Propane-1,2-diol

Dermal absorption

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other: GLP-compliant guideline study, available as both the original unpublished report and also the journal publication.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

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2009

Reference 2

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

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. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Propane-1,2-diol

EC Number:

200-338-0

EC Name:

Propane-1,2-diol

Cas Number:

57-55-6

Molecular formula:

C3H8O2

IUPAC Name:

propane-1,2-diol

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