Dihydrotachysterol

398.66

398.66

200-672-7

DTXSID5022938

Needles from 90% methanol|COLORLESS OR WHITE CRYSTALS, OR WHITE, CRYSTALLINE POWDER

A - Alimentary tract and metabolism

2936299055

20.23000

7.72090

1.003 g/cm3

125-127 °C

499.5ºC at 760 mmHg

217.6ºC

1.569

Easily sol in organic solents

2-8°C

5.2X10-10 mm Hg at 25 °C (est)

LD50 oral in mouse: 288mg/kg

D22 +97.5° (chloroform)

ODORLESS

Henry's Law constant = 3.7X10-4 atm-cu m/mol at 25 °C (est)

Hydroxyl radical reaction rate constant = 3.5X10-10 cu cm/molecule-sec at 25 °C (est)

III

6.1(b)

UN 2811 6.1/PG 3

3

22

36

WW0600000

Xn

Missing Phrase - N15.00950417

H301

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.

|Danger|H301 (97.5%): Toxic if swallowed [Danger Acute toxicity, oral]|P264, P270, P301+P310, P321, P330, P405, and P501|Aggregated GHS information provided by 40 companies from 2 notifications to the ECHA C&L Inventory.

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 DIHYDROTACHYSTEROL (6 total), please visit the HSDB record page.

Dihydrotachysterol's production and use for the treatment of hypocalcemic tetany(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2.5X10+6(SRC), determined from a structure estimation method(2), indicates that dihydrotachysterol is expected to be immobile in soil(SRC). Volatilization of dihydrotachysterol from moist soil surfaces may occur(SRC) given an estimated Henry's Law constant of 3.7X10-4 atm-cu m/mole(SRC), using a fragment constant estimation method(3). However, adsorption to soil is expected to attenuate volatilization(SRC). Dihydrotachysterol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.2X10-10 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 2.5X10+6(SRC), determined from a structure estimation method(2), indicates that dihydrotachysterol is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces may occur(3) based upon an estimated Henry's Law constant of 3.7X10-4 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 5 hours and 9 days, respectively(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column(SRC). The volatilization half-life from a model pond is about 5.3X10+5 years when adsorption is considered(5). According to a classification scheme(6), an estimated BCF of 3.2(SRC), from an estimated log Kow of 10(7) and a regression-derived equation(8), 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), dihydrotachysterol, which has an estimated vapor pressure of 5.2X10-10 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 dihydrotachysterol may be removed from the air by wet or dry deposition(SRC). Dihydrotachysterol does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of dihydrotachysterol with photochemically-produced hydroxyl radicals has been estimated as 3.5X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 20 minutes at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of dihydrotachysterol with ozone has been estimated as 1.0X10-14 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(1). This corresponds to an atmospheric half-life of about 2 minutes at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(2). Dihydrotachysterol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). Dihydrotachysterol does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3.2 was calculated for dihydrotachysterol(SRC), using an estimated log Kow of 10(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 dihydrotachysterol can be estimated to be 2.5X10+6(SRC). According to a classification scheme(2), this estimated Koc value suggests that dihydrotachysterol is expected to be immobile in soil.

The Henry's Law constant for dihydrotachysterol is estimated as 3.7X10-4 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that dihydrotachysterol may 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 5 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 9 days(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column(SRC). The volatilization half-life from a model pond is about 5.3X10+5 years when adsorption is considered(3). Dihydrotachysterol's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). However, adsorption to soil is expected to attenuate volatilization(SRC). Dihydrotachysterol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.2X10-10 mm Hg(SRC), determined from a fragment constant method(4).

While data specific to dihydrotachysterol 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 dihydrotachysterol may occur through inhalation and dermal contact with this compound at workplaces where dihydrotachysterol is produced or used. Exposure to dihydrotachysterol among the general population may be limited to those administered the drug Hytakerol. (SRC)

Bone Density Conservation Agents; Vitamins|MEDICATION (VET): Calcium regulator used in veterinary medicine to treat hypercalcemia.|Dihydrotachysterol is indicated ... for treatment of chronic and latent forms of post operative tetany and idiopathic tetany. /Included in US product labeling/|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 reduce 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/

/Dihydrotachysterol/...should not be used in presence of renal insufficiency or hyperphosphatemia. Extreme care must be used to prevent overdosage.|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/|FDA Pregnancy Risk Category: C /RISK CANNOT BE RULED OUT. Adequate, well controlled human studies are lacking, and animal studies have shown risk to the fetus or are lacking as well. There is a chance of fetal harm if the drug is given during pregnancy; but the potential benefits may outweigh the potential risk./

Onset of action: Hypercalcemic: Several hours (maximal after 1 to 2 weeks).|...Major path of elimination of dihydrotachysterol & its metabolites is probably secretion into bile & excretion in feces ... dihydrotachysterol /is also/ excreted in breast milk ...|Duration of action: following oral administration: Up to 9 weeks.|The primary route of excretion of vitamin D is the bile; only a small percentage of an administered dose is found in urine. /Vitamin D/|For more Absorption, Distribution and Excretion (Complete) data for DIHYDROTACHYSTEROL (8 total), please visit the HSDB record page.

