Effects of Sub Chronic Dermal Exposure of Gasoline Blended with Varying Concentration of Benzene on Hepatic Mixed Function Oxidases in Rats

Abstract

Interaction of chemicals in a mixture, their biotransformation and adverse impact, if any, on environment and workroom atmosphere needs to be evaluated to identify the nature of potential toxic effects elicited by constituent chemical(s) in a mixture.  The nature of chemical interaction(s) through which an individual chemical in a mixture undergoes metabolism and/or biotransformation in the target tissue could be helpful in evaluation of its toxic potential. Gasoline is a unique example of such chemical mixture where interaction of aromatics viz., benzene, toluene, ethyl benzene and xylene (BTEX) traverses through a common metabolic pathway involving cytochrome P-450 dependent mixed function oxidases.  Travis et al. [1] has quantitatively evaluated that gasoline vapor has an antagonistic effect on benzene metabolism and its biotransformation products.  It was reported that 1000 ppm gasoline vapor had the same inhibitory effect as 500 ppm toluene on the metabolism of 290 ppm benzene, indicating that there may be many confounding factors in gasoline which might affect the metabolism of benzene in turn affecting its toxicity at the molecular level. It has been reported that benzene causes myelotoxicity through its bioactive metabolites.  Such biotransformation mechanisms involve cytochrome P-450 dependent Phase-I enzymes and the products are further detoxified through Phase-II enzymes.  It was therefore considered pertinent to study the impact of gasoline blended with 1, 3 and 5% benzene concentrations.  Female albino rats weighing 200–250 gm were exposed by dermal route to gasoline blended with varying benzene concentrations, @ 2 g/kg body wt., six days a week over a period of 90 days.  The activities of hepatic mixed function oxidases, viz., aniline hydroxylase and aminopyrene demethylase as a monitor of Phase-I enzymes and Glutathione-S-Transferase for Phase-II enzyme was estimated along with free glutathione levels.  Serum creatine kinase was also estimated to assess the extent of muscular dystrophy.  The results of this sub chronic study will be discussed in the context of interaction of gasoline with varying concentration of benzene in experimental animals.

Keywords: mixed function oxidases, benzene, toxicology, gasoline