Biological fate of sulphur mustard in rat: toxicokinetics and disposition.
1. The toxicokinetics of sulphur mustard were studied after i.v. administration (10 mg/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 (Vdss) was 74.4 l/kg and total body clearance (Cl) was 21 l/h kg-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.
Maisonneuve
A
A
Laboratoire d'Analyses Toxicologiques, Centre d'Etudes du Bouchet, Vert-le-Petit, France.
Callebat
I
I
Debordes
L
L
Coppet
L
L
D000818:Animals; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008297:Male; D009151:Mustard Gas / Q000493:pharmacokinetics* / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D009151:Mustard Gas