Inhalation and Percutaneous Toxicokinetics of Sulfur Mustard and Its Adducts in Hairless Guinea Pigs and Marmosets. Efficacy of Naval Scavengers

摘要

As a follow-up to contract DAMD17-94-V-4O09, the inhalation toxicokinetics of sulfur mustard were studied in more detail in the hairless guinea pig as well as in the marmoset. Hairless guinea pigs were 5-min nose- only exposed to 0.3 and 1 LCt5O. The distribution of sulfurmustard in the respiratory tract was measured at various time-points after exposure. The DNA- adduct levels increased and subsequently decreased with time. The highest levels were found in the upper airways. Marmosets were 5-min nose-only exposed to 160 mg.m(exp -3) sulfur mustard vapor in air, corresponding with 1 LCt5O in the hairless guinea pig. Sulfur mustard was easily measurable in blood during the absorption phase, reaching a maximum concentration of ca. 30 ng.ml(exp -1) at the end of the exposure period. The post-exposure concentration-time course could be described with a hi-exponential equation. The highest concentrations of intact sulfur mustard were found in bone marrow, liver and fat tissue, whereas the concentration in the lung was very low. DNA-adduct concentrations were much higher in the upper airways than in the tissues. Very low adduct levels were found in the lung and bone marrow. The results suggest that the marmoset is a better model for man with respect to the toxicology of inhaled sulfur mustard vapor than the hairless guinea pig.