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A fatal case due to oral intake of 2-mercaptoethanol is reported (Eriksson et al., 1989). A 28-year-old single male was found dead in a research laboratory due to suicide. It was estimated that the victim had consumed about 100 mL of 2-mercapto­ethanol. An autopsy was performed within 2 h after the body was found. Very high concentrations of 2-mercaptoethanol (1000 mmol/mol creatinine) and 2-mercaptoacetate (4300 mmol/mol creatinine) were detected in urine. As the sum of the concentrations of these two compounds approximately equals that of total thiol compounds (5490 mmol/mol creatinine), no significant amounts of other thiol compounds were present in urine from the deceased. The gastric content of the victim contained very high concentrations of 2-mercaptoethanol and 2-mercaptoacetate (88.6 and 12.8 mmol/L respectively). These compounds were not detected in gastric content obtained at autopsy from 3 subjects who died from causes other than 2-mercaptoethanol poisoning. The high concentrations of 2- mercaptoacetate found in the gastric content indicate a secretion of this compound into the stomach because 2-mercaptoacetate is not an impurity in 2-mercaptoethanol and is unlikely to be formed by metabolic conversion of the latter in the strongly acidic content of the stomach. Increased amounts of inorganic sulfate were also found in the urine from the victim, although the increase was not so impressive as that of 2-mercaptoethanol and 2-mercaptoacetate. As the concentration of 2-mercaptoacetate in the urine from the victim was about 3000-fold higher than that normally found, the present investigation confirms the formation of 2-mercaptoacetate from 2-mercaptoethanol in the mammalian body.

The metabolism of 2-mercaptoethanol was examined as part of a study on the possible role of 2-mercaptoethanol as a precursor of other sulfur-containing compounds in the living animal (Federici et al., 1976). Male rats of the Wistar strain received a single dose of35S-Mercaptoethanol (0.4 mCi/mmol) by intraperitoneal injection. They were kept in metabolic cages on a conventional complete diet. Urine was collected daily, separated from feces. After two days 99% of injected radioactivity was recovered. Electrophoretic and chromatographic analysis, in various conditions, led to the identification of sulphate as a major component and small amount of isethionic acid. A number of other metabolites have also been detected but not identified. The results clearly indicate that 2-mercaptoethanol is largely metabolized by the living rat up to the conversion into sulfate.

Lambe and Williams (1965) investigated the reduction of NAD+ by a partly purified rat-liver preparation and by crystalline preparations of alcohol dehydrogenase from both yeast and horse liver in the presence of 2-mercaptoethanol. The test substance stimulated the reduction of NAD+ by the liver extract. Both yeast and horse-liver alcohol dehydrogenases were observed to reduce NAD+ in presence of 2-mercaptoethanol. The enzymic nature of the reaction is indicated by the fact that the activity can be destroyed by heating the rat-liver extract. 2-Mercaptoethanol appears to be specific for the reduction of NAD+, and has no effect on NADP+; in this respect the reaction resembles the NAD-linked alcohol dehydrogenase that is also present in the crude extract. Since the pH-activity curves for both systems over the pH range 6.0-9.0 are similar, it seems likely that 2-mercaptoethanol was being oxidized by the liver alcohol dehydrogenase.

The effects of 2-mercaptoethanol and 2-mercaptoacetate on the lipolytic activity of rat adipose tissue were investigated by Sabourault et al (1977). Because 2-mercaptoethanol can Iead in vitro to 2-mercaptoacetate through the combined effects of alcohol dehydrogenase and aldehyde dehydrogenase, the part played by these thiol-bearing compounds in the stimulation of free fatty acid mobilization and in the induction of fatty liver was also investigated. The study showed that the fatty liver induced by 2-mercaptoethanol or by 2-mercaptoacetate is accompanied by a large increase in the blood free fatty acids, an increase which seems related to a stimulatory action of these thiol-bearing compounds on the rate of free fatty acid mobilization from adipose tissue. Furthermore, this stimulatory effect appears to result from a decreased rate of free fatty acid reesterification in adipose tissue rather than from stimulated lipolysis, as shown by the fall in adipose tissue ATP level and the large increase in the free fatty acid output compared with the slight modification in the glycerol released. The data also indicate that pyrazole abolishes the ability of 2-mercaptoethanol, but not of 2-mercaptoacetate, to induce in vitro an increase in the rate of free fatty acid mobilization from adipose tissue and in vivo both a fatty liver and an increase in blood free fatty acids. Because pyrazole is a potent inhibitor of alcohol dehydrogenase and because this compound in the dosage used presently does not interfere with lipolysis both in vitro and in vivo, the following conclusions were made: The increase in free fatty acid mobilization from adipose tissue and the fatty liver induced by 2-mercaptoethanol are due to 2-mercaptoacetate or to one of its metabolites rather than to 2-mercaptoethanol per se. 2-Mercaptoethanol, which has been previously described as a substrate for rat liver alcohol dehydrogenase in vitro (Lambe and Williams, 1965), appears to be also oxidized in vivo by this enzyme. Although alcohol dehydrogenase activity in adipose tissue is low in comparison with liver (Raskin and Sokoloff, 1972), the oxidation of 2-mercaptoethanol in adipose tissue in vitro seems also to involve this enzyme, as suggested by the inhibitory action of pyrazole. Previous results concerning the relative lipolytic activity of ethanol (Bizzi and Carlson, 1965) and acetaldehyde (Giudicelli et al. 1972) in rat adipose tissue in vitro favor also the existence of a functional alcohol dehydrogenase in this tissue. Increased free fatty acid mobilization appears to be one, if not the major, mechanism involved in the pathogenesis of the 2-mercaptoethanol- and of the 2-mercaptoacetate-induced fatty liver.

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The chemical structure and the observed systemic effects after exposure via different application routes clearly indicate absorption and distribution after oral and dermal administration of 2 -mercaptoethanol. In mammals, 2 -mercaptoethanol is rapidly excreted via urine. 2 -Mercaptoacetate was detected as the main metabolite in the urine of a person who died from ingesting 2-mercaptoethanol. The available in vitro and in vivo data suggest metabolism of 2 -mercaptoethanol via formation of 2-mercaptoacetate through the combined effects of alcohol dehydrogenase and aldehyde dehydrogenase. The effects after repeated oral administration of 2 -mercaptoethanol and sodium 2 -mercaptoacetate are similar at comparable doses (cf. chapter repeated dose and reproductive toxicity), thus giving additional evidence of 2 -mercaptoacetate formation as the main metabolic pathway of 2 -mercaptoethanol.