RT Journal Article SR Electronic T1 ON DICHLORETHYLSULPHIDE (MUSTARD GAS) I. THE SYSTEMIC EFFECTS AND MECHANISM OF ACTION JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 265 OP 290 VO 12 IS 5 A1 VERNON LYNCH A1 H. W. SMITH A1 E. K. MARSHALL, JR. YR 1918 UL http://jpet.aspetjournals.org/content/12/5/265.abstract AB 1. Dichlorethylsulphide is absorbed through the lungs and produces definite, characteristic, systemic effects. 2. The symptoms of injection of the substance are salivation, vomiting and diarrhea, tonic and clonic convulsions, slow and irregular heart, followed by a rapid pulse, and stimulation of the respiration. 3. A dose of six milligrams or less per kilo, injected intravenously in aqueous solution, proves fatal for dogs. 4. Dichlorethylsulphide appears to be excreted in the urine, in part at least, as dihydroxyethylsulphide, which has been shown to be a comparatively non-toxic body. 5. The lesions in the intestine suggest that excretion of the substance may also take place here. 6. A theory of action has been advanced. The dichlorethylsulphide penetrates the cells, and in the aqueous phase of the cell, hydrolyzes to hydrochloric acid which is responsible for the damage. 7. Sodium bicarbonate in large doses somewhat alleviates the symptoms, but does not prevent death. 8. Fish are much less susceptible to this substance when kept at a low temperature after exposure rather than at room temperature. The hydrolysis of the substance is much slower at a low temperature. 9. Monochlorethylsulphide, and dichlorpropylsulphide are lipoid soluble and easily hydrolyzed. They both act similarly to mustard gas. 10. Graham's hydrochloric acid theory of chloroform poisoning has been discussed, and the application of these ideas to general problems of toxicity. 11. A review of the literature on dimethylsulphate and a few observations of our own would lead us to believe that this substance acts by intracellular liberation of sulphuric acid.