Sodium 6-amino-5-[[2-[(cyclohexylmethylamino)sulphonyl]phenyl]azo]-4-hydroxynaphthalene-2-sulphonate

Endpoint summary

Description of key information

FAT 20003 was found to be not irritating to the skin, however it did cause irritation when introduced in the eyes of rabbits.

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:

August 6, 1984 to August 13, 1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Principles of method if other than guideline:

not applicable

GLP compliance:

not specified

Specific details on test material used for the study:

Test substance: FAT 20003/G
Batch No.: EN 200106.49
Purity: 80.5 %
Physical properties: Solid
Stability: stable at room temperature
Validity: guaranteed by the sponsor until June 1989
Safety precautions: gloves and face masks
Test material received: July 5, 1984

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Maedorin AG, CH-4414 Fuellinsdorf
- Age at study initiation: 12-14 weeks
- Weight at study initiation: 2 to 3 kg
- Housing: The animals were housed individually in metal cages
- Diet: Nafag, no. 814, Gossau Switzerland; ad libitum
- Water: Fresh water; ad libitum
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
- Temperature: 22±3 °C
- Humidity: 30-70 %
- Photoperiod: 12 h dark/12 h light

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: contralateral flank

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 500 mg
- Concentration: Undiluted

Duration of treatment / exposure:

4 h

Observation period:

7 d

Number of animals:

3 males

Details on study design:

PROCEDURE:
-An area of about 6 cm2 was shaved on both flanks of the animals approx. 24 h before treatment. A gauze patch bearing 500 mg of the test substance was applied to the flank. A control gauze patch was applied to the contralateral flank. Both gauze patches were moistened before application with distilled water.
-The patches were covered with an occlusive membrane and held in place for 4 h by an adhesive tape. The skin reactions were evaluated 1, 24, 48, and 72 h after removing the gauze patches.

SCORING SYSTEM:
Dermal irritation was graded in each animal according to the following scoring scale:
- Erythema and eschar formation:
0 no erythema
1 very slight erythema (barely perceptible)
2 well-defined erythema
3 moderate to severe erythema
4 severe erythema (beet redness) to slight eschar formation (injuries in depth).

- Edema formation:
0 no edema
1 very slight edema (barely perceptible)
2 slight edema (edges of area well-defined by definite raising)
3 moderate edema (raised approximately 1 millimeter)
4 severe edema (raised more than 1 millimeter and extending beyond area of exposure).

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: Test substance induced intensive red staining of the skin, which impeded the erythema evaluation of the first 3 d. No erythema was observed when the staining was reduced.

Irritant / corrosive response data:

Test substance induced intensive red staining of the skin, which impeded the erythema evaluation of the first 3 d. No erythema was observed when the staining was reduced. No edema was induced by test substance.

Other effects:

not observed / nothing reported

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance did not induce skin irritation when applied to clipped albino rabbit skin.

Executive summary:

An in vivo study was conducted to evaluate the skin irritation potential of the test substance (at ca. 80.5 % purity) in New Zealand white rabbits according to OECD Guideline 404.

 

In this study, 500 mg of the test substance was applied on a gauze patch (i.e., moistened with distilled water) which was then applied to the shaved skin of rabbits for 4 h under occlusive conditions. A control gauze patch was applied to the contra lateral flank. After the 4 h of application period, the gauze patches were removed and the application sites were assessed for oedema and erythema at 1, 24, 48, 72 h and up to 7 d.

The test substance induced intensive red staining of the skin, which impeded the erythema evaluation of the first 3 d. No erythema was observed when the staining was reduced. No edema was induced by the test substance.

 

Under the study conditions, the test substance did not induce skin irritation when applied to clipped albino rabbit skin.

