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Description of key information

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
Absorption rate - dermal (%):
Absorption rate - inhalation (%):

Additional information

As an essential amino acid L-threonine has to be derived from dietary intake. In the normal diet, the amino acids are ingested as components of food proteins and not as free amino acids. Deducing the amount of individual amino acids from soy bean protein, an intake of 100 g protein per day (not unusual for an adult European individual)would result to an intake of 4 g L-threonine per day. 


Ingested dietary protein is denatured in the stomach due to low pH. Denaturing and unfolding of the protein makes the chain susceptible to proteolysis. Up to 15% of dietary protein may be cleaved to peptides and amino acids by pepsins in the stomach. In the duodenum and small intestine digestion continues through hydrolytic enzymes (e.g. trypsin, chymotrypsins, elastase, carboxypeptidase). The resultant mixture of peptides and amino acids is then transported into the mucosal cells by specific carrier systems for amino acids and for di- and tripeptides.


Absorbed peptides are further hydrolysed resulting in free amino acids which are secreted into the portal blood by specific carrier systems in the mucosal cell. Alternatively they are metabolised within the cell itself. Absorbed amino acids pass into the liver where a portion of the amino acids are used. The remainder pass through into the systemic circulation and are utilised by the peripheral tissue. Plasma L-threonine concentrations in normal subjects are reported to be above 100 µM (e.g. 140 µM +/- 33 with plasma samples collected from healthy volunteers after an overnight fast; Cynober, 2002).  


The use of amino acids is mainly regulated at the level of their metabolism (Peters, 1991). When dietary intake of amino acids exceeds the needs enzymes in the liver are induced breaking down the excess of amino acids. The oxidative catabolism of threonine follows either the glycine-independent or glycine-dependent pathway. The glycine-independent pathway is catalyzed by serine/threonine dehydratase (STDH), which irreversibly converts threonine to ketobutyrate. The ketobutyrate is subsequently decarboxylated to form propionyl-CoA (House et al., 2001). The activity of STDH is regulated by dietary protein, by its threonine content, and by insulin, glucagon, and cortisol (Greengard O and Dewey HK, 1967). Glycine-dependent oxidation involves conversion of L-threonine to glycine and acetyl-CoA by coupled threonine dehydrogenase (TDH) and 2-amino-3-oxobutyrate-CoA ligase enzymatic reaction.

Hepatic threonine metabolism has been examined in human adults in response to oral administration of threonine (Darlingetal., 2000 and Zhao et al., 1986). These studies show that higher threonine content in the diet results in a higher rate of oxidation of threonine. In addition, the majority of the threonine is metabolized via the STDH pathway (glycine-independent), and only 7–10% of total threonine catabolism occurred via glycine-dependent oxidation (Darlingetal., 2000). This indicates that STDH is the major catabolic pathway in human adults.


The kidney regulates amino acids in plasma through tubular reabsorption, occurring after ultrafiltration by the glomeruli. The amino acids are actively co-transported with sodium ions. The daily excretion of protein in urine amounts to 20-150 mg/day in humans, of which albumin represents about 60% (Tietz, 1986). Since there is no long term storage for amino acids in mammals, excess amino acids are degraded, mainly in the liver. Metabolism of amino acids involves removal of the amino group which in mammals is converted to urea and excreted in the urine. After removal of the amino group the rest of the acid is utilized as energy or used to synthesise endogenous substances.


It is assumed that 100% L-threonine is used by the organism after oral uptake. For risk assessment purposes oral absorption of L-threonine is set at 100%.


The substance is of low volatility due to a low vapour pressure. However, being a very hydrophilic substance with a molecular weight below 200, any L-threonine reaching the lungs might be absorbed through aqueous pores. (ECHA, 2008). For risk assessment purposes, although it is unlikely that L-threonine will be available to a high extent after inhalation via the lungs the inhalation absorption of L-threonine is set at 100%.

L-Threonine with high water solubility and the log P value below 0 may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Therefore, 10% dermal absorption of L-threonine is proposed for risk assessment purposes.



Cynober L. (2002): Plasma Amino Acid Levels With a Note on Membrane Transport: Characteristics, Regulation, and Metabolic Significance. Nutrition 18 (9), 761-766


Darling PB, Grunow J, Rafii M, Brookes S, Ball RO, and Pencharz PB. Threonine dehydrogenase is a minor degradative pathway of threonine catabolism in adult humans. Am J Physiol Endocrinol Metab 278: E877–E884, 2000.

Greengard O and Dewey HK. Initiation by glucagon of the premature development of tyrosine aminotransferase, serine dehydratase, and glucose-6-phosphatase in fetal rat liver. J Biol Chem 242: 2986–2991, 1967.


House JD, Hall BN, and Brosnan JT. Threonine metabolism in isolated rat hepatocytes.Am J Physiol Endocrinol Metab 281: E1300–E1307, 2001.


Peters, J.C., 1991.Tryptophan nutrition and metabolism: an overview. Adv. Exp. Med. Biol. 294, 345-57.


Tietz, N.W., 1986. Textbook of Clinical Chemistry. Chapter 4: Amino acids and proteins. W.B. Saunders Company Philadelphia, pp. 602-604.


Zhao XH, Wen ZM, Meredith CN, Matthews DE, Bier DM, and Young VR. Threonine kinetics at graded threonine intakes in young men. Am J Clin Nutr 43: 795–802, 1986.