A CONSIDERATION OF THE RELATIVE TOXICITY OF URANIUM NITRATE FOR ANIMALS OF DIFFERENT AGES. I

1. The toxic effect of uranium when given in a constant quantity per kilo of body weight is variable. This variation has been constantly associated with differences in the age of the animals. Uranium is more toxic for an old animal than for a young animal. The establishment of this fact, namely, that the age of an animal may modify the toxicity of a substance, should be taken into account in establishing by animal experiment the degree of activity of substances which are to be used for therapeutic purposes. 2. The toxic effect of uranium nitrate is constantly associated with its ability to induce a tissue acidosis. A severer grade of acidosis is induced in an old animal from uranium than is induced in a young animal. It would appear that in the response of dogs of different ages to uranium the animals represent a reaction system to this substance which shows an increasing susceptibility as the animal advances from youth to senility. Insufficient experimental data are as yet available to allow a discussion of the mechanism by which such an acid intoxication is produced. 3. The toxic effect of uranium is manifested locally by certain degenerative changes in the kidney. These changes are more marked in the kidney of an old animal than they are in the kidney of a young animal. Associated with the severer kidney changes which are especially characterized by a beginning swelling of the renal epithelium and by an accumulation of stainable fat in these cells is the development of a severe grade of tissue acidosis. 4. The functional capacity of the kidney shows a parallel with the degree of acid intoxication and with the severity of the histological changes which have developed in the renal epithelium.