重酒石酸コリン

This chemical does not meet GHS hazard criteria for 6.3% (4 of 63) of reports.

Warning

H315 (93.7%): Causes skin irritation [Warning Skin corrosion/irritation]

P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 63 reports by companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Chemical: Ethanaminium, 2-hydroxy-N,N,N-trimethyl-, salt with [R-(R*,R*)]-2,3-dihydroxybutanedioic acid (1:1)

Choline bitartrate: Does not have an individual approval but may be used under an appropriate group standard

Choline bitartrate used as a nutrient in food for human consumption is generally recognized as safe when used in accordance with good manufacturing practice.

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

Since 1994, dietary supplements have been regulated under the Dietary Supplement Health and Education Act (DSHEA). The DSHEA requires no proof of safety for dietary supplements on the market prior to October 15, 1994. Labeling requirements for such supplements allow warnings and dosage recommendations as well as substantiated "structure or function" claims. All claims must prominently note that they have not been evaluated by the FDA, and they must bear the statement "This product is not intended to diagnose, treat, cure, or prevent any disease".

National Academy of Sciences. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (1998). Available from: http://www.nal.usda.gov/fnic/DRI//DRI_Thiamin/390-422_150.pdf as of February 28, 2008.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Methotrexate may diminish pools of all choline metabolites. Choline supplementation reverses fatty liver caused by methotrexate admin in rats. /Choline/

Repeated admin of choline chloride to female rats incr liver necrosis caused by carbon tetrachloride.

This study was designed to examine the biochemical and embryotoxic interaction of excessive dietary vitamin A and deficiency of methylation pathway constituents, namely absence of folate and choline and a reduction of methionine. Simonsen albino rats were maintained for 36 days on a diet with either normal (4 IU per gram of diet) or excessive retinyl palmitate (RP) (100 or 1000 IU per gram of diet), and normal (2 ug folic acid, 5 mg methionine and 4.2 mg choline bitartrate per gram of diet) or absence of the three dietary factors. CD-1 mouse embryos were exposed to the diet from gestational day 0 to 8, and rat serum from day 8 to 10 during whole embryo culture. The high dose of RP induced 55.4% open anterior neuropores when methylation pathway constituents were included in the diet, but this same retinoid level produced only 12.5% embryos with this defect when these constituents were omitted. Acidic retinoid levels were low in serum (less than 5 ng/mL) via HPLC. Measurements of selected methylation and transsulfuration pathway components did not yield differences in these biochemical intermediates. Thus, dietary folate, choline and methionine facilitate the induction of retinoid-induced neural tube defects.

Choline admin significantly incr ... milk choline content during the first mo of lactation in cows ... Human milk contains 1.5 to 2 mM choline moiety per liter ... Plasma choline concn varies in response to diet and can rise as much as twofold after a 2-egg meal. Fasting plasma choline concn vary from 7 to 20 uM, with most subjects having concn of 10 uM. Individuals who have starved for up to 7 days have diminished plasma choline, but levels never drop below 50% of normal. Plasma phosphatidylcholine concn also decr in choline deficiency, but these values are also influenced by factors that change plasma lipoprotein levels. Fasting plasma phosphatidylcholine concn are approx 1 to 1.5 mM. /Choline/

/HUMAN EXPOSURE STUDIES/ /In a/ study involved a double-blind, crossover protocol, 9 g/day (wk 1) and 12 g/day (wk 2) given as a chloride or bitartrate, /choline caused/ mild cholinergic toxicity: lacrimation, blurred vision, anorexia, and diarrhea. /Chloride or bitartrate/ /From table/

/SIGNS AND SYMPTOMS/ At 7.5 g of choline daily, nausea, diarrhea and a small decr in blood pressure were reported in some patients. The upper limit (UL) for adults is 3.5 g daily. Individuals that may be at incr risk of side effects with choline intakes at the UL include those with trimethylaminuria, liver disease, renal disease, depression and Parkinson's disease. /Choline/

/SIGNS AND SYMPTOMS/ There are some reports of depression or incr symptoms of depression in those using high doses of choline bitartrate.