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:

1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

no

Specific details on test material used for the study:

Test substance: FAT 20003/G
Batch No.: EN 200106.49
Physical properties: solid
Composition: 80.5%
Stability: stable at room temperature
Validity: guaranteed by the sponsor until June 1989.
Test material received: July 5, 1984.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Maedorin AG, CH-4414 Fuellinsdorf
- Age at study initiation: Approx. 12-14 weeks old
- Weight at study initiation: 2 to 3 kg
- Housing: The rabbits were kept individually in metal cages
- Diet: Standard rabbit pellet – Nafag No. 814, Gossau, Switzerland; ad libitum
- Water: Fresh water; ad libitum
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
- Temperature: 20±3 °C.
- Humidity: 30-70 %
- Photoperiod: 12 h dark/12 h light

Vehicle:

unchanged (no vehicle)

Controls:

other: the second eye on the treated animals served as control

Amount / concentration applied:

- Amount applied: 100 mg
- Concentration: Undiluted

Duration of treatment / exposure:

Duration of treatment same as observation period.

Observation period (in vivo):

The eyes were examined for any ocular reaction approx. 1, 24, 48, and 72 h after the treatment and up to 7 d for the reversibility of the eye reactions.

Number of animals or in vitro replicates:

3 males

Details on study design:

- 100 mg of test substance was placed into the conjunctival sac of the right eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test substance.
- The left eye remained untreated and was used as untreated control.
- The ocular reaction were evaluated 1, 24, 48, and 72 h after instillation test material with the aid of slit-lamp

SCORING SYSTEM: The ocular reactions were according to the OECD scoring system.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 d

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 d

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.66

Max. score:

4

Reversibility:

fully reversible within: 7 d

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 h

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 h

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 d

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 d

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 7 d

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 d

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 d

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 d

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 d

Irritant / corrosive response data:

- Under the experimental conditions employed test substance induced irritation of the cornea, iris and conjunctiva when applied into the conjunctival sac of the rabbits.
- The eye reactions observed were reversible till the end of the observation period on 7 d.

Other effects:

The body weight of one animal decreased after the test substance instillation. However, it normalized until the end of the observation period.

none

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The test substance is considered to be irritating to the eye.

Executive summary:

An in vivo study was conducted to evaluate the acute eye irritation potential of the test substance (at ca. 80.5 % purity) in New Zealand White rabbits according to OECD Guideline 405.

 

100 mg of the test substance was placed into the conjunctival sac of the right eye of three male New Zealand White rabbits without rinsing. The left eye remained untreated and was used for control purposes. Assessment of ocular damage/irritation was made approximately 1, 24, 48 and 72 h following treatment with the aid of slit-lamp.

 

Under the conditions of the study, the test substance produced irritation of the cornea, iris and conjunctiva which was reversible within 7 d. The scores for corneal opacity were >1 in all tested animals. Similarly the scores for conjunctival redness were ≥ 2 in all the tested animals, hence the classification criteria for eye irritation category 2 as prescribed in regulation (EC) No. 1272/2008 is fulfilled. Hence, the substance is considered to be irritating to the eye.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin:

An in vivo study, designated as key, was conducted to evaluate the skin irritation potential of the test substance (at ca. 80.5% purity) in New Zealand white rabbits according to OECD Guideline 404. The test substance induced intensive red staining of the skin, which impeded the erythema evaluation of the first 3 d. No erythema was observed when the staining was reduced. No edema was induced by the test substance. Under the study conditions, the test substance did not induce skin irritation when applied to clipped albino rabbit skin.

Three supporting studies are available for FAT 20003 for skin irritation potential. No skin irritation was observed in these studies. Hence, it can be concluded that FAT 20003 is not an irritant to the rabbit skin.

Eye:

An in vivo study, designed as key, was conducted to evaluate the acute eye irritation potential of the test substance (at ca. 80.5% purity) in New Zealand White rabbits according to OECD Guideline 405 but without GLP compliance. Under the conditions of the study, the test substance produced irritation of the cornea, iris and conjunctiva which was reversible within 7 d. The scores for corneal opacity were >1 in all tested animals. Similarly the scores for conjunctival redness were ≥ 2 in all the tested animals, hence the classification criteria for eye irritation category 2 as prescribed in regulation (EC) No. 1272/2008 is fulfilled. Hence, the substance is considered to be irritating to the eye.

