Studies on the Effect of High Doses of Irradiated and Non-irradiated Ergosterol on the Albino Rat

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Abstract
Commercial preparations of irradiated ergosterol of exceptional potency were standardized by the McCollum line test and found to possess the claimed activity. Ten albino rats were placed on a stock diet plus 100 to 800 times the therapeutic rat dose of this preparation for 36 weeks without observing harmful effects. The progeny of 48 second, 35 third, 4 fourth, 18 fifth and 12 sixth generation rats were placed on the same stock diet plus doses up to 50,000 times the curative dose without observing harmful effects. The sixth generation animals were treated for 18 weeks, all others were treated for longer periods. Pure ergosterol was irradiated in the solid form by a Cooper-Hewitt mercury are lamp and fed to albino rats and their offspring in amounts up to 25,000 times the curative dose for 10 to 23 weeks without harmful effects. Albino rats were placed on the McCollum 3143 diet with and without the commercial preparation in amounts up to 10,000 times the therapeutic rat dose. Although most of the animals died in less than 30 weeks, no true hypervitaminosis could be detected. Young and adult albino rats were kept on a stock diet including bread and milk, plus 46,500 times the therapeutic rat dose for 3 weeks without harmful effects. Young albino rats were placed on a stock diet including bread and milk plus 93,000 times the curative dose for 12 months when some of them showed loss of weight. Adult animals under the same conditions showed immediate loss of weight and in some cases died with pathological findings similar to those indicated below. Young and adult albino rats were placed on a stock diet including bread and milk plus 465,000 times the therapeutic rat dose with the appearance of immediate toxic effects. There were immediate loss of appetite and weight, bloody discharge from the nose, diarrhea, marked muscular flabbiness, and gross pathological changes involving enlarged suprarenals, atrophied thymus and abnormal appearance of the kidney and heart. The adult animals were again more susceptible than the young ones. Rachitic diet was substituted for the stock diet on the 46,50093,000 and 465,000 dosage experiments on young animals. This change made the animals more susceptible. Potassium iodide was added on the dosages of 93,000 times the curative amount without changing the picture. Young from mothers on 10,000 times the therapeutic rat dose were weaned and placed on the rachitic diet. Only very slight rickets developed. Similar young, but nursed by stock diet foster mothers, developed typical rickets. These results indicate that the toxic effects observed by others on relatively low dosages of irradiated ergosterol are due to the presence of a toxic substance other than the true antirachitic agent in appreciable amounts in the preparations tested. Whether the toxic effects observed by us on our commercial preparation when given in the very high doses are due to a trace of this hypothetical by-product or to the vitamin D substitute remains to be determined. Our results again indicate that the toxicity of a given irradiated ergosterol preparation is also determined in part by the character of the diet. In general, the more complete and better balanced diets act in a more protective manner.

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