Review of the U.S. Army's Health Risk Assessments for Oral Exposure to Six Chemical-Warfare Agents (1999) / Chapter Skim
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F: Health Risk Assessment for Lewisite
F: Health Risk Assessment for Lewisite
Pages 275-294
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Appendix F Health Risk Assessment For Lewisite
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. In this study, groups of 10 male and 10 female rats were given lewisite in sesame oil by gastric intubation at doses of 0.01, 0.1, 0.5, 1.0, or 2.0 mg/kg.
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Oak Ridge, Tennessee 37831 Submitted to Material Chemical Risk Assessment Working Group Advisory and Coordinating Committee Environmental Risk Assessment Program Strategic Environmental Research Development Program * Managed by Lockheed Martin Energy Research Corp.
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278 _ ~-~~ DISCLA~ER Ash document ~ ~ Them review dam far review purposes only Id does not confirm O.S. Govemmen1 policy.
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This working group is developing toxicity values for selected chemicals of concern at federal facilities. Toxicity values will be submitted for consideration by the EPA's IRIS Consensus Process for inclusion on IRIS (EPA's Integrated Risk Information System)
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Lewisite Degradation Products .
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arsine3 1.2 ENVIRONMENTAL FATE Regardless of the method of lewisite degradation (combustion, hydrolysis, or other environmental degradation) , the arsenic component will not be eliminated and, therefore, at least some combustion product or other degradation products may be some form of arsenical.
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1 · :1 Hydrolysis Product: Chlorovinyl arsenous oxide Combustion Products: Acetylene Acetylene monochlonde Arsenic trichlonde Arsenic Dioxide Chlorine Methyl chloride _ Vinyl chloride ~ _ Acetylene dichloride Arsenic oxychlonde Chlorovinyl arsenous oxide C2H2CIAsO 1 ~H2 C2 AsCl3 A5203 C12 CH3CI C2H3CI C2H2C12 AsOC1 C2H'CI~O 3088-37-7 74-86-2 593~3-5 7784 34-1 , 1 327-53-3 7782-50-5 74-87-3 75~1 ~ 540-59~ Not found 3088-37-7 1 Sourecs: DA, 19747 1988; Small, 1984; HEAST. 1993 1.2.3 Soil Lewisite applied to soil may rapidly volatilize and/or be converted to lewisite oxide through exposure to soil moisture (Rosenblatt et al., 1975)
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The vesicant properties of lewisite are characterized by immediate onset of pain and, for ocular exposure, possible corneal necrosis. Studies in animals have shown that the target tissues and organs for systemic toxicity of lewisite include the liver, gall bladder, urinary bladder, lung, and kidneys (Cameron et al., 1946; Snider et al., 1990)
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. In this study, groups of 10 male and 10 female rats were given lewisite in sesame oil by gastric intubation at doses of 0.01, 0.1, 0.5, 1.0, or 2.0 mg/kg.
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The use of increased mortality as the critical effect for derivation of a reference dose is not appropriate. Furthermore, the intragastric intubation technique used for rabbits in this study concentrates the test article on the gastric mucosa more effectively than simple Savage administration thereby making the apparent increased sensitivity of rabbits more an artifact of administration than actual toxicodynamics.
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The cause of death for most of these animals appeared to be associated with aspiration of the test article resulting in fatal respiratory tract lesions. Exposure of rats to lewisite did not adversely affect reproductive performance, fertility, or reproductive organ weights.
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Lewisite combustion produces the inorganic arsenicals arsenic bichloride and arsenic trioxide, as well as vinyl chloride. Inorganic arsenic is carcinogenic in humans and animals and is classified as a Group A carcinogen for both oral and inhalation exposure (U.S.
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were given lewisite in sesame oil by gavage for five days at doses of 0.375, 0.75, or 1.5 mg/kg. Vehicle controls received an equivalent volume of the vehicle and positive controls were given the vehicle followed by 100 mg ethyl methanesulphonate/kg, i.p.
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The multigeneration study represents a chronic exposure situation relative to reproductive/developmental effects but would be considered subchronic duration for systemic effects in the adult animals. It must be noted that the absence of reproductive/developmental effects does not necessarily eliminate the possibility of more sensitive effects in alternate targets.
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The available data for lewisite toxicity is limited to Savage and gastric intubation administration studies. Although these routes of administration allow for more precise control of the administered dose as opposed to drinking water or feeding studies, in the case of lewisite (or any highly corrosive agent)
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The reflux and subsequent respiratory tract response would be highly unlikely in an environmental exposure situation (i.e., drinking water contamination)
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1988. Final Programmatic Environmental Impact Statementfor the Chemical Stockpile Disposal Program, Aberdeen Proving Ground, MD, Off'ce of the Program Executive Officer, Program Manager for Chemical Demilitarization.
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1989a. Toxicology studies on lewisite and sulfur mustard agents: Subchronic toxicity study of lewisite in rats.
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1985. Study of the genetic effects of sulfur mustard gas on former workers on Okunojima poison gas facto~y and their offspring.
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