THE PATHOLOGICAL EFFECTS UPON RATS OF EXCESS IRRADIATED ERGOSTEROL 1

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Abstract
Oral administration of 2 to 4 mgm. of irradiated ergosterol in the form of vigantol to rats 4 to 7 wk. old, on a normal diet, resulted in loss of weight and death in 5 to 14 days. Roentgenograms disclosed increased density at the epiphyseal ends of the diaphysis of the long bones after 3 to 4 days. Serum Ca was raised, the in-organic P slightly lowered. The bones showed lack of mineralization and even slight but definite demineral-ization. Parenchymatous degeneration, necrosis, and calcification occurred in various organs but mainly in renal tubules, vessels of kidney, muscle and heart and in the muscularis and mucosa of the stomach. Calcification also appeared in lungs and aorta, rarely in the adrenals. The irritative and toxic effects were due either to the irradiated ergosterol or to an irradiated impurity in the vigantol. The Ca deposits were probably in part a manifestation of so-called "metastatic calcification." In rats fed on diets deficient in either Ca or P, calcification was delayed and less severe but the degenerative changes were as severe as in animals fed on a normal diet. The healing of rickets which occurred in these rats, in the presence of overdosage of the therapeutic agent, was associated with deposition of Ca in the metaphysis; but analysis of the whole femur showed that the mineral content was normal or even diminished. Lack of mineralization or even demineralization of the shaft must have occurred. Therefore rickets may be healed by a rearrangement and not a retention of Ca and P in the bones.