The metabolism of 2-fluoroethanol

Abstract

1. Methods of preparation of three distinct fractions of histones have been described and applied to the thymus, spleen and liver of calves and to the liver and spleen of normal and leukaemic rats. 2. No differences in amino acid composition or in N-terminal groups of the same fractions from the different sources were found, outside the probable experimental errors. On the other hand the characteristic analytical differences between the fractions were apparent in all the preparations. 3. The purity of the fractions was examined by starch-gel electrophoresis. Apart from minor bands observed in some cases and probably due to unremoved impurities, no differences of the patterns or of the mobilities were observed which could be ascribed to tissue or species specificity. 4. Some qualification of the above statements are necessary for fractions derived from the Ehrlich ascites tumour. A complete resolution into the fractions was not achieved in this case. We are indebted to the World Health Organization for the award of a Research Fellowship to one of us (L. H.) and to Dr V. Holoubek who made available the histones from leukaemic rat spleen and liver which he had prepared. We also wish to thank Dr D. M. P. Phillips for useful discussions. This investigation has been supported by grants to the

Toxicity of Methyl- and Halogen-Substituted Alcohols in Tissue Culture Relative to Structure–Activity Models and Acute Toxicity in Mice

“…indicating again the significance of T, and P in the rationalization of in uiuo response, The significantly higher ratio for 2-fluoroethanol is consistent with its known conversion to an intrinsically more toxic intermediate (26). The ratio for 1 ,l,l-trifluoro-2-propanol was only slightly higher than for the aliphatic series.…”

“…3) generally followed the shift in magnitude of the T,/P to L D~o ratio, which was consistent with the conclusion that the variation in the ratio reflects a variation in the toxicant-receptor interaction rather than secondary time dependencies. The variation in ratios of T, to LDso for the halogenated set was of the same order of magnitude as for the aliphatic set and, excluding the fluorinesubstituted compounds, the sixfold variation of the TJP to LD50 ratios was of the same order of magnitude as for the aliphatic set, indicating again the significance of T, and P in the rationalization of in uiuo response, The significantly higher ratio for 2-fluoroethanol is consistent with its known conversion to an intrinsically more toxic intermediate (26). The ratio for 1 ,l,l-trifluoro-2-propanol was only slightly higher than for the aliphatic series.…”

Metabolic Fate

“…The assumption that 2-fluoroethanol is toxic by virtue of its biotrans- formation to fiuorocitrate has proven accurate, but the assumption that ADH mediates the initial step in this conversion has been shown to be incorrect (178). In fact, 2-fiuoroethanol competitively inhibits the oxidation of ethanol by purified horse liver ADH.…”