The effect of 2-3 dimercapto-propanol (BAL) on experimental nickel carbonyl poisoning.

The experiments recorded in this paper were designed to investigate the effects of the inhalation of nickel carbonyl by rats and rabbits, and to study in detail the distribution of nickel in the body, the development of pathological lesions, and the influence of the therapeutic agent 2-3 dimercaptopropanol (BAL) on these changes. The study was made because occasional cases of accidental poisoning in man by mixtures of nickel carbonyl and carbon monoxide occur in the production of nickel by the Mond process, which entails the formation and subsequent decomposition by heat of gaseous nickel carbonyl. When the process was first developed in this country, accidental exposure to nickel carbonyl led to some fatalities and from time to time fatal accidents have been reported in other countries. No fatal accidents have occurred in Great Britain during the past 40 years, but accidental exposure due to leaks and other technical faults in the factory sometimes leads to severe and protracted illness in workmen. The toxic material, nickel carbonyl, is a clear volatile liquid, boiling at 43°C. Its vapour rapidly decomposes in the presence of moisture to give metallic nickel and carbon monoxide; in the presence of carbon dioxide the nickel is deposited as the suboxide. Some of the earlier writers considered that the toxic action of nickel carbonyl was due to the carbon monoxide that it liberated, but this view was effectively refuted by Armit (1907, 1908) who has made the only significant contribution to the experimental study of nickel carbonyl poisoning. Armit pointed out that nickel carbonyl had a higher toxicity than could be accounted for by its carbon monoxide moiety, and that a dose of nickel carbonyl sufficient to kill a rabbit would jiberate so little carbon monoxide that only 5% of the animal's haemoglobin could be converted to carboxy-haemoglobin. In addition to the considerable pathological changes in the lung, Armit described lesions in the brain and adrenals of experimental animals and gave reasons for attributing a general systemic action to the nickel liberated from nickel carbonyl. In the present paper the way in which nickel carbonyl exerts its toxic action is reconsidered. The effects of BAL on experimental nickel carbonyl poisoning will be considered in some detail. BAL is effective in the treatment of poisoning by arsenicals and by mercury salts, and somewhat less certainly in poisoning with the salts of lead and gold. There are grounds for believing that BAL would be effective in poisoning by nickel carbonyl. Nickel in the form of its soluble salts when added to a solution of BAL is immediately precipitated as an insoluble mercaptide. Further, Braun, Lusky, and Calvery (1946) showed that rabbits given a lethal dose of nickel sulphate by subcutaneous injection could be saved by treatment with BAL. But BAL therapy in man should be introduced with caution. BAL is itself appreciably toxic, and in addition it has been shown to increase rather than diminish the toxicity of some metals such as cadmium and uranium. The experimental studies, recorded in this paper, of the effect ofBAL on nickel carbonyl poisoning will emphasize the difficulties that arise in the applications of this method of treatment of poisoning by toxic metals.