Triethanolamine

Absorption

Dermal absorption of trolamine increases with the dose . This has been found to range from 19-28% in rats with doses of 68-276 mg/kg in 190 μL of acetone without occlusion and from 60-80% in mice with doses of 79-1120 mg/kg in the same volume of acetone.

Toxicity

Trolamine produced mild erythema and edema in rabbits with dermally administered doses of 2 g/kg under occlusion . The oral LD50 was found to be 8 g/kg in guinea pigs and 4.19-11.26 g/kg in rats. Repeated oral administration in rats and guinea pigs produced hepatic and renal damage with deaths occurring in rats at doses >0.3 g/kg/day. When inhaled trolamine produced edema and inflammation in rats at doses over 100 mg/m3 after 5 days and at doses over 4.7 mg/m3 after 90 days. There is some evidence of carcinogenicity at high dermal doses (1000 mg/kg/day) in mice. Trolamine is not classified as a carcinogen in humans.

Description

Triethanolamine is a viscous, colourless/pale yellow liquid with a weak ammoniacal odour. Triethanolamine is incompatible with copper, copper alloys, galvanised iron, acids, and oxidisers. Reports indicate that in India itself, as many as six companies manufacture triethanolamine and it is manufactured by many different countries around the world. Global production and industrial application of triethanolamine is very extensive.

In industries, triethanolamine is used as a corrosion inhibitor in metal-cutting fluids; a curing agent for epoxy and rubber polymers; a copper–triethanolamine; in emulsifiers, thickeners, and wetting agents in the formulation of consumer products such as cosmetics, detergents, shampoos, and other personal products; and a neutraliser-dispersing agent in agricultural herbicide formulations. In brief, triethanolamine has wide applications as a corrosion inhibitor, a surface-active agent, and an intermediate in various products including metalworking fluids, oils, fuels, paints, inks, cement, cosmetic, and personal products and formulations of algicides and herbicides.

Chemical properties

Triethanolamine is a pale yellow and viscous liquid. It is hygroscopic with an irritant and ammoniacal odor. There are multiple industrial and domestic applications for this compound, i.e., in the manufacture of toilet products, cosmetics formulations, solvents for waxes, resins, dyes, paraffi ns and polishes, herbicides, and lubricants for textile products. In the pharmaceutical industry, triethanolamine is used as a non-steroidal, antiinfl ammatory agent, an emulsifi er, and an alkylating agent.

The Uses of Triethanolamine

Triethanolamine is used primarily as a surfactant, reducing the surface tension between two media. It is also used as a general emulsifier for preparations, such as ones involving drug penetration assays. The emulsifying agent triethanolamine can be contained in many products, such as metalwork cutting fluids and color-film developers. Traces may exist in other ethanolamines such as mono- and diethanolamine. Specifically, triethanolamine is used in fatty-acid soaps; in dry cleaning, cosmetics, shampoos, creams, waxes, cutting oils, household detergents, and emulsions; in wool scouring; textile antifume agents; water repellant; dispersion agent; corrosion inhibitor; softener; emulsifier; humectant; plasticizer; chelating agent; rubber accelerator; pharmaceutical alkalizing agent; catalyst for condensation etc.; in emulsions with mineral and vegetable oils.

Background

Trolamine, or triethanolamine (TEA), is a tertiary amine and a triol. It is a bifunctional compound that exhibits both properties of alcohols and amines. Trolamine contains small amounts of diethanolamine and ethanolamine and may also act as an antioxidant against the auto-oxidation of animal and vegetable fats. It is commonly used as a pH adjuster and surfactant in industrial and cosmetic products such as skin and hair conditioning.

Indications

Trolamine is used as an alkalizing agent, surfactant, and counter-ion in cosmetic and pharmaceutical formulations . It is not considered to be an active pharmacological ingredient and so has no official indication.

Definition

ChEBI: Triethanolamine is a tertiary amino compound that is ammonia in which each of the hydrogens is substituted by a 2-hydroxyethyl group. It has a role as a buffer and a surfactant. It is a tertiary amino compound, a triol and an amino alcohol. It is functionally related to a triethylamine. It is a conjugate base of a triethanolammonium.

Production Methods

Triethanolamine is produced with ethanolamine and diethanolamine by ammonolysis of ethylene oxide and the triethanolamine is then separated by distillation (Mullins 1978). In 1984, 139.6 million pounds of triethanolamine were produced in the United States (USTIC 1985).

Preparation

Triethanolamine is prepared commercially by the ammonolysis of ethylene oxide. The reaction yields a mixture of monoethanolamine, diethanolamine, and triethanolamine, which are separated to obtain the pure products.

brand name

Mobisyl [as salicylate] (Ascher);Sabrilex.

Composition

The dried leaves contain protein, 25.7%; fat, 6.5%; carbohydrate, 40.8%; ash, 5%; caffeine, 3.3% and tannin, 13%. The most common catechins are gallic esters (epicatechin, epicatechin gallate and epigallocatechin gallate). All are found in green tea and are claimed to be responsible for the chemopreventive benefits of the beverage.

