Tetrasodium 2-[[8-[[3-[(5-chloro-2,6-difluoro-4-pyrimidinyl)amino]benzoyl]amino]-1-hydroxy-3,6-disulphonato-2-naphthyl]azo]naphthalene-1,5-disulphonate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Remarks:

source of read across

Adequacy of study:

key study

Study period:

September from 14 to 23, 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted JuIy 17,1992

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Similar Substance 01

IUPAC Name:

Similar Substance 01

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Scientifique des Dombes F-01400 Chatillon sur Chalaronne / France.
- Age at study initiation: 14 weeks old male and 15 weeks old females.
- Weight at study initiation: male ca 2.6 kg; females ca 2.7 kg.
- Housing: individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with wood and haysticks for gnawing.
- Diet: pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no.65/99).
- Water: community tap water from Füllinsdorf, ad libitum.
- Acclimation period: 5 days, under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.
- Health check: approximately four days before treatment, a flank was clipped with an electric clipper, exposing an area of approximately 100 cm2 (10 cm x 10 cm). The skin of the animals was examined approximately 24 hours before treatment and regrown fur was again clipped. The fur was again slightly clipped in two animals (Nos. 80 - 81) just prior to the application. Animals with overt signs of skin injury or marked irritation which may have interfered with the interpretation of the results were not used in the test.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Relative humidity: 40 - 70 %
- Air changes: 10-15 air changes per hour.
- Photoperiod: 12 hour light/dark cycle.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.5 g/animal (left side only).
The test article was moistened with bi-distilled water before application.

Duration of treatment / exposure:

4 hours.

Observation period:

72 hours

Number of animals:

1 male and 2 females

Details on study design:

TEST SITE
- Area of exposure: on the day of treatment test item was setted on a surgical garuze patch (ca.2.5 cm x 2.5 cm). The gauze patch was applied to approximately 6 cm2 of the intact skin of the clipped area.
- Type of wrap if used: the patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.

REMOVAL OF TEST SUBSTANCE
- Washing: the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.
- Time after start of exposure: 4 hours.

OBSERVATIONS
- Viability/Ivlortality: daily from delivery of the animals to the termination of test.
- Clinical signs: daily from delivery of the animals to the termination of test.
- Body weights: at start of acclimatization, on the day of application and at termination of observation.

OBSERVATION TIME POINTS
The skin reaction was assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressing, gauze patch and test article.

SCORING SYSTEM:
The skin reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992.
If evident, corrosive or staining properties of the test article were described and recorded.

ERYTHEMA AND ESCHAR FORMATION
No erythema 0
Very slight erythema 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) or eschar formation (injuries in depth preventing erythema reading 4

OEDEMA FORMATION
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (edges raised approximately 1 mm) 3
Severe oedema (raised more than I mm and extending beyond the area of exposure) 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: 3/3

Time point:

24/48/72 h

Score:

< 2.3

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

animal: 3/3

Time point:

24/48/72 h

Score:

< 2.3

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Application of the test article to healthy intact rabbit skin resulted in a primary irritation score of 0.00.
Local signs (mean values from 24 to 72 hours) consisted of grade 0.00 erythema and grade 0.00 oedema. No signs of irritation were observed.
Light red staining by the test article of the treated skin was observed.
No irreversible alterations of the treated skin were observed nor were corrosive effects evident on the skin.

Other effects:

VIABILITY/MORTALITY AND CLINICAL SIGNS
No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred.

BODY WEIGHTS
The body weight of all rabbits were considered to be within the normal range of variability.

Any other information on results incl. tables

Individual reactions

Animal	Reaction	1 hr	24 hrs	48 hrs	72 hrs
79 male	Erythema	0	0	0	0
	Oedema	0	0	0	0
80 female	Erythema	0	0	0	0
	Oedema	0	0	0	0
81 female	Erythema	0	0	0	0
	Oedema	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

other: not classified, according to the CLP Regulation (EC) No 1272/2008

Conclusions:

Not skin irritating

Executive summary:

The primary skin irritation potential of the test article was investigated by topical application of 0.5 g to 6 cm2 intact dorsal skin of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing. The scores of each animal at the following reading times (24, 48, 72 hours) were used in calculating the respective mean values for each type of lesion.

The primary irritation score was calculated by totaling the individual cumulative scores at 24, 48 and 72 hours and then dividing by the number of data points. The primary irritation score was 0.00 (max. 8.0).

Local signs (mean values from 24 to 72 hours) consisted of grade 0.00 erythema and grade 0.00 oedema. The test article caused light red staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any measuring interval.

Conclusion

None of the animals showed any observable response to treatment throughout the 72 hours observation period, thus it can be concluded that the test item does not meet the criteria to be classified as irritating, according to the CLP Regulation (EC) No 1272/2008.