Further eye irritation studies with FAT 20003, designated as supporting studies, are also available, which have discussed below:

FAT 20003/F was tested for eye irritation potential according to the procedure described in US EPA § 163.81-4 "Primary eye irritation study", Federal Register,

Vol. 43, No. 163, August 22, 1978. The mean scores obtained for corneal opacity, iris, conjunctival redness and chemosis were 0, 0 , 1.11 and 0.11. Thus, the scores obtained were below the threhold scores required for classification as proposed by the Regulation (EC) No. 1272/2008. Hence, it can be concluded that, under the conditions of this experiment the test material was found to cause a minimal irritation when applied to the rabbit eye mucosa, however it does not need to be classified.

FAT 20003 was tested for eye irritation potential according to the procedure described in "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics (1959) of the US Association of Food and Drug Officials (AFDO)." FAT 20003 was found to cause moderate irritation (mean reaction score after 24 hours: 35 in rinsed and unrinsed eyes) when applied to the rabbit eye mucosa. The irritation consisted of conjunctival reaction, reflective hyperemia of the iris and reaction of the cornea. Rinsing the eyes led to practically the same results. After 6 days all findings were negative in all rinsed and in 2/3 unrinsed eyes. The mean scores obtained for corneal opacity, iris, conjunctival redness and chemosis were 1, 0.44, 1.67 and 1.22, respectively. Thus the criteria for classification of the substance as eye irritant category 2 (corneal opacity≥1) as proposed by the Regulation (EC) No. 1272/2008 is fulfilled. Hence, it can be concluded that , under the conditions of this experiment preparation FAT 20003 was found to cause moderate irritation when applied to the rabbit eye mucosa and should be classified as eye irritant category 2.

FAT 20003/A was tested for eye irritation potential according to the procedure described in "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics (1959) of the US Association of Food and Drug Officials (AFDO)." FAT 20003/A was found to cause slight irritation (mean reaction score after 6 hours: 10.7 in unrinsed and 7.3 in rinsed eyes) when applied to the rabbit eye mucosa. The irritation consisted of conjunctival reaction. Reflex hyperemia of the iris was noted in 1/3 unrinsed and 2/3 rinsed eyes after 24 hours. Reaction of the cornea was observed from day 1 onwards to day 8 in 1/3 unrinsed eyes. All findings were negative after 6 days in 2/3 unrinsed and 2/3 rinsed eyes. The scores obtained during the experiment were below the threshold required for classification as put forward by the Regulation (EC) No. 1272/2008. Hence, the test substance does not need to be classified. However, it can be concluded that, under the conditions of this experiment, preparation FAT 20003/A was found to cause slight irritation when applied to the rabbit eye mucosa.

Thus taking into consideration the outcome of the key study, as well as the outcome with FAT 20003, the substance needs to be considered as an eye irritant.

Justification for classification or non-classification

Based on the above stated assessment of the skin irritation potential of 2-​Naphthalenesulfonic acid, 6-​amino-​5-​[2-​[2-​[(cyclohexylmethylam​ ino)​sulfonyl]​phenyl]​diazenyl]​-​4-​hydroxy-​, sodium salt (1:1) the substance does not have to be classified as Irritating to skin according to Council Directive 2001/59/EC according to CLP (Regulation (EC) No 1272/2008 Of the European parliament and of the Council.

Base on the above assessment of the eye irritation potential of 2-​ Naphthalenesulfonic acid, 6-​amino-​5-​[2-​[2-​[(cyclohexylmethylam​ino)​ sulfonyl]​phenyl]​diazenyl]​-​4-​hydroxy-​, sodium salt (1:1) the substance does have to be classified as R36 Irritating to eyes according to Council Directive 2001/59/EC and Category 2 ( H319: Causes serious eye irritation)according to CLP (Regulation (EC) No 1272/2008 Of the European parliament and of the Council.

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