Toxicology of mono-, di-, and triethanolamine

Rev Environ Contam Toxicol. 1997:149:1-86. doi: 10.1007/978-1-4612-2272-9_1.

Abstract

The chemistry, biochemistry, toxicity, and industrial use of monoethanolamine (MEA), diethanolamine (DEA), and triethanolamine (TEA) are reviewed. The dual function groups, amino and hydroxyl, make them useful in cutting fluids and as intermediates in the production of surfactants, soaps, salts, corrosion control inhibitors, and in pharmaceutical and miscellaneous applications. In 1995, the annual U.S. production capacity for ethanolamines was 447,727 metric tons. The principal route of exposure is through skin, with some exposure occurring by inhalation of vapor and aerosols. MEA, DEA, and TEA in water penetrate rat skin at the rate of 2.9 x 10(-3), 4.36 x 10(-3) and 18 x 10(-3) cm/hr, respectively. MEA, DEA, and TEA are water-soluble ammonia derivatives, with pHs of 9-11 in water and pHa values of 9.3, 8.8, and 7.7, respectively. They are irritating to the skin, eyes, and respiratory tract, with MEA being the worst irritant, followed by DEA and TEA. The acute oral LD50s are 2.74 g/kg for MEA, 1.82 g/kg for DEA, and 2.34 g/kg for TEA (of bw), with most deaths occurring within 4 d of administration. MEA is present in nature as a nitrogenous base in phospholipids. These lipids, composed of glycerol, two fatty acid esters, phosphoric acid, and MEA, are the building blocks of biomembranes in animals. MEA is methylated to form choline, another important nitrogenous base in phospholipids and an essential vitamin. The rat dietary choline requirement is 10 mg kg-1 d-1; 30-d oral administration of MEA (160-2670 mg kg-1 d-1) to rats produced "altered" liver and kidney weights in animals ingesting 640 mg kg-1 d-1 or greater. Death occurred at dosages of 1280 mg kg-1 d-1. No treatment-related effects were noted in dogs administered as much as 22 mg kg-1 d-1 for 2 yr. DEA is not metabolized or readily eliminated from the liver or kidneys. At high tissue concentrations, DEA substitutes for MEA in phospholipids and is methylated to form phospholipids composed of N-methyl and N, N-dimethyl DEA. Dietary intake of DEA by rats for 13 wk at levels greater than 90 mg kg-1 d-1 resulted in degenerative changes in renal tubular epithelial cells and fatty degeneration of the liver. Similar effects were noted in drinking water studies. The findings are believed to be due to alterations in the structure and function of biomembranes brought about by the incorporation of DEA and methylated DEA in headgroups. TEA is not metabolized in the liver or incorporated into phospholipids. TEA, however, is readily eliminated in urine. Repeated oral administration to rats (7 d/wk, 24 wk) at dose levels up to and including 1600 mg kg-1 d-1 produced histopathological changes restricted to kidney and liver. Lesions in the liver consisted of cloudy swelling and occasional fatty changes, while cloudy swelling of the convoluted tubules and loop of Henle were observed in kidneys. Chronic administration (2 yr) of TEA in drinking water (0, 1%, or 2% w/v; 525 and 1100 mg kg-1 d-1 in males and 910 and 1970 mg kg-1 d-1 in females) depressed body and kidney weights in F-344 rats. Histopathological findings consisted of an "acceleration of so-called chronic nephropathy" commonly found in the kidneys of aging F-344 rats. In B6C3F1 mice, chronic administration of TEA in drinking water (0, 1%, or 2%) produced no significant change in terminal body weights between treated and control animals or gross pathological changes. TEA was not considered to be carcinogenic. Systemic effects in rats chronically administered TEA dermally (0, 32, 64, or 125 mg kg-1 d-1 in males; 0, 63, 125, or 250 mg kg-1 d-1 in females) 5 d/wk for 2 yr were primarily limited to hyperplasia of renal tubular epithelium and small microscopic adenomas. In a companion mouse dermal study, the most significant change was associated with nonneoplastic changes in livers of male mice consistent with chronic bacterial hepatitis.

Publication types

  • Review

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Ethanolamine
  • Ethanolamines / pharmacokinetics
  • Ethanolamines / toxicity*
  • Mutagenicity Tests

Substances

  • Ethanolamines
  • Ethanolamine
  • triethanolamine
  • diethanolamine