/SIGNS AND SYMPTOMS/ High doses of choline have been associated with excessive cholinergic stimulation, such as vomiting, salivation, sweating, and gastrointestinal effects. In addition, fishy body odor results from the excretion of trimethylamine, a choline metabolite from bacterial action. /Choline/

For more Human Toxicity Excerpts (Complete) data for CHOLINE BITARTRATE (7 total), please visit the HSDB record page.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ ... A serendipitous finding of urinary calculi in rats fed a semi-synthetic basal diet /is reported/. This observation was made during ongoing studies to evaluate the inhibitory effect of PSC 833, a potent inhibitor of P-glycoprotein, on development of tumors in rodent tumor model systems. A large number of specific-pathogen-free (SPF) female Sprague-Dawley and SPF male Fischer 344 rats being fed the diet were euthanized when it became evident clinically that they were uremic. At necropsy, the renal pelvis, ureters, and urinary bladder contained numerous calculi. The presence of urinary calculi was determined to be related to the source of a Food Chemical Codex grade of choline bitartrate. Rats being fed the same basal diet containing the United States Pharmacopia grade of choline bitartrate failed to develop urinary calculi. Interestingly, rats treated with the P-glycoprotein inhibitor were at significantly reduced risk of developing urinary calculi. This finding highlights how something seemingly innocuous as a minor dietary constituent can have a profound impact and, thereby, affect experimental outcome.

Individuals with trimethylaminuria (fish odor syndrome), renal disease, liver disease, depression, and Parkinson's disease may have increased susceptibility to the adverse effects of choline. /Choline/

Persistent trimethylaminuria in children is caused by autosomal recessively inherited impairment of hepatic trimethylamine (TMA) oxidation due to deficiency of flavin monooxygenase 3 (FMO3) secondary to mutations in the FMO3 gene. Trimethylaminuria or 'fish odor syndrome' is due to excessive excretion into body fluids and breath of TMA derived from the enterobacterial metabolism of dietary precursors. The disorder is present from birth but becomes apparent as foods containing high amounts of choline or of trimethylamine N-oxide (TMAO) from marine (sea or saltwater) fish are introduced into the diet. ... Trimethylaminuria (FMO3 deficiency) in children is rare. ... The dynamics and diagnostic efficacy of choline loading with marine fish meals in six children with trimethylaminuria /were compared/. Loading with a marine fish meal provides a simple and acceptable method for confirmation of diagnosis of suspected trimethylaminuria in children, with the effects being cleared more quickly than with a choline load test. However, oral loading with choline bitartrate allows estimation of residual oxidative capacity in vivo and is a useful adjunct to molecular studies. Patients homozygous for the 'common' P153L mutation in the FMO3 gene showed virtual complete lack of residual TMA N-oxidative capacity, consistent with a nonfunctional or absent FMO3 enzyme, whereas a patient with the M82T mutation showed some residual oxidative capacity. A patient compound heterozygous for two novel mutations, G193E and R483T, showed considerable residual N-oxidative capacity. A further patient, heterozygous for two novel sequence variations in the FMO3 gene, consistently showed malodor and elevated urinary TMA/TMAO ratios under basal conditions but a negative response to both choline and marine fish meal loading. Comparison of the effects of administration of antibiotics (metronidazole, amoxicillin, neomycin) on gut bacterial production of trimethylamine from choline showed they all reduced TMA production to a limited extent, with neomycin being most effective. 'Best-practice' diagnostic and treatment guidelines are summarized.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

Choline bitartrate used as a nutrient in food for human consumption is generally recognized as safe when used in accordance with good manufacturing practice.

