Tris(hydroxymethyl)aminomethane

121.13500

121.14

201-064-4

023C2WHX2V

65434|6365

DTXSID2023723

Crystalline mass|WHITE, CRYSTALLINE POWDER

B - Blood and blood forming organs

29221980

86.71000

-2.9

Liquid

0.6181 g/cm³ @ Temp: 25 °C

171-172 °C

219-220 °C @ Press: 10 Torr

100ºC

1.531

H2O: 550 g/L (25 ºC)

2-8ºC

0.0267 hPa (20 °C)

LD50 orally in Rabbit: > 5000 mg/kg LD50 dermal Rat > 5000 mg/kg

SLIGHT, CHARACTERISTIC ODOR

FAINT, SWEET, SOAPY TASTE

pH of 0.1 molar aq soln = 10.4

Henry's Law constant = 8.7X10-13 atm-cu m/mol at 25 °C (est)

pKa = 8.07

Weak, monoacidic base; aq soln do not absorb CO2 from air|REACTS WITH PROTON DONORS|Hydroxyl radical reaction rate constant = 3.4X10-11 cu cm/molecule-sec at 25 °C (est)

NONH for all modes of transport

2

R36/37/38

S26-S37/39

TY2900000

Xi

Stable. Incompatible with bases, strong oxidizing agents. Protect from moisture.

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.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl tromethamine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|Warning|H315 (99.9%): 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 1177 companies from 23 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

LD50 Rat iv 2300 mg/kg|LD50 Rat oral 5900 mg/kg|LD50 Mouse iv 3500 mg/kg

Tromethamine's production and use as an emulsifying agent, in the synthesis of surface-active agents and vulcanization accelerators(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 1(SRC), determined from a structure estimation method(2), indicates that tromethamine is expected to have very high mobility in soil(SRC). However, tromethamine has a pKa of 8.07(3) and should exist partially as a cation under environmental conditions (pH 5-9)(SRC). As a result, tromethamine may have greater adsorption and less mobility than its estimated Koc value indicates since cations generally adsorb more strongly to soils containing organic carbon and clay than neutral species(4). Volatilization of tromethamine from moist soil surfaces is not expected to be an important fate process(SRC) since cations do not volatilize and the estimated Henry's Law constant for the neutral species is 8.7X10-13 atm-cu m/mole(SRC), using a fragment constant estimation method(5). Tromethamine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.2X10-5 mm Hg(SRC), determined from a fragment constant method(6).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1(SRC), determined from a structure estimation method(2), indicates that tromethamine is not expected to adsorb to suspended solids and sediment(SRC). However, tromethamine has a pKa of 8.07(3) and should exist partially as a cation under environmental conditions (pH 5-9)(SRC). As a result, tromethamine may have greater adsorption to suspended solids and sediment than its estimated Koc value indicates(SRC). Volatilization from water is not expected(4) since cations do not volatilize and the estimated Henry's Law constant for the neutral species (free base) of tromethamine is 8.7X10-13 atm cu m/mol(SRC), calculated using a fragment constant estimation method(5). According to a classification scheme(6), an estimated BCF of 3(SRC), from an estimated log Kow of -1.56(7) and a regression-derived equation(8), suggests the potential for bioconcentration in aquatic organisms is low(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), tromethamine, which has a an estimated vapor pressure of 2.2X10-5 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase tromethamine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 11 hours(SRC), calculated from its rate constant of 3.4X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase tromethamine is removed from the atmosphere by wet and dry deposition(SRC). Tromethamine does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(4).

The rate constant for the vapor-phase reaction of tromethamine with photochemically-produced hydroxyl radicals has been estimated as 3.4X10-11 cu cm/molecule-sec at 25 °C(SRC), using a structure estimation method(1). This corresponds to an atmospheric half-life of about 11 hours(SRC) at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Tromethamine is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups(2). Tromethamine does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to undergo direct photolysis by sunlight(2).

An estimated BCF of 3 was calculated for tromethamine (SRC), using an estimated log Kow of -1.56(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 tromethamine can be estimated to be 1(SRC). According to a classification scheme(2), this estimated Koc value suggests that tromethamine is expected to have very high mobility in soil(SRC). The pKa of tromethamine is 8.07(3), indicating that this compound will partially exist as a cation in the environment. As a result, the mobility of tromethamine may be overestimated since cations generally adsorb more strongly to soils containing organic carbon and clay than neutral species(4).

Tromethamine is a weak base with pKa of 8.07(1). This estimated pKa indicates tromethamine will partially exist in the protonated form in the environment. Volatilization from moist soil and water is not expected since cations do not volatilize and the estimated Henry's Law constant for the neutral species (free base) of tromethamine is 8.7X10-13 atm cu m/mol(SRC), using a fragment constant estimation method(2). Tromethamine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.2X10-5 mm Hg(SRC), determined from a fragment constant method(3).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 40897 workers (30773 of these are female) are potentially exposed to tromethamine in the US(1). Occupational exposure to tromethamine may occur through inhalation and dermal contact with this compound at workplaces where tromethamine is produced or used(SRC).

