Vitamin D3

384.64

384.64

2339331

200-673-2

2811

DTXSID1026295

C48194

Fine needles from dilute acetone|WHITE CRYSTALS|Colorless crystals

M05BB03|A11CC05|A - Alimentary tract and metabolism

2936240000

20.2

10.2 (est)

Vitamin d3 appears as fine colorless crystals. Water insoluble. (NTP, 1992)

0.939 g/cm³

84-85 °C

496.4±24.0 °C at 760 mmHg

14 °C

1.523

In water, 1.3X10-5 mg/L at 25 deg C (est)

2-8°C

2.0 x l0 -6 Pa (20 °C, est.)

LD50 oral in rat: 42mg/kg

105 º (c=0.8, EtOH 25 ºC)

ODORLESS

Henry's Law constant = 2.3X10-4 atm-cu m/mole at 25 °C (est)

Oxidized and inactivated by moist air within a few days|Hydroxyl radical reaction rate constant = 2.7X10-10 cu cm/molec-sec at 25 °C (est)

Sensitive to moisture, air and light. (NTP, 1992). Water insoluble.

Alcohols and Polyols

VITAMIN D3 may react vigorously with strong oxidizing agents. May react exothermically with reducing agents to release hydrogen gas.

II

6.1

UN 2811 6.1/PG 2

2

24/25-26-48/25-23/24/25-20-11-48

28-36/37-45-28A-36/37/39-16-7

VS2900000

T+,T,Xn,F

Vitamin-D3 is somewhat more stable than vitamin-D2, possibly because it has one less double bond

P260-P280-P284-P301 + P310-P310

H301 + H311-H330-H372

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.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl cholecalciferol, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.|Cholecalciferol is a food additive permitted for direct addition to food for human consumption, as long as 1) the quantity of the substance added to food does not exceed the amount reasonably required to accomplish its intended physical, nutritive, or other technical effect in food, and 2) any substance intended for use in or on food is of appropriate food grade and is prepared and handled as a food ingredient.|Substance added directly to human food affirmed as generally recognized as safe (GRAS).|Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: Cholecalciferol is included in wound healing drug products.

Flash point data for this chemical are not available. It is probably combustible. (NTP, 1992)

|Danger|H300: Fatal if swallowed [Danger Acute toxicity, oral]|P260, P262, P264, P270, P271, P280, P284, P301+P310, P302+P350, P304+P340, P310, P314, P320, P321, P322, P330, P361, P363, P403+P233, P405, and P501|H300 (13.88%): Fatal if swallowed [Danger Acute toxicity, oral]|P260, P262, P264, P270, P271, P280, P284, P301+P310, P302+P350, P302+P352, P304+P340, P310, P312, P314, P320, P321, P322, P330, P361, P363, P403+P233, P405, and P501|Aggregated GHS information provided by 1715 companies from 26 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P312, P304+P340, P305+P351+P338, P312, P321, P322, P330, P332+P313, P337+P313, P362, P363, and P501|Aggregated GHS information provided by 2 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H301: Toxic if swallowed [Danger Acute toxicity, oral]|P260, P264, P270, P271, P280, P284, P301+P310, P302+P352, P304+P340, P310, P312, P314, P320, P321, P322, P330, P361, P363, P403+P233, P405, and P501|P201, P202, P262, P264, P270, P280, P281, P301+P310, P302+P350, P308+P313, P310, P321, P322, P330, P361, P363, P405, and P501

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should protect this chemical from exposure to light. Keep the container tightly closed under an inert atmosphere, and store under refrigerated temperatures. (NTP, 1992)|SMALL SPILLS AND LEAKAGE: If you spill this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then dampen the solid spill material with toluene, then transfer the dampened material to a suitable container. Use absorbent paper dampened with toluene to pick up any remaining material. Your contaminated clothing and absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Solvent-wash all contaminated surfaces with toluene followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should store this material in a refrigerator. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

