Biological fate of sulphur mustard in rat: toxicokinetics and disposition

Abstract

1. The toxicokinetics of sulphur mustard were studied after i.v. administration (10mg/kg) to rat.

2. After i.v. administration, blood concentrations of sulphur mustard were best described by a two-compartment model with distribution and elimination half-lives of 5–6 min and 3–59 h, respectively. The apparent volume of distribution at steady state (V_dss) was 74–41/kg and total body clearance (Cl) was 211/hkg⁻¹.

3. Unchanged sulphur mustard was still detectable in the systemic circulation 8 h after administration. Appreciable and long (96 h) accumulation of ¹⁴C was found in the systemic circulation, and significant high affinity of ¹⁴C-sulphur mustard for red blood cells.

4. The disposition of ¹⁴C was also investigated after i.v. injection of ¹⁴C-sulphur mustard to rat. Urine was the major route of excretion of sulphur mustard and/or its metabolites. Of the administered radioactivity 80% was excreted in urine over 96 h, the greater part in the first 24 h after administration. Residual ¹⁴C continued to be excreted until 4 days later. In urine, no sulpho- or glucuronyl-conjugates were detected. Of dose < 3% was recovered in faeces.