D020719:Glucuronides / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007422:Intestines / Q000187:drug effects / Q000201:enzymology*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats
D002210:Caprylates; D004791:Enzyme Inhibitors; D005466:Fluorocarbons; D020719:Glucuronides; C023036:perfluorooctanoic acid; D014453:Glucuronosyltransferase