Potentiation of carbon tetrachloride hepatotoxicity by inhaled methanol: Time course of injury and recovery
- Environmental Protection Agency, Research Triangle Park, NC (United States); and others
Increases in the use of methanol (MeOH) as a transportation fuel would result in greater potential for inhalation exposure. Because oral exposure to MeOH potentiates the hepatotoxicity of carbon tetrachloride (CCl{sub 4}), we examined the ability of inhaled MeOH to potentiate CCl{sub 4} hepatotoxicity and the time course of injury and recovery. Adult male F-344 rats were exposed to 0 or to 10,000 ppm MeOH by inhalation for 6 h and gavaged with 0.075 ml CCl{sub 4}/kg 24 h later. Hepatotoxicity was assessed 0.5, 1.5, 2, 3, 7, 15, 30, and 61 d after CCl{sub 4} exposure. For CCl{sub 4} alone, hepatotoxicity was most severe at 0.5 and 1 d, when minimal centrilobular hepatocellular necrosis and predominately mild centriobular hepatocellular vacuolar degeneration occurred. By d 3, the livers from the CCl{sub 4} rats were histologically normal. For MeOH + CCl{sub 4}, peak severity of hepatic injury was at 1 and 1.5 d, when moderate centrilobular necrosis and moderate/marked centrilobular degeneration occurred. MeOH + CCl{sub 4} resulted in serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) that were increased, relative to CCl{sub 4} alone, 171- and 113-fold, respectively, on d 1, and 166- and 140-fold, respectively, on d 1.5. Significant serum elevations in MeOH + CCl{sub 4} rats, relative to CCl{sub 4} alone rats, were present until d 7 and d 15 for AST and ALT, respectively. By d3 and d7, degeneration and necrosis, respectively. 22 refs., 6 figs.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 387347
- Journal Information:
- Journal of Toxicology and Environmental Health, Journal Name: Journal of Toxicology and Environmental Health Journal Issue: 2 Vol. 46; ISSN 0098-4108; ISSN JTEHD6
- Country of Publication:
- United States
- Language:
- English
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