1 -Hydroxyvitamin D2 is Less Toxic than 1 -Hydroxyvitamin D3 in the Rat

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Abstract
An LD50 of 0.2 mg/kg body wt was determined for 1.alpha.-hydroxyvitamin D3 in the rat. In comparison, the LD50 for 1.alpha.-hydroxyvitamin D2 is between 3.5-6.5 mg/kg. In terms of chronic toxicity, 1.alpha.-hydroxyvitamin D3 at a dose of 5 .mu.g/kg per day-1 causes death of 1/2 the animals in a 4-wk period. On the other hand, 20 .mu.g/kg day-1 of 1.alpha.-hydroxyvitamin D2 is required to induce similar toxicity. The body wt record and renal Ca accumulation during chronic treatment support the above conclusion. 1.alpha.-hdyroxyvitamin D2 is between 5-15 times less toxic than 1.alpha.-hydroxyvitamin D3. This surprising result prompted a reexamination of the relative biological activity of 1.alpha.-hydroxyvitamin D2 and 1.alpha.-hydroxyvitamin D3. Both compounds are equally potent in the stimulation of intestinal Ca transport, bone Ca mobilizationk in the elevation of serum P and in the healing of rickets in the rat. The reason for lower toxicity of 1.alpha.-hydroxyvitamin D2 is unknown. 1.alpha.-Hydroxyvitamin D2 might represent a therapeutically superior compound.