Choline chloride

139.624

139.076

200-655-4

45I14D8O27

0853

758473|402838

DTXSID4020325

WHITE CRYSTALS|Deliquescent crystals

2923100000

20.23

log Kow = -5.16 (est)

White crystalline powder

1.205 g/cm3

305 °C (decomp)

H2O: soluble

0-6ºC

LD50 in rats (g/kg): 0.400 i.p.; 6.64 orally (Hartung, Cornish)

4.7 (10% SOLN IN WATER)

121 Ų [M]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Aq soln is practically neutral

Deliquescent. Very soluble in water. (NTP, 1992)

Alcohols and Polyols

Choline chloride is a quaternary ammonium salt. Quaternary ammonium salts often serve as catalysts in reactions. They are incompatible with many strong oxidizers and reducing agents, such as metal hydrides, alkali/active metals, and organometallics. Quaternary ammonium salts often serve as catalysts in reactions. They are incompatible with many strong oxidizers and reducing agents, such as metal hydrides, alkali/active metals, and organometallics. Unlike the ammonium ion, [NH4]+, and the primary, secondary, or tertiary ammonium cations, the quaternary ammonium cations are permanently charged, independent of the pH of their solution.

NONH for all modes of transport

1

R36/37/38

S26-S36

KH2975000

Xi

Separated from strong oxidants.

Stable. Incompatible with strong oxidizing agents, moisture. Store under a dry atmosphere.

P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, P501

H315

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.

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

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.

This chemical is relatively nonflammable. (NTP, 1992)|Combustible. Gives off irritating or toxic fumes (or gases) in a fire.

|Warning|H315 (99.44%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 570 companies from 14 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

To fight fires involving this chemical, you should be equipped with an air line or self-contained breathing apparatus. Extinguish with a dry chemical, carbon dioxide, foam or halon extinguisher. (NTP, 1992)|Use water spray, powder.

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a strong 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 chemical under refrigerated temperatures, and protect it from moisture. (NTP, 1992)

MINIMUM PROTECTIVE CLOTHING: A laboratory coat and leather shoes should provide you with adequate protection for working with this chemical. 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)

Sweep spilled substance into covered containers. If appropriate, moisten first to prevent dusting.

Separated from strong oxidants.

A nuisance-causing concentration of airborne particles can be reached quickly when dispersed.

NO open flames.

Use ventilation.

Protective gloves.

Wear safety spectacles.

Repeated admin of choline chloride to female rats incr liver necrosis caused by carbon tetrachloride.|Lithium admin potentiates effect of exogenous choline on brain acetylcholine levels.|Toxic interaction between choline and morphine ... .|Methotrexate may diminish pools of all choline metabolites. Choline supplementation reverses fatty liver caused by methotrexate admin in rats. /Choline/|For more Interactions (Complete) data for CHOLINE CHLORIDE (6 total), please visit the HSDB record page.

Oral LD50 for man is estimated to be of the order of 200-400 g. /Choline/

LD50 Rat ip 0.400 g/kg|LD50 Rat oral 6.64 g/kg|LD50 Rat oral 3400 mg/kg|LD50 Mouse oral 3900 mg/kg|LD50 Mouse ip 320 mg/kg

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/

Mature human milk contains more phosphocholine and glycerophosphocholine than choline, phosphatidylcholine, of sphingomyelin. Human milk contains 1.5 to 2 mM choline moiety per liter. /Choline/

NIOSH (NOES Survey 1981-1983) has statistically estimated that 31,203 workers (8,214 of these are female) are potentially exposed to choline chloride in the US(1). Occupational exposure to choline chloride may occur through inhalation of dust and dermal contact with this compound at workplaces where choline chloride is produced or used(SRC).

... The fetal choline content can be estimated as approximately 5 mmol/kg (520 mg/kg) fetal weight. Human placental tissue has been estimated to average 1.26 + or - 0.24 mmol/kg ... in a small sample (n = 7) ... /Choline/

