Trisodium 5-[[4-chloro-6-(ethylphenylamino)-1,3,5-triazin-2-yl]amino]-4-hydroxy-3-[(2-sulphonatophenyl)azo]naphthalene-2,7-disulphonate

Endpoint summary

Description of key information

Skin Irritation:

Data on skin irritation study was not available for the target substance (Reactive Red 024:1). To fill the data gaps, read across approach is adapted using similar substance Reactive Red 024. A study was performed to determine the primary-irritation index, which serves as a measure of the acute irritation, provoked by the compound, FAT 40034, on the skin of the rabbits according to the "Hazardous Substances Regulations" under the U.S. Federal Hazardous Substances Labelling Act Sect. 191.11 (February 1965). 6 rabbits (3 males and 3 females), New Zealand White breed, were shaved on the whole back and flanks two days before treatment with an electric clipper. The shaven skin on the left side was slightly scarified immediately before treatment. A gauze patch 2.5 x 2.5 cm was soaked with the test substance and immediately applied to the prepared skin. The patch was covered with a plastic film 5 x 5 cm, which was fixed to the body with adhesive tape. 10 g of the test compound was mixed with 10 ml of water to make a solution of 15 ml. 0.75 ml of which was applied to each test site on a 2.5 cm square gauze pad. The gauze patches were removed 24 h after the application. The reaction of the skin was appraised upon removal and 72 h after it. The primary irritation index was calculated as 0.8. The effects were observed to be completely reversible by the end of 72 h. Therefore, based on the read across data generated from the skin irritation study of Reactive Red 024, the target substance (Reactive Red 024:1) is also considered to be as non-irritant to the skin of rabbits.

Eye Irritation:

Data on eye irritation study was not available for the target substance (Reactive Red 024:1). To fill the data gaps, read across approach is adapted using similar substance Reactive Red 024. A study performed to determine the eye irritation potential of FAT 40034/A in New Zealand White rabbits in accordance with the procedure set out in the "Hazardous Substances Regulations" under the U.S.A. Federal Hazardous Substances Labelling Act Sect. 191.12 (February 1965), with slight modification. The test substance was instilled in the eyes of 3 male and 3 female rabbits and observations for irritation were recorded at the time points of 1 h, 6 h, 1 day, 2 days, 3 days, 6 days and 10 days. One hour after application of the test compound there was slight opacity and ulceration of the cornea in 3/6 animals (unwashed eyes) and a conjunctival reaction in 6/6. The corneal changes had healed by day 3 and the conjunctivae were normal, apart from slight injection of vessels in one animal, by day 6. Staining of the cornea was visible up to 48 h. Based on the read across data generated from the eye irritation study of Reactive Red 024, the target substance (Reactive Red 024:1) is also considered as non-irritant to the rabbit eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

July 1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Justification for type of information:

Refer chapter 13 for the detailed analogue justification.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: "Hazardous Substances Regulations" under the U.S. Federal Hazardous Substances Labelling Act Sect. 191.11 (February 1965).

Deviations:

not specified

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Inhouse breeding
- Age at study initiation: 3 - 4 months
- Weight at study initiation: 2.65 Kgs. (male) and 2.53 Kgs.(female)
- Housing: caged singly
- Diet:commercial irradiated diet (Styles-Oxoid) ad libitum
- Water: Sterile filtered water ad libitum
- Acclimation period: One week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 50 - 70
- Photoperiod (hrs dark / hrs light): 10 h light

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

10 g of the test compound was mixed with 10 ml of water to make a solution of 15 ml. 0.75 ml of which was applied to each test site on a 2.5 cm square gauze pad.

Duration of treatment / exposure:

24 h

Observation period:

After 24 h the dressing was removed and the intact and abraded application sites were assessed for oedema and erythema. A further assessment was made at 72 h.

