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POTENTIATION OF CARBON TETRACHLORIDE HEPATOTOXICITY BY INHALED METHANOL:TIME COURSE INJURY AND RECOVERY
Citation:
Simmons, J., A. McDonald, J. Seely, AND Y. Sey. POTENTIATION OF CARBON TETRACHLORIDE HEPATOTOXICITY BY INHALED METHANOL:TIME COURSE INJURY AND RECOVERY. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-95/542, 1995.
Description:
Increases in the use of methanol (MeOH) as a transportation fuel would result in greater potential for inhalation exposure. ecause oral exposure to MeOH potentates the hepatotoxicity of carbon tetrachloride (CCl4), we examined the ability of inhaled MeOH to potentiate CCl4 hepatotoxicity and the time-course of injury and recovery. dult male F-344 rats were exposed to 0 or to 10,000 ppm MeOH by inhalation for 6 hr and gavaged with 0.075 ml CCl4/kg 24 hr later. epatotoxicity was assessed 0.5, 1, 1.5, 2, 3, 7, 15, 30 and 61 days after CCl4 exposure. or CCl4 alone, hepatotoxicity was most severe at 0.5 and I days, when minimal hepatocellular necrosis and predominately mild hepatocellular vacuolar degeneration occurred. y day 3, the livers from the CCl4 rats were histologically normal. or MEOH+ CCl4, peak severity of hepatic injury was at 1 and 1.5 days, when moderate necrosis and moderate/marked degeneration occurred. EOH + CCl4 resulted in serum levels of AST and ALT that were increased, relative to CCl4 alone, 172 and 113 fold, respectively, on day 1 and 166 and 140 fold, respectively, on day 1.5. Significant serum elevations in MEOH + CCl4 rats, relative to CCl4 alone rats, were present until day 7 and day 15 for AST and ALT, respectively. y day 3 and day 7, degeneration and necrosis, respectively, due to MeOH + CCl4 were essentially resolved. n day 7, the MEOH + CCl4 hepatic injury consisted mainly of chronic inflammation and centrilobular fibrosis. By day 30, the livers of MEOH + CCl4 rats were histologically normal. hese data demonstrate that inhaled MeOH potentiates the hepatotoxicity of orally ingested CCl4, increasing the severity of CCl4 hepatotoxicity as well as the time required for recovery.