Vitamin D

Rodenticides

Active substance -> EU Pesticides database: Not approved

Fine needles from dilute acetone

WHITE CRYSTALS

Colorless crystals

Insoluble (NTP, 1992)

Insoluble

Sol in the usual org solvents; slightly sol in vegetable oils

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Vitamins and minerals

Danger

H300: Fatal if swallowed [Danger Acute toxicity, oral]

P260, P262, P264, P270, P271, P280, P284, P301+P316, P302+P352, P304+P340, P316, P319, P320, P321, P330, P361+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Danger

H300 (14.3%): Fatal if swallowed [Danger Acute toxicity, oral]

P260, P262, P264, P270, P271, P280, P284, P301+P316, P302+P352, P304+P340, P316, P319, P320, P321, P330, P361+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

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

Regulation (EC) No 178/2002 (amended)

2004/129/EC

Cholecalciferol: HSNO Approval: HSR002778 Approved with controls

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)

May cause irritation; Highly toxic by ingestion and skin absorption; Toxic by inhalation; Prolonged or repeated ingestion exposure may cause organ injury; Targets the kidney and heart; May cause reproductive toxicity and teratogenicity; [Sigma-Aldrich MSDS] See Vitamin D.

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.

Acute Tox. 2 (14.3%)

Specific target organ toxicity (repeated exposure) - category 1

Acute toxicity (Oral) - Category 2

Acute toxicity (Inhalation: Dusts and mists) - Category 2

Acute Tox. 2

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.

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.

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.

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)

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.

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).

Although cholecalciferol is generally considered safe, its adverse effects can occur due to high vitamin D levels. High-loading doses of cholecalciferol, ranging from 300,000 to 600,000 international units, have been associated with falls and fractures. Therefore, the NOF guideline recommends limiting the use of such high doses to symptomatic patients or those at risk of hypocalcemia due to potent antiresorptive therapy.

On average, individuals need approximately 15 to 20 minutes of sun exposure per day to synthesize vitamin D. The likelihood of vitamin D toxicity from excessive sunlight exposure is low, as the skin naturally degrades excess vitamin D.

The first step involved in the activation of vitamin D3 is a 25-hydroxylation which is catalysed by the 25-hydroxylase in the liver and then by other enzymes. The mitochondrial sterol 27-hydroxylase catalyses the first reaction in the oxidation of the side chain of sterol intermediates. The active form of vitamin D3 (calcitriol) binds to intracellular receptors that then function as transcription factors to modulate gene expression. Like the receptors for other steroid hormones and thyroid hormones, the vitamin D receptor has hormone-binding and DNA-binding domains. The vitamin D receptor forms a complex with another intracellular receptor, the retinoid-X receptor, and that heterodimer is what binds to DNA. In most cases studied, the effect is to activate transcription, but situations are also known in which vitamin D suppresses transcription. Calcitriol increases the serum calcium concentrations by: increasing GI absorption of phosphorus and calcium, increasing osteoclastic resorption, and increasing distal renal tubular reabsorption of calcium. Calcitriol appears to promote intestinal absorption of calcium through binding to the vitamin D receptor in the mucosal cytoplasm of the intestine. Subsequently, calcium is absorbed through formation of a calcium-binding protein.

Hypercalcemia - Early symptoms of hypercalcemia, include nausea and vomiting, weakness, headache, somnolence, dry mouth, constipation, metallic taste, muscle pain and bone pain. Late symptoms and signs of hypercalcemia, include polyuria, polydipsia, anorexia, weight loss, nocturia, conjunctivitis, pancreatitis, photophobia, rhinorrhea, pruritis, hyperthermia, decreased libido, elevated BUN, albuminuria, hypercholesterolemia, elevated ALT (SGPT) and AST (SGOT), ectopic calcification, nephrocalcinosis, hypertension and cardiac arrhythmias.

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.

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.

/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/

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).

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.

A11CC05

A - Alimentary tract and metabolism

QA - Alimentary tract and metabolism

A11CC05

In both premature and normal infants, a total of 400 units per day of vitamin D ensures full antirachitic prophylaxis and optimal growth regardless of how it is obtained. During adolescence and beyond, this amount is probably also sufficient. There is some evidence that vitamin D requirements increase during pregnancy and lactation although daily intake of 400 units is sufficient in these conditions as well. The USP unit is identical with the international units (IU) and is equivalent to the specific biological activity of 0.025 ug of vitamin D3.

