1H-Indene-1,3(2H)-dione, 2-(2-quinolinyl)-, sulfonated, sodium salts

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Data source

Reference

Reference Type:

review article or handbook

Title:

Unnamed

Year:

2004

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: The skin penetration of the test item was evaluated in a glass flow-through diffusion cell system using dissected porcine ear skin.
- Short description of test conditions:
The thickness of the dissected porcine ear skin was about 400 µm. The integrity of the skin was checked by conductivity. The test substance in saline or in a conventional formulation was applied on the skin surface (exposure area: 1cm²) for 30 min and covered with Parafilm. The collecting vials of the acceptor chambers were changed after 0.5, 1, 2, 4, 6, 8, and 24 hours.
- Parameters analysed/observed: Measurement of the amount of penetrated test item in the receptor fluid and of the amount of the test item in skin extracts.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1H-Indene-1,3(2H)-dione, 2-(2-quinolinyl)-, sulfonated, sodium salts

EC Number:

305-897-5

EC Name:

1H-Indene-1,3(2H)-dione, 2-(2-quinolinyl)-, sulfonated, sodium salts

Cas Number:

95193-83-2

Molecular formula:

C18H11NO5S to C18H8NO11S3.3Na

IUPAC Name:

trisodium hydrogen bis(2-(1,3-dioxo-5-sulfonato-2,3-dihydro-1H-inden-2-yl)quinoline-8-sulfonate)

Radiolabelling:

no

Test animals

Species:

pig

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

The study was performed in vitro/ex vivo on dissected porcine ear skin (thickness about 400 µm).

Administration / exposure

Type of coverage:

other: Flow-through Franz diffusion cells

Remarks:

The test substance was applied on the skin surface (exposure area: 1cm²) for 30 min and covered with Parafilm.

Vehicle:

other: The test item was applied both dissolved in saline and in conventional formulation.

Duration of exposure:

30 minutes

Doses:

Saline sample: 5 mg/mL of test item in saline. 1mL applied to the skin, equal to 5 mg/cm² of the test item on skin.
Conventional formulation: 0.5% of test item in conventional formulation. 1.2 grams applied to the skin, equal to about 6 mg/cm² of the test item on skin.

Details on in vitro test system (if applicable):

The skin penetration of the test item was evaluated in a glass flow-through Franz diffusion cell system using dissected porcine ear skin (thickness about 400µm). The experiment was performed in 6 replicates. The integrity of the skin was checked by conductivity without any indication of substantial loss of skin barrier properties.
The test item was applied on the skin surface (exposure area: 1 cm²) dissolved in saline (5mg/mL; 1mL applied, equal to 5 mg/cm² of the test item on the skin) or in a conventional formulation (0.5%; 1.2 grams applied, equal to about 6 mg/cm² of the test item on skin) for 30 min and covered with Parafilm. The pH of both the saline sample and the conventional formulation was adjusted to 3.
After the 30 minutes application, the skin surface excess was removed with a shampoo solution and water. Following the washing procedure, the donor chamber was filled with 1 mL of saline (pH adjusted to 3.0). The collecting vials of the acceptor chambers were changed after 0.5, 1, 2, 4, 6, 8, and 24 hours (saline, pH adjusted to 3).
After skin extraction, the dye content was quantified by HPLC (Detection at 430 nm; Detection limit: 150 ng/ml). The solubility of the dye in the receptor fluid was higher than 150 ng/ml.

Results and discussion

Signs and symptoms of toxicity:

not specified

Dermal irritation:

not specified

Absorption in different matrices:

The amounts of the test item in the skin extracts were 2.86 µg/cm² for the saline solution and 12.90 µg/cm² for the formulation.

Total recovery:

The mean recovery of the test substance was 99.2% in the first and 85.3% in the second experiment.

Percutaneous absorption

Percutaneous absorption 1

Time point:

24 h

Dose:

Saline sample: 5mg/mL; 1mL applied, equal to 5 mg/cm² of the test item on the skin

Parameter:

amount

Absorption:

8.3 other: µg/cm²

Remarks on result:

other: 0.17% of the applied dose

Percutaneous absorption 2

Time point:

24 h

Dose:

Conventional formulation (0.5%; 1.2 grams applied, equal to about 6 mg/cm² of the test item on skin)

Parameter:

amount

Absorption:

18.3 other: µg/cm²

Remarks on result:

other: 0.37% of the applied dose

Any other information on results incl. tables

The amount of penetrated test substance found in the receptor fluid plus that found in the skin extracts were considered as absorbed. Since the stratum corneum was not separated from the epidermal and dermal compartments, the amount found in the skin extract is added to those in the receptor solution. The maximal possible calculated flux of the test substance across the skin barrier was in both cases (saline and formulation) 5.4 µg/cm² (0.11% of the applied dose). The amounts of the test item in the skin extracts were 2.86 µg/cm² for the saline solution and 12.90 µg/cm² for the formulation. Together with the skin extracts, the global percutaneous absorption results in 8.3 µg/cm² (0.17% of the applied dose) for the saline solution and 18.3 µg/cm² (0.37% of the applied dose) for the formulation.

Applicant's summary and conclusion

Conclusions:

A final value of 18.3 µg/cm² is reported for the percutaneous absorption of the test item, equal to 0.37% of the applied dose.

Executive summary:

The skin penetration of the test item was evaluated in a glass flow-through Franz diffusion cell system using dissected porcine ear skin. The test substance was applied to the skin in saline (5 mg/mL, equal to 5 mg/cm² of the test item on skin) or in a conventional formulation (6 mg/cm² of the test item on skin) for 30 min and covered with Parafilm. Following a washing procedure to remove excess of the test item on the skin, the donor chamber was filled with 1 mL of saline (pH 3.0). The collecting vials of the acceptor chambers (saline, pH 3.0) were changed after 0.5, 1, 2, 4, 6, 8, and 24 hours. The dye content was quantified by HPLC.

The mean recovery of the test substance was 99.2% in the first and 85.3% in the second experiment. The maximal possible calculated flux of the test substance across the skin barrier was in both cases (saline and formulation) 5.4 µg/cm² (0.11% of the applied dose). The amounts of the dye in the skin extracts were 2.86 µg/cm² for the saline solution and 12.90 µg/cm² for the formulation. Together with the skin extracts, the global percutaneous absorption results in 8.3 µg/cm² (0.17% of the applied dose) for the saline solution and 18.3 µg/cm² (0.37% of the applied dose) for the formulation. As a consequence, a final value of 18.3 µg/cm² is reported for the percutaneous absorption of the test item.