Relation of Calcium and Phosphorus of Diet to Toxicity of Viosterol. ∗

The discrepancies apparent in the literature as to the toxicity of viosterol may be attributed to (1) differences in the potency of the viosterol, (2) the character of the diet in regard to its content of calcium and phosphorus, (3) the age of the animals at the beginning of the experiment and (4) the duration of the experiments. Thus, many published results are based on the use of viosterol of unknown potency and varying methods of assay; and the diets employed range between an undescribed so-called “normal diet”, through the Steenbock and McCollum rachitogenic diets, to diets consisting of “table-left-overs”.

In the present study an attempt was made to ascertain the relation of calcium and phosphorus of the diet to the toxicity of viosterol.

The rats used were of our own breeding stock and were put on the experimental diets at the time of weaning. The viosterol was incorporated in the diet; the dosage was calculated in cod liver oil equivalents, i. e., the amount of viosterol which produced a line test in 5 days, when added to the Steenbock rachitogenic diet, equaled 1/4% of the diet in terms of cod liver oil potency.

(a) Steenbock-Bills stock diet. Ca = 0.515, P = 0.450 gm. %.

The toxicity, duration of life and well-being of animals on this diet are directly proportional to the dose of viosterol. 40,000 to 80,000 times overdosage is very rapidly fatal, sometimes with little evidence of metastatic calcifications, especially the 80,000 times overdosage. On 10,000 and 20,000 times overdosage animals do well at first, then they begin to decline in health and finally die, showing calcification of most organs, especially of the vascular system. Those on 2,000 and 4,000 times overdosage were killed at 10 months.