Registration Dossier

Administrative data

Description of key information

Skin Irritation:

Based on the available data for the structurally similar read across chemicals and applying the weight of evidence approach, it can be concluded that2-Naphthalenesulfonic acid, 7-amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium saltwill also behave in similar manner that of the read across chemicals. 2-Naphthalenesulfonic acid, 7-amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium salt was estimated to be irritating to skin. Thus it can be further classified under the category “Category 2” as per CLP regulation.

Eye Irritation:

Based on the available data for the structurally similar read across chemicals and applying the weight of evidence approach, it can be concluded that2-Naphthalenesulfonic acid, 7-amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium salt will also behave in similar manner that of the read across chemicals. 2-Naphthalenesulfonic acid, 7-amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium salt was estimated to be irritating to eyes. Thus it can be further classified under the category “Category 2” as per CLP regulation.

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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Weight of evidence based on structurally similar chemicals
Justification for type of information:
Weight of evidence based on structurally similar chemicals
Reason / purpose:
read-across: supporting information
Related information:
Composition 1
Reason / purpose:
read-across: supporting information
Related information:
Composition 1
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: Weight of evidence approach based on similar chemicals
Principles of method if other than guideline:
The weight of evidence report has been prepared based on the read across substances identified based on structural and functional similarity to assess the dermal irritation potential of 2-Naphthalenesulfonic acid, 7-amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium salt
GLP compliance:
not specified
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of the test material (IUPAC Name): 2-Naphthalenesulfonic acid, 7-amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium salt
- Molecular weight: 1035.87  g/mol
- Mol. formula: C28H25N5Na4O20S6
- Smilies: Cc1cc(N=Nc2c(S(=O)(=O)O{-}.[Na]{+})cc3c(ccc(n)c3N=Nc3ccc(S(=O)(=O)CCOS(=O)(=O)O{-}.[Na]{+})cc3S(=O)(=O)O{-}.[Na]{+})c2O)c(OC)cc1S(=O)(=O)CCOS(=O)
(=O)O{-}.[Na]{+}
- Substance type: Organic
- Physical state: Solid
Species:
rabbit
Strain:
not specified
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
no data available
Duration of treatment / exposure:
no data available
Observation period:
no data available
Number of animals:
no data available
Details on study design:
The study is based on weight of evidence approach from the read across values
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: not specified
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
SIgns of irritation observed
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Based on the available data for the structurally similar read across chemicals and applying the weight of evidence approach, it can be concluded that 2-Naphthalenesulfonic acid, 7-amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium salt will also behave in similar manner that of the read across chemicals. 2-Naphthalenesulfonic acid, 7-amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium salt was estimated to be irritating to skin. Thus it can be further classified under the category “Category 2” as per CLP regulation.
Executive summary:

Based on the available studies for the structurally similar read across substances, the weight of evidence approach was applied to assess the dermal irritation potential of2-Naphthalenesulfonic acid, 7-amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium salt .

Studies were performed to determine the dermal irritation potential of the structurally similar chemicals.

The test chemical was applied to the skin of rabbits and observed for signs of irritation (dose, duration not mentioned, observation period not mentioned). The scale for grading of the dermal reactions was

+++ - Severe irritant.

++ - Positive irritant.

+ - Mild or slight irritant.

- - Non-irritant

Mild or slight irritation was observed after exposure to the first structurally similar test chemical to rabbit skin, whereas moderate irritation was observed after exposure to the other structurally similar test chemical to rabbit skin.

Hence, both the structurally similar chemicals can be considered to be irritating to skin.

