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Toxicological information

Dermal absorption

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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:
comparable to guideline study with acceptable restrictions
Remarks:
Not performed according to GLP. An equivalent or similar guideline to OECD 428 is used.
Cross-reference
Reason / purpose:
reference to same study
Reference
Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
See attached justification
Reason / purpose:
read-across source
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

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

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. This result was used for read-across to tetrahydrolinalyl acetate.
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. This result was used for read-across to tetrahydrolinalyl acetate.

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:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Deviations:
yes
Remarks:
temperature 37°C instead of 32°C
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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.