Number of animals:

3 males and 3 females

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Remarks:

males and females

Time point:

other: 24 and 72 h

Score:

0.8

Max. score:

8

Reversibility:

fully reversible within: 72 h

Remarks on result:

other:

Irritation parameter:

erythema score

Remarks:

Intact skin

Basis:

mean

Remarks:

6 rabbits

Time point:

24 h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

erythema score

Remarks:

abraded skin

Basis:

mean

Remarks:

6 rabbits

Time point:

24 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

erythema score

Remarks:

Intact and abraded skin

Basis:

mean

Remarks:

6 rabbits

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

erythema score

Remarks:

Intact and abraded skin

Basis:

mean

Remarks:

6 rabbits

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Remarks:

Intact skin

Basis:

mean

Remarks:

6 rabbits

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

edema score

Remarks:

Abraded skin

Basis:

mean

Remarks:

6 rabbits

Time point:

24 h

Score:

1.17

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

edema score

Remarks:

Intact and abraded skin

Basis:

mean

Remarks:

6 rabbits

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Remarks:

Intact and abraded skin

Basis:

mean

Remarks:

6 rabbits

Time point:

72 h

Score:

0

Max. score:

4

Individual Animal Score:

 

Erythema Score

Animal Number	Intact skin		Abraded skin
	24 h	72 h	24 h	72 h
11	1	0	1	0
13	0	0	0	0
15	1	0	1	0
12	1	0	1	0
14	0	0	0	0
16	0	0	1	0
Mean	0.50	00	0.67	00

 

Edema Score

Animal Number	Intact skin		Abraded skin
	24 h	72 h	24 h	72 h
11	0	0	1	0
13	0	0	1	0
15	2	0	2	0
12	2	0	1	0
14	0	0	1	0
16	2	0	1	0
Mean	1.00	00	1.17	00

 

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 40034/A is to be considered as non-irritant to the skin of rabbits.

Executive summary:

A study was performed to determine the primary-irritation index, which serves as a measure of the acute irritation, provoked by the compound, FAT 40034, on the skin of the rabbits according to the "Hazardous Substances Regulations" under the U.S. Federal Hazardous Substances Labelling Act Sect. 191.11 (February 1965). 6 rabbits (3 males and 3 females), New Zealand White breed, were shaved on the whole back and flanks two days before treatment with an electric clipper. The shaven skin on the left side was slightly scarified immediately before treatment. A gauze patch 2.5 x 2.5 cm was soaked with the test substance and immediately applied to the prepared skin. The patch was covered with a plastic film 5 x 5 cm, which was fixed to the body with adhesive tape. 10 g of the test compound was mixed with 10 ml of water to make a solution of 15 ml. 0.75 ml of which was applied to each test site on a 2.5 cm square gauze pad. The gauze patches were removed 24 h after the application. The reaction of the skin was appraised upon removal and 72 h after it. The primary irritation index was calculated as 0.8. The effects were observed to be completely reversible by the end of 72 h. Therefore, FAT 40034/A is to be considered as a non-irritant to the skin of rabbits.

 

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:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

July 1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Justification for type of information:

Refer chapter 13 for the detailed analogue justification.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: "Hazardous Substances Regulations" under the U.S.A. Federal Hazardous Substances Labelling Act Sect. 191.12 (February 1965)

Deviations:

not specified

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Animals:
Healthy New Zealand White rabbits (Porton strain) aged 10-15 weeks with average body weights of 2.65 kg (Males) and 2.53 kg (Females), bred on the premises and maintained under a semi-barrier system. Six rabbits (3 males and 3 females) were acclimatised in the test area for one week prior to the start of the trial.

Husbandry:
The rabbits were caged singly in an experimental room maintained at a temperature of 20 °C. (±1°) and a relative humidity of 50-70 %. Animals were exposed to artificial light for 10 hours daily from 08.00 - 18.00 h. A commercial irradiated diet (Styles-Oxoid) was fed ad lib. Sterile filtered water was available at all times.

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

100 mg of the test compound (equivalent to 0.1 ml in volume) was applied.

