The Toxicology of Nickel Carbonyl

Abstract

Nickel carbonyl poisoning is a particular instance of nickel poisoning.The lethal dose of nickel varies according to the method of application. When applied by subcutaneous injection, the physical condition of the compound influences the rate of absorption and therefore relatively large quantities may be required. In rabbits, the lethal dose is about 7½ mgrs. per kilogram body weight under the most favourable conditions when applied subcutaneously. In cats it is about 12½ mgrs. per kilogram body weight. When applied intraperitoneally, the absorbing surface is considerably larger and consequently the dose required to kill is smaller. In rabbits it is less than 7 mgrs. When applied in the form of nickel carbonyl vapour one meets with the most favourable conditions for rapid absorption and the dose is therefore still smaller. Rabbits die after the absorption of between 3 and 4 mgrs., while cats die after absorbing about 8½ mgrs. per kilogram body weight.In the lungs, nickel carbonyl is dissociated and a nickel compound, probably the hydrated sub-carbonate, is deposited on the respiratory surface.The nickel is dissolved from the respiratory surface by the tissue fluids and is then taken up by the blood.Some of the nickel finds its way directly through the lymphatic channels into the bronchial glands.In the dissolved condition, the nickel enters into complex combination with some constituent of the body.The nickel is carried by the blood to the tissues, but a selective absorption is exercised by the brain and adrenals. In the case of other forms of nickel poisoning, the lungs also exert this specific selection. The nickel only stays for a short time in these organs.The specific pathological changes which are produced by nickel in these organs are primarily a degeneration of the endothelial cells of the capillary vessels. It is possible that some further primary action is exercised on the ganglion cells in the brain and on the parenchyma cells of the adrenals.The haemorrhages follow as the result of the fatty degeneration of the vessel walls and secondary changes result from the effects of the haemorrhages.The nickel is excreted by the kidneys and intestines.The method of poisoning with iron carbonyl is similar to that of nickel poisoning, but the amount necessary to kill in the former case is larger.Iron carbonyl poisoning like nickel carbonyl poisoning is merely a specific instance of metallic poisoning.Iron acts in a similar manner to nickel on the walls of capillary vessels, but no evidence of selection by any special tissues was obtained.Cobalt has a toxicological action which is identical to that of nickel. The lethal dose however is higher than that of nickel and lower than that of iron.After the inhalation of a quantity of nickel or iron carbonyl which is greater than the minimum required to kill, no form of treatment was found to avert death.It is with much pleasure that I again express my gratitude to Dr Ludwig Mond, F.R.S., for having rendered this investigation possible, by defraying all the expenses, and by giving me the benefit of his advice.I further desire cordially to thank Dr C. J. Martin, F.R.S., and the other members of the Staff of the Lister Institute, who have at all times been ready and willing to assist me. The work has necessitated incursions into several branches of science, and has required the acquisition of a variety of methods. I have made free use of their kind collegiality and am glad to avail myself of this opportunity of recording my indebtedness.The literature of the subject has been given in Part I, q.v.