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1. Nickel carbonyl is a highly toxic compound.2. Dissociation of nickel carbonyl takes place rapidly at the temperature of the body in the presence of air, moisture and carbon dioxide.Nickel carbonyl also dissociates at the temperature of the body in the absence of air, moisture and carbon dioxide, but not to the same extent as in the presence of these owing to the fact that a reversible action occurs between the nickel and the dissociated carbon monoxide.3. Nickel carbonyl is soluble in water to the amount of 2·36 c.cm. of vapour (i.e. 6·43 mgrs. of nickel) per 100 grs. at 9·8° C.The amount dissolved in water is directly proportional to the pressure, when the temperature is constant.The solubility in water diminishes as the temperature is raised.4. The solubility of nickel carbonyl in serum and in blood is about 2½ times greater than that in water. At 10° C. 100 grs. of serum dissolves 5·98 c.cm. of nickel carbonyl vapour (i.e. 15·71 mgrs. of nickel).5. When nickel carbonyl is brought into contact with water, serum, blood and other liquids, if oxygen and carbon dioxide are present, dissociation occurs and a substance is formed, probably a hydrated basic carbonate of nickel, which is slightly soluble, but also forms a very fine precipitate, which renders the liquid turbid. The liquid can only be cleared of the turbidity by passing it through a Berkefeld filter.6. Water dissolves about 0·0035% of the product of dissociated nickel carbonyl (reckoned as nickel) at 18° C. About the same amount is dissolved in 10% solutions of sodium carbonate.The solubility of this product of dissociated nickel carbonyl is greater in serum than in water. Serum dissolves about 0·0183% (reckoned as nickel). A solution of the salts of serum, under the same conditions, dissolves 0·005% (reckoned as nickel). Solutions of sodium phosphate of approximately the same strength as the phosphates in serum, dissolve 0·0025% (reckoned as nickel).7. Nickel hydrate is insoluble in water but is soluble in serum to the extent of 0·0225 gr. nickel per 100 grs. serum, and in sodium phosphate solutions to the extent of 0·012% (reckoned as nickel).8. Nickel carbonate is soluble in water to the extent of 0·0005% (reckoned as nickel), and in serum to an amount, corresponding to 0·016 gr.% of nickel. Salts of serum dissolve 0·0045 gr. % of nickel carbonate reckoned as nickel. Nickel carbonate is insoluble in sodium phosphate solutions.9. Dissociation product in aqueous solution is precipitated by boiling, and to a certain extent by the addition of electrolytes. Some of it is thrown out of solution spontaneously on standing for some days, whereas solutions of nickel carbonate are not precipitated by either of the above means.10. Solutions of dissociation product dialyse more slowly than solutions of similar strength of nickel carbonate, and at a certain stage in the dialysis the greater part of the nickel is adsorbed into the membrane.11. No constant ratio exists between the nickel and the nitrogen contents of solutions of dissociation product in serum of different strengths.12. When the proteids of the serum, containing the product of dissociated nickel carbonyl in solution, are precipitated by ammonium sulphate, nine-tenths of the nickel remains in solution. One-tenth is precipitated by adding sufficient ammonium sulphate to produce one-third of saturation, and about an additional one-hundredth by producing one-half of saturation.13. The product of dissociated nickel carbonyl when dissolved in serum is only incompletely removable from solution by dialysis.The product of dissociated nickel carbonyl is therefore not identical with nickel carbonate or nickel hydrate, and appears to exist in a condition of colloidal solution.14. The poisonous properties of nickel carbonyl do not depend, as was at first supposed, on the carbon monoxide of the compound.15. Nickel carbonyl when mixed with air and inhaled by an animal, cannot be absorbed as such, as it becomes split up into the nickel containing substance (? hydrated basic carbonate of nickel) and carbon monoxide, before or soon after reaching the alveoli of the lungs.16. The poisonous effects of nickel carbonyl are entirely due to the nickel of the compound. The peculiar toxicity of the compound is due to the fact that being introduced in a gaseous form and that the nickel is deposited as a slightly soluble compound in a very fine state of subdivision over the immense area of the respiratory surface.
