Registration Dossier

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
Received: 16 June 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Principle aspects are in line wtih the current OECD guideline but several deviations from guideline.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Deviations:
yes
Remarks:
one concentration tested, skin not rinsed at termination
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Supplier: Sigma Chemical Co., USA
Purity: 99%
Radiolabelling:
no

Test animals

Species:
human
Strain:
other: n.a.
Sex:
male
Details on test animals and environmental conditions:
The donors were men under 60 years of age.

Administration / exposure

Type of coverage:
other: in vitro study
Vehicle:
unchanged (no vehicle)
Duration of exposure:
30, 60, 90, 120, 150, 180 and 240 min.
Doses:
0.2 mL
No. of animals per group:
8 runs, one per determined time point
Control animals:
no
Remarks:
in vitro study
Details on study design:
Please refer to "Details on in vitro test system"
Details on in vitro test system (if applicable):
In vitro skin permeation using human skin was measured with the Franz method. A piece of full thickness human abdominal was excised at autopsy (within 24 hours post mortem), and immediately placed into palstic bags and stored in a freezer (-80°C), for a period of up to, but not exceeding, 4 months. This method of storage does not damage the barrier since no difference in permeability was observed between fresh and frozen segments of the same skin in a separate series of experiments. Before use, the skin was left to thaw gradually to room temperature, following which all subcutaneous fat was removed by scalpel. From specimen, 3x3 cm multiple pieces were cut and mounted individually on an eight-cell Franz diffusion assembly. The epidermal side if the skin was exposed to ambient conditions, while the dermal side was bathed in a physiological solution (15 mL volume). temperature was maintained at 32°C by circulating water through a jacket surrounding the chamber. After mounting, each piece of skin was allowed to stand for 2 hours before the experiments were begun. At time 0, a quantity of 0.2 mL Ehylene glycol dimethyl ether was placed on the epidermal surface. The area available for diffusion was 3.14 cm2. At selected intervals, 2 mL of the dermal bathing solution was removed and analysed. Each receptor sample was replaced with an equal volume of fresh physiological solution. The experiment was performed with eight cells at each of eight times (time 0, 30, 60, 90, 120, 150, 180 and 240 min), for a total of 64 samples.

Results and discussion

Signs and symptoms of toxicity:
not examined
Remarks:
in vitro study
Dermal irritation:
not examined
Remarks:
in vitro study
Absorption in different matrices:
Lag time: 39 +/- 3 min
Flux at steady state permeation: 3.434 +/- 1.897 mg/cm2/h

Permeation values of mixture (Ethylene glycol dimethyl ether 30% + acetone 70%)
Lag time: 35 +/- 27 min
Flux at steady state permeation: 0.837 +/- 0.474 mg/cm2/h
Total recovery:
not determined
Percutaneous absorption
Remarks on result:
other: not stated
Conversion factor human vs. animal skin:
n.a.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:
Results of the in vitro dermal absorption study performed with Ethylene glycol dimethyl ether:
The lag time was reported to be 39 +/- 3 min, the flux at steady state permeation was 3.434 +/- 1.897 mg/cm2/h.
Executive summary:

An in vitro skin absorption study was performed applying Ethylene glycol dimethyl ether to dermatomed human skin. The lag time was reported to be 39 +/- 3 min, the flux at steady state permeation was 3.434 +/- 1.897 mg/cm2/h.