The comparative toxicity of vitamin D metabolites in the weanling mouse.
The potential toxicity of vitamin D, alpha-calcidol [1 alpha(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 alpha-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 alpha-calcidol had significantly higher serum calcium and urinary calcium/creatinine ratios than other groups. Severe nephrocalcinosis was observed in the high-dose alpha-calcidol group only. We conclude that alpha-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.
D000818:Animals; D002117:Calcitriol / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D004872:Ergocalciferols / Q000633:toxicity*; D006887:Hydroxycholecalciferols / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014886:Weaning
D004872:Ergocalciferols; D006887:Hydroxycholecalciferols; D002117:Calcitriol; D002118:Calcium; C008088:alfacalcidol