For the prevention and correction of metabolic acidosis.|FDA Label

Buffers; Excipients|/Tromethamine is indicated/ for the prevention and correction of metabolic acidosis. /Included in US product label/|Metabolic Acidosis Associated with Cardiac Bypass Surgery. Tromethamine solution has been found to be primarily beneficial in correcting metabolic acidosis which may occur during or immediately following cardiac bypass surgical procedures. /Included in US product label/|Correction of Acidity of ACD Blood in Cardiac Bypass Surgery. It is well known that ACD blood is acidic and becomes more acidic on storage. Tromethamine effectively corrects this acidity. Tromethamine solution may be added directly to the blood used to prime the pump-oxygenator. When ACD blood is brought to a normal pH range the patient is spared an initial acid load. Additional tromethamine may be indicated during cardiac bypass surgery should metabolic acidosis appear. /Included in US product label/|For more Therapeutic Uses (Complete) data for TROMETHAMINE (6 total), please visit the HSDB record page.

Local reactions associated with administration of tromethamine may include local irritation and tissue inflammation or infection at the site of injection, a febrile response, chemical phlebitis, venospasm, hypervolemia, and iv thrombosis. The drug should be administered through a large needle or indwelling catheter to minimize venous irritation by the highly alkaline tromethamine solution. Extravasation may result in inflammation, necrosis, and sloughing of overlying skin. If perivascular infiltration occurs, tromethamine administration should be discontinued immediately. Infiltration of the affected area with 1% procaine hydrochloride, to which hyaluronidase has been added, will often reduce venospasm and also will dilute any tromethamine remaining in the tissues locally. Local infiltration of an alpha-adrenergic blocking agent, such as phentolamine mesylate, into the vasospastic area has been recommended. If necessary, nerve block of autonomic fibers to the affected area may be performed.|Transient decreases in blood glucose concentration may occur during administration of tromethamine. When larger than recommended doses are used or when administration is too rapid, hypoglycemia may persist for several hours after the drug is discontinued.|Tromethamine should be slowly administered and in amounts sufficient only to correct the existing acidosis, in order to avoid overdosage and alkalosis. Determinations of blood glucose concentrations should be frequently performed during and following therapy.|Respiratory depression may occur in patients receiving large doses of tromethamine, as a result of increased blood pH and reduced carbon dioxide concentrations, and in those with chronic hypoventilation or those receiving other drugs that depress respiration. Dosage must be carefully adjusted so that blood pH does not increase above normal, and facilities for providing mechanical ventilation should be readily available during administration of tromethamine. Tromethamine may be used in conjunction with mechanical ventilatory support if respiratory acidosis is present concomitantly with metabolic acidosis.|For more Drug Warnings (Complete) data for TROMETHAMINE (18 total), please visit the HSDB record page.

3. 3= MODERATELY TOXIC: PROBABLY ORAL LETHAL DOSE (HUMAN) 0.5-5 G/KG, BETWEEN 1 OZ & 1 PINT FOR 70 KG PERSON (150 LB).

A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. (See all compounds classified as Buffers.)|Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form. These include binders, matrix, base or diluent in pills, tablets, creams, salves, etc. (See all compounds classified as Excipients.)

Tromethamine is substantially eliminated by the kidneys. ... Ionized tromethamine (chiefly as the bicarbonate salt) is rapidly and preferentially excreted in urine at a rate that depends on the infusion rate. The manufacturer states that urinary excretion continues over a period of 3 days; 75% or more appears in the urine after 8 hours. In some studies, 50-75% of an iv dose was recovered in urine within 24 hours, but another study reported recovery in healthy adults to be 64% and 77% after 2 and 3 days, respectively.|It is not known whether tromethamine is distributed in human milk.|Ionized tromethamine is excreted by kidney, so the effect is that of excretion of hydrogen ions. Elimination of drug from body is entirely by renal excretion. Excretion of tromethamine is accompanied by osmotic diuresis, since clinical doses of drug considerably add to osmolarity of glomerular filtrate.|In rats of different age (5 to 240 days old) the renal excretion of Trishydroxymethylaminomethane (THAM) was studied. In 5 and in 240 days old rats the renal excretion of THAM was slower than in rats of other age groups. Stimulation of diuresis by i.p. injection of mannitol, thiazide or by oral water load resulted in an increase in THAM excretion in 5 and in 240 days old rats. The renal excretion of THAM was also increased by repeated administration of THAM in all age groups, except in new born rats. Possible mechanisms of action are discussed.|The distribution of 14C labelled THAM (tris-hydroxymethylaminomethane) was determined between intra- and extracellular space of nephrectomized Sprague-Dawley rats as a function of time at constant plasma pH of 7.4. The following results were obtained: An equilibrium in the distribution of THAM between ECS and ICS will not occur before 6-12 hours after administration. This indicates that THAM permeates very slowly into the intracellular compartment, which is in contrast to the general assumption that it quickly diffuses into the intracellular space to restore the intracellular acidosis. THAM disappears from the extracellular space in a multiexponential fashion, indicating that it equilibrates with the different body tissues at largely variable rates. The equilibrium which occurs between both body compartments 6-12 hours after THAM application does not agree with the values which are expected for transfer of only the nonionised substance. At plasma pH 7.4 and a "mean whole body pHi" of 6.88, THAM is distributed with a distribution ratio of 4 (ICS/ECS), a value quite different from the value of 11 which would be expected for exclusive nonionic diffusion. Thus THAM is also transferred across the cell membrane in ionized form. These results indicate that the influx of THAM into the intracellular space is too slow (when compared to the renal elimination kinetics) to influence intracellular pH significantly by direct buffer action. Moreover, only a fraction of THAM enters the intracellular space in the nonionized form, thus reducing (to an even greater extent) the direct effect of THAM on the intracellular acid-base equilibrium.

