1,2-bis(2-methoxyethoxy)ethane

Dermal absorption

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

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

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

Deviations:

yes

Remarks:

one concentration, skin not rinsed at termination

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Bis(2-methoxyethyl) ether

EC Number:

203-924-4

EC Name:

Bis(2-methoxyethyl) ether

Cas Number:

111-96-6

Molecular formula:

C6H14O3

IUPAC Name:

1-methoxy-2-(2-methoxyethoxy)ethane

Constituent 2

Reference substance name:

Diglyme

IUPAC Name:

Diglyme

Constituent 3

Reference substance name:

Diethylene glycol dimethyl ether

IUPAC Name:

Diethylene glycol dimethyl ether

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 or test system 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 Diehylene 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: 36 +/- 3 min
Flux at steady state permeation: 0.952 +/- 0.340 mg/cm2/h

Permeation values of mixture (Diethylene glycol dimethyl ether 30% + acetone 70%)
Lag time: 49 +/- 28 min
Flux at steady state permeation: 0.674 +/- 0.305 mg/cm2/h

Total recovery:

not determined

Conversion factor human vs. animal skin:

n.a.

Applicant's summary and conclusion

Conclusions:

Results of the in vitro dermal absorption study performed with Diethylene glycol dimethyl ether:
The lag time was reported to be 36 +/- 3 min, the flux at steady state permeation was 0.952 +/- 0.340 mg/cm2/h.

Executive summary:

Due to the high structural similarity of Triethylene glycol dimethyl ether and Diethylene glycol dimethyl ether (difference: one ethyl group; but same functional groups) it is very likely that both compounds will show a similar skin penetration behaviour. Therefore, a read across from Triethylene glycol dimethyl ether to the data generated with Diethylene glycol dimethyl ether is justified to give a rough indication for the dimension of skin penetration properties. Furthermore, since the molecular weight of Triglyme (178.23 g/mol) is higher than that of Diglyme (134.18 g/mol), the substance is expected to be absorbed by the skin in a smaller amount than Diglyme.

An in vitro skin absorption study was performed applying Diethylene glycol dimethyl ether to dermatomed human skin. The lag time was reported to be 36 +/- 3 min, the flux at steady state permeation was 0.952 +/- 0.340 mg/cm2/h.