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EC number: 219-847-4 | CAS number: 2550-26-7
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
4-phenylbutan-2-one is mainly oxidized in the dog to phenylacetic acid and excreted in urine as phenaceturic acid (glycine conjugate of phenylacetic acid). It was found that 4-phenylbutan-2-one is excreted in rabbit urine as secondary carbinol glucuronic acid conjugate and 6 % of dose as hippuric acid. Only a small amount of phenaceturic acid was detected in rabbit urine. In addition, phenylacetic acid shows a species-specific conjugation. Phenylacetic acid is efficiently excreted mainly in urine as the glutamine conjugate in man or the glycine conjugate (phenylaceturic acid) in animals.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
Additional information
The review of literature in Dakin (1909)described that 4-phenylbutan-2-one is oxidized in the animal body to phenylacetic acid, which is excreted in the usual way in animal urine as phenaceturic acid. The author performed an experimental part with a dog. A dose of 2.5 g given orally to a dog resulted a very little amount of unchanged ketone in urine and a high amount of 0.9 g (28 % of 2-phenylbutan-2-one dose) of phenaceturic acid. Actually, phenylacetic acid shows a species-specific conjugation. Phenylacetic acid is efficiently excreted mainly in urine as the glutamine conjugate in man or the glycine conjugate (phenylaceturic acid) in animals (James et al 1972). Smith (1954) investigated 4-phenylbutan-2-one metabolites in rabbit urine. 2 g of 4-phenylbutan-2-one was fed to four rabbits. Secondary carbinol glucuronic acid conjugate was found in 24 hour collected urine (500 mL). El Masry (1956) investigated 4-phenylbutan-2-one metabolites in rabbit urine as well. 2 mmol/kg of 4-phenylbutan-2-one were administered to 3 Chinchilla rabbits. In 24 hours after dosing collected urine, 6 % of dose was excreted as hippuric acid and only a minor amount was presented as phenaceturic acid. The over mentioned findings for 4-phenylbutan-2-one were confirmed in EFSA (2009) report, where six structurally similar phenyl alkyl ketones were compared. One of the six candidate substances is 4-phenylbutan-2-one. It may be concluded that the candidate substances are readily absorbed from the gut. Based on toxicokinetic data for the representative structurally related substance 4-phenyl-3-buten-2-one, it appears that orally administered phenyl alkyl ketones undergo essentially complete first pass metabolism prior to systemic distribution. They can be reduced to the corresponding secondary alcohols, then either be conjugated with glucuronic acid or glycine and excreted primarily in the urine. These ketones may also undergo omega-oxidation in the side-chain to yield intermediary metabolites (e. g. hydroxyacetophenone) that undergo further oxidation and cleavage to yield aromatic carboxylic acids (phenylacetic acid or benzoic acid, depending on the number of carbon atoms in the side-chain: in case of 4-phenylbutan-2-one, i. e. even numbered alkyl chain, the oxidation should yield phenylacetic acid). These aromatic acids are excreted primarily as glycine conjugates. In conclusion, it can be anticipated that the six candidate substances are metabolised to innocuous product. Studies showed that acetophenone as well as other ketones derived from alkyl benzenes are absorbed, metabolized and excreted as polar metabolites within 24 hours (EFSA 2009).
Dakin HD. The mode of oxidation in the animal organism of phenyl derivatives of fatty acids. Part V. Studies on the fate of phenylvaleric acid and its derivatives. The Journal of Biological Chemistry 6, 1909: 221-223.
EFSA. Flavouring Group Evaluation 16, Revision 2 (FGE.16Rev2): Aromatic ketones from chemical group 21. EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids. EFSA Journal 12(7), 2009: 1022.
El Masry. The metabolism of alkylbenzenes: n-propylbenzene and n-butylbenzene with further observations on ethylbenzene. Biochemical Journal 64(1), 1956: 50-57.
James MO, Smith RL, Williams RT, Reidenberg M. The conjugation of phenylacetic acid in man, sub-human primates and some non-primate species. Proceedings Royal Society London, B, 182,1066, 1972: 25-35.
Smith JN. Studies in detoxication. 59. The metabolism of alkylbenzenes. The biological reduction of ketones derived from alkylbenzenes. Biochemical Journal 57(1), 1954: 74-76.
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