Benzoic acid, C9-11 , C10-rich, branched alkyl esters

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Applicant's summary and conclusion

Executive summary:

Metabolism Information for Isodecyl Benzoate

Isodecyl Benzoate (IDB) is an alkyl benzyl ester, also referred to as a carboxylic ester (R-C(O)-OR’) produced by reaction with benzoic acid and isodecyl (C10) alcohol. An important feature is that such esters are poorly soluble in water. Esters are reactive with water and can hydrolyze under either acidic or basic conditions. The expected hydrolysis of IDB would be a reverse of the esterification process (generally catalyzed with esterase) and would produce benzoic acid and primary C10 alcohol. Benzoic acid can be further metabolised to hippuric acid and benzoyl glucuronide and excreted in the urine. Some benzoic acid may also be excreted in the urine. The primary C10 alcoholcan be further metabolised by mitochondrial beta-oxidation or by cytochrome P450 mediated omega and omega-minus-one oxidation (may be followed by beta-oxidation). The C10 alcohol can undergo various oxidative steps to yield other smaller alcohols, ketones, aldehydes, or carboxylic acids, and carbon dioxide (Mann, 1987). 

 

Because C10 alcohol is one of two primary metabolites of IDB, data to characterize alcohol toxicity can be very useful to describe the potential toxicological properties of IDB. Monohydric, aliphatic alcohols demonstrate a systematic variation according to molecular weight in a manner similar to many other homologous chemical series (Monick, 1968). The body handles aliphatic hydrocarbons in a similar manner via oxidative conversion to alcohols, ketones, and eventual elimination as carbon dioxide and carboxylic acids (Wislocki et al, 1980). Undegraded alcohol can be conjugated either directly or as a metabolite with glucuronic acid, sulfuric acid, or glycine, which can be rapidly excreted (Lington and Bevan, 1994).

 

References

Lington, A.W. and Bevan, C. (1994). Patty’s Industrial Hygiene and Toxicology, Fourth Edition, John Wiley & Sons, Inc, Chapter Thirty, “Alcohols,” pp. 2585-2710.

 

Mann, A.H., (1987). An assessment of the likely metabolic fate of some isomers of hexyl acetate. The Robins Institute of Industrial & Environmental Safety,of, Guildford, EBSI Document 87MRR 346.

 

Monick, J.A., (1968). Alcohols. Their Chemistry, Properties and Manufacture. Reinhold Book Corporation, NY.

 

Wislocki, P.G., Miwa, G.T., and Lu, A.Y.H.. (1980). Reactions Catalyzed by the Cytochrome P-450 System.Enzymatic Basis of Detoxification. Vol. I (ed. W.B.Jakoby), Academic Press,,.