Registration Dossier

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:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
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/m2h)

% Error in

Slope2

 

Un-Normalized

Normalized1

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.

Applicant's summary and conclusion