Chronic or acute administration of excessive doses of cholecalciferol may lead to hypervitaminosis D, manifested by hypercalcemia and its sequelae. Early symptoms of hypercalcemia may include weakness, fatigue, somnolence, headache, anorexia, dry mouth, metallic taste, nausea, vomiting, vertigo, tinnitus, ataxia, and hypotonia. Later and possibly more serious manifestation include nephrocalcinosis, renal dysfunction, osteoporosis in adults, impaired growth in children, anemia, metastatic calcification, pancreatitis, generalized vascular calcification, and seizures. Safety of doses in excess of 400 IU (10mcg) of vitamin D3 daily during pregnancy has not been established. Maternal hypercalcemia, possibly caused by excessive vitamin D intake during pregnancy, has been associated with hypercalcemia in neonates, which may lead to supravalvular aortic stenosis syndrome, the features of which may include retinopathy, mental or growth retardation, strabismus, and other effects. Hypercalcemia during pregnancy may also lead to suppression of parathyroid hormone release in the neonate, resulting in hypocalcemia, tetany, and seizures. Vitamin D is deficient in maternal milk; therefore, breastfed infants may require supplementation. Use of excessive amounts of Vitamin D in nursing mothers may result in hypercalcemia in infants. Doses of Vitamin D3 in excess of 10 µg daily should not be administered daily to nursing women.

Neither normal nor excessively high intakes of vitamin D are associated with liver injury or liver test abnormalities. Hypervitaminosis D and vitamin D intoxication generally arise with intakes above 50,000 IU daily, but lower doses may induce toxicity in susceptible individuals such as patients with renal osteodystrophy (secondary hyperparathyroidism), and a safer upper limit of recommended intake is 10,000 IU daily. Symptoms of vitamin D intoxication are caused by hypercalcemia and can include dehydration, thirst, polyuria, anorexia, nausea, vomiting, constipation, fatigue, bone pains and muscle cramps. Complications can include renal dysfunction, nephrocalcinosis, decreased consciousness and seizures. Symptoms arise a few weeks to several months after starting excess doses of vitamin D given orally or parenterally. A common cause of hypervitaminosis D is the mislabeling of an over-the-counter or locally prepared nutritional supplement, excessive fortification of milk or foods, and inadvertent prescription or dispensing errors. In clinical descriptions of vitamin D intoxication, typical laboratory findings are hypercalcemia, increase in serum creatinine, and high 25-OH vitamin D levels (usually above 200 ng/mL or 500 nmol/L). Serum aminotransferase and bilirubin levels are typically normal, while alkaline phosphatase levels may actually be lower than normal.

Corticosteroids counteract the effects of vitamin D analogs. /Vitamin D analogs/|Concurrent administration of thiazide diuretics and pharmacologic doses of vitamin D analogs in patients with hypoparathyroidism may result in hypercalcemia which may be transient and self-limited or may require discontinuance of vitamin D analogs. Thiazide-induced hypercalcemia in hypoparathyroid patients is probably caused by increased release of calcium from bone. /Vitamin D analogs/|Excessive use of mineral oil may interfere with intestinal absorption of vitamin D analogs. /Vitamin D analogs/|Orlistat may result in decreased GI absorption of fat-soluble vitamins such as vitamin D analogs. At least 2 hours should elapse between (before or after) any orlistat dose and vitamin D analog administration ... . /Vitamin D analogs/|For more Interactions (Complete) data for CHOLECALCIFEROL (6 total), please visit the HSDB record page.

A characteristic physiognomy, possibly with aortic valvular stenosis, retinopathy, and mental and/or physical retardation, has occurred following prolonged hypercalcemia in infants and in neonates of mothers with hypercalcemia during pregnancy. Hypercalcemia during pregnancy may also lead to suppression of parathyroid hormone concentrations in the neonate resulting in hypocalcemia, tetany, and seizures. Safe use of calcifediol, calcitriol, dihydrotachysterol, paricalcitol, or ergocalciferol during pregnancy and lactation has not been established; however, the risks to the mother and fetus from untreated hypoparathyroidism or hypophosphatemia may be greater than those resulting from administration of vitamin D analogs.

The protein binding documented for cholecalciferol is 50 to 80%. Specifically, in the plasma, vitamin D3 (from either diet or the skin) is bound to vitamin D-binding protein (DBP) produced in the liver, for transport to the liver. Ultimately, the form of vitamin D3 reaching the liver is 25-hydroxylated, and such 25-hydroxycholecalciferol is bound to DBP (α2-globulin) whilst circulating in the plasma.