1. Nickel carbonyl is a highly toxic compound.2. Dissociation of nickel carbonyl takes place rapidly at the temperature of the body in the presence of air, moisture and carbon dioxide.Nickel carbonyl also dissociates at the temperature of the body in the absence of air, moisture and carbon dioxide, but not to the same extent as in the presence of these owing to the fact that a reversible action occurs between the nickel and the dissociated carbon monoxide.3. Nickel carbonyl is soluble in water to the amount of 2·36 c.cm. of vapour (i.e. 6·43 mgrs. of nickel) per 100 grs. at 9·8° C.The amount dissolved in water is directly proportional to the pressure, when the temperature is constant.The solubility in water diminishes as the temperature is raised.4. The solubility of nickel carbonyl in serum and in blood is about 2½ times greater than that in water. At 10° C. 100 grs. of serum dissolves 5·98 c.cm. of nickel carbonyl vapour (i.e. 15·71 mgrs. of nickel).5. When nickel carbonyl is brought into contact with water, serum, blood and other liquids, if oxygen and carbon dioxide are present, dissociation occurs and a substance is formed, probably a hydrated basic carbonate of nickel, which is slightly soluble, but also forms a very fine precipitate, which renders the liquid turbid. The liquid can only be cleared of the turbidity by passing it through a Berkefeld filter.6. Water dissolves about 0·0035% of the product of dissociated nickel carbonyl (reckoned as nickel) at 18° C. About the same amount is dissolved in 10% solutions of sodium carbonate.The solubility of this product of dissociated nickel carbonyl is greater in serum than in water. Serum dissolves about 0·0183% (reckoned as nickel). A solution of the salts of serum, under the same conditions, dissolves 0·005% (reckoned as nickel). Solutions of sodium phosphate of approximately the same strength as the phosphates in serum, dissolve 0·0025% (reckoned as nickel).7. Nickel hydrate is insoluble in water but is soluble in serum to the extent of 0·0225 gr. nickel per 100 grs. serum, and in sodium phosphate solutions to the extent of 0·012% (reckoned as nickel).8. Nickel carbonate is soluble in water to the extent of 0·0005% (reckoned as nickel), and in serum to an amount, corresponding to 0·016 gr.% of nickel. Salts of serum dissolve 0·0045 gr. % of nickel carbonate reckoned as nickel. Nickel carbonate is insoluble in sodium phosphate solutions.9. Dissociation product in aqueous solution is precipitated by boiling, and to a certain extent by the addition of electrolytes. Some of it is thrown out of solution spontaneously on standing for some days, whereas solutions of nickel carbonate are not precipitated by either of the above means.10. Solutions of dissociation product dialyse more slowly than solutions of similar strength of nickel carbonate, and at a certain stage in the dialysis the greater part of the nickel is adsorbed into the membrane.11. No constant ratio exists between the nickel and the nitrogen contents of solutions of dissociation product in serum of different strengths.12. When the proteids of the serum, containing the product of dissociated nickel carbonyl in solution, are precipitated by ammonium sulphate, nine-tenths of the nickel remains in solution. One-tenth is precipitated by adding sufficient ammonium sulphate to produce one-third of saturation, and about an additional one-hundredth by producing one-half of saturation.13. The product of dissociated nickel carbonyl when dissolved in serum is only incompletely removable from solution by dialysis.The product of dissociated nickel carbonyl is therefore not identical with nickel carbonate or nickel hydrate, and appears to exist in a condition of colloidal solution.14. The poisonous properties of nickel carbonyl do not depend, as was at first supposed, on the carbon monoxide of the compound.15. Nickel carbonyl when mixed with air and inhaled by an animal, cannot be absorbed as such, as it becomes split up into the nickel containing substance (? hydrated basic carbonate of nickel) and carbon monoxide, before or soon after reaching the alveoli of the lungs.16. The poisonous effects of nickel carbonyl are entirely due to the nickel of the compound. The peculiar toxicity of the compound is due to the fact that being introduced in a gaseous form and that the nickel is deposited as a slightly soluble compound in a very fine state of subdivision over the immense area of the respiratory surface.
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.
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