TOXICOLOGIC STUDIES OF HORMONAL FORM OF VITAMIN-D3 - ACUTE AND SUBACUTE TOXICITY OF 1-ALPHA-HYDROXYCHOLECALCIFEROL

Toxicologic examination of 1.alpha.-hydroxycholecalciferol (1.alpha.-HCC) revealed its acute toxicity to be high, and the sex variation in sensitivity of the rat to be slightly different. In subacute toxicity studies in rats, body weight gain was extremely inhibited in the animals which received 12.5, 25 and 50 .mu.g/kg. Urinalysis revealed higher Ca concentration in the urine of experimental groups while excretion of urinary phosphate was reduced in the rats receiving 12.5, 25 and 50 .mu.g/kg. Proteinuria was seen in rats of 12.5 .mu.g/kg and higher dose groups. Blood cell counts showed moderate leukocytosis in the higher dose groups than in the 12.5 .mu.g/kg group. Laboratory tests in blood indicated that plasma Ca concentration, total protein, total cholesterol and blood urea N in the 12.5-.mu.g/kg and higher dose groups were elevated significantly. Though scattered, histological changes were seen in the kidney, heart, aorta, testes, thymus, lung, liver, thyroid and intestinal mucosa. The main action of 1.alpha.-HCC was recognized in the necrosis of the intima of the arteriole in the heart, in digestive tracts and in voluntary muscles, resulting from the degeneration and fibrosis of muscles. All those lesions which were caused by the administration of 1.alpha.-HCC were fully reversible after 50 days in the recovery group. In rats, oral administration of 2.5 .mu.g/kg of 1.alpha.-HCC for 30 days was considered to be a nontoxic dose under the conditions of this experiment.