CHOLECALCIFEROL IS VITAMIN D THAT OCCURS IN FISH LIVER OILS...CHOLECALCIFEROL IS ONE OF THE TWO STEROIDS--THE OTHER BEING ERGOCALCIFEROL (VIT D2)--THAT HAVE THE GREATEST, AND ESSENTIALLY EQUAL VITAMIN ACTIVITY.|VITAMIN D3 (CHOLECALCIFEROL) IS FORMED PHOTOCHEMICALLY FROM 7-DEHYDROCHOLESTEROL WHICH IN TURN IS FORMED FROM CHOLESTEROL.|IF THERE IS ADEQUATE EXPOSURE TO SUNLIGHT, VITAMIN D IS FORMED FROM STEROLS IN THE SKIN...|OCCURRENCE OF CHOLECALCIFEROL IN THE CALCINOGENIC PLANT TRISETUM FLAVESCENS IS DISCUSSED.

Cholecalciferol's production and use as a medication(1) may result in its release to the environment through various waste streams; it's use as a rodenticide(2) will result in its direct release to the environment(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1.5X10+6(SRC), determined from a structure estimation method(2), indicates that cholecalciferol is expected to be immobile in soil(SRC). Volatilization of cholecalciferol from moist soil surfaces may be an important fate process(SRC) given an estimated Henry's Law constant of 2.3X10-4 atm-cu m/mole(SRC), using a fragment constant estimation method(3). However, adsorption to soil is expected to attenuate volatilization(SRC). Cholecalciferol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.4X10-9 mm Hg(SRC), determined from a fragment constant method(4). Biodegradation data were not available(SRC, 2006).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1.5X10+6(SRC), determined from a structure estimation method(2), indicates that cholecalciferol is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces may be expected(3) based upon an estimated Henry's Law constant of 2.3X10-4 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column. The estimated volatilization half-life of cholecalciferol from a model pond is 85 years if adsorption is considered(5). According to a classification scheme(6), an estimated BCF of 3(SRC), from an estimated log Kow of 10.24(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2006).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), cholecalciferol, which has an estimated vapor pressure of 2.4X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase cholecalciferol may be removed from the air by wet or dry deposition(SRC). Cholecalciferol does absorb light at wavelengths >290 nm(3) and therefore may be susceptible to direct photolysis by sunlight(4).

The rate constant for the vapor-phase reaction of cholecalciferol with photochemically-produced hydroxyl radicals has been estimated as 2.7X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 1.4 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Cholecalciferol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). Cholecalciferol does absorb light at wavelengths >290 nm(2) and therefore may be susceptible to direct photolysis by sunlight(3).

An estimated BCF of 3 was calculated for cholecalciferol(SRC), using an estimated log Kow of 10.24(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of cholecalciferol can be estimated to be 1.5X10+6(SRC). According to a classification scheme(2), this estimated Koc value suggests that cholecalciferol is expected to be immobile in soil.

The Henry's Law constant for cholecalciferol is estimated as 2.3X10-4 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that cholecalciferol is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 7 hours(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 10 days(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column. The estimated volatilization half-life of cholecalciferol from a model pond is 85 years if adsorption is considered(3). Cholecalciferol's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). Cholecalciferol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.4X10-9 mm Hg(SRC), determined from a fragment constant method(4).

While data specific to cholecalciferol were not located(SRC, 2006), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2).

Occupational exposure to cholecalciferol may occur through dermal contact where cholecalciferol is produced or used. Since cholecalciferol is produced whenever skin is exposure to the sun, the general population produces cholecalciferol every time they are exposed to the sun. The general population is also exposed from the administration of cholecalciferol as a medication. (SRC)

Cholecalciferol use is indicated for the treatment of specific medical conditions like refractory rickets (or vitamin D resistant rickets), hypoparathyroidism, and familial hypophosphatemia. Concurrently, as one of the most commonly utilized forms of vitamin D, cholecalciferol is also very frequently used as a supplement in individuals to maintain sufficient vitamin d levels in the body or to treat vitamin D deficiency, as well as various medical conditions that can be associated directly or indirectly with vitamin d insufficiency like osteoporosis and chronic kidney disease, among others.|Treatment of postmenopausal osteoporosis in patients at risk of vitamin-D insufficiency.Adrovance reduces the risk of vertebral and hip fractures.|Treatment of postmenopausal osteoporosis in patients at risk of vitamin-D insufficiency., , Fosavance reduces the risk of vertebral and hip fractures.,|Treatment of postmenopausal osteoporosis in patients at risk of vitamin-D insufficiency.Vantavo reduces the risk of vertebral and hip fractures.Treatment of postmenopausal osteoporosis in patients who are not receiving vitamin-D supplementation and are at risk of vitamin-D insufficiency.Vantavo reduces the risk of vertebral and hip fractures.|Treatment of osteoporosis|Treatment of calcium and vitamin D3 deficiency, Prevention of calcium and vitamin D3 deficiency|Prevention of skeletal related events in patients with advanced malignancies involving bone|Combination treatment of osteoporosis

