Oxidative Metabolism of C14-Labeled Baygon by Living House Flies and by House Fly Enzyme Preparations12

Abstract

Oxidative processes are primarily responsible for metabolism of Baygon® ( o -isopropoxyphenyl methylcarbamate) in 2 resistant and 2-4 susceptible strains of living Musca domeslica L. and in the abdomen microsome-reduced nicotinamide-adenine dinucleotide phosphate (NADPH2.) enzyme system prepared from these strains. Hydrolysis of the carbamate ester group is not an important metabolic reaction either in vivo or in vitro and, in each case, the major metabolites, which are primary hydroxylation products or result from degradation of these products, are the following (in the order of their decreasing amounts): 2-isopropoxy-5-hydroxyphenyl methyl-carbamate (5-hydroxy Baygon), 2-hydroxyphenyl methyl-carbamate and acetone, 2-isopropoxyphenyl N -hydroxy-methylcarbamate, and 2-isopropoxyphenyl carbamate. In addition, 6 or more unidentified, organosoluble ester metabolites are formed in living flies. Acetone, formed in the presence of the microsome-NADPH2. enzyme system, volatilizes directly from the flies, and the carbamate metabolites having aliphatic and aromatic hydroxyl groups are conjugated and excreted. On incubation of the fly- or feces extracts with β -glucosidase, β -glucuronidase, aryl sulfatase, and acid phosphatase, the conjugates are hydrolyzed, liberating each of the hydroxylated carbamates with 5-hydroxy Baygon predominating. Each of the initially formed metabolites is of lower toxicity than Baygon to flies, so the metabolic reactions are detoxification mechanisms. The penetration rate of Baygon does not play a major limiting role in synergism or resistance mechanisms in house flies. Resistant house fly strains metabolize Baygon at higher rates than susceptible strains, and a higher proportion of metabolites is excreted as conjugates by the resistant strains. However, acetone, I of the metabolites, volatilizes at a similar rate from resistant and susceptible flies. There is a remarkable effect of strain on activity of the microsome-NADPH2. enzyme system, the activity increasing as the resistance increases. Baygon metabolism is inhibited by pretreatment of the flies with synergist and, based on studies involving different doses of various synergists, the reduction in metabolism rate is related to the !n. crease in Baygon toxicity in the presence of a synergist. However, at the dosage used the synergist does not entirely overcome the more rapid Baygon metabolism and the ability of resistant flies to survive large Baygon doses. These results, along with those found by other workers, suggest that detoxification by hydroxylation mechanisms is one of the major limiting factors involved in the susceptibility of house flies to substituted-aryl methy1carbamate toxicants, in the toxicity-enhancing effect of synergists on such toxicants, and in the development of resistance to them.