2-Thiazolamine, 4-(2-naphthalenyl)-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 03 July 2012 and 06 July 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Justification for type of information:

Data obtained as part of a data packaged from a third party. The registrant had no involvement in the decision making to carry out this test.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

4-(naphthalen-2-yl)-1,3-thiazol-2-amine

EC Number:

606-740-6

Cas Number:

21331-43-1

Molecular formula:

C13H10N2S

IUPAC Name:

4-(naphthalen-2-yl)-1,3-thiazol-2-amine

Test material form:

solid: particulate/powder

Details on test material:

Sponsor's identification : 4-(2-naphthalenyl)-2-thiazolamine
Description : Off white powder
Purity : 98.8%
Batch number : 107 (ex Pentagon)
Date received : 08 May 2012
Expiry date : Not supplied
Storage conditions : Room temperature in the dark

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Two New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd., Leicestershire, UK. At the start of the study the animals weighed 2.51 or 2.62 kg and were twelve to twenty weeks old. After an acclimatisation period of at least five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.
The animals were individually housed in suspended cages. Free access to mains drinking water and food (2930C Teklad Global Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 17 to 23°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

other: test material was moistened with 0.5 ml of distilled water.

Controls:

no

Amount / concentration applied:

0.5 g of the test item, moistened sufficiently with 0.5 ml of distilled water to achieve a paste

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

2

Details on study design:

On the day before the test each of a group of two rabbits was clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.
On the day of the test a suitable test site was selected on the back of each rabbit. At each test site a quantity of 0.5 g of the test item, moistened sufficiently with 0.5 ml of distilled water to achieve a paste, was introduced under a 2.5 cm x 2.5 cm cotton gauze patch. The patch was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period.
Four hours after application the corset and patches were removed from each animal and any residual test item removed by gentle swabbing with cotton wool soaked in distilled water.
Immediately following removal of the patches and approximately 1, 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the following scale:
EVALUATION OF SKIN REACTIONS
Erythema and Eschar Formation Value
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef redness) to eschar formation preventing grading of erythema 4
Oedema Formation Value
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) 4
Any other skin reactions and clinical signs of toxicity, if present, were also recorded.
Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

other: Erythema/Eschar Formation

Basis:

animal: 72168 Male

Time point:

other: Highest score at 0, 1, 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No evidence of skin irritation

Results 2

Irritation parameter:

other: Erythema/Eschar Formation

Basis:

animal: 72177 MAle

Time point:

other: Highest score at 0, 1, 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No evidence of skin irritation

Results 3

Irritation parameter:

other: Oedema Formation

Basis:

animal: 72168 Male

Time point:

other: Highest score at 0, 1, 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No evidence of skin irritation

Results 4

Irritation parameter:

other: Oedema Formation

Basis:

animal: 72177 Male

Time point:

other: Highest score at 0, 1, 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No evidence of skin irritation

Irritant / corrosive response data:

The individual scores for erythema/eschar and oedema are given in Table 1.
No evidence of skin irritation was noted during the study.

Other effects:

Individual bodyweights and bodyweight changes are given in Table 2.
Both animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

Interpretation of Results

Calculation of Primary Irritation Index and Grading of Irritancy Potential Using the Draize Scheme

The scores for erythema and oedema at the 24 and 72‑Hour readings were totalled for the two test rabbits (8 values) and this total was divided by four to give the primary irritation index of the test item. The test item was classified according to the following scheme devised by Draize J H (1959) "Dermal Toxicity" In: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Association of Food and Drug Officials of the,,, p.46‑59:

Primary Irritation Index	Classification of Irritancy
0	Non-irritant
> 0 to 2	Mild irritant
> 2 to 5	Moderate irritant
> 5 to 8	Severe irritant

If irreversible alteration of the dermal tissue is noted in any rabbit, as judged by the Study Director, which include ulceration and clear necrosis or signs of scar tissue, the test item is classified as corrosive to rabbit skin. Classification according to Draize may, therefore, not be applicable.

The results were evaluated according to EU labelling regulations Commission Directive 2001/59/EC for classification and labelling of dangerous substances and Regulation (EC) No 1272/2008, relating to the Classification, Packaging and Labelling of Dangerous Substances.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: Draize classification scheme

Conclusions:

The test item produced a primary irritation index of 0.0 and was classified as non irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.
The test item did not meet the criteria for classification as irritant or corrosive according to the EU labelling regulations Commission Directive 2001/59/EC or the criteria for classification according to Regulation (EC) No 1272/2008, relating to the Classification, Packaging and Labelling of Dangerous Substances.

Executive summary:

Introduction. The study was performed to assess the irritancy potential of the test item to the skin of the New Zealand White rabbit. The method was designed to be compatible with the following:

OECD Guidelines for the Testing of Chemicals No, 404 "Acute Dermal Irritation/Corrosion" (adopted 24 April 2002)

Method B4 Acute Toxicity (Skin Irritation) of Commission Regulation (EC) No. 440/2008

Results. A single 4-Hour, semi-occluded application of the test item to the intact skin of two rabbits produced no evidence of skin irritation.

Conclusion. The test item produced a primary irritation index of0.0and was classified as non‑irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test item did not meet the criteria for classification as irritant or corrosive according to the EU labelling regulations Commission Directive 2001/59/EC or the criteria for classification according to Regulation (EC) No 1272/2008, relating to the Classification, Packaging and Labelling of Dangerous Substances.