The comparative toxicity of vitamin D metabolites in the weanling mouse

The potential toxicity of vitamin D, α-calcidol [1α(OH)D₃], and calcitriol [1,25(OH)₂D₃] was studied by administration of these compounds at three different doses to weanling C57BL 6J mice over a 4-week period. Drug effects on calcium were monitored by serum calcium and urine calcium/creatinine ratio determinations. Tests of renal function included serum creatinine, 24-h urine volume, urinary protein, and glucose excretion, and histological evaluation of renal tissue. At 2 weeks, serum calcium was significantly elevated in animals receiving the higher doses of α-calcidol (2.78 ± 0.25 at 50 ng/kg and 3.45 ± 0.13 at 250 ng/kg body wt vs 2.14 ± 0.06 mmol/l in controls, respectively). A similar effect was seen in the urinary calcium/creatinine ratio but serum creatinine remained unchanged. By 4 weeks, all animals receiving α-calcidol had significantly higher serum calcium and urinary calcium/creatinine ratios than other groups. Severe nephrocalcinosis was observed in the highdose α-calcidol group only. We conclude that α-calcidol is more toxic than calcitriol in the mouse and suggest that the degree of toxicity is correlated to the degree of hypercalcemia and to the vitamin D metabolite used.