Toxicity
When one considers the high boiling point of mustard gas, and its consequent low vapor pressure, he is likely to conclude that such a substance would be of comparatively little value as a toxic or poison gas. While it is true that an important part of the military value of mustard gas has been because of its vesicant properties, the fact still remains that it is one of our most toxic war gases. The following comparison with a few of the other gases indicates this:
| Mg. per Liter | ||
|---|---|---|
| Mice | Dogs | |
| Mustard gas | 0.2 | 0.05 |
| Phosgene | 0.3 | ··· |
| Hydrocyanic acid | 0.2 | 0.1 |
| Chloropicrin | 1.5 | 0.8 |
| ··· | 3.0 | |
When an animal is exposed to the vapors of mustard gas in high concentration, it subsequently shows a complexity of symptoms, which may be divided into two classes:
(1) The local effects on the eyes, skin and respiratory tract. These are well recognized and consist mainly of conjunctivitis and superficial necrosis of the cornea; hyperemia, œdema and later, necrosis of the skin, leading to a skin lesion of great chronicity; and congestion and necrosis of the epithelial lining of the trachea and bronchi.
(2) The systemic effects due to the absorption of the substance into the blood stream, and its distribution to the various tissues of the body.
The most striking observation about the symptoms of mustard gas poisoning is the latent period which elapses after exposure before any serious objective or subjective effects are noted. The developments of the effects are then quite slow, unless very high superlethal doses have been inhaled.
At first it was a very serious question whether or not the temporary blindness resulting from mustard gas would not be permanent. Later, as the depth and seriousness of some of the body burns became well known, it was a seven-day wonder that no permanent blindness occurred.
The reason seems to be largely a mechanical one. The constant winking of the eyelids apparently washes the mustard gas off the eyeball and carries it away so that not enough remains to burn to the depth necessary to cause permanent blindness.
Due to the very slight concentrations ordinarily encountered in the field, resulting from a very slow rate of evaporation, the death rate is very low, probably under 1 per cent among the Americans gassed with mustard during the war.
If, on the other hand, the gas be widely and very finely dispersed by a heavy charge of explosive in the shell, the gas is very deadly. In such cases the injured breathe in minute particles of the liquid and thus get hundreds of times the amount of gas that would be inhaled as vapor. This so-called “high explosive mustard gas shell” was a German development in the very last months of the war. Its effects were great enough to make it certain that in the future large numbers of these shell will be used.
The similarity of the symptoms and pathological effects after the inhalation of large amounts of the vapor and those following an injection of an olive oil or water solution of mustard gas led Marshall and his associates to conclude that in high concentrations mustard gas is absorbed through the lungs. A further bit of evidence consists in the isolation of the hydrolysis product, dihydroxyethylsulfide, in the urine of animals poisoned by inhalation of mustard gas. This product is not toxic and is not responsible for the effects of mustard gas. Hydrochloric acid, however, does produce very definite effects upon the animal and may cause death.
From these facts Marshall[21] has proposed the following mechanism of the action of mustard gas:
“Dichlorethylsulphide is very slightly soluble in water and very freely soluble in organic solvents, or has a high lipoid solubility or partition coefficient. It would, therefore, be expected to penetrate cells very readily. Its rapid powers of penetration are practically proven by its effects upon the skin. Having penetrated within the living cell, it would undoubtedly hydrolyze. The liberation of free hydrochloric acid within the cell would produce serious effects and might account for the actions of dichlorethylsulphide. To summarize, then, the mechanism of the action of dichlorethylsulphide appears to be as follows:
“1. Rapid penetration of the substance into the cell by virtue of its high lipoid solubility.
2. Hydrolysis by the water within the cell, to form hydrochloric acid and dihydroxyethylsulphide.
3. The destructive effect of hydrochloric acid upon some part or mechanism of the cell.
“Although hydrochloric acid does not penetrate cells readily and is easily neutralized by the buffer action of the fluids of the body, we might expect by flooding the body with large quantities of acid to produce some of the characteristic effects of mustard gas. Stimulation of the respiratory center is a well known effect of acid. Convulsions and salivation may be produced by injection of hydrochloric acid and we have been able to produce slowing of the heart by rapid injection of this acid.
“The delayed action of mustard gas might be explained by the formation of some compound with some constituent of the blood. However, blood taken from dogs which had been poisoned with mustard gas and were exhibiting typical symptoms at the time, injected into normal dogs produced no effect. Serum treated in vitro with mustard gas and allowed to stand and then injected into a dog, produced no effect. The fluid which is formed in the vesicle and blebs produced by the application of mustard gas to the skin produces no mustard gas effects.”
In studying the toxicity of mustard gas for dogs, it was observed that a concentration of 0.01 mg. per liter could be tolerated indefinitely. If this value is considered as a threshold value, and subtracted from the toxicity values for varying periods of time, it is found that there is a definite relation between the toxic concentration and the time of exposure. This is expressed by the formula
(C - 0.01)t = K
where C is the concentration observed for a given time
t
. K has the approximate value of 1.7, where
t
varies between 7.5 and 480 minutes.