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: Standard Guideline GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Description: Sample is a white solid at room temperature, Clear colourless liquid at 37°C
Batch: CEC-200803388-4
Purity: 98.4% - Determined under GLP conditions by Impact Analytical, report number R09-0013
Test substance storage: In freezer (5 -15°C) in the dark under nitrogen
Stability under storage conditions: Stable
Expiry date: 03 September 2010

Radiolabelling:
yes

Test animals

Species:
human
Strain:
not specified
Sex:
female

Administration / exposure

Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: Biopredic International, Rennes, France
- Type of skin: human
- Thickness of skin (in mm): 420 to 500 micrometers
- Membrane integrity check:
Skin membranes were thawed, mounted in the diffusion cell and the skin integrity was tested by permeation of tritiated water. 200 pL saline containing tritiated water (3.7 kBq) was applied to the donor chamber of the flow-through cells. The receptor fluid consisted of saline and was collected every hour up to 3 hours after application. At the end of the experiment, the tritiated water remainina at the donor chamber was removed with a pipet and the skin was dried with two cotton swarbs (Etos BV, Beverwijk, The Netherlands). The receptor fluid samples were analyzed bv LSC. Only the results from the skin membranes with a Kp < 4.5 x 10 -3 cm/h are reported.


Results and discussion

Percutaneous absorptionopen allclose all
Dose:
0.5%
Parameter:
percentage
Absorption:
ca. 51.4 %
Remarks on result:
other: 24 hours
Remarks:
SD (+/-) 8.9
Dose:
10%
Parameter:
percentage
Absorption:
ca. 20.6 %
Remarks on result:
other: 24 hours
Remarks:
SD (+/-) 10.3

Any other information on results incl. tables

The Skin integrity tests indicated that all skin samples were acceptable for the study.

In the main study, a lag time of 2- 4 hours was observed prior to radoilable being detected in the receptor fluid for th 0.5% test concentration. This lag phase was 3 hours for the 10% test concentration. The percentage of test material penetrating the skin (absorbed) was greater at the lower test concentration of 0.5%, with approxiately 50% of the applied dose being absorbed, compared to approximately 20% absorbed at the 10% test concentration. The actual values are givi the summary table below.

The Flux (amount of compound penetrating per cm2 per hour) was almost 10 times greater at 10% test concentration compared to the 0.5% concentration.

Dose

Recovery data (%) +/- SD

Lag time (h)

Flux (mg/cm2/h)

Absorbed

Not-Absorbed

Total recovery

0.5%

51.4 +/- 8.9

47.0 +/-6.0

98.5 +/- 7.9

2-4

1.22 +/- 0.33

10%

20.6 +/- 10.3

85.2 +/- 16.8

105.8 +/- 8.7

2

11.3 +/- 6.4

Applicant's summary and conclusion

Conclusions:
3-amino-4-octanol is capable at penetrating the skin at concentrations of 0.5 and 10%, which are representative of the concentrations in metal working fluids.