Registration Dossier

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented study report which meets basic scientific principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Principles of method if other than guideline:
Percutaneous absorption of tromethamine hydrochloride was studied in 0.1% and 10% solution in-vitro in 4 samples of human abdominal skin, in a FRANZ diffusion cell.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Analytical purity: no data
Radiolabelling:
yes
Remarks:
carbon-14 labelled tromethamine solution

Test animals

Species:
other: in-vitro, human abdominal skin in a FRANZ diffusion cell
Strain:
other: in-vitro, human abdominal skin in a FRANZ diffusion cell
Sex:
not specified

Administration / exposure

Type of coverage:
other: not applicable
Vehicle:
not specified
Doses:
- Concentration: 0.1% (1 kg/L) and 10% (100 kg/L)
- Dose volume: 100 µL
No. of animals per group:
not applicable
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: human skin comes from biopsies obtained after plastic surgery of the abdomen
- Type of skin: human abdominal skin
- Preparative technique: skin is cut with a dermatome
- Thickness of skin (in mm): 0.3
- Storage conditions: stored frozen

PRINCIPLES OF ASSAY
- Diffusion cell: FRANZ diffusion cell
- Flow-through system: jacket with double circulation of water surrounds the lower part
- Test temperature: 37 °C

Results and discussion

Any other information on results incl. tables

After 24 h, the percutaneous absorption of tromethamine hydrochloride through human abdominal skin in-vitro was very low, regardless of the concentration of the solution. The mean percentages of the applied tromethamine hydrochloride dose that had passed into the survival liquid were 0.506 ± 0.765% for the 0.1% solution and 0.797 ± 0.691% for the 10% solution. These differences are not significant.

For both solutions, the maximum value of flux was reached after 4 h and remained essentially constant during the rest of the experiment. However, the value of flux was about 150 times higher for the 10% solution (6.922 ± 6.179 µg/cm2/h) than for the 0.1% solution (0.039 ± 0.052 µg/cm2/h).

After washing, the retention of the test substance in the epidermis and dermis was low: For the 0.1% solution, 0.14 ± 0.19% tromethamine hydrochloride remained in the epidermis and 0.69 ± 1.33% in the dermis. For the 10% solution, 0.13 ± 0.21% tromethamine hydrochlorde was detected in the epidermis and 0.22 ± 0.21% in the dermis. Therefore, the test substance is not retained in the horny layer (epidermis).

The test substance was almost totally eliminated by washing the skin after 24 h. For the 0.1% solution, 91.13 ± 4.67% tromethamine hydrochloride was found in the washing waters and for the 10% solution, a quantity of 90.45 ± 4.06%.

However, significant differences in permeability from one skin sample to the other were recorded. (The experiments were carried out on 4 skin samples of different origin: mulatto skin; skin 2 and 3: white skin.) The differences of the individual measurements of the skin samples were lower for the 0.1% solution.

At the end of the 24 h, regardless of the concentration of the solution, the radioactivity found in the epidermis and the dermis was low (less than 1% of the applied dose) and the washing waters contained more than 90% of the applied dose.

Applicant's summary and conclusion