Vitamin D is a fat soluble vitamin important in the regulation of calcium metabolism and bone health and deficiency of which cause rickets, a disease marked by lack of mineralization of bone. Conventional doses of vitamin D are well tolerated without appreciable adverse effects. High doses of vitamin D can be toxic, leading to a constellation of signs and symptoms but not liver injury or jaundice.

Vitamins

Bone Density Conservation Agents; Vitamins|MEDICATION (VET): Nutritional factor (Antirachitic)|Therapeutic doses of specific vitamin D analogs are used in the treatment of chronic hypocalcemia, hypophosphatemia, rickets, and osteodystrophy associated with various medical conditions including chronic renal failure, familial hypophosphatemia, and hypoparathyroidism (postsurgical or idiopathic, or pseudohypoparathyroidism). Some analogs have been found to reduct elevated parathyroid hormone concentrations in patients with renal osteodystrophy associated with hyperparathyroidism. Theoretically, any of the vitamin D analogs may be used for the above conditions, However, because of their pharmacologic properties, some may be more useful in certain situations than others. Alfacalcidol, calcitriol, and dihydrotachysterol are usually preferred in patients with renal failure since these patients have impaired ability to synthesize calcitriol from cholecalciferol and ergocalciferol; therefore, the response is more predictable. In addition, their shorter half-lives may make toxicity easier to manage (hypercalcemia reverses more quickly). Ergocalciferol may not be the preferred agent in the treatment of familial hypophosphatemia or hypoparathyroidism because the large doses needed are associated with a risk of overdose and hypercalcemia; dihydrotachysterol and calcitriol may be preferred. /Included in US product labeling/

Studies have shown that the elderly may have an increased need for vitamin D due to a possible decrease in the capacity of the skin to produce previtamin D3 or a decrease in exposure to the sun or impaired renal function or impaired vitamin D absorption.|Doses of vitamin D analogs that do not exceed the physiologic requirement are usually nontoxic. However, some infants and patients with sarcoidosis or hypoparathyroidism may have increased sensitivity to vitamin D analogs. /Vitamin D analogs/|Acute or chronic administration of excessive doses of vitamin D analogs or enhanced responsiveness to physiologic amounts of ergocalciferol or cholecalciferol may lead to hypervitaminosis D manifested by hypercalcemia. /Vitamin D analogs/|Decreased renal function without hypercalcemia has also been reported in patients with hypoparathyroidism after long-term vitamin D analog therapy. Before therapy with vitamin D analogs is initiated, serum phosphate concentrations must be controlled. To avoid ectopic calcification, the serum calcium (in mg/dL) times phosphorus (in mg/dL) should not be allowed to exceed 70. Because administration of vitamin D analogs may increase phosphate absorption, patients with renal failure may require adjustment in the dosage of aluminum-containing antacids used to decrease phosphate absorption. /Vitamin D analogs/|For more Drug Warnings (Complete) data for CHOLECALCIFEROL (10 total), please visit the HSDB record page.

The in vivo synthesis of the predominant two biologically active metabolites of vitamin D occurs in two steps. The first hydroxylation of vitamin D3 cholecalciferol (or D2) occurs in the liver to yield 25-hydroxyvitamin D while the second hydroxylation happens in the kidneys to give 1, 25-dihydroxyvitamin D. These vitamin D metabolites subsequently facilitate the active absorption of calcium and phosphorus in the small intestine, serving to increase serum calcium and phosphate levels sufficiently to allow bone mineralization. Conversely, these vitamin D metabolites also assist in mobilizing calcium and phosphate from bone and likely increase the reabsorption of calcium and perhaps also of phosphate via the renal tubules. There exists a period of 10 to 24 hours between the administration of cholecalciferol and the initiation of its action in the body due to the necessity of synthesis of the active vitamin D metabolites in the liver and kidneys. It is parathyroid hormone that is responsible for the regulation of such metabolism at the level of the kidneys.

