Abstract
The toxicity of lead given intravenously depends entirely upon the form of lead given. The fourteen compounds studied may be divided into four groups, when one considers the effect upon the erythrocytes. The most toxic group comprises ionic lead, colloidal lead hydroxide, metallic lead, glycerophosphate, oleate and stearate. The lead hydroxide and glycerophosphate are quite soluble. The metallic lead oxidizes to the hydroxide in the blood stream. All these compounds function potentially as ionic lead. The next most toxic group includes colloidal lead oxy chloride, oxy carbonate, and carbonate. These compounds are very insoluble and probably are removed from the blood stream before they have had a chance to react with the constituents of the blood. From two to four times the dose of the second group must be given to cause a drop in hemoglobin comparable to the first group. The third group includes tetra ethyl lead and tri ethyl lead chloride. These compounds bring about only a slight drop in hemoglobin even when the lethal dose is approached. Since the lead is linked to carbon, they are not capable of forming lead ions, until hydrolysis takes place. This hydrolysis is a slow process and is probably brought about outside the blood stream. Group four comprises tri lead phosphate, di lead phosphate and lead sulfide. These compounds have no demonstrable effect upon the red cells. The di lead phosphate probably goes over to the tri lead phosphate when it reaches the blood stream. Lead phosphate and sulfide are highly insoluble and stable compounds at the pH of the blood.
The lethal dose for a compound is difficult to evaluate because of the great variation in tolerance for different rabbits. For compounds which function potentially as ionic lead the lethal dose varies from 3 to 10 mgm. of lead per kilogram. For com pounds of the type of lead oxy carbonate, 16 mgm. of lead per kilogram has been given without death, although 4 mgm. have occasionally been fatal. The lethal dose for tri ethyl lead chloride is of the same order as ionic lead and that for tetra ethyl lead the same as for lead oxy carbonate. For the pregnant animal this generalization does not hold, tetra ethyl lead being no more toxic and lead oxy carbonate being extremely toxic. This difference has been accounted for by the observation that lead oxy carbonate damages the liver, the organ burdened in pregnancy, and that tetra ethyl lead does not effect the liver. The lethal dose for lead phosphate has not been ascertained, the compound apparently being without, toxic effect.2
The effect of lead in weakening the progeny could be demonstrated for lead phosphate, tetra ethyl lead, lead oxy chloride and lead carbonate. The effect upon the chorion was only certain in one instance.
Colloidal lead phosphate and ionic lead are substantially removed from the blood stream of the rabbit in two hours.
A detailed report of the preparation of suspensions of lead carbonate, lead oxy carbonate, lead oxy chloride, lead sulfide and di lead phosphate, is included.
Colloidal lead phosphate and tetra ethyl lead appear to be the only lead compounds suitable for trial in intravenous cancer therapy.
Footnotes
- Received March 24, 1928.
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