Long Time Feeding Experiments With Activated Ergosterol. I

In the earliest reference to the action of large doses of irradiated ergosterol, Rosenheim and Webster(1) reported that 10,000 times the minimum antiricketic dose was not lethal to rats.Kreitmair and Moll (2), using "enormous doses," described pathological findings for several species, and observed a species difference in susceptibility.Collazo, Rubino, and Varela (3) observed that rats died within 6 weeks when fed the McCollum high calcium, rickets-producing Diet 3143 plus 50,000 times overdosage of activated ergosterol.The important work of Harris and Moore (4) demonstrated that 1000 times overdosage of vitamin D was harmless to rats, whereas 100,000 times overdosage was rapidly fatal.The agent which produced the characteristic lesions was apparently the activated ergosterol per se, and not unchanged ergosterol or decomposition products.Light, Miller, and Frey (5) reported that while 100,000 times overdosage was fatal, 10,000 times had no effect on growth during 6 months.Numerous other papers, mostly quite uncritical, have dealt with the effects of extraordinary doses.In nearly every case the authors failed to determine the potency of the product which they employed.They stated only the quantity of irradiated ergosterol in mg.It must be accepted that remarkably large doses of activated ergosterol are not immediately toxic, although sufficiently enormous doses do produce serious effects.Up to the present, published experiments have been based on short time tests, covering at the most a few months of life in the rat.It is our purpose to describe the results of tests continued from infancy to old age.The ergosterol was activated by exposing a solution in arachis 117