Rotenone is hydroxylated to give 8′-hydroxyrotenone, 6′,7′-dihydro-6′,7′-dihydroxyrotenone, and various rotenolones when incubated with the microsome mixed function oxidase system of mammalian liver, fish liver, and insect tissues. Microsomal enzymes from these sources are similar but not identical in respect to the CO-binding pigment (P-450) and to the sensitivity to various inhibitors. The soluble fraction of the liver homogenates enhances whereas the soluble fraction of cockroach fat body and mid-gut homogenates inhibits rotenone metabolism, the inhibition resulting from the presence in the soluble fraction of a protein with a molecular weight of 6,000 to 15,000. Components in insect homogenates also inhibit the metabolism of organophosphates by the rat liver microsome- NADPH system. The results of in vivo and in vitro studies on rotenone detoxification indicate that the effects of components in the soluble fraction possibly are related to the selective toxicity of rotenone to mammals, fish, and insects. © 1969, American Chemical Society. All rights reserved.