Based on the available data for the structurally similar read across chemicals and applying the weight of evidence approach, it can be concluded that2-Naphthalenesulfonic acid, 7-amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium saltwill also behave in similar manner that of the read across chemicals. 2-Naphthalenesulfonic acid, 7-amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium salt was estimated to be irritating to skin. Thus it can be further classified under the category “Category 2” as per CLP regulation.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Weigth of evidence based on structurally similar chemicals
Justification for type of information:
Weigth of evidence based on structurally similar chemicals
Reason / purpose:
read-across: supporting information
Related information:
Composition 1
Reason / purpose:
read-across: supporting information
Related information:
Composition 1
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: Weight of evidence report
Principles of method if other than guideline:
The weight of evidence report has been prepared based on the read across substances identified based on structural and functional similarity to assess the ocular irritation potential of 2-Naphthalenesulfonic acid, 7-amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium salt
GLP compliance:
not specified
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material: 2-Naphthalenesulfonic acid, 7-amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium salt
- Molecular formula: C28H25N5Na4O20S6
- Molecular weight: 1035.87 g/mol
- Smiles notation : Cc1cc(N=Nc2c(S(=O)(=O)O{}.[Na]{+})cc3c(ccc(N)c3N=Nc3ccc(S(=O)(=O)CCOS(=O)(=O)O{}.[Na]{+})cc3S(=O)(=O)O{-}.[Na]{+})c2O)c(OC)cc1S(=O)(=O)CCOS(=O)(=O)O{-}.[Na]{+}
- Substance type: Organic
- Physical state: Solid
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
no data available
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
1. 0.1g
2. 0.1 ml undiluted test chemical
Duration of treatment / exposure:
single exposure
Observation period (in vivo):
1, 24, 48 and 72 hours till 7 days
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
6
Details on study design:
The study is based on weight of evidence approach from the read across values
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
72 h
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
Signs of irritation were observed
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Based on the available data for the structurally similar read across chemicals and applying the weight of evidence approach, it can be concluded that 2-Naphthalenesulfonic acid, 7-amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium salt will also behave in similar manner that of the read across chemicals.2-Naphthalenesulfonic acid, 7-amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium salt was estimated to be irritating to eyes. Thus it can be further classified under the category “Category 2” as per CLP regulation.
Executive summary:

Based on the available studies for the structurally similar read across substances, the weight of evidence approach was applied to assess the ocular irritation potential of2 -Naphthalenesulfonic acid, 7-amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium salt .

A study was performed in rabbits to determine the ocular irritation potential of the structurally similar test chemical. 6 New Zealand white rabbits were used for the study. The rabbits were equilibrated in the laboratory for at least seven days. Rabbits with irritated or damaged eyes were not used in this test. 0.1g test was instilled in the lower conjunctival sac of one eye of each rabbit and the lids held closed for approximately one second to insure even distribution of the test material over all surfaces of the eye. The other eye served as an untreated control. The eyes were examined and graded for irritation and corneal damage at 1, 24, 48 and 72 hours after instillation. Eyes not returning to a score of zero by 72 hours were graded on the seventh day after instillation. Eyes still not returning to a score of zero were graded on the fourteenth day after instillation. All eyes were examined by applying 1 drop of 2% fluorescein sodium ophthalmic solution, U.S.P., to the cornea pre-test, 24, 72 hours and 7 and 14 days after instillation. The fluorescein was rinsed from the eye with physiological saline. The ocular reactions were graded and interpreted as described in –Appraisal of the Safety of Food. Drugs, and Cosmetics", Association of Food and Drug Officials of the United States, 1959 with the assistance of the "Illustrated Guide for Grading Eye Irritation by Hazardous Substances". The Primary Irritation Index calculated at 1, 24, 48, 72 hours, 7 and 14 days were 11, 9.7, 14, 8, 3 and 1 respectively. Based on the scores, the test chemical can be considered to be moderately irritating to rabbit eyes.

