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Diss Factsheets

Toxicological information

Additional toxicological data

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Administrative data

Endpoint:
additional toxicological information
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
publication
Title:
Human skin penetration of the major components of Australian tea tree oil applied in its pure form and as a 20% solution in vitro
Author:
Cross S. E., Russell M, Southwell I, Roberts M. S.
Year:
2007
Bibliographic source:
European Journal of Pharmaceutics and Biopharmaceutics 69 (2008) 214-222
Report date:
2007

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: Address the lack of percutaneous penetration and disposition data of the components of tea tree oil (TTO).
- Short description of test conditions: TTO was applied as the neat oil and as a 20% solution in ethanol to the skin of three different female donors under "in use" application conditions and followed the penetration over a 24-h period. The main component of TTO is terpinen-4-ol.
- Parameters analysed / observed: skin penetration, retention of TTO components in the epidermis, examined the effect of partial occlusion
GLP compliance:
not specified

Test material

Constituent 1
Reference substance name:
Melaleuca Alternifolia /Tea Tree) Leaf oil
Cas Number:
68647-73-4
IUPAC Name:
Melaleuca Alternifolia /Tea Tree) Leaf oil
Specific details on test material used for the study:
Tea tree oil (TTO) was supplied by the Australian Tea Tree Industry Association. 100% pure TTO was used and a 20% solution in ethanol in the epidermal penetration studies.

Results and discussion

Any other information on results incl. tables

Epidermal penetration: Non-occluded application

Terpinen-4 -ol was found to penetrate epidermal membranes and could be quantified in the receptor phase in samples from each of the three different skin donors. The three donors showed varying

penetration of terpinen-4-ol (140-310 µg/cm² or 3.6–8.0% of the applied amount) over the 24 -h period following application of the pure oil. Following application of the 20% TTO formulation, amounts of

terpinen-4-ol in the receptor phase after 24 h were found to represent 18-33 lg/cm2 or 1.1–1.9% of the applied amount of TTO. Statistical differences in the penetration rate of terpinen-4 -ol was found for the three donor skins at all time points following application of the pure oil, with one skin much more permeable than the other two (p < 0.05). However, following application of the 20% TTO formulation, the more permeable skin only showed significant differences in the penetration of terpinen-4 -ol to the other two donors in the 4–12 h time period (p < 0.05).

Epidermal penetration: Partially occluded application

Following partial occlusion of the donor chamber and application of the pure oil formulation, the test substance could be detected in the receptor phase at 531.4 µg/cm². At 12 h the average absorption of the test substance following application of pure TTO was 289.72 µg/cm². Compared to non-occluded application conditions, at the 24 -h time point the mean amount of the test substance detected in the receptor phase increased approximately 2.5 -fold.

Epidermal retention: Non-occluded application

Retention of the test substancel following application of pure TTO to the three skin donors varied between 4.1 and 6.6 lg/cm2 (0.1–0.2% of the applied amount) and following application of the 20% formulation

varied between 0.25 and 0.38 lg/cm2 (<0.02% of the applied amount). There was a slight variability in the retention of TTO between the three different skin donors.

Epidermal retention: Partially occluded application

Following partial occlusion of the donor chamber compartment of the Franz cell, there was a significant increase in the amount of the test substance recovered from the epidermis following application of the pure oil. The increase in recovery of the test substance from within the epidermis in the donor chamber partially occluded experimental system was approximately three times that seen following non-occluded application.

Our data show that, under normal ‘in use’ conditions, approximately 2–4% of identifiable applied TTO components can be found either permeating the skin into receptor fluid (1.7–3.8%) or retained within the epidermis (0.23–0.37%) after 24 h application under normal ‘in use’ conditions. Under partially occluded conditions, the transdermal uptake of identifiable TTO components increased to 7% of the applied dose, 6.8% in the receptor phase and 0.3% remaining within the epidermis.

Applicant's summary and conclusion

Conclusions:
The studies demonstrated that terpinen-4-ol was able to penetrate humna epidermis and be recovered in the receptor phase solution.
In conclusion, the current study has shown that following application of pure TTO under normal ‘in use’ conditions, a small quantity of TTO components, 1.1–1.9% and 2–4% of the applied amount following application of a 20% TTO solution and pure TTO respectively, were found to penetrate into or through human epidermis. The largest TTO component penetrating the skin was terpinen-4-ol. Following partial occlusion of the application site, this penetration increased to approximately 7% of the applied TTO. These data should now be used to expand risk assessment profiles of the use of TTO and reduce speculatoin that all lipophilic components of TTO are assumed to freely penetrate the skin.
Executive summary:

The safety of topical application of Australian tea tree Oil (TTO) is confounded by a lack of transdermal penetration data, which adequately informs opinions and recommendations. In this study we applied TTO in its pure form and as a 20% solution in ethanol in vitro to human epidermal membranes from three different donors, mounted in horizontal Franz-type diffusion cells, using normal ‘in use’ dosing conditions (10 mg/cm2). In addition, we examined the effect of partially occluding the application site on the penetration of TTO components. Our data showed that only a small quantity of TTO components, 1.1–1.9% and 2–4% of the applied amount following application of a 20% TTO solution and pure TTO, respectively, penetrated into or through human epidermis. The largest TTO

component penetrating the skin was the test substance. Following partial occlusion of the application site, the penetration of the test substance increased to approximately 7% of the applied TTO. Measurement of the rate of evaporation of tea tree oil from filter paper (7.4 mg/cm²) showed that 98% of the oil evaporated in 4 hours. Overall, it is apparent that the penetration of TTO components through human skin is limited.