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Assessment of the Toxicokinetic Behaviour of Phenylalanine (CAS 63-91-2; EC 200-568-1)

L-Phenylalanine with a molecular weight of 165.19 g/mol is an odorless white crystalline powder with a slightly bitter taste and very soluble in water (25 g/L) (see chapter 4.8 water solubility). The measured log Po/w is -1.52 (see chapter 4.7 partition coefficient), indicating the hydrophilie and that a general accumulation of Phenylalanine is not given.

L-Phenylalanine is an essential aromatic amino acid in humans and therefore must be ingested from the diet and is present as protein constituent or free amino acid in various foods such as meat, seafood, eggs, and dairy products. The recommended aromatic amino acid requirement (phenylalanine or tyrosine) is set at 25 mg/kg bw/day (WHO, 2007). In the US, the Institute of Medicine sets estimated average requirement (EAR) for amino acids; phenylalanine + tyrosine EAR for adults are estimated at 27 mg/kg bw/day (IOM, 2005). The mean daily consumption of phenylalanine is estimated in the US at 3.4 g/day (IOM, 2005).

It plays a key role in the biosynthesis of other amino acids and is important in the structure and function of many proteins and enzymes. Phenylalanine is converted to tyrosine, used in the biosynthesis of dopamine and norepinephrine neurotransmitters and is a precursor of melanin. The L-form of Phenylalanine is incorporated into proteins. (Salway JG, 2012, Medical Biochemistry at a Glance, 3rd edition. Wiley-Blackwell, Chichester, UK)

Absorption, Distribution, Metabolism, Excretion

Absorption and Distribution

Absorption is a function of the potential for a substance to diffuse across biological membranes. The most useful parameters providing information on this potential are the molecular weight, the octanol/water partition coefficient (log Pow) value and the water solubility. The log Pow value provides information on the relative solubility of the substance in water and lipids (ECHA, 2012).

The smaller the molecule, the more easily it will be taken up. In general, molecular weights below 500 g/mol are favourable for oral absorption (ECHA, 2012). As the molecular weight of L-Phenylalanine is 165.19 g/mol and as it is very soluble in water absorption of this molecule in the gastrointestinal tract is given. L-Phenylalanine is a highly polar and lipophobic compound, hence passive diffusion of phenylalanine via transporters takes place.

After ingestion, proteins are denatured by the acid in the stomach, where they are also cleaved into smaller peptides by the enzyme pepsin, which is activated by the increase in stomach acidity that occurs on feeding. The proteins and peptides then pass into the small intestine, where the peptide bonds are hydrolyzed by a variety of enzymes. These bondspecific enzymes originate in the pancreas and include trypsin, chymotrypsins, elastase, and carboxypeptidases. The resultant mixture of free amino acids and small peptides is then transported into the mucosal cells by a number of carrier systems for specific amino acids and for di- and tri-peptides, each specific for a limited range of peptide substrates. After intracellular hydrolysis of the absorbed peptides, the free amino acids are then secreted into the portal blood by other specific carrier systems in the mucosal cell or are further metabolized within the cell itself. Absorbed amino acids pass into the liver, where a portion of the amino acids are taken up and used; the remainder pass through into the systemic circulation and are utilized by the peripheral tissues. (NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Acade-my Press, Washington, D.C., pg. 599, 2009. Available from, as of March 10, 2010)

Dermal absorption

Amino acids are amphoteric electrolytes and water-soluble compounds. In general, a water-soluble drug such as amino acid shows low skin permeability due to the barrier effects of stratum corneum (Hirokazu KouzukiYushifimi NomuraYuhei Iwata; Percutaneous absorption of amino acids (2);1 996 Drug Delivery System, Volume 11 Issue 5 Pages 329-335).


L-phenylalanine that is metabolized in the liver, is distributed via the systemic circulation to the various tissues of the body, where it undergoes metabolic reactions similar to those that take place in the liver.

L-phenylalanine is metabolized to phenylpyruvic acid via oxidative deamination or transamination. A product of decarboxylation is phenylethylamine. Via hydroxylation Phenylalanine is metabolized to tyrosine by phenylalanine hydropxylase (PAH). Metabolites of tyrosine are acetoacetic acid and fumaric acid. (Fenaroli's Handbook of Flavor Ingredients. Volume 2. Edited, translated, and revised by T.E. Furia and N. Bellanca. 2nd ed. Cleveland: The Chemical Rubber Co., 1975., p. 831)

The tyrosine metabolite, DOPA, is converted into the neurotransmitters epinephrine and norepinephrine. (T. Komoda, T. Matsunaga: Metabolic Pathways in the Human Body (chapter 4) in Biochemistry for Medical Professionals, p. 25-63, 2015) Furthermore, Tyrosine is a precursor of Melanin pigments. 

Although the free amino acids dissolved in the body fluids are only a very small proportion of the body's total mass of amino acids, they are very important for the nutritional and metabolic control of the body's proteins. The concentration of most amino acids is higher in tissue intracellular pools. Typically, large neutral amino acids like phenylalanine, are essentially in equilibrium with the plasma. (NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academy Press, Washington, D.C., pg. 596, 2009. Available from, as of March 10, 2010)

L- Phenylalanine is hydrolysed by phenylalanine hydrolase (PAH) to tyrosine by a reaction requiring molecular oxygen and the cofactor tetrahydrobiopterin (THB).


In addition to its distribution, metabolism and decomposition in the body, it is also excreted through the kidneys.

Key value for chemical safety assessment

Absorption rate - oral (%):
Absorption rate - dermal (%):

Additional information