Registration Dossier

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Good-quality study; considered adequate for assessment

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985
Reference Type:
publication
Title:
Unnamed
Year:
1989
Reference Type:
secondary source
Title:
Unnamed
Year:
2000

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
To assess the in vitro rate of absorption of Cereclor 56L (a C10-13 chlorinated paraffin; 56% chlorination) through human 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): Cereclor 56L
- Substance type: technical product
- Physical state: liquid
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: C10-13 chlorinated paraffin (56% chlorination)
- Purity test date: no data
- Radiochemical purity (if radiolabelling): no data
- Specific activity (if radiolabelling): 0.4 mCi/mg
- Locations of the label (if radiolabelling): 14C-labelled n-undecane, chlorinated to 58%
- Expiration date of radiochemical substance (if radiolabelling): no data
Radiolabelling:
yes

Test animals

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

Administration / exposure

Type of coverage:
other: in vitro
Vehicle:
other: Cutting oil (100 spindle oil; poly-X H50)
Duration of exposure:
up to 54 hours
Doses:
Application of an 18.5% w/w solution at a dose level of 400 µl or 158 µl/cm2, equivalent to 74 mg or 29.1 mg/cm2
No. of animals per group:
12 skin samples were used
Control animals:
no
Details on study design:
Not applicable
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: human abdomen
- Ethical approval if human skin: no data
- Type of skin: epidermal membranes
- Preparative technique: hot water
- Thickness of skin (in mm): no data
- Membrane integrity check: no data
- Storage conditions: no data

PRINCIPLES OF ASSAY
- Diffusion cell: glass
- Receptor fluid: (i) 6% VOLPO 20 in saline; (ii) 2000 ppm Marlowett in saline
- Solubility of test substance in receptor fluid: favourable solubility properties for lipophilic molecules
- Static system: yes- continually stirred
- Flow-through system: no
- Test temperature: 30 ± 1oC
- Humidity: no data
- Occlusion: no data
- Reference substance(s): no

Results and discussion

Signs and symptoms of toxicity:
not examined
Dermal irritation:
not examined
Absorption in different matrices:
mean absorption rate in to VOLPO 20 in saline: 38.73 ± 5.79 cpm/cm2/h; 0.05 ± 0.01 µg/cm2/h
mean absorption rate in to Marlowett in saline: 26.39 ± 1.74 cpm/cm2/h; 0.03 ± 0.002 µg/cm2/h
overall mean absorption rate: 0.04 ± 0.004 µg/cm2/h
Total recovery:
no data
Percutaneous absorption
Dose:
29.1 mg/cm2
Parameter:
percentage
Absorption:
< 0.01 %
Remarks on result:
other: 54 h
Conversion factor human vs. animal skin:
not applicable

Any other information on results incl. tables

The absorption of radioactivity through the epidermal membranes during the first 7 h continuous skin contact could not be quantified. An apparent steady state absorption was achieved during the time period 23-54 h and the rate of absorption during this time was calculated to be approx. 0.00014% of the applied dose/cm2/h. The overall mean calculated permeability constant was 0.87 x 10-5 ± 0.09 x 10-5 cm/h, indicating that Cereclor 56L was absorbed very slowly.

Applicant's summary and conclusion

Conclusions:
The absorption rate of Cereclor 56L, a C10-13 chlorinated paraffin (56% chlorinated), through human epidermal membrane in vitro, assessed using the 14C-labelled analogue, chlorinated n-undecane (58% chlorinated) as a marker, was approximatley 0.04 µg/cm2/h. Thus, less than 0.01% of the applied dose was absorbed during the 54 hours continuous skin contact.
Executive summary:

The absorption through human epidermal skin membranes in vitro of Cereclor 56L (a C10-13 chlorinated paraffin; 56% chlorination) was assessed. Cereclor 56L was mixed with a radiolabelled analogue (chlorinated [14C-labelled] n-undecane with 58% chlorination) to facilitate quantitation, and applied in a cutting oil as an 18.5% (w/w) solution at a dose of 158 µl/cm2 (equivalent to 29.1 mg/cm2). Absorption was determined in a static glass diffusion cell system at 30 ± 1oC using two different receptor fluids, stirred continuously and sampled at various time points over 54 hours. The receptor fluids were VOLPO 20 in saline or Marlowett in saline.

No absorption was detected over the first 7 hours, however a steady state for absorption was established during the time period 23 to 54 hours, the absortion rate being similar for both receptor fluids. The overall mean absorption rate of the chlorinated paraffin was 0.04 µg/cm2/h over this period, the overall extent of absorption was less than 0.01% of the applied dose and the overall mean permeability constant was 0.87 x 10-5 cm/h.