Metabolism of thiodiglycol (2,2′-thiobis-ethanol): isolation and identification of urinary metabolites following intraperitoneal administration to rat

Abstract

1. The metabolism of thiodiglycol, 2,2'-thiobis-ethanol, was investigated following i.p. administration to rat. 2. Approximately 90% of the administered dose was excreted in the 0-24-h urine. Four metabolites were isolated by h.p.l.c. and identified by mass spectrometry. Structural assignments were confirmed by comparison with authentic synthetic standards. 3. Thiodiglycol sulphoxide was the major metabolite accounting for approximately > or = 90% of the excreted radioactivity following i.p. injection of 13C4, 35S-thiodiglycol. Thiodiglycol sulphone, S-(2-hydroxyethylthio)acetic acid and S-(2-hydroxy-ethylsulphinyl)acetic acid were identified as minor metabolites. 4. Analysis for thiodiglycol by GC-MS indicated approximately 0.5-1% of the applied dose was excreted unmetabolized.

In vitro oxidation of the hydrolysis product of sulfur mustard, 2,2?-thiobis-ethanol, by mammalian alcohol dehydrogenase

“…Thiodiglycol sulfone ( Figure 1E) shows up as a minor metabolite after the i.p. administration of thiodiglycol to rats (17). This provides evidence of oxidative processes other than alcohol dehydrogenase at work.…”

“…However, recent work by Black et al (17)(18)(19) showed that the amount of TDG excreted in urine in free or conjugated form represented less than 1.5% of a cutaneous or intraper- itoneal dose of sulfur mustard. Black's results, plus our observation indicating that protein phosphatase inhibition in vitro was related to the concentration of TDG rather than of mustard (8), led us to investigate its metabolic fate in more detail.…”

“…Thiodiglycol sulfoxide (Figure 1C), which has been reported as a major urinary metabolite of thiodiglycol after i.p. dosing (17) and a sulfur mustard metabolite in the urine of rats after application to the skin (18,19), was a poor substrate at 16.7 mM (Figure 3). The sulfone ( Figure 1E), reported as a minor urinary metabolite of TDG (17) in the rat, was transformed at the same low The increase in the rate of NAD reduction produced by horse liver alcohol dehydrogenase with increasing TDG concentrations: ⅜ 2.1 mM, ⅷ 4.2 mM, ᭞ 8.3 mM, and ࡗ 16.7 mM.…”

Scientific Opinion on Flavouring Group Evaluation 08, Revision 4 (FGE.08Rev4): Aliphatic and alicyclic mono-, di-, tri-, and polysulphides with or without additional oxygenated functional groups from chemical groups 20 and 30

“…As an example, when 40 mg/kg bw of [ 13 C4, 35 S]-thiodiglycol ((HOCH 2 CH 2 ) 2 S) was administered intraperitoneally to male Porton rats, the major urinary metabolites were the corresponding sulphoxide (90 %) and carboxylic acid, S-(2-hydroxyethylthio)acetic acid (10 %). The corresponding sulphone and combined C-and S-oxidation product, S-(2-hydroxyethylsulphinyl) acetic acid, were only minor metabolites (Black et al, 1993).…”

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“…As an example, when 40 mg/kg bw of [ 13 C 4 , 35 S]-thiodiglycol (HOCH 2 CH 2 ) 2 S was administered intraperitoneally to male Porton rats, the major urinary metabolites were the corresponding sulphoxide (90 %) and carboxylic acid, S-(2-hydroxyethylthio)acetic acid (10 %). The corresponding sulphone and combined C-and S-oxidation product, S-(2-hydroxyethylsulphinyl) acetic acid, were only minor metabolites (Black et al, 1993).…”