Registration Dossier

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Deviations:
no
Remarks:
The study was conducted according to the guideline in effect at the time of study conduct.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Purity: 86%
Radiolabelling:
no

Test animals

Species:
other: in vitro human and rat skin

Results and discussion

Percutaneous absorption
Remarks on result:
other: Based on the aqueous concentration of the applied test material (124 mg/mL) and steady-state penetration results, the Kp for human and rat skin was calculated to be 5.0E-5 ± 4.3E-5 cm/h and 5.7E-4 ± 4.3E-5 cm/h, respectively.

Any other information on results incl. tables

Following application of an infinite dose of an aqueous dilution of the test substance to dermatomed human and rat skin, the skin barrier properties had degraded by approximately 50% (independent of species) over the 24 hour contact time. Lag time was 1.73 ± 1.01 hours and 0.82 ± 0.77 hours for human and rat skin, respectively. Steady-state penetration was 6.2 ± 5.3 μg/cm²/h and 70 ± 5.3 μg/cm²/h for human and rat skin, respectively. Based on the aqueous concentration of the applied test material (124 mg/mL) and steady-state penetration results, the Kp for human and rat skin was calculated to be 5.0E-5 ± 4.3E-5 cm/h and 5.7E-4 ± 4.3E-5 cm/h, respectively. Based on the aqueous concentration of the applied test material (124 mg/mL) and steady-state penetration results, the Kp for human and rat skin was calculated to be 5.0E-5 ± 4.3E-5 cm/h and 5.7E-4 ± 4.3E-5 cm/h, respectively.

Applicant's summary and conclusion

Conclusions:
Based on the aqueous concentration of the applied test material (124 mg/mL) and steady-state penetration results, the Kp for human and rat skin was calculated to be 5.0E-5 ± 4.3E-5 cm/h and 5.7E-4 ± 4.3E-5 cm/h, respectively.
Executive summary:

The permeability coefficient (Kp) was determined using human and rat skin mounted onto an in vitro static diffusion cell. The donor and receptor chambers were filled with saline and the water-jacketed cells maintained at 32ºC using a re-circulating water bath. Following a brief equilibration, membrane integrity was confirmed using electrical impedance (n=3 replicates per species). Saline was then removed from the donor chamber and the test material, a 86% aqueous solution, which had been further diluted with water to a concentration of 124 mg/mL, was applied to the epidermal surface via the donor chamber as an infinite dose (pilot experiments had suggested application of the neat test substance would likely degrade the barrier properties of the skin, so a more dilute sample was used). The donor chamber was then occluded with Parafilm® and serial receptor fluid samples (100 μL) were collected at 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 12 and 24 hours and analyzed for test substance anion by LC/MS/MRM (329>285 m/z). The cumulative amount of anion detected in the receptor fluid at each sampling time point was normalized to the exposure area (0.64 cm²) and the results plotted as the cumulative amount penetrated (μg/cm²) versus time (in hours) to produce a penetration profile. A permeability coefficient (Kp in cm/h) was calculated by dividing the penetration rate or slope of the line at steady-state (μg/cm²/h) by the concentration of the applied chemical (μg/cm³).

Following application of an infinite dose of an aqueous dilution of test substance to dermatomed human and rat skin, the skin barrier properties had degraded by approximately 50% (independent of species) over the 24 hour contact time. Lag time was 1.73 ± 1.01 hours and 0.82 ± 0.77 hours for human and rat skin, respectively. Steady-state penetration was 6.2 ± 5.3 μg/cm²/h and 70 ± 5.3 μg/cm²/h for human and rat skin, respectively.

Based on the aqueous concentration of the applied test material (124 mg/mL) and steady-state penetration results, the Kp for human and rat skin was calculated to be 5.0E-5 ± 4.3E-5 cm/h and 5.7E-4 ± 4.3E-5 cm/h, respectively.