INCREASED ENDOBIOTIC FATTY-ACID METHYL-ESTERS FOLLOWING EXPOSURE TO METHANOL

Human exposure to methanol is likely to increase in the future due to its proposed use as an alternate automobile fuel. Since alcohols are k nown to esterify the fatty acids in the body and some of those esterif ied esters are toxic, we studied the formation of fatty acid esters of methanol in Long-Evans male rats given a single oral dose of 3.5 g/kg body weight of methanol in saline. Animals given an equal volume of s aline served as control. Three rats were euthanized at 1, 3, 6, 12, an d 24 hr following the treatment. Fatty acid methyl esters, extracted f rom whole blood, liver, pancreas, acid brown fat were separated by thi n-layer chromatography and quantitated by gas chromatography (GC). The ir identity was then confirmed by GC-mass spectrometry. Average levels as high as 596, 5293, 2239, 1106, 9665, 7728, 562, and 2792 mu g/g (w et weight basis) of 14:0, 16:0, 16:1, 18:0, 18:1, 18:2, 18:3, and 20:4 fatty acid methyl esters, respectively, were found in the pancreas of methanol-treated rats. The average concentration of total fatty acid methyl esters was computed to be 4513, 29594, 22871, 18956, 17014, and 9702 mu g/g in the pancreas compared to 1.9, 25.4, 36.8, 18.5, 18.9, and 14.2 mu g/g in the liver at 0, 1, 3, 6, 12, and 24 hr, respectivel y, following methanol exposure. On dry lipid weight basis, the levels were significantly higher again in pancreas followed by brown fat and liver. In whole blood, only low levels of 16:0, 18:0, and 20:4 fatty a cid methyl esters could be detected at all time points. The highest co ncentration of total fatty acid methyl esters in the pancreas, liver, and brown fat was detected at 1, 3, and 24 hr, respectively. Most of t he fatty acid methyl esters found in the liver and pancreas decreased after 6 hr of methanol exposure. The fatty acid methyl esters of highe r concentrations were 16:0 in the whole blood, 18:0, 18:1, 18:2, and 2 0:4 in liver, 18:1, and 18:2 in pancreas and 16:0, 18:1, and 18:2 in b rown fat. These fatty acid methyl esters were also detected in the tis sues of control rats indicating their endogenous formation. Significan t increase in methylation of the fatty acids during methanol exposure, as found in this study, may serve as a defense mechanism for preventi ng available methanol from oxidative metabolism to render toxicity. Ho wever, the biological significance of these fatty acid methyl esters i s yet to be understood. (C) 1995 Society of Toxicology