Retinyl acetate

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

18 September 1984 - 21 September 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study was conducted equivalent to 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:

1984

Report date:

1984

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:

Retinyl acetate

EC Number:

204-844-2

EC Name:

Retinyl acetate

Cas Number:

127-47-9

Molecular formula:

C22H32O2

IUPAC Name:

(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraen-1-yl acetate

Details on test material:

- Name of test material (as cited in study report): Vitamin-A-Acetate 14C, Retinyl acetate
- Physical state: Test material was dissolved in TWEEN-20 and NEOBEE-M-5

Radiolabelling:

yes

Remarks:

14C

Test animals

Species:

rat

Strain:

other: naked rat

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: TWEEN-20 and NEOBEE-M-5

Duration of exposure:

6 hours

Doses:

- Nominal doses:
In TWEEN-20: 150 ug/cm2 (2.5% solution)
In NEOBEE-M-5: 600 ug/cm2 (10% solution)
- Dose volume: 6 ul/cm2

No. of animals per group:

Not relevant

Control animals:

no

Remarks:

not relevant

Details on study design:

DOSE PREPARATION
- Method for preparation of dose suspensions: Mix active and non-labeled material to reach the activity of 1-5 uCi/5 cm2 skin site

VEHICLE
- Amount(s) applied (volume or weight with unit): 30 ul on 5 cm2
- Concentration (if solution): 2.5% (TWEEN-20) and 10% (NEOBEE-M-5)

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 6 hours

ANALYSIS
- Method type(s) for identification: Liquid scintillation counting

Details on in vitro test system (if applicable):

SKIN PREPARATION
- Source of skin: Naked rat
- Preparative technique:
Fresh operation material is used. Connective and adipose tissue is removed. Round flaps of 20 cm2 are formed, which are cleaned under floating water.
Skin is marked with 5 cm2 stamps and 30 ul of the test material is applied regularly with a micropipette on the marked areas. Then skin is placed in the penetration chamber: lower part is in contact with physiological salt solution, slightly moved by a magnetic stirrer throughout the whole experiment.
- Storage conditions: -20 degrees Celsius in aluminium foil

PRINCIPLES OF ASSAY
- Diffusion cell: Two bell jars between which the skin is tightened
- Receptor fluid: Physiological saline
- Test temperature: 32 degrees Celsius
- Occlusion: Closed system

Results and discussion

Signs and symptoms of toxicity:

not examined

Remarks:

not relevant

Dermal irritation:

not examined

Remarks:

not relevant

Absorption in different matrices:

- Skin test site:
In TWEEN-20: 130.83 ug/cm2
In NEOBEE-M-5: 546.41 ug/cm2

- Receptor fluid, receptor chamber, donor chamber (in vitro test system):
In TWEEN-20: 0.17 ug/cm2
In NEOBEE-M-5: 2.67 ug/cm2

- Skin preparation (in vitro test system)
Remaining skin tissue layers:
In TWEEN-20: 17.56 ug/cm2
In NEOBEE-M-5: 44.84 ug/cm2

- Stratum corneum (in vitro test system):
In TWEEN-20: 1.44 ug/cm2
In NEOBEE-M-5: 6.08 ug/cm2

Total recovery:

- Total recovery: 100%
- Recovery of applied dose acceptable: Yes

Percutaneous absorption

Percutaneous absorption 1

Dose:

2.5% in TWEEN-20

Parameter:

percentage

Absorption:

12.8 %

Remarks on result:

other: 6 hours

Remarks:

Based on amount in stratum corneum, remaining skin tissue layers and chamber liquid

Percutaneous absorption 2

Dose:

10% in NEOBEE-M-5

Parameter:

percentage

Absorption:

8.9 %

Remarks on result:

other: 6 hours

Remarks:

Based on amount in stratum corneum, remaining skin tissue layers and chamber liquid

Conversion factor human vs. animal skin:

No data

Any other information on results incl. tables

Vitamin-A-acetate does penetrate into and through the animal skin.

The penetration rates determined on naked rat skin are about 5-times higher than those found for pig skin.

Applicant's summary and conclusion

Conclusions:

Under the current test conditions, the in vitro skin penetration rates of vitamin-A-acetate in naked rat skin were 12.8% and 8.9% in TWEEN-20 and NEOBEE-M-5 respectively, after 6 hours of exposure.

Executive summary:

Skin penetration rate for Vitamin-A-Acetate labelled with 14C was determined in naked rat and pig skin. Test solution (test substance in TWEEN-20 or NEOBEE-M-5) was applied for 6 hours.

Penetration rates in rat were respectively 12.8 and 8.9%. For pig these were 2.2 and 1.8% respectively.

The authors conclude that the skin penetration rates determined in these "in vitro" studies with Vitamin-A-Acetate on naked rat and pig skin are more concentrationand animal-species-dependent than vehicle-type-dependent. As expected the penetration rates determined on naked rat skin are about 5-times higher than those found for pig skin.