DHT3 /vitamin D3/ undergoes 25-hydroxylation to yield 25-hydroxydihydrotachysterol3 (25-OHDHT3), which appears to be active form of DHT (dihydrotachysterol) in both intestine & bone.|High specific radioactivity (14)C- and (3)H-labeled dihydrotachysterol were prepared and their metabolites studied in rachitic chicks and rats. 20% dihydrotachysterol was excreted in the bile in the first 24 hours, about 50% as a carboxylic acid derivative. No hydroxylation at C-1 was observed, although polar metabolites were detected in all tissues. Larger proportions of the parent steroid and its 25-OH derivative were detected in tissues compared with cholecalciferol but no single metabolite was detected at the intracellular site of action of cholecalciferol.

Absorbed vitamin D circulates in blood in association with vitamin D-binding protein, which is a specific alpha-globulin. Vitamin D disappears from plasma with /a half-life/ of 19 to 25 hr, but it is stored in body for prolonged periods (6 months or longer in rat) apparently in fat deposits throughout body. /Vitamin D/

Elevates serum calcium concentration by increasing intestinal absorption of calcium & possibly by enhancing urinary excretion of inorganic phosphate... /drug-induced/ phosphaturia may be ... due to increased serum calcium level and its effect on phosphate clearance by kidneys.

EXPL THER: ... Immediate withdrawal of vitamin, low-calcium diet, administration of glucocorticoids, & generous intake of fluid. ... Hydrocortisone has been shown exptl to decrease calcium absorption, & in man it does cause more rapid reversion of elevated plasma calcium concentration to normal. /Vitamin D/

/SIGNS AND SYMPTOMS/ Adverse effects result mainly from hypercalcemia. They include anorexia ... languor ... weight loss, metastatic calcification, renal damage, anemia, band keratitis, and convulsions. In severe hypercalcemia there may be ... vertigo, tinnitus, abdominal cramps ... thirst, ataxia, albuminuria, and xanthemia.|/SIGNS AND SYMPTOMS/ The initial signs and symptoms of vitamin D toxicity are those associated with hypercalcemia. ... Hypercalcemia with hypervitaminosis D is due generally to very high circulating levels or 25-OHD (25-hydroxycholecalciferol), and plasma concentrations of PTH (parathyroid hormone) and calcitriol are typically but not uniformly suppressed. /Vitamin D/|/SIGNS AND SYMPTOMS/ In children, a single episode of moderately severe hypercalcemia /caused by vitamin D toxicity/ may arrest growth completely for 6 months or more, and the deficit in height may never be fully corrected. /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/|For more Human Toxicity Excerpts (Complete) data for DIHYDROTACHYSTEROL (6 total), please visit the HSDB record page.

Oral: Capsules 0.125 mg Hytakerol, (Sanofi-Aventis); Solution, concentrate: 0.2 mg/mL DHT Intensol (with alcohol 20%), (Roxane).

USP unit is identical with international unit & is equivalent to specific biological activity of 0.025 ug of vitamin D3 (ie 1 mg equals 40,000 units). /Vitamin D/|Dihydrotachysterol (DHT) is analog of vitamin D that may be regarded as reduction product of either vitamin D2 (DHT2) or vitamin D3 (DHT3). DHT is about 1/450 as active as vitamin D in usual antirachitic assay, but at high doses it is much more effective than high doses of vitamin D in mobilizing calcium from bone.|Dihydrotachysterol or vitamin D2, both at 10-50 mg/L, increased production of adventitious roots in herbaceous cuttings of populus tremula (aspen) by approximately 60 and 100%, respectively.

THREE SEPARATION TECHNIQUES & UV SPECTROPHOTOMETRY ARE DESCRIBED FOR DIHYDROTACHYSTEROL.|PROCEDURE IS DESCRIBED FOR SEPARATION OF VITAMIN D & RELATED COMPD BY GAS-LIQUID CHROMATOGRAPHY USING FLAME IONIZATION DETECTION.|Analyte: dihydrotachysterol; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: dihydrotachysterol; matrix: chemical identification; procedure: ultraviolet absorption spectrophotometry with comparison to standards|For more Analytic Laboratory Methods (Complete) data for DIHYDROTACHYSTEROL (11 total), please visit the HSDB record page.