2-aminopyridin-3-ol

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

Type of information:

experimental study

Adequacy of study:

other information

Study period:

08.09. - 12.14.2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Type of study / information:

Type: In vitro penetration

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD 428

GLP compliance:

yes

Test material

Test material information

1

Reference substance name:

2-aminopyridin-3-ol

EC Number:

240-886-8

EC Name:

2-aminopyridin-3-ol

Cas Number:

16867-03-1

Molecular formula:

C5H6N2O

IUPAC Name:

2-aminopyridin-3-ol

Applicant's summary and conclusion

Conclusions:

The systemic availability, after dermal exposure to A 132 under normal conditions from this cream formulation, in combination with a hydrogen peroxide developer, would be low.

Executive summary:

Study Design

The penetration of A 132 has been measured in vitro through dermatomed pig skin from a standard cream formulation mixed 1:1w/w with a developer containing hydrogen peroxide. The formulated material, containing 1.04% w/w A 132, was applied to the dermatomed membranes at a nominal rate of 20 mg/cm2 and left unoccluded.  The application was washed off after a 0.5 h contact period, with the penetration of A 132 through the membrane being assessed throughout the entire 48 h experiment duration.  At the end of the experiment, the distribution of A 132 in the test system was assessed, which included a tape stripping technique to determine its distribution in the skin.

The application and exposure conditions were designed to simulate potential human dermal exposure to the formulation during normal use.

The penetration and distribution of A 132 was followed using [14C]-A 132, which was incorporated into the formulation prior to dosing.  Samples collected during this study were analysed by liquid scintillation counting (LSC).

Results

The vast majority of the A 132 dose was recovered in the wash at 0.5 h (93.7%).  After 0.5 h, 0.024µg/cm² (≡0.011%) had penetrated the skin and after 48h the amount had increased to 0.638 µg/cm² (≡0.306%).  Most of the penetration occurred during the first hour, with a penetration rate of 0.161 µg/cm²/h.  After 6 hours, the penetration rate remained relatively constant at 0.006 µg/cm²/h.  The penetration rate over the 0–48h period was 0.012 µg/cm²/h.  

A small proportion of the dose was recovered from the stratum corneum (0.152%; ≡ 0.316 µg/cm²) and the dose in the remaining epidermis/dermis after tape stripping was 0.300% (≡ 0.625 µg/cm²), giving a potential systemically available dose of 0.606% (≡ 1.26 µg/cm2).

The total recovery of A 132 following this procedure was 95.0% of the applied dose.