Linalool

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

This human study was reported with limited information on test substance composition and applied concentration. Test was performed in human with one male subject and no details on health history were reported. Furthermore, no other effects of dermal exposure were monitored. However, the methods and results are reported concise but clear.

Data source

Reference

Reference Type:

publication

Title:

Percutaneous absorption of lavender oil from a massage oil

Author:

W. Jäger, G. Buchbauer, L. Jirovetz and M. Fritzer

Year:

1991

Bibliographic source:

J. Soc. Cosmet. Chem., 43, 49-54 (January/February 1992)

Materials and methods

Type of study / information:

Toxicokinetic study

Endpoint addressed:

dermal absorption

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

One male subject was treated with massage oil (containing 0.5% linalool and 0.6% linalyl acetate) on the skin. Blood samples were taken at 0, 5, 10, 15, 20, 30, 45, 60, 75, and 90 minutes thereafter to obtain the quantity of linalool and linalyl acetate (main components of lavender oil) present in the blood, using GC-FID and GC-MS. For statistics, test was repeated 3 times in the same subject.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Linalool

EC Number:

201-134-4

EC Name:

Linalool

Cas Number:

78-70-6

Molecular formula:

C10H18O

IUPAC Name:

3,7-dimethylocta-1,6-dien-3-ol

Details on test material:

- Name of test material (as cited in study report): Lavender oil (2% in massage oil, containing 98% peanut oil)
- Physical state: Liquid (pale yellow)
- Composition of test material (lavender oil) , percentage of components:
24.79% linalool
29.59% linalyl acetate
Tiglinic acid benzyl ester (ST)
Peanut oil

Method

Ethical approval:

not specified

Details on study design:

One male subject was treated with 1.5 g massage oil (containing 0.5% linalool and 0.6% linalyl acetate) on the skin for 10 minutes. Massage oil was spread on a defined skin area of the stomach (376 cm^2 of the body) and gently massaged into the skin. The remaining oil was completely removed. As a vehicle, peanut oil was used. Blood samples were taken at 0, 5, 10, 15, 20, 30, 45, 60, 75, and 90 minutes thereafter from the left cubital vein to obtain the quantity of linalool and linalyl acetate (main components of lavender oil) present in the blood, using GC-FID and GC-MS. Therefore, heparine was added, plasma centrifuged, and the samples stored at -20 Degrees Celsius until chromatographic and spectroscopic investigations. Plasma extracted by solid-phase-extraction. For statistics, test was repeated 3 times in the same subject.

Exposure assessment:

measured

Details on exposure:

TYPE OF EXPOSURE: Dermal exposure (open)

TYPE OF EXPOSURE MEASUREMENT: Biomonitoring (blood)

EXPOSURE LEVELS:
Linalool
- Nominal doses: 0.5% or 7.437 mg linalool (calculated as: 1.5 g massage oil * 2% lavender oil * 24.79% linalool)
- Actual doses: 0.12 mg/kg linalool (pharmacokinetic model)

Linalyl acetate
- Nominal doses: 0.6% or 8.877 mg (calculated as: 1.5 g massage oil * 2% lavender oil * 29.59% linalyl acetate)
- Actual doses: 0.144 mg/kg linalyl acetate (pharmacokinetic model)

EXPOSURE PERIOD: 10 minutes

POSTEXPOSURE PERIOD: 0, 5, 10, 15, 20, 30, 45, 60, 75 and 90 minutes

DESCRIPTION OF GROUP: One male, 34 years old subject, weighting 60 kg

Results and discussion

Results:

Linalool was absorbed by the skin and detected in blood within 5 minutes after finishing the massage. Almost all linalool was eliminated from the blood after 90 minutes.

Invasion rate constant: 0.11/min
Elimination rate constant: 0.46/min
Half life of invasion: 6.16 min
Biological half life: 13.76 min
Peak plasma concentration: 19 min
Mean plasma concentration: 100 ng/mL
AUC (0-90 min): 4927.25 (mg/mL) min

Linalyl acetate was absorbed in the skin and detected in blood within 5 minutes after finishing the massage. Almost all linalool was eliminated from the blood after 90 minutes.

Invasion rate constant: 0.11/min
Elimination rate constant: 0.48/min
Half life of invasion: 6.29 min
Biological half life: 14.30 min
Peak plasma concentration: 19 min
Mean plasma concentration: 121 ng/mL
AUC (0-90 min): 4174.50 (mg/mL) min

Any other information on results incl. tables

Plasma concentration of linalool was significantly higher than that of linalyl acetate (represented by a larger AUC)

Applicant's summary and conclusion

Conclusions:

Under the conditions of this test, it can be concluded that linalool is absorbed in the blood after dermal application in humans, but is also readily excreted.

Executive summary:

The dermal absorption of lavender oil (in massage oil) containing linalool was studied in one male human subject. Massage oil was massaged onto the skin for ten minutes. In total 7.23 mg linalool was applied, which corresponds with a dose of 0.12 mg/kg bw. Linalyl acetate dose was 8.64 in total, representing 0.144 mg/kg bw. Subsequently, the concentration of linalool and linalyl acetate in the blood was determined at several time points by GC-FID and GC-MS. The experiment was repeated three times in the same subject for statistical evaluation. Toxicokinetic parameters were estimated with an open two-compartment standard pharmacokinetic model.

 

The results indicate that linalool and linalyl acetate can be detected in the blood after absorption through skin within 5 minutes after application. The mean plasma concentration (100 ng/mL linalool, 121 ng/mL linalyl acetate) is reached after 19 minutes. Within 90 minutes linalool has been eliminated almost completely. Calculated AUC of linalool is 4927.25 (ng/mL)min, for linalyl acetate this was 4174.50 (ng/mL)min, indicating that the concentration of linalool is significantly higher than that of linalyl acetate. Under the conditions of this test, it can be concluded that linalool and linalyl acetate are absorbed in the blood after dermal application in humans, but are also readily excreted.