Registration Dossier

Administrative data

Endpoint:
skin irritation / corrosion
Remarks:
in vitro
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 November 2013 - 2 November 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test method according to OECD Guideline 430. GLP study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 430 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test Method (TER))
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.40 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER))
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): [1-(3-Methoxy-phenyl)-ethyl]-methyl-amine Hydrobromide.
- Physical state: white powder
- Analytical purity: 100.2% (Potentiometric assay)
- Batch number: I13015A

Test animals

Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
SOURCE OF THE BIOLOGICAL MATERIAL:
TEST ANIMALS:
- Source: Centre for Experimental Medicine at the Medical University in Katowice
- Age at study initiation: 29 days old (hair follicles in dormant phase)
- Housing: Plastic cage covered with a wire bar lid. Dimensions: 58 x 37 x 21 cm. Bedding: UV-sterilized wood shavings.
- Diet (e.g. ad libitum): ad libitum, "Murigran” standard granulated laboratory fodder
- Water (e.g. ad libitum): ad libitum, tap water
- Acclimation period: 2 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20ºC
- Humidity (%): 49-52%
- Air changes (per hr): about 16 times/hour
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Test system

Type of coverage:
other: Not applicable: in-vitro test
Preparation of test site:
other: Not applicable: in-vitro test
Vehicle:
water
Controls:
yes, concurrent vehicle
Amount / concentration applied:
VEHICLE
- Amount(s) applied (volume or weight with unit): 150 ul of distilled water
Duration of treatment / exposure:
24 hours
Number of animals:
2

Results and discussion

In vivo

Irritant / corrosive response data:
On the grounds of the study, it may be stated that the test ite belongs to a group of substances which do not lead to skin corrosion/severe irritation. The mean TER values for the test item were higher than 5 kΩ and there were not any visible changes on the skin discs

Any other information on results incl. tables

Results of the control transcutaneous electrical resistance test (TER):

Animal number

Skin disc number

TER value (kΩ)

1

1

17.28

2

18.79

2

1

14.91

2

15.07

The skin discs gave the resistance values greater than 10 kΩ; therefore, the remainder of the skin discs of the animals could have been used in the experiment.

Results of the transcutaneous electrical resistance test (TER):

Animal number

Tested substance

Skin disc number

TER value (kΩ)

Mean TER value ± SD (kΩ)

1

Positive control –

36% HCl

1

0.88

0.88 ± 0.02

2

0.87

3

0.90

Negative control – distilled water

1

17.03

16.35 ± 0.51

 

2

15.29

3

16.74

Test item

1

5.72

6.18 ± 0.51

 

2

6.08

3

6.73

2

Positive control –

36% HCl

1

0.92

0.90 ± 0.02

2

0.88

3

0.90

Negative control – distilled water

1

17.17

17.68 ± 1.11

 

2

16.92

3

18.95

Test item

1

6.75

6.65 ± 0.52

 

2

6.08

3

7.11

The concurrent mean values for the positive and negative controls were within the acceptable ranges for the method:

Positive control: 0.5-1.0 kΩ

Negative control: 10 -25 kΩ

The mean TER results for the skin discs treated with the test item were equal to 6.18 kΩ (animal no. 1) and 6.65 kΩ (animal no. 2).

Gross changes on the surface of the treated skin discs:

Animal number

Tested substance

Skin disc number

Gross changes

1

Positive control –

36% HCl

1

perforation

2

perforation

3

perforation

Negative control – distilled water

1

no changes

2

no changes

3

no changes

Test item

1

no changes

2

no changes

3

no changes

2

Positive control –

36% HCl

1

perforation

2

perforation

3

perforation

Negative control – distilled water

1

no changes

2

no changes

3

no changes

Test item

1

no changes

2

no changes

3

no changes

The gross examination showed that the positive control skin discs exhibited skin perforation, whereas the negative control skin discs and the ones treated with the test item did not reveal any changes.

Applicant's summary and conclusion

Interpretation of results:
other: non-corrosive
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The substance do not lead to skin corrosion/severe irritation. The mean TER values for the test item were higher than 5 kΩ and there were not any visible changes on the skin discs.
Executive summary:

The in vitro skin corrosion: transcutaneous electrical resistance test (TER) was performed according to OECD Guideline 430 Guideline and EU Method B.40. (GLP study). Skin discs used in the experiment were obtained from two 29-day-old rats. The test item (ground to a powder) was uniformly applied to the epidermal surface of the skin disc placed inside a tube. Positive (36% hydrochloric acid) and negative (distilled water) controls were conducted concurrently. Three skin discs obtained from each animal were used for the test item and three for each control item. The test item and the control items were evenly applied to the discs for 24 hours and kept at 21-22°C. Then, they were removed by washing with a jet of tap water and the surface tension of the skin was reduced by adding 70% ethanol. After removing the ethanol the tissue was hydrated by the addition of 3 mL of a solution of MgSO4 (154 mM). A LCR 6401 low-voltage, alternating current databridge was used to measure the electrical resistance of the skin in kΩ by placing the databridge electrodes on either side of the skin disc. The skin discs were subjected to a gross examination. The mean TER results were equal to 6.18 kΩ (animal no. 1) and 6.65 kΩ (animal no. 2). The concurrent positive and negative control values fell within the acceptable ranges for the method. Gross examinations of the skin discs did not reveal any pathological changes. On the grounds of the study, it may be stated that the test item do not lead to skin corrosion/severe irritation. The mean TER values for the test item were higher than 5 kΩ and there were not any visible changes on the skin discs.