Duration of treatment / exposure:

30 seconds

Observation period (in vivo):

The rabbits were examined 1, 6, 24, 48 and 72 h after application of the test compound and for any further period that was considered necessary.

Number of animals or in vitro replicates:

3 males and 3 females

Details on study design:

The eyes of the experimental animals were examined and found normal prior to the test. 100 mg of the test compound (equivalent to 0.1 ml in volume) were instilled into the conjunctival sac of the left eye. The eyelids were then held closed for 1 second. The right eye served as a control. After 30 seconds the compound was, as far as possible, flushed out of the eyes of three of the rabbits with 30 ml of warm water. The rabbits were examined 1, 6, 24, 48 and 72 h after application of the test compound and for any further period that was considered necessary. The ocular reactions were scored by the method described in "Appraisal of the Safety of Chemicals in Food Drugs and Cosmetics", published by the Association of Food and Drug Officials of the UCS.A.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

6 rabbit

Time point:

24 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

6 rabbits

Time point:

48 h

Score:

0.17

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

6 rabbit

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Remarks:

6 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

6 rabbits

Time point:

24/48/72 h

Score:

0.83

Max. score:

3

Reversibility:

fully reversible within: 10 days

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

6 rabbits

Time point:

24 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48h

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

6 rabbit

Time point:

48 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

6 rabbit

Time point:

72 h

Score:

0

Max. score:

4

Evaluation of the Eye Reactions: Individual animal score

Cornea

Animal No	Observation time (Hr)	Degree of intensity	Area of cornea involved
Rabbit 11	24	1	1
	48	1	1
	72	0	0
Rabbit 13	24	0	0
	48	0	0
	72	0	0
Rabbit 15	24	0	0
	48	0	0
	72	0	0
Rabbit 12	24	1	1
	48	0	0
	72	0	0
Rabbit 14	24	0	0
	48	0	0
	72	0	0
Rabbit 16	24	0	0
	48	0	0
	72	0	0

 

Iris

Animal No	Observation time (Hr)	Score
Rabbit 11	24	0
	48	0
	72	0
Rabbit 13	24	0
	48	0
	72	0
Rabbit 15	24	0
	48	0
	72	0
Rabbit 12	24	0
	48	0
	72	0
Rabbit 14	24	0
	48	0
	72	0
Rabbit 16	24	0
	48	0
	72	0

 

 

Conjunctiva

Animal No	Observation time (Hr)	Redness	Chemosis	Discharge
Rabbit 11	24	1	0	2
	48	1	0	0
	72	1	0	0
Rabbit 13	24	1	1	0
	48	1	0	0
	72	1	0	0
Rabbit 15	24	0	0	0
	48	0	0	0
	72	0	0	0
Rabbit 12	24	2	1	0
	48	2	0	0
	72	1	0	0
Rabbit 14	24	1	0	0
	48	1	0	0
	72	1	0	0
Rabbit 16	24	0	0	0
	48	0	0	0
	72	0	0	0

 

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 40034/A is considered as non-irritant to the rabbit eyes.

Executive summary:

A study performed to determine the eye irritation potential of FAT 40034/A in New Zealand White rabbits in accordance with the procedure set out in the "Hazardous Substances Regulations" under the U.S.A. Federal Hazardous Substances Labelling Act Sect. 191.12 (February 1965), with slight modification. The test substance was instilled in the eyes of 3 male and 3 female rabbits and observations for irritation were recorded at the time points of 1 h, 6 h, 1 day, 2 days, 3 days, 6 days and 10 days. One hour after application of the test compound there was slight opacity and ulceration of the cornea in 3/6 animals (unwashed eyes) and a conjunctival reaction in 6/6. The corneal changes had healed by day 3 and the conjunctivae were normal, apart from slight injection of vessels in one animal, by day 6. Staining of the cornea was visible up to 48 h. Based on the study results, FAT 40034/A is considered to be a non-irritant to the eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the findings in the skin as well as eye irritation studies with read across substance, the Reactive Red 024:1 also does not considered to be classified according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 to be irritating to the skin and eyes.