Registration Dossier

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-compliant guideline study, available as both the original unpublished report and also the journal publication. Mminor restrictions in design, but otherwise acceptable for assessment.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2009
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)
Deviations:
yes
Remarks:
The applied dose exceeds the limit established by the guideline
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): monopropylene glycol
- Physical state: colorless liquid
- Purity: 99.5%
- Stability: The test substance appeared to be stable under the conditions of the study; no evidence of instability was observed.
- Haskell number: 28464
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:
6 skin replicates representing 5 human subjects
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: human cadaver skin
- Thickness of skin: 397.5 ± 58.6 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 monopropylene glycol in the receptor fluid: GC-FID
Neat monopropylene glycol was applied at a rate of approximately 1200 μl/cm2 to the surface of 6 dermatomed skin replicates representing 5 donors. The concentration of the applied chemical was taken as its density (1.036 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 affected by continuous exposure to monopropyelene glycol under occlusive conditions. The ratio of the post-EI values to pre-EI values was 0.33 confirming that the barrier properties of the stratum corneum were altered bij monopropylene glycol.

By the conclusion of the 24-hour exposure interval, only a negligible portion of the applied dose of neat monopropylene glycol (0.14%) had penetrated through the skin into the receptor fluid.

In general, monopropylene glycol 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 (95.4 μg/cm2/h) and the concentration of monopropylene glycol in the applied solution, taken as its density (1,036,000μg/cm3), the permeability coefficient was calculated to be 9.21×10-5cm/h.

Results (Mean ± SD):

Skin Thickness:      397.5 ± 58.6 μm

Skin Damage Ratio: 0.33 ± 0.10 (unitless)

Lag Time:              6.64 ± 4.58 hours

Steady-State Penetration:       95.4 ± 71.8 μg/m2/h

Cumulative Amount Penetrated at 24 hours:       1775.8 ± 1391.7 μg/cm2

Cumulative percent Penetrated at 24 hours:       0.14 ± 0.11%

Permeability Coefficient (Kp) :                         9.21 ×10-5 ± 6.93 × 10-5 cm/hr

Applicant's summary and conclusion