9,10-Secoergosta-5,7,10(19),22-tetraen-3-ol, (3beta,5Z,7E,22E,24S)-

Ergocalciferol capsules, oral solution, and tablets should be stored in tight, light-resistant containers at a temperature less than 40 °C, preferably between 15-30 °C.

Ergocalciferol injection should be protected from light and stored at a temperature less than 40 °C, preferably between 15-30 °C.

(Non-Specific -- Medicines, n.o.s.) Keep unnecessary people away; isolate hazard area and deny entry. Stay upwind; keep out of low areas. Shut off ignition sources; no flares, smoking or flames in hazard area. Keep combustibles (wood, paper, oil, etc.) away from spilled material. Do not touch spilled material.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

For emergency situations, wear a positive pressure, pressure-demand, full facepiece self-contained breathing apparatus (SCBA) or pressure- demand supplied air respirator with escape SCBA and a fully-encapsulating, chemical resistant suit. (EPA, 1998)

The treatment of hypervitaminosis D with hypercalcemia consists in immediate withdrawal of the vitamin, a low calcium diet, generous intake of fluids, along with symptomatic and supportive treatment. Hypercalcemic crisis with dehydration, stupor, coma, and azotemia requires more vigorous treatment. The first step should be hydration of the patient. Intravenous saline may quickly and significantly increase urinary calcium excretion. A loop diuretic (furosemide or ethacrynic acid) may be given with the saline infusion to further increase renal calcium excretion. Other reported therapeutic measures include dialysis or the administration of citrates, sulfates, phosphates, corticosteroids, EDTA (ethylenediaminetetraacetic acid), and mithramycin via appropriate regimens. (L1712)

The effect of calcitriol (1,25-dihydroxyvitamin D3) on the conversion of ergocalciferol (vitamin D2) to 25-hydroxyvitamin D in 20 normal subjects receiving 2 separate doses of ergocalciferol, one with and one without concomitant administration of calcitriol is described. The concurrent administration of the 2 drugs made no difference to serum calcitriol concentrations.

The effects of glutethimide therapy, 500 mg/day, on the metabolism of vitamin D in a 77 yr old female patient who had taken an overdose of vitamin D2 are reported. Hypercalcemia in this patient was associated with raised serum concentrations of total 25-hydroxyvitamin D and total 1,25-dihydroxyvitamin D. Eight days after administration of glutethimide, plasma gamma-glutamyltransferase activity rose above the upper limit of normal, peaking at 90 IU/L on days 18-22 of therapy. The plasma calcium concentration fell to within the normal range on day 13. The serum concentration of 1,25-dihydroxyvitamin D began to fall within 4 days, and after 8 days it was near the lower limit of the reference range, at 70 pmol/L. The serum concentration of total 25-hydroxyvitamin D did not change appreciably until hepatic enzymes were induced; thereafter it fell gradually. Although the 25-hydroxyvitamin D concentration remained high, the concentration of 1,25-dihydroxyvitamin D did not rise again but remained within the lower part of the normal range.

The effect of a high cholesterol diet and corticosteroids on the toxicity of vitamin D2 in rats was studied. Vitamin D2 was administered orally at the dosage of 5X10+4 to 60X10+4 IU/kg, once daily for 4 days. Animals fed cholesterol showed a decrease in mortality due to vitamin D2 treatment. Dietary cholesterol inhibited toxic responses such as a diminished growth rate following anorexia, elevated serum calcium level and calcium deposition in tissues, which were produced by a sublethal dose of vitamin D2 (20X10+4 IU/kg, once daily for 4 days). Animals pretreated with the high cholesterol diet from 2 wk before the first vitamin D2 administration showed much more symptomatic relief than those given this diet after the first vitamin D2 administration. On the other hand, dexamethasone as well as corticosterone remarkably increased the mortality due to vitamin D2. The degree of vitamin D2 toxicity, enhanced by dexamethasone, was correlated with the degree of hypercalcemia and tissue calcification. Therefore, the inhibitory effect of cholesterol is not likely to be due to activation of the cholesterol corticosterone system in the adrenal gland.

The effect of short term treatment with pharmacological doses of vitamin D2 or vitamin D3 on the serum concentration of 1,25(OH)2D metabolites was examined in epileptic patients on chronic anticonvulsant drug therapy. Nine patients were studied before and after treatment with vitamin D2 4000 IU daily for 24 wk and 10 before and after treatment with vitamin D3 in the same dose. Before treatment the serum concentrations of 1,25(OH)2D and 25(OH)D were significantly lower in epileptics than in normal subjects (p< 0.01). Vitamin D2 treatment increased the serum concentration of 1,25(OH)2D2, but a corresponding decrease in 1,25(OH)2D3 resulted in an unchanged serum concentration of total 1,25(OH)2D. The serum concentration of 25(OH)D2 and 25(OH)D increase significantly, whereas there was a small decrease in 25(OH)D3. Vitamin D3 treatment did not change the serum concentration of 1,25(OH)2D3 whereas serum 25(OH)D3 increased significantly. The correlation between the serum ratio of 1,25(OH)2D2/1,25(OH)2D3 and 25(OH)D2/25(OH)D3 estimated on vitamin D2 treated epileptic patients and normal subjects was highly significant (p< 0.01). The data indicate that the serum concentration of 1,25(OH)2D2 and 1,25(OH)2D3 are directly proportional to the amount of their precursors 25(OH)D2 and 25(OH)D3 and that the concentration of total 1,25(OH)2D is tightly regulated.

