Toxicology Studies of Lewisite and Sulfur Mustard Agents:genetic Toxicity of Lewisite (L) in Chinese Hamster Ovary Cells

Jostes, R. F.; Lb, Sasser; Rausch, R. J.

doi:10.2172/929775

Cited by 7 publications

(6 citation statements)

References 6 publications

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“…Evidence of dose-related pathology was not found in the intestine. We found no evidence that the forestomach lesions observed in this study were precancerous nor did our genic in the Ames Assay or in Jostes, et al, 1989). earlier studies show that Lewisite was mutaChinese hamster ovary cells (Stewart, et al •. Lesions of the forestomach have been reported for many chemical irritants after oral or gavage exposure.…”

Section: Discussioncontrasting

confidence: 61%

Toxicology Studies on Lewisite and Sulfur Mustard Agents: Subchronic Toxicity Study of Lewisite in Rats Final Report

Sasser¹,

Cushing²,

Kalkwarf³

et al. 1989

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Occupational health standards have not been established for arsine], a potent toxic vesicant wh1ch reacts with the sulfhydryl groups of proteins through its arsenic group. Sixty Sprague-Dawley rats of each sex, 6-7 weeks old, were divided into six 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 days/week for 13 weeks. 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 platlets 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 gradular 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 tract ibl from tion 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.

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Section: Discussioncontrasting

confidence: 61%

Toxicology Studies on Lewisite and Sulfur Mustard Agents: Subchronic Toxicity Study of Lewisite in Rats Final Report

Sasser¹,

Cushing²,

Kalkwarf³

et al. 1989

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“…Besides mutation at a specific locus, cytogenic assays were used in the study of Lewisite effects on mammalian cells. Although evidence for a weakly positive SCE response to Lewisite was observed, the SCE rate was not significantly different from control values (94 (60,61). Several cases of Bowen's disease were also noted among former workers of the Okuno-jima facility (10).…”

Section: Agents Ht/tmentioning

confidence: 63%

Toxicity of vesicant agents scheduled for destruction by the Chemical Stockpile Disposal Program.

Watson

Griffin

1992

Environ Health Perspect

107

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The vesicant agents of the unitary chemical munitions stockpile include various formulations of sulfur mustard [bis-(2-chloroethyl) sulfide; agents H, HD, and HT] and small quantities of the organic arsenical Lewisite [dichloro(2-chlorovinyl) arsine; agent L]. These agents can be dispersed in liquid, aerosol, or vapor form and are capable of producing severe chemical burns upon direct contact with tissue. Moist tissues such as the eyes, respiratory tract, and axillary areas are particularly affected. Available data summarizing acute dose response in humans and laboratory animals are summarized. Vesicant agents are also capable of generating delayed effects such as chronic bronchitis, carcinogenesis, or keratitis/keratopathy of the eye under appropriate conditions of exposure and dose. These effects may not become manifest until years following exposure. Risk analysis derived from carcinogenesis data indicates that sulfur mustard possesses a carcinogenic potency similar to that of benzo[a]pyrene. Because mustard agents are alkylating compounds, they destroy individual cells by reaction with cellular proteins, enzymes, RNA, and DNA. Once begun, tissue reaction is irreversible. Mustard agents are mutagenic; data for cellular and laboratory animal assays are presented. Reproductive effects have not been demonstrated in the offspring of laboratory rats. Acute Lewisite exposure has been implicated in cases of Bowen's disease, an intraepidermal squamous cell carcinoma. Lewisite is not known to generate reproductive or teratogenic effects.

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“…We recently reported that HD induced point mutations in tester strain TA102 and frameshift mutations in TA97 in the Ames test (Stewart, 1987;Stewart et al, 1989) and caused marked chromosome damage and rearrangement and was mutagenic at the HGPRT locus in CHO cells (Jostes et al,1989). In a study of 174 agents Epstein et al (1972) found only 16 which unequivocally induced dominant lethal effects; the majority of these are known alkylating agents.…”

Section: Discussionmentioning

confidence: 99%

Toxicology Studies on Lewisite and Sulfur Mustard Agents: Modified Dominant Lethal Study of Sulfur Mustard in Rats Final Report

Sasser¹,

Cushing²,

Kalkwarf³

et al. 1989

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Toxicology Studies of Lewisite and Sulfur Mustard Agents:genetic Toxicity of Lewisite (L) in Chinese Hamster Ovary Cells

Cited by 7 publications

References 6 publications

Toxicology Studies on Lewisite and Sulfur Mustard Agents: Subchronic Toxicity Study of Lewisite in Rats Final Report

Toxicology Studies on Lewisite and Sulfur Mustard Agents: Subchronic Toxicity Study of Lewisite in Rats Final Report

Toxicity of vesicant agents scheduled for destruction by the Chemical Stockpile Disposal Program.

Toxicology Studies on Lewisite and Sulfur Mustard Agents: Modified Dominant Lethal Study of Sulfur Mustard in Rats Final Report

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