Terpenoid biotransformation in mammals. V. Metabolism of (+)-citronellal, (±)-7-hydroxycitronellal, citral, (−)-perillaldehyde, (−)-myrtenal, cuminaldehyde, thujone, and (±)-carvone in rabbits

Abstract

1. The metabolism of (+)-citronellal, (+-)-7-hydroxycitronellal, citral, (-)-perillaldehyde, (-)-myrtenal, cuminaldehyde, thujone, and (+-)-carvone was studied in rabbits. 2. In (+-)-7-hydroxycitronellal, (-)-perillaldehyde, (-)-myrtenal and cuminaldehydes, both primary alcohols and carboxylic acids were formed. 3. In (-)-citronellal and citral, regioselective oxidation was found and a trans-positioned methyl group was carboxylated in each case. 4. In o-cuminaldehyde, reduction but not oxidation, was found.

Percutaneous Permeation Enhancement by Terpenes: Mechanistic View

“…The primary metabolites are further transformed into more polar compounds and are excreted via urine. Most of the data available pertains to rat (92)(93)(94)(95) or rabbits (96,97) which were fed with terpene rich diets. However, it is not certain that these dispositional characteristics can be extrapolated to humans, particular in view of the relatively large doses administered to animals.…”

Scientific Opinion on Flavouring Group Evaluation 12, Revision 2 (FGE.12Rev2): Primary saturated or unsaturated alicyclic alcohol, aldehyde, acid, and esters from chemical group 7

“…The same is true for the monocyclic aldehyde (candidate substance 4-(2,6,6-trimethylcyclohexenyl)-2-methylbutanal [FL-no: 05.183]) and structurally related substances perillaldehyde and isophorone), which contain alkyl ring substituents. In a minor pathway, the aldehyde may be reduced to the alcohol and excreted as the glucuronide (Ishida et al, 1989b;Haag & Gould, 1994). If an endocyclic double bond is present, reduction of this double bond may occur.…”

“…To a lesser extent, pmentha-1,8-dien-7-al was reduced to perillyl alcohol, which can be selectively hydrogenated to yield pmentha-8-en-7-ol (see Figure III.1) (Ishida et al, 1989b …”

Scientific Opinion on Flavouring Group Evaluation 12, Revision 5 (FGE.12Rev5): Primary saturated or unsaturated alicyclic alcohol, aldehyde, acid, and esters from chemical groups 1, 7 and 8)

“…Aromatisation of the cyclohexene ring and reduction of the isopropenyl double bond converted perillic acid in part to p-isopropylbenzoic acid. To a lesser extent, p-mentha-1,8-dien-7-al was reduced to perillyl alcohol, which can be selectively hydrogenated to yield p-mentha-8-en-7-ol (see Figure C.1) (Ishida et al, 1989). Only a fairly low part of the administered dose was recovered.…”

“…The presence of perillic acid indicates some cleavage of the strained bicyclic ring. To a lesser extent, the aldehyde can either be reduced to myrtenol, which may be conjugated with glucuronic acid and excreted or it may undergo hydrogenation of the double bond to yield dihydromyrtenol (myrtanol), see Figure C.2, which is one of the candidate substances ], shown to be the major neutral metabolite and excreted unchanged with the urine (Ishida et al, 1989). Urine was collected during 3 days post dosing.…”