Lipotropic Agents; Nootropic Agents|Patients receiving long-term total parenteral nutrition (TPN) develop hepatic steatosis as a complication. Our previous studies have shown this to be caused, at least in part, by choline deficiency. ... four patients (1 man, 3 women) aged 50 +/- 13 years who had low plasma-free choline concentrations 4.8 +/- 1.7 (normal, 11.4 +/- 3.7 nmol/mL) /were studied/. The patients had received TPN for 9.7 +/- 4.7 years. They received parenteral nutrition solutions containing choline chloride (1 to 4 g/d) for 6 weeks. ... During choline administration, the plasma-free choline concentration increased into the normal range within 1 week in all four patients and remained at or above the normal range for all 6 weeks, but decreased back to baseline when choline supplementation was discontinued. Hepatic steatosis resolved completely, as estimated by abdominal computed tomography (CT). Liver density increased from -14.2 +/- 22.3 Hounsfield units (HU) to 8.4 +/- 10.3 HU at week 2 (P = .002); 9.6 +/- 10.7 HU at week 4 and 13.1 +/- 7.3 HU at week 6, as determined by the liver-spleen CT number difference obtained by the subtraction of the average spleen CT number (in HU) from the average liver CT number. This improvement continued up to 4 weeks after choline supplementation (13.8 +/- 2.8 HU). Hepatic steatosis was shown to have recurred in one patient after 10 weeks of return to choline-free parenteral nutrition. The hepatic steatosis associated with parenteral nutrition can be ameliorated, and possibly prevented, with choline supplementation. ...|Previous studies have shown that plasma free choline concentrations are significantly decreased in many long-term home total parenteral nutrition (TPN) patients. Furthermore, low choline status has been associated with both hepatic morphologic and hepatic aminotransferase abnormalities. A preliminary pilot study suggested choline-supplemented TPN may be useful in reversal of these hepatic abnormalities. ... : Fifteen patients (10 M, 5 F) who had required TPN for > or =80% of their nutritional needs were randomized to receive their usual TPN (n = 8), or TPN to which 2 g choline chloride had been added (n = 7) for 24 weeks. Baseline demographic data were similar between groups. Patients had CT scans of the liver and spleen, and blood for plasma free and phospholipid-bound choline, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, gamma glutamyl transferase (GGT), bilirubin, serum lipids, complete blood count (CBC), and chemistry profile obtained at baseline, and weeks 2, 4, 6, 12, 16, 20, 24, and 34. CT scans were analyzed for Hounsfield unit (HU) densities. RESULTS: There were no significant differences in any measured parameters after 2 weeks. However, at 4 weeks, a significant difference in liver HU between groups was observed (13.3+/-5.0 HU [choline] vs 5.8+/-5.2 HU [placebo], p = .04). This significant trend continued through week 24. Recurrent hepatic steatosis and decreased HU were observed at week 34, 10 weeks after choline supplementation had been discontinued. A significant increase in the liver-spleen differential HU was also observed in the choline group (10.6+/-6.2 HU [choline] vs 1.3+/-3.3 HU [placebo], p = .01). Serum ALT decreased significantly (p = .01 to .05) in the choline group vs placebo at weeks 6,12, 20, and 24. Serum AST was significantly decreased in the choline group by week 24 (p = .02). The serum alkaline phosphatase was significantly reduced in the choline group at weeks 2, 12, 20, 24, and 34 (p = .02 to 0.07). Total bilirubin was normal in these patients and remained unchanged during the study. Serum GGT tended to decrease more in the choline group, but the greater decrease was not statistically significant. ... Choline deficiency is a significant contributor to the development of TPN-associated liver disease. The data suggest choline is a required nutrient for long-term home TPN patients.|Choline salts (...chloride...) are used in treatment of fatty degeneration and cirrhosis of the liver. Results in treatment of advanced fibrotic cirrhosis of liver has been disappointing. It has not been shown conclusively that choline therapy is superior to an adequate diet in treatment of liver diseases.|For more Therapeutic Uses (Complete) data for CHOLINE CHLORIDE (17 total), please visit the HSDB record page.

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. (See all compounds classified as Nootropic Agents.)|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. (See all compounds classified as Lipotropic Agents.)

A study of choline pharmacokinetics was undertaken in four patients receiving long-term total parenteral nutrition. On consecutive days, 7, 14, 28, and 56 mmol choline chloride were intravenously infused over a 12-hour period in each subject. The choline concentration was determined in plasma at baseline, 1/4, 1, 3, 6, and 12 hours, and 3 and 12 hours after the infusion ended, and in daily 24-hour urine collections. Analysis of variance showed the data fit a two-compartment model in which elimination from the central compartment was saturable significantly better than a one-compartment model in all four subjects (p < 10-8 in all cases), and significantly better than a nonsaturating model in three of the four subjects (p = 1.0 x 10-9, 7.5 x 10-6, 9.4 x 10-11, respectively). The model allowed estimates of the rate constant for choline elimination at ambient levels, first-order rate constants for transfer between central and peripheral compartments, the dissociation constant for the saturable elimination process, the apparent volume of distribution in the central compartment, the steady-state volume of distribution, and the quantities of choline in the central compartment and in the readily exchangeable pool.|Choline chloride, a strong base, was surprisingly well absorbed at pH 7, but absorption was less at lower ph values.|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 chloride (1-2 g, 4 times daily, increasing every 2 days, reaching max of 2-5 g 4 times daily, orally) dose-dependently incr serum choline levels in patients with Huntington's Disease, & incr cerebrospinal fluid choline levels not related to serum levels.|For more Absorption, Distribution and Excretion (Complete) data for CHOLINE CHLORIDE (11 total), please visit the HSDB record page.

