Registration Dossier

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2004-11-15 to 2004-11-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study, to GLP

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005
Reference Type:
secondary source
Title:
Unnamed
Year:
2008

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Cereclor S52
- Substance type: technical product
- Physical state: colourless liquid
- Analytical purity: >99.9%
- Impurities (identity and concentrations): no data concerning presence/absence of stabiliser
- Composition of test material, percentage of components: C14-17 chlorinated paraffin (52% chlorination).
- Purity test date: no data
- Lot/batch No.: CD9327
- Expiration date of the lot/batch: July 2005
- Radiochemical purity (if radiolabelling): >98%
- Specific activity (if radiolabelling): 39.22 MBq/g (49.34 MBq/ml; 1.33 mCi/ml)
- Locations of the label (if radiolabelling): [8-14C]C14-17 chlorinated paraffin (52% chlorination)
- Expiration date of radiochemical substance (if radiolabelling): no data
- Stability under test conditions: no data
- Storage condition of test material: ambient conditions in the dark (unlabelled) ; refrigerated (labelled)
Radiolabelling:
yes

Test animals

Species:
human
Sex:
not specified
Details on test animals and environmental conditions:
Not relevant

Administration / exposure

Type of coverage:
other: occluded and unoccluded
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 hours
Doses:
- Actual doses: 12.6 and 125.8 mg/cm2- Actual doses calculated as follows: volume x specific gravity- Dose volume: 10 and 100 µl/cm2- Rationale for dose selection: "to simulate predicted possible and maximal human exposure"
No. of animals per group:
not relevant
Control animals:
no
Details on study design:
2 epidermal membranes from each of 3 subjects used in studyAt recorded intervals (2, 4, 8, 12, 16, 20 & 24 h), 0.5 ml samples of the receptor fluid were taken for analysis by liquid scintillation counting (LSC).Residual activity on membrane surface was removed by washing off with sponges soaked in 3% Teepol detergent (first wash) followed by water. Radioactivity recovered was determined by LSC.Dermal penetration was determined by stripping dried membrane with adhesive tape (max. 5 strips) and analysing by LSC.Residual activity on membrane determined by LSC.
Details on in vitro test system (if applicable):
SKIN PREPARATION- Source of skin: human (surgery or post mortem)- Ethical approval if human skin: no data- Type of skin: epidermal membrane- Preparative technique: warm (60oC) water- Thickness of skin (in mm): no data- Membrane integrity check: yes - electrical resistance >10 kohms- Storage conditions: no data- Justification of species, anatomical site and preparative technique: PRINCIPLES OF ASSAY- Diffusion cell: yes- Receptor fluid: 6% Polyoxyethylene 20 oleyl ether (Volpo N20) in water- Solubility of test substance in receptor fluid: 1.85 mg/ml- Static system: yes; receptor fluid stirred continuously- Flow-through system: no- Test temperature: 32oC- Humidity: no data- Occlusion: occluded and non-occluded- Reference substance(s): no

Results and discussion

Signs and symptoms of toxicity:
not specified
Dermal irritation:
not specified
Absorption in different matrices:
Unoccluded:- Skin wash: 99.1%- Receptor fluid, receptor chamber, donor chamber (in vitro test system): receptor fluid 0.002% ; donor chamber 0.16%- Skin preparation (in vitro test system): residual membrane after stripping 0.70%- Stratum corneum (in vitro test system): (i.e tape strips) 2.15%
Total recovery:
Mean recovery for 6 membranes - 102%
Percutaneous absorption
Dose:
12.6 mg/cm2
Parameter:
percentage
Absorption:
ca. 0.7 %
Remarks on result:
other: 24 hours
Remarks:
unoccluded; Cereclor S52
Conversion factor human vs. animal skin:
Not applicable

Any other information on results incl. tables

The absorption rate for the unoccluded application was 0.01 µg/cm2/h, equivalent to an absorption of 0.243 µg/cm2 or 0.002% of the dose. The corresponding values for the occluded application were 0.057 µg/cm2/h, equivalent to an absorption of 1.367 µg/cm2 or 0.001% of the dose.

Applicant's summary and conclusion

Conclusions:
In a study to investigate the likely absorption of Cereclor S52 (a C14-17 chlorinated paraffin; 52% chlorination) through human epidermis under the most conservative conditions (epidermal membrane, solubilising receptor fluid, prolonged exposure), the maximum dermal absorption was determined to be approximately 0.7%.
Executive summary:

The in vitro absorption and distribution of Cereclor S52, a C14-17 chlorinated paraffin (52% chlorination), through human epidermis has been determined using 14C-labelled test material in a static cell system with a stirred solubilising receptor phase. The distribution of radiolabel within the test system (skin wash, donor chamber, stratum corneum and residual epidermal tissue) following 24 h exposure to an unoccluded 10 μl/cm² dose and an occluded 100 μl/cm² dose was determined. This study was performed according to OECD guidelines 428, and to GLP.

The mean overall recovery of the (unoccluded) 10 µl/cm2 dose (about 12.6 mg/cm2) was 102% of the applied dose recovered. The vast majority of the applied dose (mean 99.1%) was washed off the skin, with only a small proportion recovered from the stratum corneum (2.15%) and the remaining epidermis (0.702%). The absorption through the epidermis was very slow, with an absorption rate of 0.01 μg/cm²/h during the 24 h (unoccluded) exposure period. The amount absorbed over 24 h was therefore 0.243 μg/cm2 (0.002% of the dose).

The absorption of Cereclor S52 from a 100 μl/cm² occluded dose (about 126 mg/cm2) through human epidermis was also very slow, with an absorption rate of 0.057μg/cm²/h during the 24 h exposure period. The amount absorbed over 24 h was 1.367 μg/cm2 (0.001% of the dose).

The overall skin absorption of Cereclor S52 determined by this study (0.7%) is likely to be an overestimate, as the study was designed to measure skin penetration through human epidermis under the most conservative conditions.