This is supported by the results of another ocular irritation study performed to determine the irritation potency of the other structurally similar chemical. 6 New Zealand white rabbits were used for the study. Both eyes of each animal were examined with Fluorescein Sodium Ophthalmic solution U.S.P. 96 hours before testing and only those animals without observable eye defects or irritation were used. 0.1 ml undiluted test chemical was instilled into the conjunctival sac of 6 New Zealand White rabbits. The lids were held closed for 1-second for even distribution of the test substance. The other eye served as an untreated control. The eyes were not washed following instillation of the test material. The animals were immobilized in a suitable animal restrainer 1 hour subsequent to treatment. After the initial examination at 24 hours all eyes were washed with sufficient clean tap water at body temperature to remove the residual test sample. All eyes were further examined by placing one drop of Fluorescein Sodium Ophthalmic solution U.S.P. on the cornea. After 5 minutes the excess fluorescein was flushed out with sufficient tap water. Fluorescein Sodium in 2% aqueous solution when applied topically to the eye is used as an ophthalmic diagnostic aid for the detection of corneal lesions, injured areas of the cornea appear greenish yellow following application of fluorescein. The eyes were examined and the grade of ocular reaction was recorded at 1, 24, 48 and 72 hours, using the scale for scoring ocular lesions as outlined by Lehman. The evaluation of the data was done in accordance with Section 191.12 Chapter 1, Title 21, Code of Federal Regulations under the FHSA. Since the results from the initial test were unsatisfactory to classify the substance according to F.H.S.A Guidelines, an additional group of 6 rabbits were selected and tested using the same procedure to obtain suitable information to classify the test chemical. The eyes of animals of Group II were examined with fluorescein approximately 4 hours prior to treatment. A maximum average score of 10.2 was recorded at 24 hours in the initial test. This score was not sufficient to classify the test chemical as per F.H.S.A Guidelines, so a confirmatory test was performed using 6 additional rabbits. In the confirmatory test, ocular damage in the form of erythema, chemosis, discharge and corneal opacity was observed. Minimal to slight conjunctival irritation (6 anims18) and corneal opacity (5 animals) persisted through 72 hours post-treatment. A maximum average score of 30.3 was recorded at 24 hours. Based on the observations and score in the confirmatory test, the test chemical can be considered to be irritating to eyes.

Based on the available data for the structurally similar read across chemicals and applying the weight of evidence approach, it can be concluded that 2-Naphthalenesulfonic acid, 7 -amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium salt will also behave in similar manner that of the read across chemicals.2-Naphthalenesulfonic acid, 7-amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium salt was estimated to be irritating to eyes. Thus it can be further classified under the category “Category 2” as per CLP regulation.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation:

Based on the available studies for the structurally similar read across substances, the weight of evidence approach was applied to assess the dermal irritation potential of2 -Naphthalenesulfonic acid, 7-amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium salt .

Studies were performed to determine the dermal irritation potential of the structurally similar chemicals.

The test chemical was applied to the skin of rabbits and observed for signs of irritation (dose, duration not mentioned, observation period not mentioned). The scale for grading of the dermal reactions was

+++ - Severe irritant.

++ - Positive irritant.

+ - Mild or slight irritant.

- - Non-irritant

Mild or slight irritation was observed after exposure to the first structurally similar test chemical to rabbit skin, whereas moderate irritation was observed after exposure to the other structurally similar test chemical to rabbit skin.

Hence, both the structurally similar chemicals can be considered to be irritating to skin.

Based on the available data for the structurally similar read across chemicals and applying the weight of evidence approach, it can be concluded that2-Naphthalenesulfonic acid, 7 -amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium saltwill also behave in similar manner that of the read across chemicals. 2-Naphthalenesulfonic acid, 7-amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium salt was estimated to be irritating to skin. Thus it can be further classified under the category “Category 2” as per CLP regulation.

 

Eye Irritation:

Based on the available studies for the structurally similar read across substances, the weight of evidence approach was applied to assess the ocular irritation potential of2 -Naphthalenesulfonic acid, 7-amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium salt .

A study was performed in rabbits to determine the ocular irritation potential of the structurally similar test chemical.

6 New Zealand white rabbits were used for the study. The rabbits were equilibrated in the laboratory for at least seven days. Rabbits with irritated or damaged eyes were not used in this test. 0.1g test was instilled in the lower conjunctival sac of one eye of each rabbit and the lids held closed for approximately one second to insure even distribution of the test material over all surfaces of the eye. The other eye served as an untreated control. The eyes were examined and graded for irritation and corneal damage at 1, 24, 48 and 72 hours after instillation. Eyes not returning to a score of zero by 72 hours were graded on the seventh day after instillation. Eyes still not returning to a score of zero were graded on the fourteenth day after instillation. All eyes were examined by applying 1 drop of 2% fluorescein sodium ophthalmic solution, U.S.P., to the cornea pre-test, 24, 72 hours and 7 and 14 days after instillation. The fluorescein was rinsed from the eye with physiological saline.

