[Comparative study of the toxicity of 1 alpha-hydroxyvitamin D3 and 24,25 (RS)-dihydroxyvitamin D3 in rats]

The toxic effects of 1 alpha (OH)D3 and 24,25 (OH)2D3 administered in doses of 0.25, 2.5 and 25 micrograms per animal a day were compared in rats weighing initially 230-260 g and fed an artificial diet containing 0.65 and 0.50% of Ca and P, respectively. After 5 days of administering different doses of 1 alpha (OH) D3 hypercalcemia and hyperphosphatemia developed whatever the dose, the animals' weight and density of the osseous tissue dropped starting with a dose of 2.5 micrograms, together with a high death rate and Ca accumulation by soft tissues at a dose of 25 micrograms per animal. Unlike 1 alpha (OH)D3, 24,25 (OH)2D3 did not exert any hypercalcemic or hyperphosphatemic action when given in a high dose (25 micrograms). On the contrary, it promote the decrease of the Ca and P blood levels. 24,25 (OH)2D3 did not bring about Ca accumulation by the organs or reduction of the osseous tissue density whatever the dose applied. In addition, the metabolite administered in a dose of 25 micrograms arrested the animals' growth. Thus, when given in comparable doses (the physiologic requirement of 1 alpha (OH)D3 and 24,25 (OH)2D3 for rats are 0.025 and 0.25 micrograms/day, respectively), 24,25 (OH)2D3 was at least one order of magnitude less active as regards its capacity to increase the Ca and P blood levels and to resorb the osseous tissue. The data obtained and the inhibitory effect on the growth of the 100-fold dose of 24,25 (OH)2D3 point to the feasibility of the short-term use of the metabolite in doses that do not exceed more than 10-fold the physiologic dose.