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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Principles of method if other than guideline:
In vitro penetration studies using human and porcine skin
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Uvinul N 539
No further data
Radiolabelling:
no

Test animals

Species:
other: pig and human

Administration / exposure

Vehicle:
other: oil water emulsion
Duration of exposure:
16 hours
Doses:
3 mg/cm² (8% test substance)
Details on in vitro test system (if applicable):
Human Skin
SKIN PREPARATION
- Type of skin: Human caucasian skin from mammalian or abdominal surgery of females aged between 20 and 65 years
- Preparative technique: freshly dermatomed
- Thickness of skin: 350 ± 50 µm
- Membrane integrity check: yes: visually (no cuts, scars, reddish marks, spots, injuries), TEWL
- Storage conditions: 4°C for 24 hours

PRINCIPLES OF ASSAY
- Diffusion cell: static
- Receptor fluid: 1% of bovine serum albumin, 0.9 % of NaCl, 0.02 % of KCI, 0.04 % of gentamicin sulfate and 0.8% of phosphate buffer in water; pH 7.4.
- Test temperature: mean skin membrane temperature of 32 °C
- Samples assessed: Tapes (16 strippings); epidermis, dermis, receptor fluid, washing solution

Pig Skin
SKIN PREPARATION
- Type of skin: Unboiled back skin of selected female pigs ( 130 days old, weighing about 100 kg). Fresh skin from 6 different animals was used in triplicate.
- Preparative technique: freshly dermatomed
- Thickness of skin: 700 ± 50 µm
- Membrane integrity check: yes: visually (no cuts, scars, scratches, injuries), TEWL

PRINCIPLES OF ASSAY
- Diffusion cell: static
- Receptor fluid: 1% of bovine serum albumin, 0.9 % of NaCl, 0.02 % of KCI, 0.04 % of gentamicin sulfate and 0.8% of phosphate buffer in water; pH 7.4.
- Test temperature: mean skin membrane temperature of 32 °C
- Samples assessed: Tapes (16 strippings); epidermis, dermis, receptor fluid, washing solution

Results and discussion

Total recovery:
Pig skin experiments: 90+/-2% recovery
Percutaneous absorptionopen allclose all
Time point:
16 h
Dose:
3 mg/cm²
Parameter:
percentage
Absorption:
ca. 0.2 %
Remarks on result:
other: Human Skin: Application of test substance as 8% in formulation
Time point:
16 h
Dose:
3 mg/cm²
Parameter:
percentage
Absorption:
ca. 3 %
Remarks on result:
other: Porcine Skin: Application of test substance as 8% in formulation

Any other information on results incl. tables

Pig skin - Distribution of the total amount of Caffeine and Uvinul N 539 in six skin samples

Mean % of applied amount (confidence interval of 95%)

Octocrilene Uvinul N539 Caffeine
Surface 74 (4) 83 (2)
Stratum corneum 14 (3) 5.0 (1)
Epidermis 2.8 (0.9) 3.0 (1)
Dermis 0.3 (0.1) 1.0 (0.5)
Receptor medium 0.0 (0) 0.6 (0.4)
Recovery 90 (2) 93 (4)

Caffeine

% of applied dose

skin 1

skin 2

skin 3

skin 4

skin 5

skin 6

loss

3.28

7.56

9.39

4.35

6.88

9.37

surface

92.63

89.19

82.31

85.26

84.16

82.24

SC

1.91

1.09

4.85

5.49

3.82

4.72

epidermis

0.64

1.28

2.12

2.12

3.38

1.99

dermis

0.65

0.39

0.78

1.41

1.13

0.69

receptor

0.89

0.49

0.45

0.36

0.64

0.98

Uvinul N 539

% of applied dose

skin 1

skin 2

skin 3

skin 4

skin 5

skin 6

loss

8.04

10.47

7.15

10.12

10.96

10.82

surface

75.02

75.53

72.9

73.37

67.38

76.98

SC

13.78

10.83

15.15

14.3

18.89

9.8

epidermis

2.78

2.95

4.34

2

2.4

1.03

dermis

0.38

0.22

0.46

0.21

0.39

0.37

receptor

0

0

0

0

0

0

Comparison between the repartition profiles in pig an human skin

skin compartment

µg of applied substance per cm² skin

Caffeine

Octocrilene

Uvinul N 539

pig

n = 12

human

n = 12

pig

n = 18

human

n = 9

surface

139 ± 12

82 ± 7

157 ± 15

216 ± 17

SC

8 ± 2

2 ± 2

30 ± 8

13 ± 6

epidermis

4 ± 2

0.13 ± 0.08

6 ± 2

0.3 ± 0.7

dermis

1.7 ± 0.9

0.3 ± 0.2

0.7 ± 0.2

0.3 ± 1.0

receptor

1.0 ± 0.6

1.4 ± 0.9

0.0 ± 0.0

0.0 ± 0.0

Considering the concentration of the test substance (8%) and the amount applied (3 mg/cm²), 5.4%, 0.125% and 0.125% of the applied dose was found in human stratum corneum, epidermis and dermis respectively. No octocrilene was detectable in the receptor fluid.

Applicant's summary and conclusion