World Health Organization (WHO)

Trolamine is widely used as an emulsifier in combination with fatty acids in pharmaceutical and cosmetic products. The World Health Organization is not aware of restrictive action having been taken elsewhere.

General Description

Oily liquid with a mild ammonia odor. Denser than water. Freezing point is 71°F.

Reactivity Profile

Triethanolamine is an aminoalcohol. Neutralize acids to form salts plus water in exothermic reactions. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated in combination with strong reducing agents, such as hydrides. Reacts violently with strong oxidants. [Handling Chemicals Safely 1980. p. 928].

Health Hazard

Exposures to triethanolamine, in contrast with other chemical compounds, is known to cause low toxicity to animals and the acute oral LD50 to rats and guinea pigs ranges from 8000 to 9000 mg/kg. Triethanolamine was found to be a moderate eye irritant. A 5%–10% solution of triethanolamine did not induce skin irritation or skin sensitization. Studies of Inoue et al. and many other workers have indicated the absence of the mutagenic potential of triethanolamine as evidenced by both in vivo and in vitro studies (Salmonella typhimurium tests, Chinese hamster ovary cells, and rat liver chromosome analysis). Further, extensive studies have demonstrated the absence of potential carcinogenicity of triethanolamine in rats and mice, suggesting a low or lack of acute or chronic toxicity of the chemical to mammals.

Fire Hazard

Special Hazards of Combustion Products: Poisonous gases, such as NOx, may be produced

Chemical Reactivity

Reactivity with Water No reaction; Reactivity with Common Materials: No reactions; Stability During Transport: Stable; Neutralizing Agents for Acids and Caustics: Dilute with water; Polymerization: Not pertinent; Inhibitor of Polymerization: Not pertinent.

Pharmaceutical Applications

Triethanolamine is widely used in topical pharmaceutical formulations, primarily in the formation of emulsions.
When mixed in equimolar proportions with a fatty acid, such as stearic acid or oleic acid, triethanolamine forms an anionic soap with a pH of about 8, which may be used as an emulsifying agent to produce fine-grained, stable oil-in-water emulsions. Concentrations that are typically used for emulsification are 2–4% v/v of triethanolamine and 2–5 times that of fatty acids. In the case of mineral oils, 5% v/v of triethanolamine will be needed, with an appropriate increase in the amount of fatty acid used. Preparations that contain triethanolamine soaps tend to darken on storage. However, discoloration may be reduced by avoiding exposure to light and contact with metals and metal ions.
Triethanolamine is also used in salt formation for injectable solutions and in topical analgesic preparations. It is also used in sun screen preparations.
Triethanolamine is used as an intermediate in the manufacturing of surfactants, textile specialties, waxes, polishes, herbicides, petroleum demulsifiers, toilet goods, cement additives, and cutting oils. Triethanolamine is also claimed to be used for the production of lubricants for the rubber gloves and textile industries. Other general uses are as buffers, solvents, and polymer plasticizers, and as a humectant.

Industrial uses

Triethanolamine undergoes reactions characteristic of tertiary amines and of alcohols. Two industrially important reactions of the ethanolamines involve reaction with carbon dioxide or hydrogen sulfide to yield water soluble salts, and reaction with long chain fatty acids to form neutral ethanolamine soaps (Mullins 1978). Substituted ethanolamine compounds, such as soaps, are used extensively as emulsifiers, thickeners, wetting agents, and detergents in cosmetic formulations (including skin cleaners, creams, and lotions) (Beyer et al 1983).
The largest uses for triethanolamine are in the production of fatty acid soaps and detergents and in cosmetic formulations. In cosmetics, triethanolamine is an important raw material and is used in combination with fatty acids as emulsifiers for creams, lotions, skin cleaners, and shampoos. Triethanolamine is also used in cement and concrete to reduce particle agglomeration within the grinding mill; as an antistatic agent in the textile industry; in the metal industry for metal plating and in alkaline derusting formulations; in the rubber industry as a vulcanization accelerator; and in the manufacture of herbicides and pesticides. Triethanolamine may also be used as a surface active agent in cutting fluids; as an absorption agent for acidic gases in air pollution control; as a component of coating on fruits and vegetables; as a solvent for casein, shellac, and dyes; and as a penetrating agent for organic liquids in wood and paper (Bayer et al 1983; Mullins 1978; Windholz 1983). Triethanolamine is permitted in articles intended for use in the production, processing, or packaging of food (CFR 1981).

Contact allergens

This emulsifying agent can be contained in many products such as cosmetics, topical medicines, metalworking cut- ting fluids, and color film developers. Traces may exist in other ethanolamines such as monoand diethanolamine. Contact allergy seems to be rarer than previously thought.

