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The Comparative Toxicity of Calciferol, A.T. 10, and Cod Liver Oil Concentrate for Chicks

Research Laboratories, The Upjohn Company, Kalamazoo, Michigan

1. Vitamin D from cod liver oil at 3 I.U. (11.1 mg.) daily affected normal mineral responses in chicks. When given at high levels no deviation from normal was seen with this particular concentrate, in the serum calcium, phosphorus, and phosphatase or the bone ash values; toxic manifestations were noted at about 5,000 times the minimal dose. It is recognized that the observed toxicity for the concentrate may be due to something besides its vitamin D activity.

2. Calciferol at 100 I.U. (2.5 µg.) yielded normal values; toxicity was apparent at about 1,000 times this dose. In enormous doses a slight hypercalcemia and bone dissolution was found. Phosphatase values remained low at these high levels.

3. Only 0.5 I.U. (16.6 µg.) of antirachitic activity was required daily from A.T. 10 to produce normal mineral metabolism in the chick. This emphasizes the individuality of the antirachitic substance present in A.T. 10 when compared with the other rickets-preventing sterols studied. A.T. 10 was toxic for chicks in these experiments at levels around ten times the minimal daily requirement. In the massive doses there was a hypercalcemia and bone dissolution.

4. A.T. 10, like vitamin D, will prevent rickets in chicks. Its effect in increasing serum calcium and lowering bone ash appears to be of a degree that resembles parathyroid hormone. However, even in massive doses it caused no increase in serum phosphatase. Thus this sterol preparation influences calcium metabolism in a manner which resembles both vitamin D and parathyroid hormone.

5. In no case where massive doses of sterols resulted in bone ash depletion, was there observed any increase in serum phosphatase concentration.