The ocular reactions were graded and interpreted as described in –Appraisal of the Safety of Food. Drugs, and Cosmetics", Association of Food and Drug Officials of the United States, 1959 with the assistance of the "Illustrated Guide for Grading Eye Irritation by Hazardous Substances".

The Primary Irritation Index calculated at 1, 24, 48, 72 hours, 7 and 14 days were 11, 9.7, 14, 8, 3 and 1 respectively.

Based on the scores, the test chemical can be considered to be moderately irritating to rabbit eyes.

This is supported by the results of another ocular irritation study performed to determine the irritation potency of the other structurally similar chemical. 6 New Zealand white rabbits were used for the study. Both eyes of each animal were examined with Fluorescein Sodium Ophthalmic solution U.S.P. 96 hours before testing and only those animals without observable eye defects or irritation were used. 0.1 ml undiluted test chemical was instilled into the conjunctival sac of 6 New Zealand White rabbits. The lids were held closed for 1-second for even distribution of the test substance. The other eye served as an untreated control. The eyes were not washed following instillation of the test material. The animals were immobilized in a suitable animal restrainer 1 hour subsequent to treatment. After the initial examination at 24 hours all eyes were washed with sufficient clean tap water at body temperature to remove the residual test sample. All eyes were further examined by placing one drop of Fluorescein Sodium Ophthalmic solution U.S.P. on the cornea. After 5 minutes the excess fluorescein was flushed out with sufficient tap water. Fluorescein Sodium in 2% aqueous solution when applied topically to the eye is used as an ophthalmic diagnostic aid for the detection of corneal lesions, injured areas of the cornea appear greenish yellow following application of fluorescein. The eyes were examined and the grade of ocular reaction was recorded at 1, 24, 48 and 72 hours, using the scale for scoring ocular lesions as outlined by Lehman. The evaluation of the data was done in accordance with Section 191.12 Chapter 1, Title 21, Code of Federal Regulations under the FHSA.

Since the results from the initial test were unsatisfactory to classify the substance according to F.H.S.A Guidelines, an additional group of 6 rabbits were selected and tested using the same procedure to obtain suitable information to classify the test chemical. The eyes of animals of Group II were examined with fluorescein approximately 4 hours prior to treatment.

A maximum average score of 10.2 was recorded at 24 hours in the initial test. This score was not sufficient to classify the test chemical as per F.H.S.A Guidelines, so a confirmatory test was performed using 6 additional rabbits. In the confirmatory test, ocular damage in the form of erythema, chemosis, discharge and corneal opacity was observed. Minimal to slight conjunctival irritation (6 anims18) and corneal opacity (5 animals) persisted through 72 hours post-treatment.

A maximum average score of 30.3 was recorded at 24 hours.

Based on the observations and score in the confirmatory test, the test chemical can be considered to be irritating to eyes.

Based on the available data for the structurally similar read across chemicals and applying the weight of evidence approach, it can be concluded that2-Naphthalenesulfonic acid, 7-amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium saltwill also behave in similar manner that of the read across chemicals. 2-Bromoethylamine hydrobromide was estimated to be irritating to eyes. Thus it can be further classified under the category “Category 2” as per CLP regulation.

Justification for classification or non-classification

The results of the experimental studies from the structurally similar read across substances indicate a possibility that2-Naphthalenesulfonic acid, 7-amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium saltcan be irritating to skin and eyes.

Hence, by applying the weight of evidence approach,2-Naphthalenesulfonic acid, 7-amino-4-hydroxy-3-[[2-methoxy-5-methyl-4-[[2-(sulfooxy)ethyl]sulfonyl] phenyl]azo]-8-[[2-sulfo-4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]-, tetrasodium saltcan be considered to be irritating to skin and eyes. It can be classified under the category “Category 2” as per CLP regulation.