Biological Fate of Sulfur Mustard, 1,1′-Thiobis(2-chloroethane). Urinary Excretion Profiles of Hydrolysis Products and β-Lyase Metabolites of Sulfur Mustard after Cutaneous Application in Rats

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Abstract
The urinary excretion profiles of some metabolites of sulfur mustard were determined by gas chromatography/mass spectrometry after cutaneous application of sulfur mustard in rats. Excretion profiles of the individual metabolitee thiodiglycol and thiodiglycol sulfoxide, derived from the hydrolysis of sulfur mustard, were determined in different groups of three rats. Concentrations of thiodiglycol detected increased up to 10 fold after treatment of the urine with hydrochloric acid, presumably because of the excretion of acid-labile esters of thiodiglycol. Free thiodiglycol, free plus eeterified thiodigiycol, and thiodiglycol sulfoxlde excreted over 8 days accounted for <0.3%, 1–1.5%, and 3.4–4.3%, respectively, of the applied dose of sulfur mustard. In a further study, a modified analytical method was applied to determine these hydrolysis products and their acid-labile esters as the single analyte thiodiglycol, after treatment with acidic titanium trichloride. The excretion profile of the combined hydrolysis products was compared with the excretion profile of a different group of metabolitas of sulfur mustard derived from the glutathione/β-lyase pathway. These were also reduced to a common analyte, 1,1′-sulfonylbis-[2-(methylthio)ethane], after similar treatment with titanium trichloride. Urinary excretion of hydrolysis products determined in 4 rats over 8 days accounted for 3.7–13.6% of an applied cutaneous dose of sulfur mustard. Urinary excretion of β-lyase metabolites accounted for 2.5–5.3% of the applied dose in the same group of rats. The excretion of β-lyase products showed a much sharper decline than was observed for the hydrolysis products of sulfur mustard.

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