γ-butyrolactone

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented scientifically reliable study

Data source

Reference

Reference Type:

publication

Title:

Permeability of Commercial Solvents Through Living Human Skin

Author:

Ursin, C. et. al.

Year:

1995

Bibliographic source:

American Industrial Hygiene Association Journal, 56: 7, 651-660

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

γ-butyrolactone

EC Number:

202-509-5

EC Name:

γ-butyrolactone

Cas Number:

96-48-0

Molecular formula:

C4H6O2

IUPAC Name:

dihydrofuran-2(3H)-one

Details on test material:

Reported as "the highest available commercial quality"

Radiolabelling:

no

Test animals

Species:

human

Strain:

other: breast tissue removed during plastic surgery of the breast

Sex:

female

Administration / exposure

Type of coverage:

open

Vehicle:

unchanged (no vehicle)

Details on study design:

Skin samples were stored in Dulbecco's medium, with gentamicin, at 4°C until thinned (< or =48h). A Downs-Watson dermatome was used to remove the dermal tissue from the epidermis to create the "split skin." The thickness of the unstretched split-skin after thinning was 1 to 2 mm.

Details on in vitro test system (if applicable):

SKIN PREPARATION
- Source of skin: Removed during plastic surgery of the breast
- Type of skin: human breast (female)
- Preparative technique: Dulbecco's medium, with gentamicin. A Downs-Watson dermatome was used to create the "split skin
- Thickness of skin (in mm): 1 to 2 (unstretched); 0.3 to 0.6 mm (stretched)
- Membrane integrity check: Yes, radiolabeled water.
- Membrane permeability calibrated: Yes, radiolabeled water.
- Membrane viability: Yes, determined by measurement of DNA synthesis.
- Storage conditions: 4°C until thinned (< or = 48h)

PRINCIPLES OF ASSAY
- Diffusion cell: Franz, two-chamber cell, with water jacket and magnetic stirrer in collection cell
- Receptor fluid: isotonic nurished saline solution (Dulbecco's medium, with gentamycin)
- Solubility of test substance in receptor fluid: none
- Test temperature: 37°C
- Analytical Method: GC, detection limit of 0.2 ppm
- Statistics: linear regression of data from 1 to 6 hours (region of steady-state permeation)

Results and discussion

Any other information on results incl. tables

Trial #	Permeability Constant (g/m^2h)		% Error in Slope^2
	Un-Normalized	Normalized^1
1	0.76	1.02	8.4
2	1.08	1.21	8.1
3	0.79	1.03	15.8
	0.88 + 0.17	1.09 + 0.10

¹Adjusted for the permeability rate of radiolabeled water through the specimen.

²A measure of the linearity of the steady state region. A value of 0 indicates perfect linearity.

Mean permeability constant = 1.1 g/m2/hr or 1.0 cm3/m2/hr, equivalent to 0.0001 cm/hr. Amount permeated after 1h was approximately 1.5 g/m2 and approximately 2.5 g/m2 after 2 h.