Vitamin D analogs should be administered with caution in patients receiving cardiac glycosides, because hypercalcemia in these patient may result in cardiac arrhythmias. Vitamin D analogs should also be used with caution in patients with increased sensitivity to these drugs. /Vitamin D analogs/

Vitamin D2 is the form of vitamin D most commonly added to foods and nutritional supplements. Vitamin D2 must be transformed (hydroxylated) into one of two active forms via the liver or kidney. Once transformed, it binds to the vitamin D receptor that then leads to a variety of regulatory roles. Vitamin D plays an important role in maintaining calcium balance and in the regulation of parathyroid hormone (PTH). It promotes renal reabsorption of calcium, increases intestinal absorption of calcium and phosphorus, and increases calcium and phosphorus mobilization from bone to plasma. Vitamin D2 and its analogs appear to promote intestinal absorption of calcium through binding to a specific receptor in the mucosal cytoplasm of the intestine. Subsequently, calcium is absorbed through formation of a calcium-binding protein. Activated ergocalciferol increases serum calcium and phosphate concentrations, primarily by increasing intestinal absorption of calcium and phosphate through binding to a specific receptor in the mucosal cytoplasm of the intestine. Subsequently, calcium is absorbed through formation of a calcium-binding protein. 25-hydroxyergocalciferol is the intermediary metabolite of ergocalciferol. Although this metabolite exhibits 2-5 times more activity than unactivated ergocalciferol in curing rickets and inducing calcium absorption and mobilization (from bone) in animals, this increased activity is still insufficient to affect these functions at physiologic concentrations. Activated ergocalciferol stimulate resorption of bone and are required for normal mineralization of bone. Physiological doses of ergocalciferol also promotes calcium reabsorption by the kidneys, but the significance of this effect is not known.

/HUMAN EXPOSURE STUDIES/ There is a relationship between excess maternal vitamin D intake or extreme sensitivity to the vitamin and nonfamilial congenital supravalvular aortic stenosis. In infants, this anomaly is often found in association with other stigmata of hypercalcemia. /Vitamin D/

/HUMAN EXPOSURE STUDIES/ Serious toxicity may result from excessive ingestion of vitamin, and even as little as 1800 USP units per day in infants may lead to possible inhibition of growth. /Vitamin D/

/HUMAN EXPOSURE STUDIES/ Maternal hypercalcemia may also result in suppression of parathyroid function in the newborn with resultant hypocalcemia, tetany, and seizures. /Vitamin D/

Benchmark Dataset for the Liver Toxicity Knowledge Base (LTKB)

ergocalciferol

Drisdol®

Vitamins

Not Applicable

no-DILI-concern

/LABORATORY ANIMALS: Acute Exposure/ Lethal dose in dog is said to be ... 13 mg/kg (530,000 iu/kg) body weight. Immediate effects are bloody diarrhea, anorexia, thirst, polyuria & prostration. In surviving animals calcium is deposited as in chronic hypervitaminosis-d. /vitamin D/

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Topical application of ergocalciferol to hairless mouse dorsal skin, and exposure to solar-simulating ultraviolet (UV) radiation at a dose of 10.8 J/cm(2) (UVA) were performed for 15 weeks, five times a week on weekdays. At the end of the final irradiation, histological and analytical studies were performed. Topical application of ergocalcifero significantly prevented wrinkle formation and abnormal accumulation of extracellular matrix components. In addition, ergocalcifero suppressed excessive secretion of IL-6 induced by UV irradiation in cultured human normal keratinocytes, in a dose-dependent manner. Ergocalcifero promoted keratinocytes differentiation in the epidermis and showed diverse physiological effects, the same as the active form of VD(3). The results suggested that the suppression of skin photodamage involved the promotion of keratinocytes differentiation and suppression of IL-6 secretion induced by exposure to UV. Topical application of ergocalciferol may become an effective means to suppress solar UV-induced human skin damage.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ ... Excessive doses ... over extended period of time, hypercalcemia & calcification of blood vessels, muscles & other tissues may result in experimental animal. In hypervitaminosis D calcium salts are laid down in mucopolysaccharide matrix in soft tissues.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Similar lesions /of congenital supravalvular aortic stenosis/ have been produced experimentally in offspring of rabbits treated with large doses of vitamin D during pregnancy. /Vitamin D/

For more Non-Human Toxicity Excerpts (Complete) data for VITAMIN D2 (6 total), please visit the HSDB record page.

