3-phenylpropan-1-ol

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1998

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

detailed publication of an in vitro study

Data source

Reference

Reference Type:

publication

Title:

Skin permeation model of phenyl alcohols: comparison of experimental conditions

Author:

López, A., Faus, V., Díez-Sales, O., Herráez, M.

Year:

1998

Bibliographic source:

International Journal of Pharmaceuticals 173: 183-191

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The skin permeability of the test substance and further phenyl alcohols was investigated using rat skin in a diffusion chamber.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-phenylpropan-1-ol

EC Number:

204-587-6

EC Name:

3-phenylpropan-1-ol

Cas Number:

122-97-4

Molecular formula:

C9H12O

IUPAC Name:

3-phenylpropan-1-ol

Radiolabelling:

no

Test animals

Species:

rat

Strain:

Wistar

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Department of Pharmacy and Pharmaceutical Technology, University of Valencia, Spain

Administration / exposure

Type of coverage:

other: not applicable

Vehicle:

other: buffer, pH 6.2, not further specified

Duration of exposure:

7 h

Doses:

- Dose volume: 22 mL in donor compartment of diffusion chamber

No. of animals per group:

no data

Control animals:

yes

Remarks:

other phenyl alcohols were also tested

Details on study design:

APPLICATION OF DOSE:
The skin samples were placed in the static diffusion cell in a vertical position to give an effective surface area available for diffusion of 4.52 cm^2. The receiver compartment capacity was also 22 mL and the temperature was maintained at 37 (± 0.5) °C by immersion of the cells in a water bath, the dermal side of the skin was continuously washed with saline solution buffered to p H 7.4 and stirred by a rotating teflon-coated magnet placed inside the cell.

SAMPLE COLLECTION
One millilitre samples were taken from the receptor compartment every 1 h.

Details on in vitro test system (if applicable):

SKIN PREPARATION
- Source of skin: Wistar rat skin, obtained from a laboratory colony (Department of Pharmacy and Pharmaceutical Technology, University of Valencia, Spain)
- Preparative technique: Epidermal membranes were prepared by a heat-separation technique.

PRINCIPLES OF ASSAY
- Diffusion cell: Diffusion studies were done using epidermal membranes in a 6-cell battery system with the stratum corneum towards the stirred donor compartment which contained 22 mL of penetrant solution. The compounds were dissolved in buffer solution (pH 6.2) at a concentration equivalent to approximately 75 % of their solubility in that medium to keep constant the degree of saturation of the solution in contact with the stratum corneum (i.e. thermodynamic activity). In order to ensure that the concentration of the permeants and the diffusion state were kept constant throughout the experiment the donor cell content was entirely replaced by fresh test solution every 30 min for all. For this reason, assay duration was only 7 h. In the second experiment the test compounds were used as saturated solution (added with an excess of the penetrant) in buffer medium at p H 6.2. Then, the effective concentration in the donor compartment was equal to the solubility value. In both experiments the receptor solution was added with polysorbate 80 at a clearly supramicellar concentration (1 %, w/w) in order to provide a micellar reservoir. Consequently, sink conditions were completely fulfilled.
- Test temperature: 37 (± 0.5) °C

Results and discussion

Signs and symptoms of toxicity:

not examined

Dermal irritation:

not examined

Total recovery:

- Total recovery: not examined

Percutaneous absorption

Key result

Time point:

7 h

Dose:

75 % and 100 % solubility concentration

Parameter:

percentage

Absorption:

< 10 %

Conversion factor human vs. animal skin:

no data given

Applicant's summary and conclusion

Conclusions:

The test substance was able to penetrate rat skin in this in vitro assay.

Executive summary:

Skin permeability assays were performed using rat skin in a diffusion cell similar to that proposed by Durrheim et al.(Durrheim, H., Flynn, G. L., Higuchi. W. I. Behl. Ch. R. (1980) J. Pharm.Sci. 69: 781). The skin samples were placed in the static diffusion cell in a vertical position to give an effective surface area available for diffusion of 4.52 cm^2. The receiver compartment capacity was also 22 mL and the temperature was maintained at 37 (± 0.5) °C by immersion of the cells in a water bath, the dermal side of the skin was continuously washed with saline solution buffered to pH 7.4 and stirred by a rotating teflon-coated magnet placed inside the cell. Diffusion studies were done using epidermal membranes in a 6-cell battery system with the stratum corneum towards the stirred donor compartment which contained 22 mL of penetrant solution. The compounds were dissolved in buffer solution (pH 6.2) at a concentration equivalent to approximately 75% of their solubility in that medium to keep constant the degree of saturation of the solution in contact with the stratum corneum (i.e. thermodynamic activity). In order to ensure that the concentration of the permeants and the diffusion state were kept constant throughout the experiment the donor cell content was entirely replaced by fresh test Solution every 30 min for all. For this reason, assay duration was only 7 h. In the second experiment the test compounds were used as saturated solution (added with an excess of the penetrant) in buffer medium at p H 6.2. Then, the effective concentration in the donor compartment was equal to the solubility value. In both experiments the receptor solution was added with polysorbate 80 at a clearly supramicellar concentration (1 %, w/w) in order to provide a micellar reservoir. Consequently, sink conditions were completely fulfilled. 1 mL samples were taken every 60 min. The concentration in the samples was determined by HPLC. As a result, skin permeation was observed for all tested substances but less than 10 % of the donor phase was transported. However, due to the short duration of 7 h, it was not possible to ensure that a steady state had been reached. Nevertheless, as a conclusion, the test substance has been shown to be able to penetrate rat skin.