Abstract
The hepatotoxic properties of concurrent chronic oral ethanol ingestion and acute toluene inhalation were evaluated. Male rats were maintained on ethanol-containing or control liquid diets for 29 days. Animals of each group were subjected to five 20-min exposures to 10 000 ppm toluene with 30 min of room air inhalation between exposures on days 22, 24, 26, and 28 of liquid diet feeding. Some of the ethanol-fed animals were withdrawn from ethanol 14 h before exposure. Ethanol-withdrawn animals displayed an increased sensitivity to the narcotic action of toluene. Animals were sacrificed and assays performed on day 29. Stress markers (plasma corticosterone, free fatty acid, and glucose) were not affected by treatments. A modest elevation in plasma aspartate aminotransferase occurred in non-withdrawn animals receiving both ethanol and toluene. Ethanol-toluene exposure increased both relative liver weight and liver triglycerides. Toluene antagonized the hypertriglyceridemia associated with chronic ethanol ingestion. This study indicates that combined ethanol and toluene exposure has minor potential to induce acute liver injury, but results in altered deposition of hepatic triglycerides.
Similar content being viewed by others
References
Baraona E, Leo MA, Borowsky SA, Lieber CS (1977) Pathogenesis of alcohol-induced accumulation of protein in the liver. J Clin Invest 60: 546–554
Barman ML, Sigel NV, Beedle DB, Larson RK (1964) Acute and chronic effects of glue sniffing. California Medicine 100: 19–22
Brodie BB, Maickel RP (1963) Role of sympathetic nervous system in drug-induced fatty liver. Ann N Y Acad Sci 104: 1049–1058
Bruckner JV, Peterson RG (1981) Evaluation of toluene and acetone inhalant abuse. II. Model development and toxicology. Toxicol Appl Pharmacol 61: 302–312
Butler WM, Maling HM, Horning MG, Brodie BB (1961) The direct determination of liver triglycerides. J Lipid Res 2: 95–96
Duncombe WG (1964) The colorimetric micro-determination of non-esterified fatty acids in plasma. Clin Chim Acta 9: 122–125
Ellis FW (1966) Effects of ethanol on plasma corticosterone levels. J Pharmacol Exp Ther 153: 121–127
Elovaara E, Collan Y, Pfaffli P, Vainio H (1980) The combined toxicity of technical grade xylene and ethanol in the rat. Xenobiotica 10: 435–445
Fletcher MJ (1968) A colorimetric method for estimating serum triglycerides. Clin Chim Acta 22: 393–397
Freund G (1975) Induction of physical dependence on alcohol in rodents. In: Majchrowicz E (ed) Advances in experimental medicine and biology. Plenum Press, New York, Vol 56 pp 311–323
Guillemin R, Clayton GW, Lipscomb HS, Smith JD (1959) Fluorometric measurement of rat plasma and adrenal corticosterone concentration. J Lab Clin Med 53: 830–832
Hemmingson O, Barry DI (1979) Adaptive changes in cerebral blood flow and oxygen consumption during ethanol intoxication in the rat. Acta Physiol Scand 106: 249–255
Hudak A, Szeberenyi S, Molnar J, Cseh I, Suveges M, Folly G, Manyi S, Ungvary G (1978) Effect on the liver of chronic exposure to toluene and ethanol in the rat. Acta Physiol Acad Sci Hung 51: 128
IFCC (1978) Expert panel on enzymes of the International Federation of Clinical Chemistry: Part 3. Revised IFCC method for aspartate aminotransferase. Clin Chem 24: 720–721
Kadish AH, Little RL, Sternberg JC (1968) A new and rapid method for the determination of glucose by measurement of rate of oxygen consumption. Clin Chem 14: 116–131
Leal H, Mejia L, Gomez L, Slinas de Valle O (1978) Naturalistic study on the phenomenon of inhalant use in a group of children in Mexico City. In: Sharp CW, Carroll LT (ed) Voluntary inhalation of industrial solvents. National Institute on Drug Abuse. Rockville MD, pp 95–108
Lieber CS, DeCarli LM (1974) An experimental model of alcohol feeding and liver injury in the baboon. J Prim Med 3: 153–163
Lieber CS, DeCarli LM (1982) The feeding of alcohol in liquid diets: two decades of applications and 1982 update. Alc Clin Exp Res 6: 523–531
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275
Mezey E, Potter JJ, Sluser RJ, Abdi W (1977) Changes in hepatic collagen metabolism in rats produced by chronic ethanol feeding. Lab Invest 36: 206–214
O'Brian ET, Yeoman WB, Hobby JA (1971) Hepato-renal damage from toluene in a “glue sniffer”. Br Med J 2: 29–30
Perlman ES (1958) The effect of ethyl alcohol on the secretion from the adrenal medulla in man. Acta Physiol Scand 44: 241–244
Press E, Done AK (1967) Physiological effects and community control measures for intoxication from the intentional inhalation of organic solvents. Pediatrics 39: 451–461
Sato A, Nakajima T, Koyama Y (1980) Effects of chronic ethanol consumption on hepatic metabolism of aromatic and chlorinated hydrocarbons in rats. Br J Ind Med 37: 382–386
Smyth HF, Weil CS, West JS, Carpenter CP (1969) An exploration of joint toxic action: twenty-seven industrial chemicals intubated in rats in all possible pairs. Toxicol Appl Pharmacol 14: 340–347
Stumph MJ, Weir FW, Noall MW (1985) Comparison of blood and brain toluene concentrations and circulating triglyceride levels resulting from acute and repeated exposures in rats. Am Ind Hyg J 46: 244–250
Summer KH, Rozman K, Coulston F, Greim H (1979) Urinary excretion of mercapturic acids in chimpanzees and rats. Toxicol Appl Pharmacol 50: 207–212
Toftgard R, Nilsen OG, Gustafsson JA (1982) Dose dependant induction of rat liver microsomal cytochrome P-450 and microsomal enzymatic activities after inhalation of toluene and dichoromethane. Acta Pharmacol Toxicol 51: 108–114
Ungvary G, Tatrai E, Szeberenyi S, Rodics K, Lorincz M, Barcza M (1982) Effect of toluene exposure on the liver under different experimental conditions. Exp Mol Pathol 36: 347–360
van Doorn R, Bos RP, Brouns RME, Leijdekkers CM, Henderson PT (1980) Effect of toluene and xylene on live glutathione and their urinary excretion as mercapturic acids in the rat. Arch Toxicol 43: 293–304
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Howell, S.R., Christian, J.E. & Isom, G.E. The hepatotoxic potential of combined toluene-chronic ethanol exposure. Arch Toxicol 59, 45–50 (1986). https://doi.org/10.1007/BF00263957
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00263957