Chronic Toxicity of Dinitrophenol

Abstract

Conclusions

1. Daily subcutaneous injections in rabbits of alpha dinitrophenol in doses up to and including fatal ones, and for as long as 77 days, did not modify renal function as indicated by quantitative counts of the formed elements in the urinary sediment, according to Addis'method, and by excretion of phenolsulphon-phthalein. 2. Therefore, it is unlikely that dinitrophenol, in ordinary clinical dosage, will injure the kidneys.

In connection with the clinical use of alpha dinitrophenol (2–4), 1 it is important to know whether administration over long periods of time will produce changes in the functions of vital organs. Previous papers 2 from this laboratory contain limited data on this problem. This paper deals with the results of experiments designed to determine whether dinitrophenol in repeated subfatal doses injures the kidneys.

Two series of experiments were performed, the first, a quantitative study of the urinary sediment, and the second, an estimation of the phenolsulphonphthalein excretion. Adult male rabbits were used throughout.

Urinary sediment. Six rabbits were put on a diet consisting of rolled oats and water. This diet causes an acid urine, in which the casts do not dissolve. Each sample of urine was tested with phenol red to be sure it had the required acidity. Once or twice every 24 hours the rabbits were fastened to a board, catheterized, and the bladder washed out with physiological saline solution. They were then released, and after a measured interval of several hours, catheterized again, and the urine and bladder washings quantitatively collected. The washings were centrifuged and the casts, red blood cells, white blood and epithelial cells counted, according to Addis'method. 3 From these counts, the output of the formed elements in 24 hours was readily calculated. The cast count is claimed to be the most sensitive test for renal injury, since even slight degrees of renal damage are revealed by the increased numbers of casts. The other elements are also informative, although not so significant under our conditions, since slight trauma or infection from the frequent catheterization may increase the red and white cells in the urine.