1α-Hydroxyvitamin D 2 is Less Toxic than 1α-Hydroxyvitamin D 3 in the Rat

Abstract

Abstract

An LD₅₀ of 0.2 mg/kg body wt has been determined for 1α-hydroxyvitamin D₃in the rat. In comparison, the LD₅₀ for 1α-hydroxyvitamin D₂ is between 3.5 and 6.5 mg/kg. In terms of chronic toxicity, lα-hydroxyvitamin D₃ at a dose of 5 μg/kg/day causes death of one-half the animals in a 4-week period. On the other hand, 20 μg/kg/day of 1α-hydroxyvitamin D₂ is required to induce similar toxicity. The body weight record and renal calcium accumulation during chronic treatment support the above conclusion. It therefore appears that 1α-hydroxyvitamin D₂ is between 5 and 15 times less toxic than 1α-hydroxyvitamin D₃. This surprising result prompted a reexamination of the relative biological activity of 1α-hydroxyvitamin D₂and 1α-hydroxyvitamin D₃, Both compounds are equally potent in the stimulation of intestinal calcium transport, bone calcium mobilization, in the elevation of serum phosphorus, and in the healing of rickets in the rat. The reason for lower toxicity of 1α-hydroxyvitamin D₂ is unknown. The results suggest that 1α-hydroxyvitamin D₂might represent a therapeutically Superior compound.