Agents that inhibit BONE RESORPTION and/or favor BONE MINERALIZATION and BONE REGENERATION. They are used to heal BONE FRACTURES and to treat METABOLIC BONE DISEASES such as OSTEOPOROSIS. (See all compounds classified as Bone Density Conservation Agents.)|Organic substances that are required in small amounts for maintenance and growth, but which cannot be manufactured by the human body. (See all compounds classified as Vitamins.)|Hormones and molecules with calcium-regulating hormone-like actions that modulate OSTEOLYSIS and other extra-skeletal activities to maintain calcium homeostasis. (See all compounds classified as Calcium-Regulating Hormones and Agents.)

Cholecalciferol is readily absorbed from the small intestine if fat absorption is normal. Moreover, bile is necessary for absorption as well. In particular, recent studies have determined aspects about the absorption of vitamin D, like the fact that a) the 25-hydroxyvitamin D metabolite of cholecalciferol is absorbed to a greater extent than the nonhydroxy form of cholecalciferol, b) the quantity of fat with which cholecalciferol is ingested does not appear to largely affect its bioavailability, and c) age does not apparently effect vitamin D cholecalciferol.|It has been observed that administered cholecalciferol and its metabolites are excreted primarily in the bile and feces.|Studies have determined that the mean central volume of distribution of administered cholecalciferol supplementation in a group of 49 kidney transplant patients was approximately 237 L.|Studies have determined that the mean clearance value of administered cholecalciferol supplementation in a group of 49 kidney transplant patients was approximately 2.5 L/day.|Readily absorbed from small intestine (proximal or distal); cholecalciferol may be absorbed more rapidly and completely than ergocalciferol.|Elimination: Biliary/renal. /Vitamin D and analogs/|Many vitamin D analogs are readily absorbed from the GI tract following oral administration if fat absorption is normal. The presence of bile is required for absorption of ergocalciferol and the extent of GI absorption may be decreased in patients with hepatic, biliary, or GI disease (e.g., Crohn's disease, Whipple's disease, sprue). Because vitamin D is fat soluble, it is incorporated into chylomicrons and absorbed via the lymphatic system; approximately 80% of ingested vitamin D appears to be absorbed systemically through this mechanism, principally in the small intestine. Although some evidence suggested that intestinal absorption of vitamin D may be decreased in geriatric adults, other evidence did not show clinically important age-related alterations in GI absorption of the vitamin in therapeutic doses. It currently is not known whether aging alters the GI absorption of physiologic amounts of vitamin D. /Vitamin D analogs/|After absorption, ergocalciferol and cholecalciferol enter the blood via chylomicrons of lymph and then associate mainly with a specific alpha-globulin (vitamin D-binding protein). The hydroxylated metabolites of ergocalciferol and cholecalciferol also circulate associated with the same alpha-globulin. 25-Hydroxylated ergocalciferol and cholecalciferol are stored in fat and muscles for prolonged periods. Once vitamin D enters systemic circulation from lymph via the thoracic duct or from skin, it accumulates in the liver within a few hours.|For more Absorption, Distribution and Excretion (Complete) data for CHOLECALCIFEROL (7 total), please visit the HSDB record page.

