Biological fate of sulphur mustard, 1,1′-thiobis(2-chloroethane): identification of β-lyase metabolites and hydrolysis products in human urine

Abstract

1. Samples of urine from two human subjects accidentally exposed to sulphur mustard were analysed for metabolites derived from hydrolysis (thiodiglycol, thiodiglycol sulphoxide), conjugation with glutathione (1,1′-sulphonylbis[2-S-(N-acetylcysteinyl)ethane]) and from further metabolism of glutathione conjugates by the β-lyase pathway (1,1-sulphonylbis[2-(methylsulphinyl)ethane], 1-methylsulphinyl-2-[2-(methylthio)ethylsulphonyl]ethane).

2. Thiodiglycol sulphoxide was excreted in much higher concentrations than thiodiglycol, as was observed previously in rat exposed to sulphur mustard. However, the use of thiodiglycol sulphoxide as a biological marker for sulphur mustard poisoning is limited by its presence at low concentrations in normal human urine.

3. β-lyase metabolites were detected at concentrations comparable with those of thiodiglycol sulphoxide. No background levels of β-lyase metabolites have been detected in normal human urine, and they are proposed as unequivocal diagnostic and forensic indicators of sulphur mustard poisoning in man.