Cholecalciferol
Properties
| State | Solid (white to yellowish crystalline powder) |
| Color | White to yellowish |
| Solubility | Insoluble in water; soluble in ethanol, acetone, ether, and fats/oils |
| Melting Point | 83-86°C |
| Boiling Point | Decomposes before boiling |
About Cholecalciferol
Cholecalciferol is a secosteroid — a steroid where one of the rings has been broken open — and the broken ring (the B ring of the parent cholesterol skeleton) is what makes it a vitamin D rather than a regular steroid. The biosynthesis runs in your skin: 7-dehydrocholesterol absorbs a UVB photon between 290 and 315 nm, the B ring undergoes a six-electron pericyclic ring-opening to give pre-vitamin D3, and that thermally isomerizes over the next few hours to cholecalciferol via a [1,7]-sigmatropic hydrogen shift. The product itself is hormonally inactive — it has to be hydroxylated twice to do anything. The first hydroxylation runs in the liver via CYP2R1 and CYP27A1 to give 25-hydroxyvitamin D (calcidiol), which is the metabolite measured in your blood test because it has a half-life of about three weeks and reflects long-term status. The second hydroxylation runs in the kidney via CYP27B1 under tight PTH and FGF23 control to give 1,25-dihydroxyvitamin D (calcitriol), which is the actual hormone. Calcitriol binds the vitamin D receptor (a nuclear hormone receptor in the same family as the thyroid and retinoic acid receptors), heterodimerizes with RXR, and activates transcription of calcium-binding protein, the epithelial Ca2+ channel TRPV6, and a few hundred other genes that handle Ca2+ and phosphate handling. Deficiency gives rickets in kids and osteomalacia in adults — soft bones — and remained a major public health problem in northern latitudes until milk fortification rolled out in the US starting in the 1930s.
Where you'll encounter it
If you've ever had a 25-OH vitamin D blood test come back below 30 ng/mL, the supplement your doctor handed you is cholecalciferol, almost always made by UV-irradiating 7-dehydrocholesterol extracted from sheep's wool lanolin. The lanolin connection is why D3 is technically not vegan — the vegan alternative is ergocalciferol (D2) made by UV-irradiating ergosterol from yeast, but D2 raises serum 25-OH-D less efficiently than D3 at the same dose. In a clinical lab, the LC-MS/MS method for measuring 25-OH-D simultaneously quantifies the D2 and D3 forms and reports total — important because vegan patients on D2 supplements can look deficient on assays that don't distinguish.
Common Uses
- Oral supplement for treating and preventing 25-OH-D deficiency at doses from 600 to 50,000 IU per dose
- Fortification of milk, breakfast cereals, orange juice, and infant formula to public health targets
- Treatment for nutritional rickets in children and osteomalacia in adults at prescription doses
- Adjunctive therapy for chronic kidney disease patients alongside calcium and phosphate management
- Veterinary feed additive for poultry, swine, and dairy cattle to prevent rickets and milk fever
- Reference compound in LC-MS/MS clinical assays for serum 25-hydroxyvitamin D quantification
- Active ingredient in some rodenticides (very high doses cause fatal hypercalcemia in rodents)
- Research substrate for studying vitamin D receptor-mediated transcriptional regulation
Safety Information
Acute toxicity from a single dose is essentially impossible at supplement levels — the LD50 in rats is around 42 mg/kg, which would be roughly 3 grams in an adult human, equivalent to 120 million IU. Chronic supplementation above 10,000 IU/day eventually causes hypervitaminosis D: serum 25-OH-D climbs above 150 ng/mL, calcitriol-driven calcium absorption pushes serum calcium above 11 mg/dL, and you get nausea, polyuria, kidney stones, and metastatic calcification of soft tissues including the kidneys and arteries. The Tolerable Upper Intake Level set by the IOM is 4000 IU/day for adults, with a no-observed-adverse-effect level around 10,000 IU/day. Sun exposure cannot cause toxicity because previtamin D3 photoisomerizes to inactive lumisterol and tachysterol once skin levels saturate — the skin self-regulates. The OSHA-relevant occupational hazard is dust exposure during pharmaceutical manufacturing; the manufacturing limit is typically set at 0.1 mg/m3.
This safety summary is for educational reference only and may not be complete. It is not a substitute for Safety Data Sheets (SDS), medical advice, or professional chemical safety guidance. Always consult appropriate SDS and qualified professionals before handling chemicals. We deliberately do not publish occupational exposure limits or other regulatory thresholds: those values are revised over time and differ between jurisdictions, so the only correct source is the current SDS and the regulations that apply where you work.