SUBCHRONIC TOXICITY EVALUATION OF SULFUR MUSTARD IN RATS

Occupational exposure criteria have not been established for sulfur mu stard (bis(2-chlorethyl) sulfide), a strong alkylating agent with know n mutagenic properties. Seventy-two Sprague-Dawley rats of each sex, 6 -7 weeks old, were divided into six groups (12 of each sex per group) and gavaged with 0, 0.003, 0.01, 0.03, 0.1 or 0.3 mg kg(-1) sulfur mus tard in sesame oil for 5 days a week for 13 weeks. No dose-related mor tality was observed. A significant decrease (P > 0.05) in body weight was observed in both sexes of rats only in the 0.3 mg kg(-1) group. He matological evaluations and clinical chemistry measurements found non consistent treatment-related effects at the doses studied. The only tr eatment-related lesion associated with gavage exposure upon histopatho logical evaluation was eipthelial hyperplasia of the forestomach of bo th sexes at 0.3 mg kg(-1) and of males at 0.1 mg kg(-1). The hyperplas tic change was minimal and characterized by cellular disorganization o f the basilar layer, apparent increase in mitotic activity of the basi lar epithelial cells and thickening of the epithelial layer due to the apparent increase in cellularity. The estimated no-observed-effect le vel (NOEL) for sulfur mustard in this 90-day study was 0.1 mg kg(-1) d ay(-1) when administered orally.