Propane-1,3-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:

guideline study

Remarks:

PDO from biological process.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: OECD Guidance Document for the Conduct of Skin Absorption Studies. OECD Environmental Health and Safety Publication Series on Testing and Assessment No. 28. (2004)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: European Commission Guidance Document on Dermal Absorption. Sanco/222/2000 rev 7 (2004)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Propane-1,3-diol

EC Number:

207-997-3

EC Name:

Propane-1,3-diol

Cas Number:

504-63-2

Molecular formula:

C3H8O2

IUPAC Name:

propane-1,3-diol

Details on test material:

- Purity: 99.953%

Radiolabelling:

no

Test animals

Species:

other: in vitro (human skin)

Details on test animals or test system and environmental conditions:

Samples of human cadaver skin obtained from the abdominal region were obtained from the National Disease Research Interchange (NDRI, Philadelphia, PA), and were stored frozen at approximately -20°C until prepared for use. Samples were collected from donors within 24 hours of death.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

not specified

Duration of exposure:

Exposure was terminated following steady-state determination.

Doses:

Dose volume: 1200 μL/cm2
Density: 1,059,700 ug/cm3

No. of animals per group:

6 representing 3 donors

Details on study design:

SKIN PREPARATION
- Preparative technique: Full thickness skin was immersed in 60°C water for 45 seconds to 2 minutes and the epidermis peeled away from the dermis.
- Membrane integrity check: Skin integrity was confirmed by electrical impedance following system equilibration.
- Storage conditions: Samples were stored frozen at approximately -20°C until prepared for use.

PRINCIPLES OF ASSAY
- Diffusion cell: The in vitro cells had an exposure area of 0.64 cm2, and a receptor fluid chamber volume of approximately 5 ml, which was continuously stirred throughout the exposure interval using a magnetic stir bar.
- Receptor fluid: 0.9% saline
- Static system: Static diffuse cell model with an exposure area of 0.64 cm square.
- Test temperature: Receptor fluid temperature of 32°C.
- Occlusion: Following dose application, the donor chamber opening was occluded with Parafilm®. The receptor chamber arm remained occluded with Parafilm® at all times other than at sampling.
- Sampling and analysis: Serial receptor fluid samples were taken at 0, 4, 8, 12, 18, 24, 30, 36, 42 and 48 hours post-application and analyzed by GC/FID.

Steady state penetration was determined by plotting the cumulative amount of test substance detected in the receptor fluid at each sampling point, adjusted for total receptor fluid volume, against time to produce an absorption profile. Kp was calculated by dividing the penetration rate or slope of the line at steady-state represented by at least 4 data points, by the concentration of applied chemical.

Results and discussion

Total recovery:

At the end of the 48 hour exposure interval, 0.12% of the applied chemical was detected in the receptor chamber.

Any other information on results incl. tables

The test substance was detected in the receptor fluid at the 4 hour serial sampling timepoint (74.6 μg/cm²). The final receptor fluid sample (48 hour) was 1481.5 μg/cm².

Steady state penetration of the test substance, which was represented by a minimum of 4 data points, had a slope of 15.9 μg/cm2/h.

At the end of the 48-hour period exposure interval, 0.12% of the applied test substance was detected in the receptor chamber demonstrating that the static diffusion cell receptor fluid (0.9% saline) offered sink conditions to the test substance.

The permeability coefficient was calculated to be 1.50e-5 cm/h, based on the slope at steady state (15.9 μg/cm2/h) and the concentration of the test substance in the applied formulation taken as its density (1,059,700 μg/cm3).

Applicant's summary and conclusion

Conclusions:

The permeability coefficient was calculated to be 1.50e-5 cm per hour based on the slope at the steady-state (15.9 µg/cm square per hour) and the concentration of applied dose of test substance taken as its density (1,059,700 µg/cm3).

Executive summary:

The permeability coefficient (Kp) was determined using human abdominal skin from cadavers mounted in an in vitro static diffusion cell model. Human cadaver skin was heat treated at approximately 60°C and the epidermis was peeled from the dermis and the section mounted onto an in vitro diffusion cell, stratum corneum uppermost, with an exposure area of 0.64 cm2. Using a recirculating water bath system, the receptor fluid (0.9 % saline) was set at 32°C. Following system equilibration, skin integrity was confirmed by electrical impedance. The saline in the donor and receptor chambers was removed and discarded and the receptor chamber was filled with fresh 0.9% saline.

 

An infinite dose of the test substance was applied to the epidermal surface, via the donor chamber, at a target range of 1200 µL/cm2, to 6 skin replicates representing 3 human subjects, and the donor chamber opening was occluded with a Parafilm®. Serial receptor fluid samples were taken at 0, 4, 8, 12, 18, 24, 30, 36, 42, and 48 hours post-application and analyzed by GC/FID.

 

Based on the slope at steady-state (15.9 µg/cm2/h) and the concentration of the applied dose of the test substance taken as its density (1,059,700 µg/cm3), the permeability coefficient was calculated to be 1.50x10e-5 cm/h.