Abstract: | Following ip administration of 14C-diphenyl ether (5 mg/kg) to rats, a significant amount of radioactivity was found to bind irreversibly with tissue proteins of liver, lung and kidney, indicating the in vivo formation of reactive diphenyl ether metabolite(s). Irreversibly bound 14C-diphenyl ether-derived radioactivity to these organs peaked 2-4 h after the chemical was administered. Incubation of 14C-diphenyl ether in rat liver microsomes demonstrated that the hepatic mixed-function oxidase system mediated the formation of the chemically reactive metabolite(s) of 14C-diphenyl ether. The apparent Vmax and Km were, respectively, 23.3 pmol/mg microsomal protein/min and 1.33 x 10(-4)M. |