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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23.09.2005 to 03.11.2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
yes
Remarks:
14C-L4

Test animals

Species:
human
Sex:
male

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 hours
Doses:
- Target doses: 10 mg of 14C-L4/cm2 of skin.
- Actual doses: 8.28-10.47 mg/cm2 of skin and applied radioactivity was in the range 10.29-13.01 µCi/cm2 of skin.
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: Four samples of male abdominal skin from four human subjects.
- Ethical approval if human skin: No data
- Type of skin: Abdominal
- Preparative technique: Skin samples were cleaned of underlying fat and thawed at the room temperature. Once thawed each skin sample was dermatomed with a mini-dermatome to separate epidermis from most of the dermis.
- Thickness of skin (in mm): 300-470 microns
- Membrane integrity check: Each skin piece received an infinite dose of 3H-H2O for 20 minutes in order to determine if the barrier of the skin had been compromised.
- Storage conditions: Freezer
- Justification of species, anatomical site and preparative technique: None

PRINCIPLES OF ASSAY
- Diffusion cell: Three disc shaped pieces, large enough to fit 0.64 cm2 flow-through diffusion cells, which were punched out from each skin sample and rinsed with water. The thickness of all skin pieces was measured with a digimatic micrometer before placing each piece of epidermis side up in the diffusion flow-through cells.
- Receptor fluid: Hank's Balanced Salt Solution with 0.6% HEPES, 0.005% Gentamicin and 4% Bovine Serum Albumin was mixed, the pH adjusted to 7.3-7.4 with NaOH and then filtered through a 0.45 micron filter.
- Solubility of test substance in receptor fluid: It was demonstrated that solubility of L4 was more than ten times higher than the amount of test substance that penetrated into the receptor fluid over 24 hours of skin exposure (average 0.001% of applied dose).
- Flow-through system: (Bronaugh) The receptor fluid was pumped beneath the skin samples (2.0-2.2 ml/hr) and collected in a fraction collector at predetermined time points. Collected for 24 hours. Immediately after dosing a charcoal basket was placed in each diffusion cell above the skin exposure site and secured into a custom designed holder to capture any volatilised material. The receptor fluid was collected for 24 hours. At the end of the 24 hours exposure, skin was washed, tape stripped and solubilised. The charcoal baskets, holders and diffusion cells were extracted. Total dose absorbed was estimated based on radioactivity found in the skin and receptor fluid.
- Test temperature: No data
- Humidity: No data
- Occlusion: Semi-occlusive
- Reference substance(s): No data
- Other: Skin samples from four donors were assessed in triplicate.

Results and discussion

Signs and symptoms of toxicity:
not examined
Dermal irritation:
not examined
Absorption in different matrices:
Only a small amount of applied dose (0.06%) was found on the skin surface after a 24 hour exposure or remained in the skin after washing and tape stripping (0.03%).

Almost all (99.9%) of the recovered 14C-L4 volatilised from the skin surface and was captured in the charcoal baskets placed above the exposure site.
Total recovery:
- Total recovery: 104.69%
- Recovery of applied dose acceptable: yes
- Results adjusted for incomplete recovery of the applied dose: No


- Limit of detection (LOD):
- Quantification of values below LOD or LOQ:
Percutaneous absorptionopen allclose all
Time point:
24 h
Parameter:
percentage
Absorption:
ca. 0.03 %
Remarks on result:
other: Virtually all of this absorbed test substance was retained in the skin.
Time point:
24 h
Parameter:
percentage
Absorption:
ca. 0.001 %
Remarks on result:
other: The percentage of applied dose that penetrated through the skin into the receptor fluid.

Applicant's summary and conclusion

Conclusions:
In an in vitro dermal penetration study using human skin, conducted using a study comparable to OECD 428 and to GLP (reliability score 1) almost all (99.9%) of the recovered 14C-decamethyltetrasiloxane (L4) volatilised from the skin surface and was captured in the charcoal baskets placed above the exposure site. Only a small amount of applied dose (0.06%) was found on the skin surface after 24 hours exposure or remained in the skin after washing and tape stripping (0.03%). Little, if any (0.001%) of the applied dose penetrated through the skin into the receptor fluid. The total percent dose absorbed was estimated to be 0.03% of applied dose with virtually all of the absorbed test substance retained in the skin.