lewisite and sodium-arsenite

The acute intravenous toxicity of sodium arsenite and dichloro(2-chlorovinyl)arsine (lewisite) has been compared in rabbits to provide a quantitative and qualitative model for future assessment of treatments of lewisite poisoning. The LD50 of sodium arsenite was 7.6 mg.kg-1; that for lewisite was 1.8 mg.kg-1. On the basis of arsenic content the former was 6.5 times less toxic than the latter. Significant differences in tissue arsenic content and pathology were found between the 2 materials. Histologically, changes were observed in the lungs and gall bladder after lewisite injection but not after sodium arsenite. It was concluded that use of sodium arsenite is not a suitable substitute model for lewisite poisoning.

Topics: Animals; Arsenic; Arsenic Poisoning; Arsenicals; Arsenites; Biliary Tract; Lethal Dose 50; Liver; Lung; Rabbits; Sodium Compounds; Tissue Distribution

meso-Dimercaptosuccinic acid (DMSA), 2,3-dimercapto-1-propanesulfonic acid, Na salt (DMPS), and N-(2,3- dimercaptopropyl )- phthalamidic acid (DMPA) are water soluble analogs of 2,3-dimercapto-1-propanol (BAL). The relative effectiveness or therapeutic index of these dimercapto compounds in protecting mice from the lethal effects of an LD99 of sodium arsenite is DMSA greater than DMPS greater than DMPA greater than BAL in the magnitude of 42:14:4:1, respectively. DMPS, DMPA, or DMSA will mobilize tissue arsenic. BAL, however, increases the arsenic content of the brain of rabbits injected with sodium arsenite. These results raise the question as to the appropriateness of BAL as the treatment for systemic arsenic poisoning. Either DMSA or DMPS, when given sc or po, will protect rabbits against the lethal systemic effects of subcutaneously administered Lewisite . DMPS and DMSA have promise as prophylactics for the prevention of the vesicant action of Lewisite . The sodium arsenite inhibition of the pyruvate dehydrogenase (PDH) complex can be prevented and reversed in vitro or in vivo by DMPS, DMSA, DMPA, or BAL. Of them all, DMPS is most potent and BAL appears to be the least potent. The usefulness of all these dimercapto compounds would be enhanced by a careful study of their metabolism and biotransformation. These dimercapto compounds are in a great many respects orphan drugs. At this stage of their development, it is very difficult for the clinician to obtain funds to study them clinically even though they appear to be useful for treatment of poisoning by any one of the heavy metals.

Topics: Animals; Antidotes; Arsenates; Arsenic; Arsenic Poisoning; Arsenicals; Arsenites; Brain; Dimercaprol; Guinea Pigs; Male; Mice; Organ Size; Phthalic Acids; Pyruvate Dehydrogenase Complex; Rabbits; Sodium Compounds; Succimer; Sulfhydryl Compounds; Unithiol