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Toxicological information

Dermal absorption

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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 absorptionopen allclose all
Dose:
312 µg/cm2
Parameter:
percentage
Absorption:
3.6 %
Remarks on result:
other: 6 h
Remarks:
rat skin intact
Dose:
312 µg/cm2
Parameter:
percentage
Absorption:
6.9 %
Remarks on result:
other: 16 h
Remarks:
rat skin intact
Dose:
312 µg/cm2
Parameter:
percentage
Absorption:
10 %
Remarks on result:
other: 6 h
Remarks:
rat skin damaged
Dose:
312 µg/cm2
Parameter:
percentage
Absorption:
2.9 %
Remarks on result:
other: 6 h
Remarks:
pig skin intact
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.