3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-benzopyran-6-ol

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:

key study

Study period:

11 October 1994 - 11 November 1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study was conducted according to an equivalent of OECD guideline 428, but not under GLP conditions.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

Deviations:

no

Principles of method if other than guideline:

Not relevant

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-benzopyran-6-yl acetate

EC Number:

231-710-0

EC Name:

3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-benzopyran-6-yl acetate

Details on test material:

- Name of test material (as cited in study report): Vitamin E Acetate
- Physical state: Liquid (cream)

Radiolabelling:

yes

Remarks:

3H

Test animals

Species:

pig

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

Not relevant

Administration / exposure

Type of coverage:

other: closed system

Vehicle:

other: alpha-hydroxy-acid cream (3 different formulations)

Duration of exposure:

1, 6 and 18 hours

Doses:

- Nominal doses: 5%
- Dose volume: 6 mg/cm2 (300 ug active substance/cm2)
- Activity: 20 uCi/g

No. of animals per group:

Not relevant

Control animals:

no

Results and discussion

Percutaneous absorption

Percutaneous absorption 1

Dose:

5% in AHA-cream

Parameter:

percentage

Absorption:

1.1 %

Remarks on result:

other: 1 hr

Remarks:

Cream A: Based on penetration in stratum corneum, remaining skin tissue layers and chamber liquid

Percutaneous absorption 2

Dose:

5% in AHA-cream

Parameter:

percentage

Absorption:

3.8 %

Remarks on result:

other: 6 hr

Remarks:

Cream A: Based on penetration in stratum corneum, remaining skin tissue layers and chamber liquid

Percutaneous absorption 3

Dose:

5% in AHA-cream

Parameter:

percentage

Absorption:

4.2 %

Remarks on result:

other: 18 hr

Remarks:

Cream A: Based on penetration in stratum corneum, remaining skin tissue layers and chamber liquid

Percutaneous absorption 4

Dose:

5% in AHA-cream

Parameter:

percentage

Absorption:

1.3 %

Remarks on result:

other: 1 hr

Remarks:

Cream B: Based on penetration in stratum corneum, remaining skin tissue layers and chamber liquid

Percutaneous absorption 5

Dose:

5% in AHA-cream

Parameter:

percentage

Absorption:

4.1 %

Remarks on result:

other: 6 hr

Remarks:

Cream B: Based on penetration in stratum corneum, remaining skin tissue layers and chamber liquid

Percutaneous absorption 6

Dose:

5% in AHA-cream

Parameter:

percentage

Absorption:

3.1 %

Remarks on result:

other: 18 hr

Remarks:

Cream B: Based on penetration in stratum corneum, remaining skin tissue layers and chamber liquid

Percutaneous absorption 7

Dose:

5% in AHA-cream

Parameter:

percentage

Absorption:

1.3 %

Remarks on result:

other: 1 hr

Remarks:

Cream H: Based on penetration in stratum corneum, remaining skin tissue layers and chamber liquid

Percutaneous absorption 8

Dose:

5% in AHA-cream

Parameter:

percentage

Absorption:

2.6 %

Remarks on result:

other: 6 hr

Remarks:

Cream H: Based on penetration in stratum corneum, remaining skin tissue layers and chamber liquid

Percutaneous absorption 9

Dose:

5% in AHA-cream

Parameter:

percentage

Absorption:

3.1 %

Remarks on result:

other: 18 hr

Remarks:

Cream H: Based on penetration in stratum corneum, remaining skin tissue layers and chamber liquid

Conversion factor human vs. animal skin:

Not relevant

Any other information on results incl. tables

The same test performed on stripped skin (removed stratum corneum) showed a higher absorption rate for the remaining skin tissue layers in all three formulations.

Applicant's summary and conclusion

Conclusions:

Based on the experimental data, it is concluded that Vitamin-E-Acetate-3H penetrates into and through the intact and stripped pig skin from the 3 formulations tested. The total skin penetration rates of Vitamin E acetate 3H from the 3 cream were time-, formulation type- and skin condition-dependent, although not significantly different.

Executive summary:

This study was set up to test the penetrating ability of vitamin-E-acetate (activity: 20 uCi/g) in AHA (alpha-hydroxy-acid) creams into and through explanted domestic pig skin.

The penetration into the stratum corneum and into the living layers of the intact pig skin was time-, and formulation type-dependent. After 6 hours of exposure the mean penetration rates into the horny and living skin layers were: 11.32 ug/cm2 (formulation A), 12.19 ug/cm2 (formulation B) and 7.84 ug/cm2 (formulation H).

Penetration into the stratum corneum was higher than absorption into the living skin layers.

No significant further increase of the total pentration rates occurred by increasing the exposure time up to 18 hours.

In general, removal of the stratum corneum by stripping resulted in non significant increase of the penetration rate, a property likely to be accounted for by the lipophilic nature of the compound.

Based on these experimental data, it is concluded that Vitamin-E-Acetate3H penetrates into and through the intact and stripped pig skin from the 3 formulations tested.