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

Endpoint summary

Description of key information

The substance is not a skin irritant nor an eye irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

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:

None

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

Principles of method if other than guideline:

None

GLP compliance:

no

Specific details on test material used for the study:

None

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Animals:
Healthy New Zealand White rabbits (Porton strain) aged 3 -4 months 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 (3M and 3F) were acclimatized 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 hours. A commercial irradiated diet (Styles-Oxoid) was fed ad lib. Sterile filtered water was available at all times.

Type of coverage:

semiocclusive

Preparation of test site:

other: the backs of the rabbits were shaved over an area consisting of at least 10$ of the total body surface.

Vehicle:

water

Controls:

not required

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 hours

Observation period:

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

Number of animals:

3 males and 3 females

Details on study design:

None

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:

2

Reversibility:

fully reversible within: 72 h

Remarks on result:

other:

Irritation parameter:

erythema score

Remarks:

intact skin

Basis:

mean

Time point:

24 h

Score:

0.5

Max. score:

1

Reversibility:

fully reversible within: 72h

Irritation parameter:

erythema score

Remarks:

abraded skin

Basis:

mean

Time point:

24 h

Score:

0.67

Max. score:

1

Reversibility:

fully reversible within: 72h

Irritation parameter:

edema score

Remarks:

intact skin

Basis:

mean

Time point:

24 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 72h

Irritation parameter:

edema score

Remarks:

abraded skin

Basis:

mean

Time point:

24 h

Score:

1.17

Max. score:

2

Reversibility:

fully reversible within: 72h

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Basis:

mean

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

None

Other effects:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 40034 is to be considered as a 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 hours after the application. The reaction of the skin was appraised upon removal and 72 hours after it. The primary irritation index was calculated as 0.8. The effects were observed to be completely reversible by the end of 72 hours. Therefore FAT 40034 is to be considered as a non-irritant to the skin of rabbits.

 

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

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

Adequacy of study:

key study

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:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that the source and the target substance have very similar physicochemical and (eco)toxicological properties because their chemical structures are nearly identical. An analogue approach has thus been employed. The target substance is Reactive Red 24 carrying a methyl group, while the source chemical is Reactive Red 24:1 carrying an ethyl group.
The presence of sulphonate groups make both dyes highly water soluble and therefore less critical for human health and environmental issues. Based on their chemical similarity, similar properties are expected in both humans and the environment.
2. SOURCE AND TARGET CHEMICAL(S)
Source: Reactive Red 24:1 (CAS# 72829-25-5 / EC# 276-911-4)
Target: Reactive Red 24 (CAS# 70210-20-7 / EC# 274-417-3)
3. ANALOGUE APPROACH JUSTIFICATION
see attachment under 4.12 Auto flammability

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Remarks:

males and females

Time point:

other: 24h and 72h

Score:

0.8

Max. score:

2

Reversibility:

fully reversible within: 72h

Remarks on result:

probability of weak irritation

Irritation parameter:

erythema score

Remarks:

intact skin

Basis:

mean

Time point:

24 h

Score:

0.5

Max. score:

1

Reversibility:

fully reversible within: 72h

Remarks on result:

probability of weak irritation

Irritation parameter:

erythema score

Remarks:

abraded skin

Basis:

mean

Time point:

24 h

Score:

0.67

Max. score:

1

Reversibility:

fully reversible within: 72h

Remarks on result:

probability of weak irritation

Irritation parameter:

edema score

Remarks:

intact skin

Basis:

mean

Time point:

24 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 72h

Remarks on result:

probability of weak irritation

Irritation parameter:

edema score

Remarks:

abraded skin

Basis:

mean

Time point:

24 h

Score:

1.17

Max. score:

2

Reversibility:

fully reversible within: 72h

Remarks on result:

probability of weak irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Basis:

mean

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

After 24h on intact skin: 3/6 slight erythema, 3/6 slight oedema
After 72h on intact skin: no erythema and no oedema found
After 24h on abraded skin: 4/6 slight erythema, 5/6 very slight oedema and 1/6 slight oedema
After 72h on abraded skin: no erythema and no oedema found

Interpretation of results:

GHS criteria not met

Conclusions:

The substance does not need to be classified as a skin irritant according to CLP.

