Subchronic Toxicity Evaluation of Lewisite in Rats

Abstract

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.

Effect of Some Kindof Vegetable Oils on Hypercholesterolemic Rats

“…In accordance with results of table (6) Sasser et al,(1996)reported that sesame oil lowered SGOT and SGPT. Nakai et al, (2003) reported that sesamin has anti-oxidative activity in the liver by conversion to prominent anti-oxidative metabolites, where they exert protective action against oxidative damage in the liver.…”

Wildlife Toxicity Assessment for Lewisite

“…In a 13-week subchronic lewisite toxicity study, 10 Sprague Dawley rats per sex per group received 0, 0.01, 0.1, 0.5, 1.0, or 2.0 mg/kg/day lewisite in sesame oil by gavage 5 days/week [11]. These values converted to 7 days/ week average doses of 0, 0.007, 0.07, 0.36, 0.71, and 1.43 mg/kg/day, respectively.…”

“…Several toxicological studies [11][12][13][14] contain data relevant to the determination of lewisite toxicity reference values (TRVs). The subchronic study of lewisite in Sprague Dawley rats [11] identified the primary effect of lewisite to be necrotic lesions of the forestomach that occurred in animals receiving 1.0 mg/kg/day, equivalent to an average 7-day dose LOAEL of 0.71 mg/kg/day.…”

Evaluation of the Army's Interim Reference Dose for Lewisite

“…ORN L estim ated the N OAEL for lew isite by considering two studiesa tw o-gen era tion reprod uctive study (Sasser et al,1 98 9a), and a 90 -d toxicity study (Sasser et al, 1989b(Sasser et al, , 1996. In the tw o-generation rep roductive study (Sasser et al, 1989a), Sprag ue-D aw ley rats (20 m ales and 25 fem ales p er gro u p) w ere intragastrically intubated w ith lew isite dissolved in sesame oil at doses of 0.10, 0.25, and 0.60 m g/kg/d.…”

“…In the 90-d toxicity study (Sasser et al, 1989b(Sasser et al, , 1996, Spragu e-D aw ley rats (10 male and 10 females per group) w ere intragastrically intubated with lew isite dissolved in sesam e oil at doses of 0.01, 0.1, 0.5, 1.0, and 2.0 mg/kg/d for 5 d/wk for 13 w k. The most significant adverse effects observed w e re n ecro sis an d hyp erplasia of the fo resto m ach . Tho se fo resto m ach lesions w ere found only in rats treated w ith lew isite at 1.0 or 2.0 mg/kg/d; the incidence was 1 of 20 and 12 of 20, resp ectively.…”