METABOLISM IN RELATION TO MODE OF ACTION OF METHYLENEDIOXYPHENYL SYNERGISTS IN HOUSEFLIES

Each of the 10 C14-labeled methylenedioxyphenyl (MDP) compounds studied is metabolized in living houseflies (Musca domestica L.) by one or more of the following mechanisms: oxidative attack at the methylene carbon resulting in scission of the MDP moiety; oxidative attack at the aliphatic side chain; conjugation of aromatic acid metabolites, resulting from side chain oxidation, as β-D-glucosides or as derivatives of various amino acids. Side chain oxidation occurs at the alcohol group of piperonyl alcohol, the aldehyde group of piperonal. the acetal group of tropital. each of the three aliphatic ether groups of piperonyl butoxide, the unsaturated side chain of safrole or isosafrole. and the sulfinyl group of sulfoxide-A and sulfoxide-B. Evidence from in vivo and in vitro investigations is presented for the hypothesis that the synergistic activity of MDP compounds results from competitive inhibition of the microsomal mixed-function oxidases responsible for insecticide detoxification. © 1969, American Chemical Society. All rights reserved.