Farnesol

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Remarks:

Including in vivo

Type of information:

experimental study

Adequacy of study:

key 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:

In vivo and in vitro skin absorption of lipophilic compounds, dibutyl phthalate, farnesol and geraniol in the hairless guinea pig

Author:

Doan K, Bronaugh RL, Yourick JJ

Year:

2010

Bibliographic source:

Food and Chemical Toxicology, 48:18-23

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Dermal absorption of farnesol was investigated in guinea pigs in an in vivo test using radiolabelled material and also in an in vitro study by mounting skin grafts in diffusion cells and measuring receptor fluid fractions.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Farnesol

EC Number:

225-004-1

EC Name:

Farnesol

Cas Number:

4602-84-0

Molecular formula:

C15H26O

IUPAC Name:

farnesol

Radiolabelling:

yes

Remarks:

Radiochemical purity greater than 99% and a specific activity of 20.0 mCi/mmol

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Housing: Single
- Individual metabolism cages: polycarbonate shoe box cages on hardwood chip contact bedding
- Diet: ad libitum pelleted guinea pig chow
- Water: ad libitum
- Acclimation period: 3-days in quarantine

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±1°C
- Humidity (%): 50±10 % relative humidity
- Air changes (per hr): 10 complete room changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light/dark full spectrum lighting cycle (no twilight)

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: oil-in-water emulsion prepared with: 3% polyglycerate distearate; 3% cetyl stearyl alcohol; 10% light mineral oil; 5% propylene glycol; 0.5% propyl-p-hydroxybenzoate; 0.5% methyl-p-hydroxybenzoate and 78% water

Doses:

An oil-in-water emulsion containing 5.0% of unlabelled farnesol, spiked with 3H-farnesol so that approximately 0.5 µCi of radiolabelled farnesol was applied per cm2 of skin in vivo or to the skin in vitro diffusion cell. The emulsion was applied to the skin at a dosage of 1 mg/cm2.

No. of animals per group:

3

Control animals:

no

Details on study design:

In vivo skin absorption study - A 3.0 x 3.0 cm treatment site was marked on the mid-scapular region of the guinea pig’s back and enclosed with a Stomahesive® patch glued directly to the animal’s skin, the dosing area and patch were then covered with a vinyl coated fibreglass screen (to prevent dosing formulation being rubbed off the skin) and carbon impregnated filter paper to trap volatile test material. In vivo skin absorption was determined 24-hours after dosing. Urine and faeces were collected throughout the study duration. Animals were euthanized with Isoflurane. The skin at the treatment site, ovaries, liver and kidneys were excised and dissoluted in potassium hydroxide (5M). Radioactivity was measured by liquid scintillation counting.

Details on in vitro test system (if applicable):

Skin grafts (200-300 µm thick) were obtained from hairless guinea pigs euthanized with carbon dioxide. The skin was washed with 1% (v/v) liquid detergent solution, rinsed with distilled water and patted dry. Diffusion cells (0.64 cm2) and the perfusion system were prepared and flushed with 70% (v/v) ethanol solution and the receptor fluid was sterilised by vacuum filtration through a 0.2 µm filter. The skin was mounted in the diffusion cell and equilibrated to the test conditions (1.5 ml/hour) and the dosing was applied to the surface, in a manner comparable to the in vivo tests (oil-in-water emulsion). Receptor fluid fractions were collected at 6-hour intervals for 24-72 hours.

Results and discussion

Signs and symptoms of toxicity:

not examined

Dermal irritation:

not examined

Absorption in different matrices:

In vivo absorption of farnesol in three animals, 24 hours after dermal application, resulted in systematic absorption of 39.8±2.5 %AD (mean ± SEM) percent of the applied dose (% AD). At 24-hours, 2.1±0.2 %AD of farnesol remained in the skin and 5.0±2.2 %AD was extracted from carbon impregnated filter papers. The total penetration (systemically absorbed + skin absorption + recovery of materials in skin around the dosing site) corresponded to 44.1 ± 2.2% AD, 5.4 ± 1.3%AD was recovered in the urine. The total recovery (mass balance) corresponded to 65.9 ± 6%.


Twenty-four hour in vitro absorption studies suggested total penetration of farnesol to be 69.9±4.3 %AD, with 43.5 ± 3.3%AD in the receptor fluid, with 26.4 ± 4.1%AD remaining in the skin (approximately 19.2 ± 4.6%AD in the viable skin and 7.2 ± 1.3%AD in the stratum corneum). Extended 72-hour studies found 77.5±4.7 %AD in the receptor fluid with 8.0±1.9 %AD remaining in the skin (approximately 2.8 ± 0.7%AD in the viable skin and 5.2 ± 1.2%AD in the stratum corneum). The total 72-hour in vitro penetration of farnesol was calculated to be 85.5±6.7 %AD. The total recovery was 105.8 ± 6.2% at 72 h.

Total recovery:

The systemic in vivo absorption value coincided with the 24 -hour in vitro absorption value. However, the evaporation test for 3H-Farnesol suggested that there is a potential for evaporative loss.

Applicant's summary and conclusion

Conclusions:

As a lipophilic compound, farnesol has been shown to be readily absorbed and distributed in Hartley guinea pigs in vitro and in vivo.

Executive summary:

The dermal absorption of farnesol was investigated in Hartley guinea pigs in vivo using radiolabelled material and in vitro by mounting skin grafts in diffusion cells and measuring receptor fluid fractions. Comparable in vitro and in vivo dermal absorption of farnesol was observed. The in vivo absorption of farnesol led to systematic absorption of 39.8±2.5 % of the applied dose (AD) (mean ± SEM). At 24-hours, 2.1±0.2 %AD of farnesol remained in the skin and 5.0±2.2 %AD was extracted from carbon impregnated filter papers. In vitro farnesol absorption studies suggested penetration of 69.9±4.3 %AD. Extended 72-hour studies found 77.5±4.7 %AD in the receptor fluid with 8.0±1.9 %AD remaining in the skin. The total 72-hour in vitro penetration of farnesol was calculated to be 85.5±6.7 %AD. Under the experimental conditions stated, farnesol is readily absorbed and systemically distributed. This study is considered to be reliable without restriction (Klimisch 1) as it was a published study with adequate experimental design and sufficient reporting.