Effect of Simultaneous Exposure to Benzene and Ethanol on Urinary Phenol Excretion in Mice

Abstract

Benzene has been widely used as a solvent, but its use is declining in most developed countries because it is a well established human carcinogen. An association between occupational exposure to benzene and health effects such as aplastic anaemia and leukaemia has been reported in studies of workers in various industries. For many solvent uses benzene has been replaced by other less toxic organic solvents and is considered a toxic impurity in other industrial solvents, but it is still used as a starting material in numerous chemical syntheses. In addition to industrial sources, benzene is present in the environment as a component of cigarette smoke and automobile emissions. Benzene induces hematotoxicity as a result of chronic exposure. Acute exposure to benzene causes neurotoxic and hepatotoxic effects. Toxic effects of benzene, chronic as well as acute, are the consequence of the unknown reactive metabolite produced by cytochrome P-450. Benzene is metabolized mainly by ethanol inducible cytochrome P-4502E1 (CYP2E1) in animal and human liver microsomes. Ethanol is consumed worldwide in tremendous amounts and is an effective inducer of hepatic xenobiotic metabolism, especially involving pathways accomplished by the isoform CYP2E1 of cytochrome P-450. Therefore, whenever xenobiotics that are substrates of CYP2E1, such as many organic solvents, are taken in by an individual who is also chronically consuming ethanol, the accelerated metabolism of these agents has to be considered. In contrast to the long-term consumption of ethanol, which induces the hepatic metabolism of xenobiotics, short-term consumption inhibits their metabolism because of direct competition for CYP2E1. Ethanol, when given to a living body, exerts dual effects on the xenobiotic metabolizing enzymes, i.e., inhibition and stimulation. Which one is more predominant over the other depends on the time that has elapsed after ethanol ingestion. In an early period when ethanol exists in the body in high concentrations, it may preferentially act as an inhibitor . In this study, effect of simultaneous exposure to benzene and ethanol on benzene metabolism in mice were investigated by measuring the concentration of phenol, the main metabolite of benzene.