Subchronic toxicity evaluation of lewisite in rats.
Health and exposure criteria have not been established for lewisite [dichloro(2-chlorovinyl)arsine], a potent toxic vesicant that reacts with the sulfhydryl groups of proteins through its arsenic group. Sixty Sprague-Dawley rats of each sex, 6-7 wk old, were divided into 6 groups (10/group/sex) and gavaged with either 0, 0.01, 0.1, 0.5, 1.0, or 2.0 mg/kg of lewisite in sesame oil 5 d/wk for 13 wk. No significant dose-related change in body weight was observed. At the high dose, serum protein, creatinine, SGOT, and SGPT were decreased in males; lymphocytes and platelets were increased in females. A treatment-related lesion was detected in the forestomach of both sexes at 2.0 mg/kg. These lesions were characterized by necrosis of the stratified squamous epithelium accompanied by infiltration of neutrophils and macrophages, proliferation of neocapillaries, hemorrhage, edema, and fibroblast proliferation. Mild acute inflammation of the glandular stomach was also observed in some cases at 1.0 and 2.0 mg/kg. Early deaths were attributed to severe inflammation of the upper and/or lower respiratory tract, possibly from deposition or reflux of test material into the pharynx. Estimated dose range for NOEL appears to be >0.5 and <1.0 mg/kg when administered orally.
Sasser
L B
LB
Battelle, Pacific Northwest Laboratory, Richland, Washington 99352-0999, USA.
Cushing
J A
JA
Mellick
P W
PW
Kalkwarf
D R
DR
Dacre
J C
JC
D000818:Animals; D020261:Arsenic Poisoning; D001152:Arsenicals; D001772:Blood Cell Count / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000633:toxicity*; D005260:Female; D008111:Liver Function Tests; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D051381:Rats; D017207:Rats, Sprague-Dawley; D012140:Respiratory Tract Diseases / Q000139:chemically induced; D013270:Stomach / Q000473:pathology; D013276:Stomach Ulcer / Q000139:chemically induced; D018675:Toxicity Tests
D001152:Arsenicals; D002619:Chemical Warfare Agents; C035965:lewisite