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Diss Factsheets

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:
weight of evidence
Study period:
2006-04-11 to 2006-10-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: study was conducted according to OECD 428 guideline and conducted under GLP conditions
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Principles of method if other than guideline:
not applicable
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Climbazole
EC Number:
253-775-4
EC Name:
Climbazole
Cas Number:
38083-17-9
Molecular formula:
C15H17ClN2O2
IUPAC Name:
1-(4-chlorophenoxy)-1-(1H-imidazol-1-yl)-3,3-dimethylbutan-2-one
Radiolabelling:
yes

Test animals

Species:
other: not applicable
Strain:
other: not applicable
Details on test animals or test system and environmental conditions:
not applicable

Administration / exposure

Type of coverage:
open
Vehicle:
other: Shampoo matrix
Duration of exposure:
0.5 h
Doses:
2% formulation was applied which was approximately 10 mg/cm2 (or 25.4 mg/cell; 200 μg crinipan/cm2)
No. of animals per group:
not applicable
Details on study design:
not applicable
Details on in vitro test system (if applicable):
One dose was prepared to mimic a shampoo formulation containing nominal 2% (w/w) crinipan. The standard crinipan and [14C]-radiolabelled crinipan were mixed to obtain a concentration of crinipan of 19.8 mg/g with a specific activity of 300 μCi/g. Human skin samples were obtained post mortem. The skin samples were cut at a thickness setting of 400μm using an electric dermatome. The type of static glass diffusion cell used in this study has an exposed membrane area of 2.54 cm2 and a volume of approximately 4.5 mL. Discs of approximately 3.3 cm diameter of prepared skin membrane were mounted. Diffusion cells containing intact skin membranes were selected to give 12 diffusion cells (plus 2 controls) from 4 subjects with 3 replicate samples per subject. The dose was applied as a nominal 2% formulation to the skin at a rate of 10 mg/cm2 (actual mean amount applied = 19.8 mg crinipan/g formulation; 198 μg crinipan/cm2). After 0.5 h of contact, a sample of receptor fluid was taken and fresh receptor fluid was added to replace the volume removed. The cells were returned to the water bath and sampling continued at recorded intervals throughout the exposure period (1, 2, 4, 6 & 24 h). To assess penetration through human stratum corneum, successively deeper layers of the stratum corneum were removed by the repeated application of adhesive tape to a maximum of 5 strips. All samples were analysed by LSC.

Results and discussion

Absorption in different matrices:
There was no penetration of crinipan through human skin during the 0.5 h contact period from the 2% shampoo formulation into the receptor fluid. Almost all the applied dose was washed off at 0.5 h (96.9%). A very small proportion of the dose, which had either penetrated into the stratum corneum and epidermis or was not washed off at 0.5 h, penetrated very slowly over the entire 24 h sampling period to give a penetration rate of 0.003 μg/cm²/h. There was a lag phase of approximately 4 h and the fastest rate of penetration was achieved between 6 and 24 h giving an penetration rate of 0.004 μg/cm²/h. At the end of the 24 h sampling period <1% of the applied dose was found in the final wash and <0.2% recovered in the stratum corneum (0.075%) and epidermis (0.109%). The total amount that penetrated over 24 h was 0.041% (0.081μg/cm²).
Total recovery:
At the end of the 24 h sampling period <1% of the applied dose was found in the final wash and <0.2% recovered in the stratum corneum (0.075%) and epidermis (0.109%). Approx. total 98% of the applied dose for was recovered.
Percutaneous absorption
Dose:
2% formulation
Parameter:
percentage
Absorption:
0 - 0.041 %
Remarks on result:
other: 0.5 - 24 h
Remarks:
Percentage penitration
Conversion factor human vs. animal skin:
no data

Any other information on results incl. tables

Penetration rate (0 -24 h) 0.003 µg/cm2/h.

Applicant's summary and conclusion

Conclusions:
The amount of crinipan systematically available from a standard shampoo formulation containg 2% was found to be 0.297 µg/cm2 (0.15%) after a 30 minute exposure period and 24 hours sampling period.
Executive summary:

The penetration and distribution of crinipan from a shampoo formulation was measured in vitro through human dermatomed skin. A nominal 2% formulation was prepared and applied by weight at approximately 10 mg/cm2 (or 25.4 mg/cell; 200 μg crinipan/cm2) for an exposure period of 0.5 h and then washed off with a mild soap solution. Samples of receptor fluid were taken at recorded intervals up to 24 h and the skin was unoccluded throughout. This application was designed to simulate potential human dermal exposure to the formulation during normal use. The penetration of crinipan was measured using [14C]crinipan, which was incorporated with the crinipan standard material, prior to mixing with the shampoo formulation, to give a specific activity of approximately 10 MBq/g. The distribution of crinipan within the test system and a 24 h penetration profile were determined. The samples were analysed by LSC.

There was no penetration of crinipan through human skin during the 0.5 h contact period from the 2% shampoo formulation into the receptor fluid. Almost all the applied dose was washed off at 0.5 h (96.9%). A very small proportion of the dose, which had either penetrated into the stratum corneum and epidermis or was not washed off at 0.5 h, penetrated very slowly over the entire 24 h sampling period to give a penetration rate of 0.003 μg/cm2/h. There was a lag phase of approximately 4 h and the fastest rate of penetration was achieved between 6 and 24 h giving an penetration rate of 0.004 μg/cm2/h. At the end of the 24 h sampling period <1% of the applied dose was found in the final wash and <0.2% recovered in the stratum corneum (0.075%) and epidermis (0.109%). The total amount that penetrated into the receptor fluide over 24 h was 0.041% (0.081μg/cm2).

The total amount that penetrated into the receptor fluid over 24 h was 0.041% (0.081μg/cm2).

The amount of crinipan systematically available from a standard shampoo formulation containg 2% was found to be 0.297 µg/cm2 (0.15%).