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Journal Article

Human metabolism of Delta(3)-carene and renal elimination of Delta(3)-caren-10-carboxylic acid (chaminic acid) after oral administration.


Belov,  V. N.
Department of NanoBiophotonics, MPI for biophysical chemistry, Max Planck Society;

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Schmidt, L., Belov, V. N., & Göen, T. (2015). Human metabolism of Delta(3)-carene and renal elimination of Delta(3)-caren-10-carboxylic acid (chaminic acid) after oral administration. Archives of Toxicology, 89(3), 381-392. doi:10.1007/s00204-014-1251-5.

Cite as: http://hdl.handle.net/11858/00-001M-0000-0025-B2FA-D
We studied the human in vivo metabolism of Delta(3)-carene (CRN), a natural monoterpene which commonly occurs in the human environment. Four healthy human volunteers were orally exposed to a single dose of 10 mg CRN. Each volunteer gave one urine sample before administration and subsequently collected each urine sample within 24 h after administration. The concentration of the proposed CRN metabolites Delta(3)-caren-10-ol (CRN-10-OH), Delta(3)-caren-10-carboxylic acid (chaminic acid, CRN-10-COOH), and Delta(3)-caren-3,4-diol (CRN-3,4-OH) were determined using a very specific and sensitive GC-MS/MS procedure. Other CRN metabolites were investigated using GC-PCI-MS Q1 scan analyses. CRN-10-COOH was detected in each urine sample with maximum concentration (113.0-1,172.9 A mu g L-1) 2-3 h after administration, whereas CRN-10-OH and CRN-3,4-OH were not detected in any of the samples. The renal excretion kinetics of CRN-10-COOH showed an elimination half-life of about 3 h. The cumulative excretion of CRN-10-COOH within 24 h after exposure correlated with about 2 % of the applied dose. The GC-PCI-MS Q1 scan analysis indicated several additional human CRN metabolites; thereof, six spectra enabled the prediction of the corresponding chemical structure. The results of the study indicate that CRN-10-COOH is a relevant product of the human in vivo metabolism of CRN. The oxidation of its allylic methyl group proceeds until the acidic structure without interruption. Thus, the generation of the alcoholic intermediate appeared to be the rate-determining step of this metabolic route. Nevertheless, the proportion of CRN-10-COOH in the CRN metabolism is low, and other oxidative metabolites are likely. This hypothesis was confirmed by the discovery of additional human CRN metabolites, whose predicted chemical structures fit in with further oxidative products of CRN metabolism.