Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 232-077-3 | CAS number: 7785-26-4
None of the volunteers reported any adverse health effects due to the supplementation with 10 mg of αPN. Though, all volunteers mentioned a characteristic aromatic smell of the exhaled breath which occurred about 1 h after oral exposure and subsequently vanished within 2–3 h after exposure. It was assume that respiratory elimination of unmetabolized αPN was a substantial elimination pathway, as well, which may have contributed to a large extend to the 78 % of the oral dose which was not recovered in form of renal metabolites. This is in accordance with the volunteers’ reports on olfactory perception during the exposure experiments. However, the amount of αPN exhaled was not quantified.
The synchronous and steep metabolite time courses observed in blood and urine may be explained by simultaneous and competing reactions during first-pass metabolism. This first-pass effect, which rapidly yields in polar phase I and II metabolites, is presumably responsible for the low blood concentrations as well as the short elimination half-lives in the first elimination phases. The second, slower elimination phases observed for all metabolites are most probably caused by release of low amounts of αPN or its metabolites from tissue compartments. However, the cumulative elimination indicate that the second phase only plays a minor role to the cumulatively eliminated amount. At the elimination peak, MYR and MYRA are almost entirely conjugated to glucuronic acid (or sulphate), whereas cVER and tVER are only conjugated up to 76 %. This effect may be due to steric hindrance of the secondary hydroxyl groups caused by the bicyclic backbone or due to instability of the conjugates.
Table1: Characteristics of the blood kinetics ofαPN metabolites after oral exposure to 9.0±0.4 mg (66±2.8 µmol)αPN (mean val- ues±range;n=2 volunteers)
a Elimination not completed within 5 h observation period
Table 2: Characteristics of the renal αPN metabolite elimination kinetics after oral exposure to 9.0±0.4 mg (66±2.8 µmol)αPN (mean values±SD;n=4 volunteers)
Share of oral dose(%)
RE,maxmaximum renal excretion;tmaxtime to reach maximum renal excretion;t1/2elimination half-life;AUC0→tfarea under the renal excretion vs. time curve (from time 0 to final sampling timetf);Vtotalsummarized excreted urine volume
In a metabolism study, four healthy human volunteers were orally exposed to a single dose of 9 mg of (1S,5S)-(−)-α- pinene (αPN) via spiked gelatin capsules. Each volunteer gave one urine sample before administration and subsequently collected each urine sample within 24 h after administration. Blood samples were collected directly after administration of the capsule and every hour until 5 hours exposure for 2 volunteers. The concentration of the αPN metabolites were determined using a very specific and sensitive GC-PCI-MS/MS procedure. Concentration of αPN was analysed in blood by HS-GC-MS procedure.
αPN metabolites cVER (cis- verbenol) , tVER (trans-verbenol) , and MYR (myrtenol) were detected in blood samples over the entire blood sampling period of 1–5 h, unmetabolised αPN were below the limit of detection.
The metabolite concentrations showed synchronous time courses even though the levels were low and varied between the two volunteers. Metabolite blood levels were low. The non-detection of αPN in blood after low oral doses in contrast to the detectable metabolite levels indicates a fast and approximately entire pre-systemic metabolism such as hepatic or intestinal firstpass metabolism.
αPN metabolites were detected in urine in considerably higher amounts in contrast to blood levels. The low blood concentrations compared to the high urinary levels, thus, indicate a fast transfer from blood to urine and a rapid renal elimination.
In addition to the known and established αPN metabolites cVER and tVER, the relevance of MYR and MYRA as products of the human in vivo metabolism of αPN was confirmed. Two unknown human metabolites were identified and these structures could be predicted as 4-hydroxymyrtenic acid (MYRA-4-OH) and dihydromyrtenic acid (DHMYRA).
Human in vivo metabolism of αPN is similarly dominated by extensive oxidation reactions on the methyl side-chains yielding in carboxylic acid structures. Nonetheless, only 22% of the applied dose was quantified as metabolite. Thus, further metabolites and the share of αPN eliminated unchanged via lungs remain unclear.
Human metabolism of αPN proceeds fast and the body is almost entirely cleared from the metabolites 10 h after exposure
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Close Do not show this message again