Tetrasodium 4-amino-6-[[2,5-dimethoxy-4-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]azo]-5-hydroxy-3-[[4-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]azo]naphthalene-2,7-disulphonate

Endpoint summary

Description of key information

No irritating or corrosive effects

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 to 28 May 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions.

Qualifier:

according to guideline

Guideline:

other: FDA Federal Register 38, No 187

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

FDA Federal Register 38, No 187, Patch-Test, occusive scarified and intact skin

GLP compliance:

no

Species:

rabbit

Strain:

Himalayan

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG
- Weight at study initiation: 1.8 to 2.2 kg
- Housing: single
- Diet (ad libitum): ERKA Z-6000
- Water (ad libitum): tap water
- Acclimation period: NA


IN-LIFE DATES: From: 25. May To: 28. May 1982

Type of coverage:

occlusive

Preparation of test site:

other: shaved and abraded areas

Vehicle:

physiological saline

Controls:

not required

Amount / concentration applied:

2 x 500 mg moistened with 0.2 mL physiological saline solution (abraded and intact skin)

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

6

Details on study design:

The flank skin was shaved at an area of 6 cm x 3 cm. One half of 3 x 3 cm was abraded by means of a scarificator. A gauze pad (2.5x2.5 cm) with 500 mg pasted test substance was applied to each 3x3 cm test area.

TEST SITE
- Area of exposure: 2 x 3 cm x 3 cm
- Type of wrap if used: polyethylene film


REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: 24 hours


SCORING SYSTEM:

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24+72 hours

Score:

0.3

Max. score:

8

Reversibility:

fully reversible

Remarks on result:

other: abraded and shaved skin

Irritation parameter:

erythema score

Remarks:

shaved skin

Basis:

mean

Remarks:

animals 1 to 6

Time point:

other: 24 to72 h

Score:

0.1

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Remarks:

shaved skin

Basis:

mean

Remarks:

animals 1 to 6

Time point:

other: 24 to 72 h

Score:

0

Max. score:

4

Time after application		24 h						48 h						72 h
Animal number		1	2	3	4	5	6	1	2	3	4	5	6	1	2	3	4	5	6
abraded	erythema	1	1	1	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0
	edema	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0
shaved	erythema	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
	edema	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
sum		8						1						0
primary irritation index (24+72)		0.33

Classification Index:

0.0 to 0.5 non irritant

0.6 to 3.0 slightly irritant

3.1 to 5.0 moderately irritant

5.1 to 8.0 severely irritant

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

not irritating according to Federal Register 38, No 187
no labelling according to EU guideline

Executive summary:

A group of six rabbits was clipped over a wide area on their backs approximately 24 hours prior to application. One side of the animals' backs was abraded at two sites with a lancet sufficiently deep to penetrate the stratum corneum but not enter the derma to produce bleeding. Two intact skin sites were also selected on the other side of the back.

A 0.5 g portion of the experimental material was applied to two abraded and two intact skin sites on the same rabbit. Gauze patches were then placed over the treated areas and an impervious material wrapped snugly around the trunks of the animals to hold the patches in place. The wrapping was removed at the end of the twenty-four hour contact period, the sites wiped but not washed, and the treated areas examined. Readings were also made after 72 hours. The Draize method of scoring was employed. All other lesions observed were recorded. No irritating effects were observed at any reading. The Mean Primary Irritation Score was: 0.3

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 to 28 May 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study without GLP

Qualifier:

according to guideline

Guideline:

other: Federal Register 38, No 187

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

Federal Register 38, No 187

GLP compliance:

no

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG
- Weight at study initiation: 1.8 to 2.2 kg
- Housing: single
- Diet (e.g. ad libitum): ERKA Z-6000
- Water (e.g. ad libitum): tap water
- Acclimation period: NA


IN-LIFE DATES: From: 25. May To: 28. May 1982

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

100 mg pasted with 1 drop physiological saline solution

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

6

Details on study design:

The test item was applied to the left eye of each rabbit. The contra-lateral eye surved as intra-individual control. Evaluation 1, 7, 24, 48, and 72 hours after test item application by means of a magnifying lens. After 24 hours the eyes were rinsed with physiological saline solution. At 48 and 72 hours evaluation, fluorescein staining was used to verify the absence of corneal lesions.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 to 72 hours

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24 to 72 hours

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 to 72 hours

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 to 72 hours

Score:

0

Max. score:

4

Other effects:

up to 48 h the nictitating membranes were blueish discoloured

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Classification according to EC: not irritating

Executive summary:

A group of 6 New Zealand White rabbit, weighing 1.8 – 2.2 kg, was used for this study.

A 100 mg portion of the experimental material was instilled into the right eyes of the test animals while the other eyes remained untreated to serve as controls.

The eyes were examined at 1, 7, 24, 48, and 72 hours following instillation of the test material into the eyes. The readings of the eyes were made in accordance with the Draize technique for scoring ocular lesions.

No signs for eye irritating properties were observed throughout the study; up to 48 h the nictitating membranes were blueish discoloured.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin irritation / Corrosion

A group of six rabbits was clipped over a wide area on their backs approximately 24 hours prior to application. One side of the animals' backs was abraded at two sites with a lancet sufficiently deep to penetrate the stratum corneum but not enter the derma to produce bleeding. Two intact skin sites were also selected on the other side of the back.

A 0.5 g portion of the experimental material was applied to two abraded and two intact skin sites on the same rabbit. Gauze patches were then placed over the treated areas and an impervious material wrapped snugly around the trunks of the animals to hold the patches in place. The wrapping was removed at the end of the twenty-four hour contact period, the sites wiped but not washed, and the treated areas examined. Readings were also made after 72 hours. The Draize method of scoring was employed. All other lesions observed were recorded. No irritating effects were observed at any reading. The Mean Primary Irritation Score was: 0.3

The evaluation of the erythema and edema scores at the 24, 48, and 72 hour time points showed that the test item is not irritating to skin according to GHS and CLP evaluation schemes.

Eye irritation

A group of 6 New Zealand White rabbit, weighing 1.8 – 2.2 kg, was used for this study.

A 100 mg portion of the experimental material was instilled into the right eyes of the test animals while the other eyes remained untreated to serve as controls.

The eyes were examined at 1, 7, 24, 48, and 72 hours following instillation of the test material into the eyes. The readings of the eyes were made in accordance with the Draize technique for scoring ocular lesions.

No signs for eye irritating properties were observed throughout the study; up to 48 h the nictitating membranes were blueish discoloured.

Respiratory irritation

Respiratory irritation was not assessed; howeverno signs for irritating effects on the respiratory tract noted in the respiratory sensitisation studies with the structural analogue Reactive Black 5.

Justification for classification or non-classification

No irritating effect according to EU classification system - No classification necessary