Executive summary:

A study was performed to determine the primary-irritation index, which serves as a measure of the acute irritation, provoked by the source substance, 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 hours after the application. The reaction of the skin was appraised upon removal and 72 hours after it. The primary irritation index was calculated as 0.8. The effects were observed to be completely reversible by the end of 72 hours. Therefore the source substance is to be considered as a non-irritant to the skin of rabbits.

The structurally related target substance will show similar behaviour and will not be classified as a skin irritant either.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

key study

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:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that the source and the target substance have very similar physicochemical and (eco)toxicological properties because their chemical structures are nearly identical. An analogue approach has thus been employed. The target substance is Reactive Red 24 carrying a methyl group, while the source chemical is Reactive Red 24:1 carrying an ethyl group.
The presence of sulphonate groups make both dyes highly water soluble and therefore less critical for human health and environmental issues. Based on their chemical similarity, similar properties are expected in both humans and the environment.
2. SOURCE AND TARGET CHEMICAL(S)
Source: Reactive Red 24:1 (CAS# 72829-25-5 / EC# 276-911-4)
Target: Reactive Red 24 (CAS# 70210-20-7 / EC# 274-417-3)
3. ANALOGUE APPROACH JUSTIFICATION
see attachment under 4.12 Auto flammability

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0.17

Max. score:

1

Reversibility:

fully reversible within: 72h

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

0.83

Max. score:

2

Reversibility:

fully reversible within: 10d

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.11

Max. score:

2

Reversibility:

fully reversible within: 48h

Irritation parameter:

conjunctivae score

Remarks:

discharge

Basis:

mean

Time point:

24/48/72 h

Score:

0.11

Max. score:

3

Reversibility:

fully reversible within: 48h

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritant / corrosive response data:

Washing the eyes immediately after exposure reduces conjunctival effects (redness, chemosis and discharge) while no corneal opacity was observed.

Interpretation of results:

GHS criteria not met

Conclusions:

The substance does not need to be classified as an eye irritant according to CLP.

Executive summary:

In a study performed to determine the eye irritation potential of the source substance, 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 hour, 6 hours, 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 hours. Based on these findings, the source substance is considered to be a non-irritant to the eyes.

The structurally related target substance will show the same behaviour and will therefore not be classified as an eye irritant either.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

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:

None

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

Principles of method if other than guideline:

None

GLP compliance:

no

Specific details on test material used for the study:

None

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 hours after application of the test compound and for any further period that was considered necessary.

Duration of post- treatment incubation (in vitro):

None

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 hours 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

Time point:

24/48/72 h

Score:

0.17

Max. score:

1

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

0.83

Max. score:

2

Reversibility:

fully reversible within: 10 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.11

Max. score:

2

Reversibility:

fully reversible within: 48h

Irritation parameter:

conjunctivae score

Remarks:

discharge

Basis:

mean

Time point:

24/48/72 h

Score:

0.11

Max. score:

3

Reversibility:

fully reversible within: 48h

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritant / corrosive response data:

None

Other effects:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 40034 is considered to be a non-irritant to the eyes.

Executive summary:

In a study performed to determine the eye irritation potential of FAT 40034, 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 hour, 6 hours, 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 hours. Based on these findings, FAT 40034 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

Additional information

In a key skin irritation study in rabbits, the source substance showed slight irritation after 24h exposure, but after 72h no skin effects were apparent anymore. The primary dermal irritation index was calculated to be 0.8. The substance therefore does not need to be classified as a skin irritant.

In a key eye irritation study in rabbits, the source substance showed minimal to moderate eye irritation after 1 and 6 hours, no to slight eye irritation after 1 day, and no to minimal irritation after 2, 3 and 6 days. After 10 days no irritation was apparent anymore. The substance therefore does not need to be classified as an eye irritant.

Justification for classification or non-classification

The source substance is non-irritant to rabbit skin and rabbit eyes. It is anticipated that the structurally related target substance will show the same behaviour. Therefore it will not be classified as a skin or eye irritant either.