BIOLOGICAL FATE OF SULFUR MUSTARD, 1,1'-THIOBIS(2-CHLOROETHANE) - URINARY-EXCRETION PROFILES OF HYDROLYSIS PRODUCTS AND BETA-LYASE METABOLITES OF SULFUR MUSTARD AFTER CUTANEOUS APPLICATION IN RATS

The urinary excretion profiles of some metabolltes of sulfur mustard were determined by gas chromatography/mass spectrometry after cutaneous application of sulfur mustard in rats. Excretion profiles of the individual metabolitee thlodiglycol and thlodlglycol sulfoxide, derived from the hydrolysis of sulfur mustard, were determined in different groups of three rats. Concentrations of thlodiglycol detected increased up to 10 fold after treatment of the urine with hydrochloric acid, presumably because of the excretion of acid-labile esters of thlodlglycol. Free thlodlglycol, free plus eeterlfled thlodlglycol, and thiodiglycol aulfoxlde 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 thiodlglycol, after treatment with acidic titanium trlchlorlde. The excretion profile of the combined hydrolysis products was compared with the excretion profile of s different group of metabolitae of sulfur mustard derived from the glutathlone/β-Iysee pathway. These were also reduced to a common analyte, 1, l’-sulfonylbla-[2-(methylthio)ethane], after similar treatment with titanium trlchlorlde. 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 13-1yaae metabolltes accounted for 2.5-5.3% of the applied dose in the same group of rats. The excretion of β-Iysse products showed a much sharper decline than was observed for the hydrolysis products of sulfur mustard. © 1992, Oxford University Press. All rights reserved.