Protection Against Systemic Poisoning by Mustard Gas, Di(2‐chloroethyl) Sulphide, by Sodium Thio‐sulphate and Thiocit in the Albino Rat

Abstract

The lethal effects of mustard gas, di(2-chloroethyl) sulphide, in the albino rat have been counteracted by Thiocit, a mixture of sodium thiosulphate and trisodium citrate in the ratio 10: 1, administered intraperitoneally in a dose of 2.75 g./kg. Thiocit afforded complete protection against greater than the median lethal dose of mustard gas whether given 10 min. before or 10 min. after mustard gas and raised the LD50 of mustard gas by approximately three times. The protection appeared whether the total dose of Thiocit was given in one injection or serially over 30 min. The effective doses of sodium thiosulphate and of Thiocit in rats were of the order of 3.0 g./kg. Sodium thiosulphate alone and Thiocit have been administered in single doses by slow infusion, by stomach tube and in drinking water. Both have shown activity by all routes of administration, but activity was greatest by intraperitoneal injection. The use of Thiocit in conjunction with mustard gas therapy is suggested.Many attempts have been made to find a substance which offers effective protection against the systemic effects and death produced by poisoning with mustard gas, di(2-chloroethyl) sulphide. Numerous authors have demonstrated some alleviation of the local or systemic effects of mustard gas by cysteine and glutathione. Paulet and Chappet (1956) have discussed the more recent work and showed that phenylallylthiourea was as active as cysteine, but somewhat more effective than glutathione in reducing the severity of the leucopenia produced by sublethal injections of mustard gas into albino rats.In spite of this extensive search, however, little success has been achieved in protecting against lethal doses of mustard gas. A large number of thio compounds has been tested on the basis of theoretical bonding with, and high competition factor for, mustard gas (Ogston, 1948). Sodium thiosulphate has a high competition factor (2.7x 104), and has probably a relatively high permeability through the cell membrane; it is nontoxic in very high doses and theoretically could combine with mustard gas. Citrates also have a high competition factor (1.7 x 102) (Callaway and Pearce, unpublished observations) for mustard gas; they are natural constituents of body fluids and probably possess a fairly high permeability at the cellular level.These two compounds were therefore investigated for possible prophylactic or therapeutic effects against poisoning by mustard gas. Each was tried separately and also in combination as Thiocit by several routes against lethal doses of the mustard gas. METHODSSodium thiosulphate 500 mg./ml. and sodium citrate 100 mg./ml. were used in aqueous solution both for injection and for drinking purposes. Thiocit consisted of Na2S203,5H20 (50 g.) and NaC6HFO07,5H20 (5 g.) made up to 100 ml. with distilled water to give a total concentration of 550 mg./ml.Male albino rats of the Wistar strain weighing 190 to 215 g. were used. Mustard gas solution in propylene glycol was freshly prepared for each experiment, such that the volume injected in m...

Treatment for sulfur mustard lung injuries; new therapeutic approaches from acute to chronic phase

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Chronic health effects of sulphur mustard exposure with special reference to Iranian veterans

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Evaluation of analogues of DRDE-07 as prophylactic agents against the lethality and toxicity of sulfur mustard administered through percutaneous route

“…Though several antidotes have been reported for the systemic toxicity of SM in experimental animals (Dacre and Goldman, 1996;Callaway and Pearce, 1958;Vojvodic et al, 1985;Vijayaraghavan et al, 1991;Kumar et al, 2001), none of them are approved so far and decontamination of SM immediately after contact is recommended as the best protection (Somani and Babu, 1989). Hence, decontamination has to be achieved quickly to limit absorption.…”