In adults, vitamin D deficiency results in osteomalacia, a disease characterized by generalized accumulation of undermineralized bone matrix. Severe osteomalacia may be associated with extreme bone pain and tenderness. Muscle weakness, particularly of large proximal muscles, is typical. Its basis is not fully understood but may reflect hypophosphatemia and inadequate vitamin D action on muscle. Gross deformity of bone occurs only in advanced stages of the disease. Circulating 25-OHD (25-hydroxycholecalciferol) concentrations below 8 ng/mL are highly predictive of osteomalacia. /Vitamin D/

The exact physiologic function of vitamin D in brain, heart, pancreas, mononuclear cells, activated lymphocytes, and skin remains unknown, and although the vitamin exhibits potent antiproliferative and prodifferentiation effects, there currently is little evidence that vitamin D deficiency results in major disorders in these organs and cellular systems. The possibility that vitamin D deficiency may be associated with an increased risk of colon, breast, and prostate cancer has been suggested by epidemiologic evidence from individuals living in higher latitudes, but current evidence is too limited to indicate categorically a cancer risk associated with deficiency. /Vitamin D/

Vitamin D deficiency causes decreased ionized calcium concentrations in blood and a resultant increase in the production and secretion of PTH. PTH stimulates the mobilization of skeletal calcium, inhibits renal excretion of calcium, and stimulates renal excretion of phosphorus resulting in normal fasting serum calcium concentrations and low or near-normal serum phosphorus. The enhanced mobilization of skeletal calcium induced by this secondary hyperparathyroidism results in porotic bone. /Vitamin D/

Vitamin D deficiency results in inadequate mineralization of bone or compensatory skeletal demineralization. In children, vitamin D deficiency leads to rickets as a result of inadequate mineralization of bone and is characterized by widening of the end of long bones, rachitic rosary, skeletal deformations (e.g., frontal bossing), and outward and inward deformities of the lower limbs resulting in bowed legs and knocked knees, respectively. In adults, vitamin D deficiency leads to a mineralization defect resulting in osteomalacia. /Vitamin D/

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.

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.

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/

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 ...

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.

Within the liver, cholecalciferal is hydroxylated to calcidiol (25-hydroxycholecalciferol) by the enzyme 25-hydroxylase. Within the kidney, calcidiol serves as a substrate for 1-alpha-hydroxylase, yielding calcitriol (1,25-dihydroxycholecalciferol), the biologically active form of vitamin D3. Half Life: Several weeks

1C6V77QF41

CHOLECALCIFEROL

Chemical Structure [CS] - Vitamin D

Established Pharmacologic Class [EPC] - Vitamin D

Cholecalciferol is a Vitamin D.

CHOLECALCIFEROL (VITAMIN D3)

Hormones and molecules with calcium-regulating hormone-like actions that modulate OSTEOLYSIS and other extra-skeletal activities to maintain calcium homeostasis.

Organic substances that are required in small amounts for maintenance and growth, but which cannot be manufactured by the human body.

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.

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/

An essential mediator of intestinal calcium absorption and bone calcium metabolism; High concentrations found in fish liver oils; Used as a therapeutic vitamin; [Merck Index] Active product registrations in the US for use as a rodenticide; [NPIRS] Used as a nutritional supplement; [FDA] Permitted for use as an inert ingredient in non-food pesticide products; [EPA]

For cholecalciferol (USEPA/OPP Pesticide Code: 202901) ACTIVE products with label matches. /SRP: Registered for use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

MEDICATION

MEDICATION (VET):

Medicine (antirachtic vitamin)

For more Uses (Complete) data for CHOLECALCIFEROL (6 total), please visit the HSDB record page.

Prepd by irradiation of its provitamin 7-dehydrocholestrol

...Isolated in crystalline state from the 3,5-dinitrobenzoate; produced by irradiation & equivalent in activity to the vitamin D3 of tuna liver oil.

... Occurs in and is isolated from fish liver oils. It also is manufactured by ultraviolet irradiation of 7-dehydrocholesterol produced from cholesterol and is purified by crystallization.

...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.