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: Test procedure in accordance with national standard methods with acceptable restrictions

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
In vitro dermal absorption rate testing of certain chemicals of interest to the Occupational Safety and Health Administration: summary and evaluation of USEPA's mandated testing
Author:
Fasano WJ, McDougal JN.
Year:
2008
Bibliographic source:
Regul Toxicol Pharmacol., 51(2):181-94. doi: 10.1016/j.yrtph.2008.04.005
Reference Type:
other:
Title:
In Vitro Dermal Absorption Rate Testing of Certain Chemicals of Interest to the Occupational Safety and Health Administration
Author:
US Environmental Protection Agency
Year:
2004
Bibliographic source:
Federal Register, 69 FR 22402, 22402 -22441 (https://federalregister.gov/a/04-9409)
Report Date:
2004

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Federal Register, 69 FR 22402, 22402 -22441. "Test Rule; In Vitro Dermal Absorption Rate Testing of Certain Chemicals of Interest to the Occupational Safety and Health Administration"
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
yes

Test animals

Species:
human

Administration / exposure

Vehicle:
water
Duration of exposure:
10 and 60 min
Doses:
25 mg/cm² (313 µl/cm² of a 80 mg/ml solution)
No. of animals per group:
minimum of six replicates represented by at least three donors (for each of the three experimental scenarios)
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: human cadaver
- Ethical approval if human skin: no data
- Type of skin: abdominal region
- Preparative technique: either dermatomed or heat-separated epidermal membranes (HEM)
- Thickness of skin: 200-500 µm
- Membrane integrity check: electrical resistance (impedance)
- Storage conditions: frozen (-20° C) for up to 3 months
- Justification of species, anatomical site and preparative technique:

PRINCIPLES OF ASSAY
- Diffusion cell: standard in vitro diffusion cell modeI, eilher static or flow-through
- Receptor fluid: no data
- Solubility of test substance in receptor fluid: yes
- Static system:
- Flow-through system:
- Test temperature: 32°C
- Humidity:
- Occlusion:
- Reference substance(s):
- Other: Kp = steady-state rate of absorption (in µg/ hr x cm² )/ concentration of the test substance (measured in µg/cm3) applied to the skin.

Results and discussion

Dermal irritation:
no effects
Remarks:
No change in pre- and post-dose electrical impedance (El) values for Kp, 10 minute and 60 min experiments
Total recovery:
Kp study: 89.6%
10 min: 90.8%
60 min: 91.7%
Percutaneous absorptionopen allclose all
Time point:
10 min
Dose:
25 mg/cm²
Parameter:
percentage
Absorption:
ca. 0.04 %
Remarks on result:
other: skin: 0.04%; recepto fluid < 0.001%
Key result
Time point:
60 min
Dose:
25 mg/cm²
Parameter:
percentage
Absorption:
ca. 0.15 %
Remarks on result:
other: skin: 0.11%; receptor fluid: 0.04%
Key result
Time point:
24 h
Dose:
25 mg/cm²
Parameter:
percentage
Absorption:
ca. 5.71 %
Remarks on result:
other: skin: 0.7%; receptor fluid: 5.01%
Key result
Time point:
8 h
Dose:
25 mg/cm²
Parameter:
percentage
Absorption:
ca. 1 %
Remarks on result:
other: Extrapolated from the polynomial % absorption/exposure time curve y = 1E-06x² + 0,0021x + 0,0188 (R² = 1)
Parameter:
other: Kp
Remarks:
5.77e-4 cm/h
Dose:
25 mg/cm²
Parameter:
rate
Absorption:
56.6 other: µg/cm²/h
Time point:
60 min
Dose:
25 mg/cm²
Parameter:
rate
Absorption:
37.3 other: µg/cm²/h

Applicant's summary and conclusion

Executive summary:

In vitro dermal penetration rate of diacetone alcohol, as permeability coefficient (Kp) and short-term dermal absorption rates at 10 and 60 min, was determined using human cadaver skin mounted in an in vitro diffusion cell model. Total recovery, based on liquid scintillation count data for total radioactivity, was between 89.6 and 91.7% of the applied dose. Skin penetration was 0.04, 0.15 and 5.71 % of the dose after 10 min, 60 min and 24 h, respectively. Kp was 5.77e-4 cm/h. From the polynomial % absorption/exposure time curve (y = 1E-06x² + 0,0021x + 0,0188, R² = 1), a skin penetration of 1% was estimated for a 8-hour exposure.