Tromethamine is not metabolized appreciably.

Tromethamine is an alkalinizing agent which acts as a proton (hydrogen ion) acceptor. Tromethamine is a weak base; following IV injection, it attracts and combines with hydrogen ions and their associated acid anions and the resulting salts are excreted in urine. Tromethamine can combine with lactic, pyruvic, and other metabolic acids and with carbonic acid. ... At pH 7.4, approximately 70% of the tromethamine present in plasma is in the ionized (protonated) form; if pH is decreased from pH 7.4, the ionized fraction of the drug is increased. In contrast to the ionized fraction of tromethamine, which upon administration reacts only with acid in the extracellular fluids, the fraction of the dose which remains un-ionized at physiologic pH is thought to be capable of penetrating the cell membrane to combine with intracellular acid. Since administration of tromethamine reduces hydrogen ion concentration, there is a decrease in proton donor and an increase in proton acceptor concentrations in body buffers. In the bicarbonate:carbonic acid buffer, the concentration of dissolved carbon dioxide is decreased (at least until regulatory mechanisms compensate) and the concentration of bicarbonate is increased. The reduction of carbon dioxide tension removes a potent stimulus to breathing and may result in hypoventilation and hypoxia.|Tromethamine ... acts as a weak, osmotic diuretic, increasing the flow of alkaline urine containing increased amounts of electrolytes.|By removing protons from hydronium ions, ionization of carbonic acid is shifted so as to decrease pCO2 and to increase bicarbonate. Excess bicarbonate is then gradually excreted in kidney. /Tromethamine is an/ especially useful way to manage excessively high pCO2 in respiratory acidosis...

/HUMAN EXPOSURE STUDIES/ In studies of tromethamine administration in healthy individuals, the ventilatory rate remained constant, but a reduced tidal volume produced a decrease in minute ventilation and in carbon dioxide output; arterial oxygen saturation decreased by an average of about 5%.|/SIGNS AND SYMPTOMS/ Too rapid administration and/or excessive amounts of tromethamine may cause alkalosis, hypoglycemia, overhydration or solute overload.

Tri(hydroxymethyl)aminomethane

Tromethamine formulations: Parenteral injection 36 mg/mL (18 g) Tham, Hospira.|TROMETHAMINE, NF (THAM), IS AVAIL AS 0.3 MOLAR SOLN ADJUSTED TO PH 8.6 WITH ACETIC ACID. IT IS ALSO SUPPLIED AS POWDER (THAM-E) TO BE DISSOLVED IN 1 L OF STERILE WATER. EACH L CONTAINS 300 MMOLES (36 G) OF TROMETHAMINE, 30 MMOLES OF SODIUM CHLORIDE, & 5 MMOLES OF POTASSIUM CHLORIDE.

All other basic organic chemical manufacturing|1,3-Propanediol, 2-amino-2-(hydroxymethyl)-: ACTIVE

ELECTROPHORESIS.|Analyte: tromethamine; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: tromethamine; matrix: chemical identification; procedure: reaction with salicylaldehyde and glacial acetic acid produces a yellow color|Analyte: tromethamine; matrix: chemical identification; procedure: reaction with ceric ammonium nitrate in nitric acid produces color change from light yellow to orange|For more Analytic Laboratory Methods (Complete) data for TROMETHAMINE (9 total), please visit the HSDB record page.

GC METHOD FOR QUANTITATIVE DETERMINATION OF TRIS(HYDROXYMETHYL)AMINOMETHANE IN PLASMA.|Analyte: tromethamine; matrix: blood (plasma, dried), amniotic fluid, cerebrospinal fluid, urine; procedure: high-performance liquid chromatography with ultraviolet detection at 254 nm|Analyte: tromethamine; matrix: blood (plasma); procedure: high-performance liquid chromatography with ultraviolet detection at 237 nm; limit of detection: 282 ng/mL|Analyte: tromethamine; matrix: blood (plasma), urine; procedure: high-performance liquid chromatography with fluorescence detection at 460 nm (excitation) and 532 nm (emission); limit of quantitation: 5 ug/mL (urine); 1 ug/mL (plasma)

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