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

Since 1994, dietary supplements have been regulated under the Dietary Supplement Health and Education Act (DSHEA). The DSHEA requires no proof of safety for dietary supplements on the market prior to October 15, 1994. Labeling requirements for such supplements allow warnings and dosage recommendations as well as substantiated "structure or function" claims. All claims must prominently note that they have not been evaluated by the FDA, and they must bear the statement "This product is not intended to diagnose, treat, cure, or prevent any disease".

State of deficiency: deficiency state is really one of available methyl groups, & consequently can only be produced as a result of combined deficiency of choline & other methyl donors. In animals, amt of choline needed is affected by growth rate, age, quantity of dietary fat, & quality of dietary protein... /Choline/

State of deficiency: ...accumulation of fat in liver, followed by cirrhosis... hemorrhagic renal lesions & motor incoordination from nerve degeneration... observed. ...damage to fetus, including atrophy of thymus, when pregnant rat is fed diet with marginal contents of choline... none...identified in man... /Choline/

Choline has several roles in body. It is an important component of phospholipids, affects mobilization of fat from liver (lipotropic action), acts as methyl donor, & is essential for formation of neurotransmitter acetylcholine. /Choline/

The 3 major metabolic functions of choline are as a precursor for phosphatidylcholine biosynth, as a precursor for acetylcholine biosynth and as methyl donor. In addition to serving as a precursor for phosphatidylcholine, choline is the precursor of the phospholipid sphingomyelin. Phosphatidylcholine and sphingomyelin are structural components of biological membranes. These phospholipids also serve as precursors for the intracellular messengers ceraminde and diacylglycerol. Choline is also the precursor of the signaling lipids, platelet-activating factor (PAF) and sphingosylphosphoryl-choline ... Choline is important for normal cellular membrane composition and repair, normal brain function and normal cardiovascular function ... /Choline/

For more Bionecessity (Complete) data for CHOLINE BITARTRATE (15 total), please visit the HSDB record page.

Several mechanisms are suggested for the cancer-promoting effect of a choline-devoid diet. These incl incr cell proliferation related to regeneration after parenchymal cell death occurs in the choline deficient liver, hypomethylation of DNA (alters expression of genes), reactive oxygen species leakage from mitochondria with incr lipid peroxidation in liver, activation of protein kinase C signaling due to accumulation of diacylglycerol in liver, mutation of the fragile histidine triad (FHIT) gene, which is a tumor suppressor gene, and defective cell-suicide (apoptosis) mechanisms. Loss of phposphatidylethanolamine N-methyl-transferase (PEMT) function may also contribute to malignant transformation of hepatocytes. /Choline/

Acetylcholine is one of the most important neurotransmitters used by neurons in the memory centers of the brain (hippocampus and septum). Choline accelerates the synth and release of acetylcholine in nerve cells. /Choline/

... Choline deficiency in cell culture causes apoptosis or programmed cell death. This appears to be due to abnormalities in cell membrane phosphatidylcholine content and an incr in ceramide, a precursor, as well as a metabolite of sphingomyelin. Ceramide accumulation, which is caused by choline deficiency, appears to activate a caspase, a type of enzyme that mediates apoptosis. /Choline/

Free choline is not fully absorbed, especially after large doses, and intestinal bacteria metabolize choline to trimethylamine. /Choline/

/The/ ability to form choline /de novo via the methylation of phosphatidylethanolamine using S-adenosylmethionine as the methyl donor, mostly in the liver,/ means that some of the demand for choline can ... be met using methyl groups derived from 1-carbon metabolism (via methyl-folate and methionine). Several vitamins (folate, vitamin B12, vitamin B6, and riboflavin) and the amino acid methionine interact with choline in 1-carbon metabolism ... Methionine, methyl-tetrahydrofolate (THF), and choline can be fungible sources of methyl groups. /Choline/

Before choline can be absorbed in the gut, some is metabolized by bacteria to form betaine and methylamines (which are not methyl donors) ... Although some free choline is excreted with urine, most is oxidized in the kidney to form betaine ... /Choline/

Acetylcholine is one of the most important neurotransmitters used by neurons in the memory centers of the brain (hippocampus and septum). Choline accelerates the synth and release of acetylcholine in nerve cells. Choline used by brain neurons is largely derived from membrane lecithin /(phosphatidylcholine)/, or from dietary intake of choline and lecithin ... Choline derived from lecithin may be especially important when extracellular choline is in short supply, as might be expected to occur in advanced age because of decr brain choline uptake ... /Choline/

For more Metabolism/Metabolites (Complete) data for CHOLINE BITARTRATE (6 total), please visit the HSDB record page.

