Toxicokinetics of Sulfur Mustard and its DNA-Adducts in the Hairless Guinea Pig - DNA-Adducts as a Measure for Epithelial Damage.
Abstract
In order to provide a quantitative basis for pretreatment and therapy of intoxications with sulfur mustard (SM) the toxicokinetics of this agent as well as its major DNA-adduct, 7-SM-guanine, are studied in male hairless guinea pigs for the intravenous (i.v.), respiratory and percutaneous routes. A highly sensitive method for bioanalysis of the intact agent in blood and tissues was developed, involving gas chromatography with mass-spectrometric detection. Deuterated sulfur mustard (D8-SM) is used as the internal standard. 7-SM-guanine is measured with an immuno-slot-blot assay. In this midterm report the first results on the i.v. toxicokinetics of SM and 7-SM-guanine in hairless guinea pigs are presented. The 96-h i.v. LD50 appeared to be 8.2 mg/kg (95% confidence interval 7.1-8.8 mg/kg). The i.v. toxicokinetics of SM for a dose corresponding with 1 LD50 are characterized by a very rapid distribution phase and very slow elimination phase, with half-lives of 0.77 and 107 min, respectively. At 3 min after i.v. administration of 1 LD50 SM, 7-SM-guanine was already present in blood, lung, spleen, bone marrow, liver and small intestine. The highest initial adduct levels were found in lung. Whereas most of the adducts had disappeared within 6 h after SM administration, significant adduct levels were still present in most tissues at 48 h after administration.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 1996
- Accession Number
- ADA315126
Entities
People
- Govert P. Van Der Schans
- Hendrik P. Benschop
- Johannes P. Langenberg
Organizations
- Prins Maurits Laboratorium TNO