US EPA

32326 

Journal Article 

Abstract 

Methanol (MEOH) potentiation of carbon tetrachloride (CCl4) hepatotoxicity depends on MEOH concentration 

Simmons, JE; Allis, JW; McDonald, A; Svendsgaard, D; Robinson, BL; Seely, JC 

1991 

1 

Toxicologist
ISSN: 0731-9193 

11 

219 

Increased MEOH use as a transportation fuel would result in greater potential for inhalation exposure. We examined potentiation of CCl4 hepatotoxicity by exposure to inhaled MEOH as a function of MEOH concentration. Adult, male F-344 rats were exposed to 0, 1000, 2500, 5000 or 10,000 ppm MEOH by inhalation, 6 hr/day, for 1 or 3 days and gavaged 24 hr later with 0 or 0.075 ml CCl4/kg. Hepatotoxicity was assessed 24 hr later. Inhaled MEOH alone was not overtly hepatotoxic; exposure to CCl4 alone resulted in mild/minimal centrilobular degeneration and necrosis and a -2-3 fold increase in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) relative to control. 10,000 ppm MEOH strongly enhanced CCl4 hepatotoxicity (moderate/marked centrilobular degeneration/necrosis, -100-fold increase in AST and ALT relative to CCl4 alone). 5000 ppm MEOH was above, 2500 ppm MEOH was close to, and 1000 ppm MEOH was below the potentiation threshold concentration. The hepatic response to CCl4 was qualitatively similar after 1 and 3 days of MEOH exposure. In conclusion, acute exposure to inhaled MEOH resulted in a concentration-dependent increase in CCl4 hepatotoxicity. (This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.) 

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