Reaction products of 7-amino-4-hydroxynaphthalene-2-sulfonic acid reacted with 2-((1,3,5-triazin-2-yl)amino)ethan-1-ol, coupled with diazotised 3-amino-4-hydroxybenzenesulfonic acid, subsequently coupled with diazotised 2-amino-5-methoxybenzenesulfonic acid, chelated with copper, sodium salt

Skin irritation / corrosion

Some information in this page has been claimed confidential.

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991-04- 30 to 1991-05-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

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

Test material form:

solid: particulate/powder

Details on test material:

Direct Red 83:1

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

New Zealand White rabbit (Safepharm Definitive Protocol Number TX 3076)
Source: (David percival Ltd. Moston, Sandbach, Cheshire, U.K.)
Identification: Numbering
Husbandry: Individually housed in suspended metal cages.
-free access to food to mains drinking water and food.
3 animals (only with a healthy intact epidermis were selected for the study)
2 females, 1 male
2.25 – 2.50 kg weight
approximately. 12 – 16 weeks old
Minimum acclimatisation period of 5 days
The animal room was maintained at a temperature of 17 -21°C and relative humidity of 48-58%.
The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give 12 hours light and 12 hours darkness.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Remarks:

On the day of the test rabbits were clipped free of fur from the dorsal/flank area suitable test site selected on the back of each rabbit.

Vehicle:

water

Remarks:

0.5 mL distilled water to form a paste

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.5g of the test material, moistened with 0.5 mL of distilled water, Introduced under a 2.5 cm x 2.5 cm gauze

Duration of treatment / exposure:

4 hours

Observation period:

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 irritation and scored according to the Draize scale J.H. (1959) Association of food and Drug Officials of the United States, Austin, Texas, 'The Appraisal of the Safety of Chemicals 1n Foods, Drugs and Cosmetics".

Reversibility of skin reactions were additionally examined on day 7

Number of animals:

3 animals (only with a healthy intact epidermis were selected for the study)
2 females, 1 male
2.25 – 2.50 kg weight
Approximately. 12 – 16 weeks old

Details on study design:

TEST SITE
0.5g of the test material, moistened with
0.5 mL of distilled water, Introduced under a 2.5 cm x 2.5 cm gauze
patch and placed in position on shorn skin. The patch was secured
in position with a strip of surgical adhesive tape {BLENDERH: 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 (TUBIGRIP)

REMOVAL OF TEST SUBSTANCE

4 hours after application the corset and patches were removed from each animal and
any residual test material removed by gentle swabbing with cotton wool soaked in distilled water followed by diethyl ether.


SCORING SYSTEM: Draize scale

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

female N0 154 (mean score 0.0)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

Male No 155 (mean score 1.0)

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

Female N0 160 (mean score 0.3)

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

edema score

Basis:

animal: 1, 2, 3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Very slight erythema was seen at 2 treated skin sites at hour 24 and at one treated skin site at hour 48 and 72 of observation.
Desquamation was confined to one treated skin site at the 7 day observation.
The slight purple staining of the skin did not interfere with the evaluation of the test site.

Any other information on results incl. tables

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 (beet redness) to slight eschar formation (injuries in depth) 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  

		Individual scores – rabbit no. and sex (bodyweight kg)
Skin reaction	Observation time	154 f (2,25)	155 m (2,5)	160 f (2,37)	Total
Erythema / Eschar Formation	1 h	0 STA	0 STA	0 STA	(0)
	24 h	0 STA	1 STA	1 STA	2
	48 h	0	1 STA	0 STA	(1)
	72 h	0	1 STA	0 STA	1
	7 d	0	0 STAD	0 STA	(0)
Oedema Formation	1 h	0	0	0	(0)
	24 h	0	0	0	0
	48 h	0	0	0	(0)
	72 h	0	0	0	0
	7 d	0	0	0	(0)
Sum of 24 – 72 h readings (S)	3
Primary Irritation index (S/6)	3/6 = 0.5
Classification	Mild Irritant ( ): total values not used for calculations of primary irritation index STA: faint purple/red-coloured staining   Individual daily and individual mean scores for dermal irritation following 4 h exposure required for EEC labelling regulations       Individual scores rabbit no. and sex (Bodyweight kg) Skin reaction Reading (hours) 154 female (2.25) 155 male (2.5) 160 (2.37) Erythema/Escher Formation 24 0 1 1 48 0 1 0 72 0 1 0 Total   0 3 1 Mean score   0.0 1.0 0.3 Odema Formation 24 0 0 0 48 0 0 0 72 0 0 0 Total   0 0 0 Mean score   0.0 0.0 0.0

 

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Very slight transient reddening was seen in 2 of 3 rabbits. Hence, Direct Red 83:1 is not a skin irritating substance.

Executive summary:

The aim of this study was to obtain information on the irritant effect of Direct Red 83:1 on the skin after a single dermal administration.

In a 4 hours skin irritation/corrosion study, 500 mg of Direct Red 83:1, moistened with 500 mL of distilled water, was introduced under a 2.5 cm x 2.5 cm gauze patch and placed in position with a strip of surgical adhesive tape; and was applied in the position of the shorn skin of 3 healthy young adult new Zealand white Rabbits under semi occlusive conditions.

Four hours after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in distilled water followed by diethyl ether.

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 irritation and scored according to the Draize scale J.H. (1959) Association of food and Drug Officials of the United States, Austin, Texas, 'The Appraisal of the Safety of Chemicals 1n Foods, Drugs and Cosmetics":

An additional observation was made on day 7 to asses reversibility of skin reactions

 

The test substance produced very slight erythema at 2 treated skin sites at hour 24 and at one treated skin site at hour 48 and 72 of observation. Desquamation was confined to one treated skin site at the 7 day observation.

No corrosive effects were noted. 

Test material was classified as non-irritant according to CLP-labelling regulations. No symbol and risk phrase are required.

Testing of Direct Red 83:1 for primary dermal irritation showed that the substance is non-irritant to the skin.

Results Synopsis

Test Substance	Test animals	ENVIRONMENTAL CONDITIONS	Control	Results	Conclusion (based on the test conditions)
Direct Red 83:1	New Zealand albino rabbit	- Temperature (°C): 17 -21 - Relative humidity: 48 -58% - Air changes (per hr): at least 15 changes - Photoperiod (hrs dark / hrs light): 12 hours daily	patch (the substance was administered over the whole surface of 2.5 x 2.5 cm cellulose patch on a piece of surgical plaster)	Faint purple/red-coloured staining was commonly noted during the study. This did not affect evaluation of skin response.   The test substance produced very slight erythema at 2 treated skin sites at hour 24 and at one treated skin site at hour 48 and 72 of observation. Desquamation was confined to one treated skin site at the 7 day observation.	Direct Red 83:1 is non-irritant to skin. No symbol and risk phrase are required.