Within the liver, cholecalciferol is hydroxylated to calcifediol (25-hydroxycholecalciferol) by the enzyme vitamin D-25-hydroxylase. At the kidney, calcifediol subsequently serves as a substrate for 1-alpha-hydroxylase, yielding calcitriol (1,25-dihydroxycholecalciferol), the biologically active form of vitamin D3.|Metabolic activation of cholecalciferol and ergocalciferol occurs in 2 steps, the first in the liver and the second in the kidneys. Metabolic activation of calcifediol occurs in the kidneys; dihydrotachysterol, alfacalcidol and doxercalciferol are activated in the liver.|Normal combined (ie, 25-hydroxyvitamin D) plasma concentrations of 25-hydroxycholecalciferol (calcifediol) and 25-hydroxyergocalciferol, which are the major circulating metabolites of cholecalciferol and ergocalciferol, have been reported to range from 8-80 ng/mL, depending on the assay used, and vary with exposure to UV light. A commonly reported range for the lower limit of normal is 8-15 ng/mL, depending on geographic location (eg, Southern California would be higher than Massachusetts).|In the liver, ergocalciferol and cholecalciferol are converted in the mitochondria to their 25-hydroxy derivatives by the enzyme vitamin D 25-hydroxylase. Vitamin D 25-hydroxylase activity is regulated in the liver by concentrations of vitamin D and its metabolites; therefore, increases in the systemic circulation of the 25-hydroxy metabolites following exposure to sunlight or ingestion of vitamin D are relatively modest compared with cumulative production or intake of the vitamin. Serum concentrations of nonhydroxylated vitamin D are short-lived as a result of storage in fat or metabolism in the liver. In the kidneys, these metabolites are further hydroxylated at the 1 position by the enzyme vitamin D 1-hydroxylase to their active forms, 1,25-dihydroxycholecalciferol (calcitriol) and 1,25-dihydroxyergocalciferol. ... Activity of the vitamin D 1-hydroxylase enzyme requires molecular oxygen, magnesium ion, and malate and is regulated principally by PTH in response to serum concentrations of calcium and phosphate, and perhaps by circulating concentrations of 1,25-dihydroxyergocalciferol and 1,25-dihydroxycholecalciferol. Other hormones (ie, cortisol, estrogens, prolactin, and growth hormone) also may influence the metabolism of cholecalciferol and ergocalciferol.|The hepatic enzyme system responsible for 25-hydroxylation of vitamin D /(vitamin D-25 hydroxylase)/ is associated with the microsomal and mitochondrial fractions of homogenates and requires NADPH (nicotinamide adenine dinucleotide phosphate, reduced form) and molecular oxygen. ... The enzyme system /in kidney/ responsible for 1-hydroxylation of 25-OHD (25-hydroxycholecalciferol) /(25-OHD-1-alpha-hydroxylase)/ is associated with mitochondria in the proximal tubules. It is a mixed function oxidase and requires molecular oxygen and NADPH as cofactors. Cytochrome P450, a flavoprotein, and ferredoxin are components of the enzyme complex.

At this time, there have been resources that document the half-life of cholecalciferol as being about 50 days while other sources have noted that the half-life of calcitriol (1,25-dihydroxyvitamin D3) is approximately 15 hours while that of calcidiol (25-hydroxyvitamin D3) is about 15 days. Moreover, it appears that the half-lives of any particular administration of vitamin d can vary due to variations in vitamin d binding protein concentrations and genotype in particular individuals.|The Vitamin /D/ disappears from plasma with a half-life of 19 to 25 hr but is stored in fat depots for prolonged periods. ... The 25-hydroxy derivative has a biological half-life of 19 days ... The plasma half-life of calcitriol /(1,25-dihydroxy-vitamin D)/ is estimated to be between 3 and 5 days in human beings ...

