Acute toxicity tissues involved

Studies of occupational exposures to sulfur mustard indicate an elevated risk of respiratory tract and skin tumors following long-term exposure to acutely toxic concentrations. Overall, several factors are important regarding the assessment of the carcinogenicity of sulfur mustard. Increased cancer incidence in humans appears to be associated only with exposures that caused severe acute effects, and occupational exposures tended to involve repeated exposures and repeated injury of the same tissues. Because the therapeutic use of the sulfur mustard analog nitrogen mustard is associated with an increased incidence of CML, the reports of CML in HD-exposed individuals appear to be relevant to the eareinogenicity of sulfur mustard. 

Acute toxicity studies in two animal species are required by the FDA for all new drugs prior to their use in humans. Subacute and chronic toxicity studies are required for drugs that are intended for chronic systemic use. Toxicity testing in animals usually involves the determination of lethal dose, monitoring of blood, hepatic, renal, and respiratory functions, gross and histopathologic examination of tissues, and tests of reproductive effects and potential carcinogenicity. 

Some birds may not die immediately after drinking lethal cyanide solutions. Sodium cyanide rapidly forms free cyanide in the avian digestive tract (pH 1.3-6.5), whereas formation of free cyanide from metal cyanide complexes is comparatively slow. A high rate of cyanide absorption is critical to acute toxicity, and absorption may be retarded by the lower dissociation rates of metal-cyanide complexes. In Arizona, a red-breasted merganser (Mergus senator) was found dead 20 km from the nearest known source of cyanide, and its pectoral muscle tissue tested positive for cyanide. A proposed mechanism to account for this phenomenon involves weak-acid dissociable (WAD) cyanide compounds. Cyanide bound to certain metals, usually copper, is dissociable in weak acids such as stomach acids. It has been suggested that drinking of lethal cyanide solutions by animals may not result in immediate death if the cyanide level is... 

Methods for Reducing Toxic Effects. The usefulness of methods and treatments for reducing peak absorption and reducing the body burden of carbon tetrachloride are rather limited due to the chemical s rapid rates of absorption and tissue disposition. On the other hand, investigations of antidotal therapy based on the mechanism of action has been limited to a few studies involving the administration of compounds to reduce free radical injury. Additional studies would be useful to better establish the effectiveness of both acute and prolonged antidotal therapy, since carbon tetrachloride is persistent in the body. 

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