1,5-dimethyl-1-vinylhept-4-enyl acetate

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Not performed according to GLP. An equivalent or similar guideline to OECD 428 is used.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Cutaneous absorption and elimination of three acyclic terpenes

Author:

Cal. K., Sznitowska

Year:

2003

Bibliographic source:

Journal of Controlled Release, 93, pp 369-376

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

Deviations:

yes

Remarks:

temperature 37°C instead of 32°C

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): (±)-linalool
- Analytical purity: >95%
- Source: Fluka, Buchs, Switzerland

Radiolabelling:

no

Test animals

Species:

human

Strain:

other: not relevant

Sex:

female

Details on test animals or test system and environmental conditions:

Not relevant

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

1, 2, and 4 hours

Doses:

- Nominal dose: 500 mg

No. of animals per group:

Not relevant

Control animals:

no

Remarks:

not relevant

Details on study design:

DOSE PREPARATIONTest article applied undilutedTEST SITESkin extracts of 0.65 cm2REMOVAL OF TEST SUBSTANCE- Washing procedures and type of cleansing agent: Skin was rinsed shortly with methanol- Time after start of exposure: 1, 2 or 4 hoursSKIN PREPARATION AFTER EXPOSUREAfter 1, 2, or 4 h, the stratum corneum layers were separated, and every fraction of the stratum corneum as well as the remaining skin were extracted with methanol and stored for analysis. The acceptor medium was also collected for analysis.ANALYSIS - Method type(s) for identification: GC-MS

Details on in vitro test system (if applicable):

SKIN PREPARATION- Source of skin: 40-year old woman- Ethical approval if human skin: Yes, ethics committee of the Medical University of Gdansk- Type of skin: Thorax - Storage conditions: At -20 degrees Celsius- Justification of species, anatomical site and preparative technique: PRINCIPLES OF ASSAY- Diffusion cell: flow-through Teflon diffusion cells- Receptor fluid: isotonic phosphate buffer (pH 7.3) preserved with 0.005% sodium azide- Solubility of test substance in acceptor fluid: 1.34 mg/ml - Flow-through system: yes, constant rate of 10 ml/h- Test temperature: 37 +/- 0.5 degrees Celsius- Humidity: No data- Occlusion: Donor compartment occluded with parafilm

Results and discussion

Signs and symptoms of toxicity:

not examined

Remarks:

(not relevant)

Dermal irritation:

not examined

Remarks:

(not relevant)

Absorption in different matrices:

At 1 hour after application (ug/cm2):- Stratum corneum (tape strips): 78 +/- 4.1- Skin preparation (epidermis + dermis): 827.0 +/- 66.5- Acceptor fluid: 0At 2 hours after application (ug/cm2):- Stratum corneum (tape strips): 109.1 +/- 5.6- Skin preparation (epidermis + dermis): 1083.5 +/- 106.1- Acceptor fluid: 0At 4 hours after application (ug/cm2):- Stratum corneum (tape strips): 478.9 +/- 18.8- Skin preparation (epidermis + dermis): 1343.0 +/- 127.1- Acceptor fluid: 0

Total recovery:

- Total recovery: 0.23% (1821.9/(769.2*1000)- Recovery of applied dose acceptable: No, not within 100 +/- 10% as stated in the OECD guideline- Limit of detection (LOD): No data

Conversion factor human vs. animal skin:

Not relevant

Any other information on results incl. tables

Linalool easily penetrated into the skin, however it was not detected in the acceptor fluid.

The percutaneous absorption of linalool into the skin layers (ug/cm2), is summarized in the following table. The applied dose was 500 mg/0.65 cm2 (= 769.2 mg/cm2).

Skin layer	Time
	1h	2h	4h
Stratum corneum SC1	34.3±8.8	65.9±36.5	242.6±36.4
Stratum corneum SC2	22.4±3.5	22.4±4.7	144.3±13.2
Stratum corneum SC3	21.6±3.7	20.8±6.1	92.0±12.9
Total Stratum corneum	78.3±4.1	109.1±5.6	478.9±18.8
Remaining skin (epidermis and dermis)	827.0±66.5	1083.5±106.1	1343.0±127.1
Skin total	905.3±64.7	1192.6±104.1	1821.9±135.8

Applicant's summary and conclusion

Conclusions:

Under the conditions of this in vitro penetration study in human skin, 0.17% of the applied dose could be recovered in epidermis and dermis.

Executive summary:

The in vitro skin absorption and elimination of linalool was studied by applying linalool (500 mg/0.65 cm2) to human skin and determine the amount of linalool in the stratum corneum and epidermis and dermis after 1, 2, and 4h. Linalool was analysed using gas chromatography.

Linalool easily penetrated into the skin, however it was not detected in the acceptor fluid. Additionally, 1343 +/- 127.1 ug linalool/cm2 was found in epidermis and dermis. The percentage of applied dose in epidermis and dermis is therefore calculated to be 0.17%. Considering results of another in vitro penetration study conducted by Green et al (2007), it is likely that most of the applied material is evaporated.