Marginal Role of Impaired Aldehyde Metabolism in m-Xylene Vapour-induced Biochemical Effects in the Rat

Rats were exposed to 300 ppm m-xylene vapour for 1 or 2 weeks, 6 h daily, 5 days a week. One group was simultaneously given disulfiram in the drinking water (53 mu mol kg(-1), daily). The disulfiram treatment inhibited propionaldehyde dehydrogenase; such inhibition did not occur when rn-methylbenzaldehyde (i.e., the aldehyde of m-xylene metabolism) was used as the substrate. Gastric gavage with higher drug doses (0.5 g kg(-1), administered one or three times) confirmed this finding. Intermittent inhalation exposure to rn-xylene for 2 weeks lowered the non-protein sulphhydryl group content in liver and increased the activities of microsomal NADPH-cytochrome c reductase, 7-ethoxycoumarin O-deethylase and UDP-glucuronosyltransferase in liver. Concomitantly, the oxidation of rn-xylene in vitro was also enhanced. Combined exposure to the solvent and the drug somewhat inhibited the increases in the hepatic drug metabolism and in the rate of microsomal xylene oxidation in vitro which m-xylene had induced, whereas the renal drug metabolism remained almost unaffected. Despite the changes in the monooxygenase, the solvent burden in the perirenal fat remained comparable. The significance of impaired aldehyde metabolism in m-xylene toxicity could not be confirmed in male Wistar rats at the above exposure levels.