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Toxicology Studies on Lewisite and Sulfur Mustard Agents: Subchronic Toxicity of Sulfur Mustard (HD) In Rats (Final Report)

Technical Report ·
DOI:https://doi.org/10.2172/1086507· OSTI ID:1086507
 [1];  [1];  [1];  [1];  [1]
  1. Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Occupational health standards have not been established for sulfur mustard [bis(2- chlorethyl)-sulfide], a strong alkylating agent with known mutagenic properties. Seventy-two Sprague-Dawley rats of each sex, 6-7 weeks old, were divided into six groups (12/group/ sex) and gavaged with either 0, 0.003 , 0.01 , 0.03 , 0.1 or 0.3 mg/kg of sulfur mustard in sesame oil 5 days/week for 13 weeks. No dose-related mortality 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 group. Hematological evaluations and clinical chemistry measurements found no consistent treatment-related effects at the doses studied. The only treatment-related lesion associated with gavage exposure upon histopathologic evaluation was epithelial hyperplasia of the forestomach of both sexes at 0.3 mg/kg and males at 0.1 mg/kg. The hyperplastic change was minimal and characterized by cellular disorganization of the basilar layer, an apparent increase in mitotic activity of the basilar epithelial cells, and thickening of the epithelial layer due to the apparent increase in cellularity. The estimated NOEL for HD in this 90-day study is 0.1 mg/kg/day when administered orally.
Research Organization:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE; U.S. Army Medical Research and Development Command
OSTI ID:
1086507
Report Number(s):
PNL--6870
Country of Publication:
United States
Language:
English