Endogenous factors or drugs that increase the transport and metabolism of LIPIDS including the synthesis of LIPOPROTEINS by the LIVER and their uptake by extrahepatic tissues.

Drugs used to specifically facilitate learning or memory, particularly to prevent the cognitive deficits associated with dementias. These drugs act by a variety of mechanisms.

Choline is absorbed from diet as such or as lecithin. Latter is hydrolyzed by intestinal mucosa to glycerophosphoryl choline, which either passes to liver to liberate choline or to peripheral tissues via intestinal lymphatics. /Choline/

Choline are absorbed via the portal circulation ... The liver takes up the majority of choline and stores it in the form of phosphatidylcholine and sphingomyelin. Kidney and brain also accumulate choline ... Some free choline is excreted with urine ... A specific carrier is needed for the transport of free choline across the blood-brain barrier, and the capacity is especially high in neonates. /Choline/

Free choline is transported across the blood-brain barrier at a rate that is proportional to serum choline level ... In advanced age ... brain choline uptake /is decr/ ... /Choline/

During pregnancy, large amt of choline are delivered to the fetus across the placenta and this depletes maternal stores. Choline concn in amniotic fluid is 10-fold greater than that in maternal blood. At birth, humans and other mammals have plasma choline concn that are much higher than those in adults ... In rats, the liver choline concn in late pregnancy decr to less than one-third that of nonpregnant females ... /Choline/

For more Absorption, Distribution and Excretion (Complete) data for CHOLINE BITARTRATE (8 total), please visit the HSDB record page.

Medicine, dietary supplement, nutrient

MEDICATION

MEDICATION (VET)

(1972) No Data

(1975) No Data

(1972) No Data

(1975) No Data

(1972) PROBABLY GREATER THAN 4.54X10+5 GRAMS

(1975) PROBABLY GREATER THAN 4.54X10+5 GRAMS

Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#2626]

REACTION OF TRIMETHYLAMINE WITH ETHYLENE OXIDE FOLLOWED BY TREATMENT WITH TARTARIC ACID

... The dominating industrial process /for choline/ is reacting ethylene oxide with trimethylamine and water, or an acid if one of its salts is desired, in a batch or continuous manufacturing process.

AVAILABLE GENERICALLY: TABLETS 250 MG...

Grade: FCC

Ethanaminium, 2-hydroxy-N,N,N-trimethyl-, (2R,3R)-2,3-dihydroxybutanedioate (1:1): ACTIVE

QUALITATIVELY CHOLINE HAS THE SAME PHARMACOLOGICAL ACTIONS AS DOES ACETYLCHOLINE, BUT IT IS FAR LESS ACTIVE. /CHOLINE/

SINCE HUMAN BREAST MILK CONTAINS 7 MG CHOLINE/100 KCAL, COMMITTEE ON NUTRITION OF AMERICAN ACADEMY OF PEDIATRICS (1976) RECOMMENDS THE FORTIFICATION OF INFANT FORMULAS TO THIS LEVEL. /CHOLINE/

CHOLINE IS NOT AT PRESENT AN OFFICIAL DRUG. HOWEVER, PREPN OF CHOLINE BITARTRATE...AVAILABLE.

... The dominating industrial process /for choline/ is reacting ethylene oxide with trimethylamine and water, or an acid if one of its salts is desired, in a batch or continuous manufacturing process.