Emergency and supportive measures: Treat fluid loses caused by gastroenteritis with intravenous crystalloid solutions. Treat vitamin ... D induced hypercalcemia if /it/ occurs.

Recommended treatment includes the following: Hypervitaminosis D is treated by withdrawal of the vitamin, low-calcium diet, and generous fluid intake. If hypercalcemia persists, prednisone may be started. Severe hypercalcemia may be treated with calcitonin, etidronate, pamidronate, or gallium nitrate. Hypercalcemic crisis requires vigorous hydration with intravenous saline to increase calcium excretion, with or without a loop diuretic. Cardiac arrhythmias may be treated with small doses of potassium with continuous cardiac monitoring. Therapy may be reinstituted at a lower dose when serum calcium concentrations return to normal. Serum or urinary calcium levels should be obtained twice weekly after dosage changes. / Vitamin D and analogs/

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

Vitamin D2 used as a dietary supplement in food for human consumption is generally recognized as safe when used in accordance with good manufacturing practice.

Vitamin D2 used as a nutrient and/or dietary supplement in animal drugs, feeds, and related products is generally recognized as safe when used in accordance with good manufacturing or feeding practice.

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Ergocalciferol is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 1,000/10,000 lbs.

Synthetic form of vitamin D used as a rodenticide and therapeutic vitamin; [Merck Index] Used as a nutritional supplement; [FDA]

No active pesticide product registrations in the US; [NPIRS]

MEDICATION

MEDICATION (VET)

Rodenticide.

For use in the management of hypocalcemia and its clinical manifestations in patients with hypoparathyroidism, as well as for the treatment of familial hypophosphatemia (vitamin D resistant rickets). This drug has also been used in the treatment of nutritional rickets or osteomalacia, vitamin D dependent rickets, rickets or osteomalacia secondary to long-term high dose anticonvulsant therapy, early renal osteodystrophy, osteoporosis (in conjunction with calcium), and hypophosphatemia associated with Fanconi syndrome (with treatment of acidosis).

/Is/ the synthetic form of vitamin D. Prepared from ergosterol by UV irradiation in a suitable solvent. ... The best wavelengths for production of vitamin D2 seem to be from 275 to 300 nm ... Prepn by electron bombardment of ergosterol using longer waves ... .

Usually obtained from yeast which synthesizes it from simple sugars such as glucose.

Ergocalciferol capsules usually consist of the drug in an edible oil solution encapsulated with gelatin. Commercially available ergocalciferol solution is a clear solution of the drug in an edible vegetable oil or in propylene glycol. Ergocalciferol injection is a sterile solution of the drug in sesame oil.

Ergocalciferol is also commercially available in combination with other vitamins and minerals, analgesic-antipyretics, amino acids, infant formulas, laxatives, and protein supplements.

Parenteral: Injection (for IM use only): 12.5 mg (500,000 units) per mL, Calciferol (in oil), (Schwarz)

Ergocalciferol (calciferol; Drisdol) is pure vitamin D2. ... Available in capsules or tablets that contain 1.25 mg (50,000 USP units) each. An oral solution (8,000 units/mL) of the vitamin in propylene glycol is also available. An injection in oil (500,000 units/mL) is available for im administration. ... Dihydrotachysterol (DHT; hytakerol) is the pure crystalline compound obtained by reduction of vitamin D2 ... Available as tablets (0.125 to 0.4 mg), capsules (0.125 mg), an oral soln (0.2 mg/mL) & a soln in oil (0.2 mg/mL).

For more Formulations/Preparations (Complete) data for VITAMIN D2 (7 total), please visit the HSDB record page.

Cyclohexanol, 4-methylene-3-[(2E)-2-[(1R,3aS,7aR)-octahydro-7a-methyl-1-[(1R,2E,4R)-1,4,5-trimethyl-2-hexen-1-yl]-4H-inden-4-ylidene]ethylidene]-, (1S,3Z)-: ACTIVE

Information available in 2004 indicated that Ergocalciferol was used in the manufacture of pharmaceutical preparations in the following countries: Argentina, Australia, Austria, Brazil, Canada, Chile, Czech Republic, Denmark, Ecuador, Finland, France, Germany, Greece, Hong Kong, Ireland, Israel, Italy, Luxembourg, Malaysia, Mexico, Norway, Portugal, Romania, Slovakia, South Africa, Spain, Switzerland, Thailand, United Kingdom, USA (1,2)

International & USP units of vitamin D are equivalent in activity to 0.025 ug of crystalline vitamin D2.

Ergosterol, which is present in plants, is provitamin for vitamin D2 (calciferol). ... Vitamin D2 is active constituent in a number of commercial vitamin preparations as well as in irradiated bread & irradiated milk.

Vitamin D2 crystals have a potency of 40 units of vitamin D (USP)/ug.

Because of vitamin D2's sensitivity to oxygen and light, USP allows traces of antioxidants in crystalline compound.