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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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Publication with detailed documentation, used for assessment

Data source

Reference
Reference Type:
publication
Title:
In Vitro Human Skin Penetration of Geraniol and Citronellol
Author:
Gilpin S., Hui X., Maibach H.
Year:
2010
Bibliographic source:
Dermatitis, Vol 21, No 1 (January/February): pp 41-48

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: aqueous solution
Details on test material:
- Name of test material (as cited in study report): citronellol (1-14C)
- Physical state: aqueous solution
- Analytical purity: 99%
- Specific activity (if radiolabelling): 52 mCi/mmol
Radiolabelling:
yes

Test animals

Species:
human
Strain:
other: not applicable
Sex:
not specified

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: DEP and ethanol (3:1)
Duration of exposure:
24 hours
Doses:
2% and 5% citronellol (weight per volume). 20 µl dose solution of approximately 0.5 µCi radioactivity applied.
No. of animals per group:
Skin was obtained from four donors
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: Department of Pathology at the University of California,San Francisco
- Type of skin: Human cadaver skin without obvious signs of skin disease
- Preparative technique: dermatomed with a Padgett ElectroDermatome
- Thickness of skin (in µm): approx. 400
- Membrane integrity check: checked visually, transepidermal water loss (TEWL): TEWL values of less than 15 g/m2h were considered acceptable
- Storage conditions: obtained within 24 hours of donor death, immediately placed in aluminum foil and amply sealed and stored at ~ 20°C until used.


PRINCIPLES OF ASSAY
- Diffusion cell: continuous-flow diffusion cell (item LG-1084, Laboratory Glass Apparatus, Inc., Berkeley, CA)
- Receptor fluid: 6% polyethylene glycol and sodium phosphate-buffered saline (pH=7.4)
- Test temperature: approx. 32°C skin surface temp.
- Occlusion: Yes (plastic chamber with a 2.2 cm2 cotton pad, sealed with Parafilm M Laboratory Wrapping Film and a layer of adhesive tape)

Results and discussion

Percutaneous absorptionopen allclose all
Dose:
2%
Parameter:
percentage
Absorption:
3.8 %
Remarks on result:
other: 24 hours
Dose:
5%
Parameter:
percentage
Absorption:
4.7 %
Remarks on result:
other: 24 hours

Any other information on results incl. tables

After 24 hours, citronellal had relatively low skin absorption rates. Dose recoveries for all compartments measured are given in a graph only. However, key information for the assessment of bioavailability and total recovery are given as table:

Mass Balance and Percutaneous Absorption of Citronellol by Human Skin in Vitro

Compound Removed dose after 24h [%]* Penetrated dose absorbed after 24h [%]*
Citronellol 2% 86.3+/-5.2 3.8+/-2.1
Citronellol 5% 81.6+/-3.8 4.7+/-1.9

*Values are means +/- SD. Number of determinations = 12.

Based on the text given in the results section, the following has been reported by the authors:

Increasing concentration increased absorption; Recovery for fragrance materials was good; Most of the dose was recovered in the skin washes; Recovery was much less for all other compartments; the cover compartments for 2% and 5% citronellol had the next highest dose recoveries (15.5% ± 3.9% and 10.7% ± 0.9%, respectively), followed by the tape strips (6.1%± 4.3% and 4.3% ± 0.3%, respectively). Examination of the time variable in box plots for the receptor fluid collection points showed a linear increase in the amounts of citronellol that penetrated the skin even though the overall values of absorption were quite small.

 

Applicant's summary and conclusion