Registration Dossier

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
01 December 2011 - 31 July 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
other: human
Details on test animals and environmental conditions:
N/A

Administration / exposure

Type of coverage:
open
Vehicle:
unchanged (no vehicle)
Duration of exposure:
8 hours
Doses:
- Actual doses: 100 mg
No. of animals per group:
1
Control animals:
no
Details on study design:
TEST SITE
- Coverage: 0.64 cm2
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: abdominal human skin (from autopsy or surgery)
- Ethical approval if human skin: not specified
- Preparative technique:
Full thickness abdominal human skin (from autopsy or surgery) was obtained from the National Disease Research Interchange (NDRI), Philadelphia, Pennsylvania. The whole skin was stored frozen at -85 °C. Before starting the experiments, the skin was placed in a Petri dish containing a buffer solution at room temperature. The subcutaneous fat was removed with blunt forceps, and the skin was cleaned with a buffer solution and placed on a dissecting board. Circular pieces of skin sections (0.64 cm2) were prepared from the skin with the help of a metallic Arch Punch (18 mm; Osborne and Company). The epidermis was teased from dermis as described by Frasch et al. 2011. The skin discs were wrapped in Saran® Wrap and submerged in a 60°C buffer for approximately 70 seconds. The skin was unwrapped and placed in a Petri dish containing a buffered solution. The dermis of the skin discs was teased from the epidermis carefully using blunt forceps or cotton swabs under a binocular microscope. Care was taken not to damage the skin. During epidermal membrane separation, a thin layer of stratum corneum was easily separated from the skin. The epidermal membranes remaining were used for testing. The epidermal membranes were evaluated under a dissection microscope to ensure that they were free of any damage. The epidermal membranes (without stratum corneum) were placed on wax paper moistened with a buffered solution and frozen (-30°C) prior to experimental use.

Results and discussion

Percutaneous absorption
Key result
Time point:
8 h
Dose:
100 mg
Parameter:
rate
Absorption:
ca. 0.002 %

Applicant's summary and conclusion

Conclusions:
The analysis of the absorbed chemical in the receptor fluid data showed that steady state fluxes to an infinite dose (100 milligrams (mg)) of neat DNAN was 1.1 μg/cm2 /hr.

The cumulative dermal absorption of DNAN over 8 hours was 12.5 μg/cm2