Most individuals naturally generate adequate amounts of vitamin D through ordinary dietary intake of vitamin D (in some foods like eggs, fish, and cheese) and natural photochemical conversion of the vitamin D3 precursor 7-dehydrocholesterol in the skin via exposure to sunlight. Conversely, vitamin D deficiency can often occur from a combination of insufficient exposure to sunlight, inadequate dietary intake of vitamin D, genetic defects with endogenous vitamin D receptor, or even severe liver or kidney disease. Such deficiency is known for resulting in conditions like rickets or osteomalacia, all of which reflect inadequate mineralization of bone, enhanced compensatory skeletal demineralization, resultant decreased calcium ion blood concentrations, and increases in the production and secretion of parathyroid hormone. Increases in parathyroid hormone stimulate the mobilization of skeletal calcium and the renal excretion of phosphorus. This enhanced mobilization of skeletal calcium leads towards porotic bone conditions. Ordinarily, while vitamin D3 is made naturally via photochemical processes in the skin, both itself and vitamin D2 can be found in various food and pharmaceutical sources as dietary supplements. The principal biological function of vitamin D is the maintenance of normal levels of serum calcium and phosphorus in the bloodstream by enhancing the efficacy of the small intestine to absorb these minerals from the diet. At the liver, vitamin D3 or D2 is hydroxylated to 25-hydroxyvitamin D and then finally to the primary active metabolite 1,25-dihydroxyvitamin D in the kidney via further hydroxylation. This final metabolite binds to endogenous vitamin d receptors, which results in a variety of regulatory roles - including maintaining calcium balance, the regulation of parathyroid hormone, the promotion of the renal reabsorption of calcium, increased intestinal absorption of calcium and phosphorus, and increased calcium and phosphorus mobilization of calcium and phosphorus from bone to plasma to maintain balanced levels of each in bone and the plasma. In particular, calcitriol interacts with vitamin D receptors in the small intestine to enhance the efficiency of intestinal calcium and phosphorous absorption from about 10-15% to 30-40% and 60% increased to 80%, respectively. Furthermore, calcitriol binds with vitamin D receptors in osteoblasts to stimulate a receptor activator of nuclear factor kB ligand (or RANKL) which subsequently interacts with receptor activator of nuclear factor kB (NFkB) on immature preosteoclasts, causing them to become mature bone-resorbing osteoclasts. Such mature osteoclasts ultimately function in removing calcium and phosphorus from bone to maintain blood calcium and phosphorus levels. Moreover, calcitriol also stimulates calcium reabsorption from the glomerular filtrate in the kidneys. Additionally, it is believed that when calcitriol binds with nuclear vitamin D receptors, that this bound complex itself binds to retinoic acid X receptor (RXR) to generate a heterodimeric complex that consequently binds to specific nucleotide sequences in the DNA called vitamin D response elements. When bound, various transcription factors attach to this complex, resulting in either up or down-regulation of the associated gene's activity. It is thought that there may be as much as 200 to 2000 genes that possess vitamin D response elements or that are influenced indirectly to control a multitude of genes across the genome. It is in this way that cholecalciferol is believed to function in regulating gene transcription associated with cancer risk, autoimmune disorders, and cardiovascular disease linked to vitamin D deficiency. In fact, there has been some research to suggest calcitriol may also be able to prevent malignancies by inducing cellular maturation and inducing apoptosis and inhibiting angiogenesis, exhibit anti-inflammatory effects by inhibiting foam cell formation and promoting angiogenesis in endothelial colony-forming cells in vitro, inhibit immune reactions by enhancing the transcription of endogenous antibiotics like cathelicidin and regulate the activity and differentiation of CD4+ T cells, amongst a variety of other proposed actions.|The principal biologic function of vitamin D is to maintain serum calcium and phosphorus concentrations within the normal range by enhancing the efficiency of the small intestine to absorb these minerals from the diet. Calcitriol (activated vitamin D) enhances the efficiency of intestinal calcium absorption along the entire small intestine, but principally in the duodenum and jejunum. Calcitriol also enhances phosphorus absorption along the entire small intestine, but principally in the jejunum and ileum. The activated forms of ergocalciferol, doxercalciferol, and cholecalciferol may have a negative feedback effect on parathyroid hormone (PTH) production.|The most two important mechanisms by which vitamin D acts to maintain normal concentration of calcium and phosphate in plasma are to facilitate their absorption by the small intestine and to enhance their mobilization from bone. /Vitamin D/

SYMPTOMS: Symptoms of exposure to this compound may include weakness, fatigue, lassitude headache, nausea, vomiting, diarrhea, polyuria, polydipsia, nocturia, decrease urinary concentrating ability, proteinuria, tissue calcification, hypertension and osteoporosis. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. If symptoms (such as redness or irritation) develop, immediately transport the victim to a hospital. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

Treatment of vitamin D analog intoxication consists of withdrawal of both the drug and calcium supplements, maintenance of a low-calcium diet, administration of oral or IV fluids and, if needed, corticosteroids or other drugs, particularly calciuric diuretics (e.g., furosemide and ethacrynic acid) to decrease serum calcium concentrations. Hemodialysis or peritoneal dialysis against a calcium-free dialysate may also be used. If ingestion is recent, gastric lavage or emesis may prevent further absorption. If the drug has passed through the stomach, administration of mineral oil may promote fecal elimination. Because the 25-hydroxylated metabolites of ergocalciferol and cholecalciferol are stored in the body, hypercalcemia can last for 2 or more months following chronic administration of excessive doses of these drugs. ... Signs and symptoms of hypercalcemia are usually reversible; however, metastatic calcification may result in severe renal or cardiac failure and death.