Free choline is not fully absorbed, especially after large doses, & 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 CHLORIDE (6 total), please visit the HSDB record page.

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/|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/|Female Sprague-Dawley rats received approximately 300 mg/kg per day of choline chloride through their drinking water on days 11 of pregnancy through birth and the level of nerve growth factor (NGF) in the hippocampus and frontal cortex of their male offspring was measured at 20 and 90 days of age. Prenatal choline supplementation caused significant increases in hippocampal NGF levels at 20 and 90 days of age, while levels of NGF in the frontal cortex were elevated in choline-supplemented rats at 20 days of age, but not 90 days of age. These results suggest that increases in NGF levels during development or adulthood may be one mechanism underlying improvements in spatial and temporal memory of adult rats exposed to elevated levels of choline chloride perinatally.

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. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. 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)

Fresh air, rest.

Rinse and then wash skin with water and soap.

Rinse with plenty of water for several minutes (remove contact lenses if easily possible).

/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/

/HUMAN EXPOSURE STUDIES/ Single oral doses of 10 g produce no obvious pharmacodynamic response /Choline/|/HUMAN EXPOSURE STUDIES/ Humans with and without cirrhosis have been treated with large doses of choline chloride (6 g/day for 4 weeks) with no resultant liver toxicity ...|/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/ ...Fishy body odor, vomiting, salivation, sweating, and gastrointestinal effects ... were reported in patients with tardive dyskinesia and cerebellar ataxia treated with choline chloride at 150 and 220 mg/kg of body weight/day for 2 to 6 weeks (10 and 16 g/day, respectively) ...|For more Human Toxicity Excerpts (Complete) data for CHOLINE CHLORIDE (17 total), please visit the HSDB record page.

2-Hydroxy-N,N,N-trimethylethanaminium

FORMS AVAILABLE GENERICALLY: TABLETS 250 MG (CHOLINE BITARTRATES); POWDER (CHOLINE CHLORIDE, CHOLINE DIHYDROGEN CITRATE).

Agriculture, forestry, fishing and hunting|Ethanaminium, 2-hydroxy-N,N,N-trimethyl-, chloride (1:1): ACTIVE|A SELECTED FOOD ADDITIVE CLASSIFIED AS A NUTRIENT AND DIETARY SUPPLEMENT. /FROM TABLE/|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 @ PRESENT AN OFFICIAL DRUG. HOWEVER, PREPN OF...CHOLINE CHLORIDE ARE 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.

Analyte: choline chloride; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: choline chloride; matrix: chemical purity; procedure: dissolution in water; add glacial acetic acid; potentiometric titration with silver nitrate|Analyte: choline chloride; matrix: pharmaceutical preparation (capsule, tablet), food (bovine liver, cereal, egg yolk, infant formula, meat-based pet food, soybean); procedure: capillary zone electrophoresis with indirect ultraviolet detection at 214 nm; limit of detection: 50 ug/g|Analyte: choline chloride; matrix: pesticide formulation (herbicide); procedure: capillary electrophoresis with indirect ultraviolet detection at 200 nm or electrospray mass spectrometry detection; limit of detection: 5 ug/mL|For more Analytic Laboratory Methods (Complete) data for CHOLINE CHLORIDE (9 total), please visit the HSDB record page.

Analyte: choline chloride; matrix: blood (plasma); procedure: high-performance liquid chromatography with ultraviolet detection at 254 nm; limit of quantitation: 1 nmole/mL|Analyte: choline chloride; matrix: blood (plasma, red blood cell); procedure: high-performance liquid chromatography with electrochemical detection; limit of detection: 10 nM|Analyte: choline chloride; matrix: blood (plasma); procedure: high-performance liquid chromatography with electrochemical detection; limit of quantitation: 3.58 uM|Analyte: choline chloride; matrix: cerebrospinal fluid, dialysate, tissue (brain); procedure: high-performance liquid chromatography with electrochemical detection; limit of detection: 10 fmole|For more Clinical Laboratory Methods (Complete) data for CHOLINE CHLORIDE (12 total), please visit the HSDB record page.

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