Pharmacokinetics

Acts as a surfactant or alkalizing agent to aid in emulsification and solubilizing of compounds or in raising the pH of a solution

Safety Profile

Moderately toxic by intraperitoneal route. Mildly toxic by ingestion. Liver and kidney damage have been demonstrated in animals from chronic exposure. A human and experimental skin irritant. An eye irritant. Questionable carcinogen with experimental carcinogenic data. Combustible liquid when exposed to heat or flame; can react vigorously with oxidizing materials. To fight fire, use alcohol foam, CO2, dry chemical. When heated to decomposition it emits toxic fumes of NOx and CN-.

Safety

Triethanolamine is used primarily as an emulsifying agent in a variety of topical pharmaceutical preparations. Although generally regarded as a nontoxic material, triethanolamine may cause hypersensitivity or be irritant to the skin when present in formulated products. The lethal human oral dose of triethanolamine is estimated to be 5–15 g/kg body-weight.
Following concern about the possible production of nitrosamines in the stomach, the Swiss authorities have restricted the use of triethanolamine to preparations intended for external use.
LD50 (guinea pig, oral): 5.3 g/kg
LD50 (mouse, IP): 1.45 g/kg
LD50 (mouse, oral): 7.4 g/kg
LD50 (rat, oral): 8 g/kg

Potential Exposure

Monoethanolamine is widely used in industry for scrubbing acid gases and in production of detergents and alkanolamide surfactants; to remove carbon dioxide and hydrogen from natural gas, to remove hydrogen sulfide and carbonyl sulfide; as an alkaline conditioning agent; as an intermediate for soaps, detergents, dyes, and textile agents. Diethanolamine is an absorbent for gases; a solubilizer for 2,4- dichlorophenoxyacetic acid (2,4-D); and a softener and emulsifier intermediate for detergents. It also finds use in the dye and textile industry. Triethanolamine is used as plasticizers, neutralizer for alkaline dispersions; lubricant additive; corrosion inhibitor; and in the manufacture of soaps, detergents, shampoos, shaving preparations; face and hand creams; cements, cutting oils, insecticides, surface active agents; waxes, polishes, and herbicides.

Carcinogenicity

Results of carcinogenicity studies have been controversial. Hoshino and Tanooka reported that triethanolamine in the diet of mice at levels of 0.03% or 0.3% caused a significant increase in the occurrence of tumors, both benign and malignant. Females showed a 32% increase, mostly of thymic lymphomas. The increase of all other tumors, in both sexes, was 8.2%. They also found that triethanolamine reacted with sodium nitrite to produce N-nitrosodiethanolamine and that the product caused mutagenesis in bacteria. Maekawa et al. reported that no carcinogenic activity was found when given orally to rats in drinking water at concentrations of 1% and 2% for 2 years. However, the dosage to females was halved after week 69 of treatment owing to nephrotoxicity. Histological examination of renal damage in treated animals revealed acceleration of chronic nephropathy, mineralization of the renal papilla, nodular hyperplasia of the pelvic mucosa, and pyelonephritis with or without papillary necrosis. Nephrotoxicity seemed to affect life span adversely, especially in females. Tumor incidence and histology were the same in the treated group as in controls.

Metabolism

Trolamine is excreted mostly as the unchanged compound . No diethanolamine or ethanolamine has been found. Very small amounts of trolamine glucuronide have been detected but not quantified.

storage

Triethanolamine may turn brown on exposure to air and light.
The 85% grade of triethanolamine tends to stratify below 15℃; homegeneity can be restored by warming and mixing before use. Triethanolamine should be stored in an airtight container protected from light, in a cool, dry place.
See Monoethanolamine for further information.

Shipping

UN2491 Ethanol amine or Ethanolamine solutions, Hazard class: 8; Labels: 8-Corrosive material.

Purification Methods

Shake the amine gently with Linde type 4A molecular sieves for 24hours, filter and fractionate it under a vacuum, and preferably in the presence of N2. Store it in dark stoppered bottles under N2 as it is hygroscopic, and turns brown in air and light. It has a strong ammoniacal odour (like diethanolamine). It is miscible with H2O, MeOH and Me2CO, and its solubilities at 25o in n-heptane, Et2O and *C6H6 are 0.4%, 1.6% and 4.2%, respectively. [See diethanolamine above, Beilstein 4 IV 1524.]

Incompatibilities

Triethanolamine is a tertiary amine that contains hydroxy groups; it is capable of undergoing reactions typical of tertiary amines and alcohols. Triethanolamine will react with mineral acids to form crystalline salts and esters. With the higher fatty acids, triethanolamine forms salts that are soluble in water and have characteristics of soaps. Triethanolamine will also react with copper to form complex salts. Discoloration and precipitation can take place in the presence of heavy metal salts.
Triethanolamine can react with reagents such as thionyl chloride to replace the hydroxy groups with halogens. The products of these reactions are very toxic, resembling other nitrogen mustards.

Waste Disposal

Controlled incineration; incinerator equipped with a scrubber or thermal unit to reduce nitrogen oxides emissions

Regulatory Status

Included in the FDA Inactive Ingredients Database (rectal, topical, and vaginal preparations). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.