Butanamide, N-(3-ethoxypropyl)-2,4-dihydroxy-3,3-dimethyl-

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

from 1987-11-17 to 1987-11-27

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

Deviations:

not specified

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Test material form:

liquid: viscous

Radiolabelling:

yes

Test animals

Species:

other: in vitro: skin of naked rat and domestic pig

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not applicable

Administration / exposure

Type of coverage:

other: not applicable (in vitro method)

Vehicle:

other: incorporated in formulation of Bepanthen-Ointment-Roche

Duration of exposure:

6 and 16 h

Doses:

The test sample was applied to a skin area of 5 cm2 at a dose of 6 mg/cm2, resulting in a dose of 312 µg the test item/cm2.

No. of animals per group:

not applicable

Control animals:

no

Details on study design:

not applicable

Details on in vitro test system (if applicable):

Only exposure times of 6 and 16 hours were chosen, and no studies concerning the distribution of the drug in single skin layers were performed. The experimental design of this technique is the first step to remove unabsorbed test material from the skin surface at 6 and 16 h after application (rest material). As a next step the amount of labelled material in the stratum corneum, in the stripped skin, and in the chamber liquid is estimated. Finally the total penetration rate of the test material per cm2 skin surface is calculated. Besides this a 6 h penetration study on striped (damaged) naked rat skin was performed by scotch tape strippings before application of the formulation was initiated.

Results and discussion

Signs and symptoms of toxicity:

not examined

Dermal irritation:

not examined

Absorption in different matrices:

not applicable

Total recovery:

The test item does penetrate into and through the skin of naked rat and domestic pig. The total penetration rates were less species than time and skin condition dependent. On the intact naked rat skin the total penetration rate of the test item after 6 hours exposure amounted to 11.11 µg/cm2 and increased to 21.57 µg/cm2 after 16 h. On stripped naked rat skin a total penetration rate of 31.20 µg/cm2 was measured. On contact with domestic pig skin the penetration rates amounted to 9.26 µg/cm2/6 h and 17.67 µg/cm2/16h.

Percutaneous absorption

Percutaneous absorption 1

Dose:

312 µg/cm2

Parameter:

percentage

Absorption:

3.6 %

Remarks on result:

other: 6 h

Remarks:

rat skin intact

Percutaneous absorption 2

Dose:

312 µg/cm2

Parameter:

percentage

Absorption:

6.9 %

Remarks on result:

other: 16 h

Remarks:

rat skin intact

Percutaneous absorption 3

Dose:

312 µg/cm2

Parameter:

percentage

Absorption:

10 %

Remarks on result:

other: 6 h

Remarks:

rat skin damaged

Percutaneous absorption 4

Dose:

312 µg/cm2

Parameter:

percentage

Absorption:

2.9 %

Remarks on result:

other: 6 h

Remarks:

pig skin intact

Percutaneous absorption 5

Dose:

312 µg/cm2

Parameter:

percentage

Absorption:

6 %

Remarks on result:

other: 16 h

Remarks:

pig skin intact

Conversion factor human vs. animal skin:

not applicable

Applicant's summary and conclusion

Conclusions:

The test item does penetrate into and through the skin of naked rat and domestic pig.

Executive summary:

This study indicates that the skin penetration rates of the test item, incorporated into Bepanthen-Ointment-Roche at a concentration of 5.2 %, were less species- than time- and skin- condition dependent. On intact naked rat and domestic pig skin they amount to about 10 µg/cm2/6h and reach about 20 mg/cm2/16h. If applied for 6 h to the naked rat skin which had been damaged by stripping the total penetration rate of the test item increase to 31.2 µg/cm2.