/SIGNS AND SYMPTOMS/ Vitamin D toxicity in infancy and childhood is characterized by supravalvular aortic stenosis, mental retardation, a characteristic facies, renal tubular acidosis, nephrocalcinosis infantum, and generalized infantile arteriosclerosis. /Vitamin-D/|/SIGNS AND SYMPTOMS/ Vitamin D toxicity may be manifested in the fetus. There is a relationship between excess maternal vitamin D intake or extreme sensitivity and nonfamilial congenital supravalvular aortic stenosis. In infants, this anomaly is often associated with other stigmata of hypercalcemia. Maternal hypercalcemia also may result in suppression of parathyroid function in the newborn, with resultant hypocalcemia, tetany, and seizures. /Vitamin D/|/SIGNS AND SYMPTOMS/ Patients should be informed of the dangers and symptoms of vitamin D intoxication. Early symptoms of hypercalcemia may include weakness, fatigue, somnolence, headache, anorexia, dry mouth, metallic taste, nausea, vomiting, abdominal cramps, constipation, diarrhea, vertigo, tinnitus, ataxia, exanthema, hypotonia (in infants), muscle pain, bone pain, and irritability. Later and sometimes more serious consequences of hypercalcemia may include rhinorrhea, pruritus, decreased libido, nephrocalcinosis, impairment of renal function (resulting in polyuria, nocturia, polydipsia, hyposthenuria, and proteinuria), osteoporosis in adults, decreased growth in children, weight loss, anemia, calcific conjunctivitis, photophobia, metastatic calcification, pancreatitis, generalized vascular calcification, and seizures. Rarely, patients may develop hypertension or overt psychosis. Urinary calcium, phosphate, and albumin; BUN; and serum cholesterol, AST (SGOT), and ALT (SGPT) concentrations may increase. Serum alkaline phosphatase concentrations may decrease. Serum electrolyte imbalances along with mild acidosis may result in cardiac arrhythmias. /Vitamin D/

(3 beta,5Z,7E)-9,10-Secocholesta-5,7,10(19)-trien-3-ol

...May be obtained as crystals, standardized oil solutions, emulsions or beadlets. ...usually stabilized with antioxidants.|Grade: USP, FCC|Trade Names. Sorexa-CD (ergocalciferol with difenacoum), Sorexa-CR (ergocalciferol with warfarin), both Sorex. Quintox (cholecalciferol), Bell Laboratories.

Cyclohexanol, 3-[(2E)-2-[(1R,3aS,7aR)-1-[(1R)-1,5-dimethylhexyl]octahydro-7a-methyl-4H-inden-4-ylidene]ethylidene]-4-methylene-, (1S,3Z)-: ACTIVE|Cholecalciferol is vitamin D that occurs in fish liver oils ... cholecalciferol is one of the two steroids--the other being ergocalciferol (vit D2)--that have the greatest, and essentially equal vitamin activity.|Vitamin D3 (cholecalciferol) is formed photochemically from 7-dehydrocholesterol which in turn is formed from cholesterol.|If there is adequate exposure to sunlight, vitamin D is formed from sterols in the skin...|Vitamin D2 is only 1-2% as potent for the chick as vitamin D3. Because of this difference, it is important that poultry feeds are supplemented with vitamin D3 rather than D2.

AS LITTLE AS 2 NG EACH OF VIT D2 & D3 CAN BE SEPARATED & IDENTIFIED BY HPLC IN FORMULATIONS.|PROCEDURE IS DESCRIBED FOR SEPARATION OF VITAMIN D & RELATED COMPD BY GAS-LIQUID CHROMATOGRAPHY USING FLAME IONIZATION DETECTION.|Method: AOAC 2002.05; Procedure: liquid chromatography with ultraviolet detection; Analyte: cholecalciferol; Matrix: vitamin D3 (0.4-12 ug/100 g) in fortified milk, infant formula, gruel, margarine, cooking oil, and fish oil; Detection Limit: not provided.|Method: AOAC 992.26; Procedure: liquid chromatography with ultraviolet detection; Analyte: cholecalciferol; Matrix: ready-to-feed milk-based infant formulas containing 488-533 IU/L vitamin D3; Detection Limit: not provided.|For more Analytic Laboratory Methods (Complete) data for CHOLECALCIFEROL (11 total), please visit the HSDB record page.

Agrochemicals -> Rodenticides|Human drugs -> Adrovance -> EMA Drug Category|Drugs for treatment of bone diseases -> Human pharmacotherapeutic group|Human drugs -> Fosavance -> EMA Drug Category|Human drugs -> Vantavo (previously Alendronate sodium and colecalciferol, MSD) -> EMA Drug Category|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Lipids -> Sterol Lipids [ST] -> Secosteroids [ST03] -> Vitamin D3 and derivatives [ST0302]