Registration Dossier

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-compliant guideline study, minor restrictions in design, but otherwise acceptable for assessment.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007
Reference Type:
publication
Title:
Dermal penetration of propylene glycols: measured absorption across human abdominal skin in vitro and comparison with a QSAR model.
Author:
Fasano WJ, ten Berge WF, Banton MI, Heneweer M, Moore NP.
Year:
2011
Bibliographic source:
Toxicology in vitro, 25(8) 1664-70

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Dipropylene Glycol
- Molecular formula (if other than submission substance): C6H14O3
- Molecular weight (if other than submission substance): 134.1736
- Smiles notation (if other than submission substance): CCC(O)OC(O)CC
- InChl (if other than submission substance): InChI=1/C6H14O3/c1-3-5(7)9-6(8)4-2/h5-8H,3-4H2,1-2H3
- Physical state: colorless liquid
- Purity: 99.9%
- Stability: The test substance appeared to be stable under the conditions of the study; no evidence of instability was observed.
- Haskell number: 27231
Radiolabelling:
no

Test animals

Species:
other: Human cadaver skin
Strain:
other: Not applicable
Sex:
male/female

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 hours
Doses:
- Nominal dose: 1200 μL/cm2
- Dose volume: 768 μL
No. of animals per group:
7 skin replicates representing 4 human subjects
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: human cadaver skin
- Thickness of skin: 389 ± 54 μm

PRINCIPLES OF ASSAY
- Receptor fluid: deionized water
- Solubility of test substance in receptor fluid: infinitely soluble
- Test temperature: 32 ± 1 ˚C
- Occlusion: tape
- Detection of dipropylene glycol in the receptor fluid: GC-FID
Neat dipropylene glycol was applied at a rate of approximately 1200 μl/cm2 to the surface of 7 dermatomed skin replicates representing 4 donors. The concentration of the applied chemical was taken as its density (1.02 g/ml). Following application, the donor chamber opening was occluded with tape. Serial receptor fluid samples were collected hourly during the first 8 h post-application, and then every other hour until 24 h post-application.

Results and discussion

Percutaneous absorption
Dose:
1200 μL/cm2
Parameter:
percentage
Absorption:
0.1 %
Remarks on result:
other: 24 h post-application

Any other information on results incl. tables

Key observations of mean data:

The integrity of human skin, as determined by EI, was unaffected by continuous exposure to DPG under occlusive conditions. The ratio of the post-EI values to pre-EI values was 0.97 confirming that the barrier properties of the stratum corneum were unaltered by DPG.

By the conclusion of the 24-hour exposure interval, only a negligible portion of the applied dose of neat DPG (0.075%) had penetrated through the skin into the receptor fluid.

In general, DPG was detected in receptor fluid within about an hour of application (lag time = 1hour and 3 minutes; 1.05 hours); steady-state penetration, which was represented by no less than 10 data points, was determined to be 39,3 μg/cm2/h (r2 ≥0.999).

Based on the slope at steady-state (39.3 μg/cm2/h) and the concentration of DPG in the applied solution, taken as its density (1,020,000 μg/cm3), the permeability coefficient was calculated to be 3.85*10-5 cm/h

Results (Mean ± SD):

Skin Thickness:      389 ± 54 μm

Skin Damage Ratio: 0.97 ± 0.23 (unitless)

Lag Time:              1.05 ± 0.33 hours

Steady-State Penetration:       39.3 ± 10.7 μg/m2/h

Cumulative Amount Penetrated at 24 hours:       912.6 ± 219.0 μg/cm2

Cumulative percent Penetrated at 24 hours:       0.075 ± 0.018%

Permeability Coefficient (Kp) :                         3.85*10-5 ± 1.05*10-5 cm/hr

Applicant's summary and conclusion