Studies on the metabolism of d-limonene (p-mentha-1,8-diene). IV. Isolation and characterization of new metabolites and species differences in metabolism.

1. The main route of elimination of d-limonene administered orally was via the urine in animals and man, 75-95% of the administered radioactivity being excreted in the urine during 2-3 days. Faecal excretion accounted for less than 10% of the dose in animals during 2-3 days. 2. In addition to six metabolites, namely p-mentha-1,8-dien-10-ol (M-I), p-menth-1-ene-8,9-diol (M-II), perillic acid (M-III), perillic acid-8,9-diol (M-IV), p-mentha-1,8-dien-10-yl-beta-D-glucopyranosiduronic acid (M-V) and 8-hydroxy-p-meth-1-en-9-yl-beta-D-glucopyranosiduronic acid (M-VI) isolated from rabbit urine previously (Kodama et al., 1974), five new metabolites have been isolated from dog and rat urine, and which were characterized as 2-hydroxy-p-menth-8-en-7-oic acid (M-VII), perillylglycine (M-VIII), perillyl-beta-D-glucopyranosiduronic acid (M-IX), p-mentha-1,8-dien-6-ol (M-X) and probably p-menth-1-ene-6,8,9-triol (M-XI). 3. The major metabolite of d-limonene in the urine was M-IV in rat and rabbit, M-IX in hamster, M-II in dog and M-VI in guinea pig and man.