ON THE PENETRATION OF DICHLOROETHYLSULPHIDE (MUSTARD GAS) INTO MARINE ORGANISMS, AND THE MECHANISM OF ITS DESTRUCTIVE ACTION ON PROTOPLASM

¹ From he Marine Biological Laboratory, Woods Hole, Massachusetts

1. Developing eggs and larvae of starfish and sea urchins, larvae of Arenicola, Nereis, etc., and young and adult fish (Fundulus) have been used to study the nature of the toxic effects exerted by mustard gas on protoplasm.

2. In order to secure a true solution of "mustard gas" and to reduce hydrolysis to a minimum, saturated solutions in sea water and distilled water were prepared at a temperature of 0°C.

3. One of the most characteristic features of "mustard gas" poisoning is the latent period which elapses before retardation and deformation develop as a result of exposure to dilute solutions, and necrosis and death after exposure to concentrated solutions.

4. The toxic action, which may be measured by variations in length of exposure and concentration of solution required to produce given effects, is found to exhibit an increase of rate with increase in temperature in a manner comparable to that of a chemical reaction.

5. "Mustard" solutions gradually lose their toxicity on standing, and more rapidly at high than at low temperatures. A any given temperature the curve of loss of toxicity appears to correspond very closely with the monomolecular curve of hydrolysis of mustard, indicating that undecomposed "mustard" is the toxic agent.

6. Di-hydroxy-ethyl-sulphide, one of the products of hydrolysis, is nontoxic, and the acid formed, if not neutralized by the buffer system of sea water, produces a less marked and somewhat different effect from that of undecomposed "mustard."

7. A lag in loss of toxicity, as compared with hydrolysis, after decomposition has proceeded for a considerable period, suggests a strong selective adsorptive capacity for "mustard gas" possessed by protoplasmic structures.

8. Attempts to counteract the effect of "mustard gas" by subsequent exposure of the developing eggs to weak solutions of ammonia, aniline, amyl alcohol, etc., have met with very limited success.

9. Arenicola larvae exhibit very persistent negative phototaxis after exposure to concentrations of "mustard" insufficient to cause death. This persistence is probably due to deferred production of acid within the organism.

10. "Mustard gas" appears under certain circumstances to exert an anaesthetic effect upon Arenicola larvae.

11. Intravitam staining affords some evidence of abnormally rapid production of acid within the protoplasm of poisoned eggs.

12. Injections of fresh aqueous solutions of "mustard gas," and of aqueous solutions which have undergone hydrolysis, into the interior of the eggs by means of a capillary pipette, show that undecomposed "mustard" when first injected exerts no greater effect than distilled water or salt solution, but after a latent period corresponding with that observed when mustard is applied externally, causes necrosis and death of the cell. The decomposed "mustard" solution when injected into the cell causes an immediate destructive effect corresponding with that produced by a solution of hydrochloric acid of the same strength, and far in excess of the effect obtained by application of the mineral acid to the exterior of the cell.

13. These and other experiments lend strong support to the theory advanced by Lynch, Smith and Marshall (1), that "mustard gas" penetrates, the cell on account of its organo-solubility, and within the cell undergoes hydrolysis with the liberation of nascent hydrochloric acid, which exerts the destructive effect.

14. The prolonged latent period may well be explained as attributable either to the high solubility of "mustard" in lipoids, retarding its passage into the water phase, or the formation of protoplasmic "mustard gas" molecular aggregates which undergo hydrolysis less rapidly than "mustard" in contact with water.

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