Sodium 6-amino-5-[[4-chloro-3-[[(2,4-dimethylphenyl)amino]sulphonyl]phenyl]azo]-4-hydroxynaphthalene-2-sulphonate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation / corrosion, other

Remarks:

in vivo

Type of information:

other: read across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

June from 9th to 16th, 1993

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:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

similar substance 1, AR336

IUPAC Name:

similar substance 1, AR336

Specific details on test material used for the study:

The test material was used as supplied.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: approximately 12 to 16 weeks old.
- Weight at study initiation: 2.32 - 2.36 kg.
- Housing: animals were individually housed in suspended metal cages.
- Diet: mains food RABMA Rabbit Diet, ad libitum.
- Water: mains drinking water, ad libitum.
- Acclimation period: minimum 5 days.
- Health check: on the day before the tes,t each rabbit 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.

ENVIRONMENTAL CONDITIONS
- Temperature: 18 - 23 °C
- Humidity: 58 - 74 %. On one occasion the humidity was above the limit specified in the protocol (70 %).
- Air changes: approximately 15 changes per hour.
- Photoperiod: 12 hours light and 12 hours darkness.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.5 g of the test material, moistened with 0.5 ml of distilled water

Duration of treatment / exposure:

4 hours

Number of animals:

Two males and one female

Details on study design:

TEST SITE
- Area of exposure: on the day of the test a suitable test site was selected on the back of each rabbit. The test material was introduced under a 2.5 cm x 2.5 cm gauze patch and placed in position on the shorn skin.
- Type of wrap if used: the patch was secured in position with a strip of surgical adhesive tape (approximate size 2.5 cm x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset.

REMOVAL OF TEST SUBSTANCE
- Removal: any residual test material was removed by gentle swabbing with cotton wool soaked in distilled water followed by diethyl ether.
- Time after start of exposure: 4 hours.

SCORING SYSTEM
Approximately one hour following the removal of the patches and 24,48 and 72 hours later, the test sites were examined for evidence of primary irritatin and scored according to the scale from Draize J.H. (1959) Association of Food and Drug Officials of the united states, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics".
An additional observation was made on day 7 to assess the reversibility of skin reactions.
The scores for erythema and oedema at the 24 and 72-hour readings were totalled for the three test rabbits (12 values) and this total was divided by 6 to give the primary irritation index of the test material. If irreversible alteration of the dermal tissue is noted in any rabbit, which may include ulceration and clear necrosis or signs of scar tissue, the test material is classified as corrosive to rabbit skin.

Ervthena and Eschar Formation
No erythena 0
Very stight erythena (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythena 3
Severe erythena (beet redness) to slight eschar formation (injuries in depth) 4

Oedena Formation
No oedena 1
Very slight oedena (barely perceptible) 1
Slight oedena (edges of area well-defined by definite raising) 2
Moderate oedena (raised approxinately 1 millimetre) 3
Severe oedena (raised more than 1 millimetre 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

Reversibility:

fully reversible within: 7 days

Results 2

Irritation parameter:

edema score

Basis:

animal: 3/3

Time point:

24/48/72 h

Score:

< 2.3

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

Pink-coloured staining caused by the test material was noted at all treated skin sites following patch removal. The staining did not affect evaluation of erythema.
Very slight erythema was noted at all treated skin sites one hour after patch removal. Very slight to well-defined erythema was noted at two treated skin sites at the 24 and 48-hour observations. Well-defined erythema persisted at one treated skin site at the 72-hour observation.
Very slight oedema was noted at two treated skin sites one hour after patch removal with very slight or slight oedema at 24-hour observation. Slight oedema persisted 72-hour observations.
Skin reactions noted at all treated skin sites seven days after treatment were crust formation or desquamation.

Any other information on results incl. tables

INDIVIDUAL DERMAL REACTIONS

Animal	Reaction	Time After Treatment					Mean 24/48/72 hrs
		1 hr	24 hrs	48 hrs	72 hrs	7 dy
Female n. 168	Erythema/Eschar	1 STA	2 STA	2 STA	2 STA	0CfSTA	2.00
	Oedema	1	2	2	2	0	2.00
Male n. 169	Erythema/Eschar	1 STA	1 STA	1 STA	0STA	0DSTA	0.66
	Oedema	1	1	0	0	0	0.33
Male n. 171	Erythema/Eschar	1 STA	0STA	0STA	0STA	0DSTA	0.00
	Oedema	0	0	0	0	0	0.00

STA: pink-coloured staining

Cf: crust formation

D: desquamation

Applicant's summary and conclusion

Interpretation of results:

other: not classified, according to the CLP Regulation (EC 1272/2008)

Conclusions:

Not irritating

Executive summary:

The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used that described in the OECD Guidelines 404. A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced very slight to well-defined erythema and very slight to slight oedema. Skin reactions noted at all treated skin sites seven days after treatment were crust formation and desquamation.

The test material produced a primary irritation index of 1.7 and was classified as a mild irritant to rabbit skin, according to the Draize classification scheme. No corrosive effects were noted.

Conclusion

The mean values from gradings at 24, 48 and 72 hours after patch removal were lower than 2.3 in all animals for both erythema/eschar and oedema reactions, thus the test item does not meet the criteria to be classified as irritating, according to the CLP (EC 1272/2008) Regulation.