5-amino-2-anilinobenzenesulphonic acid

Endpoint summary

Description of key information

Skin Irritation:

The skin irritation potential for Benzenesulfonic acid, 5-amino-2-(phenylamino)- is estimated using OECD QSAR toolbox version 3.4

The test substance Benzenesulfonic acid, 5-amino-2-(phenylamino)- is estimated to be not irritating to skin of rabbit.

Eye Irritation:

The ocular irritation potential of 5-amino-2-anilinobenzenesulfonic acid was estimated using OECD QSAR toolbox v3.4.

5-amino-2-anilinobenzenesulfonic acid was estimated to be not irritating to 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:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Prediction is done using QSAR Toolbox version 3.4

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): Benzenesulfonic acid, 5-amino-2-(phenylamino)-
- Molecular formula: C12H12N2O3S
- Molecular weight: 264.304 g/mol
- Smiles: O=S(=O)(O)c1c(Nc2ccccc2)ccc(N)c1
- InChl): - 1S/C12H12N2O3S/c13-9-6-7-11(12(8-9)18(15,16)17)14-10-4-2-1-3-5-10/h1-8,14H,13H2,(H,15,16,17)
-Substance type: organic
- Physical state: solid

Species:

rabbit

Strain:

not specified

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

not specified

Amount / concentration applied:

no data

Duration of treatment / exposure:

4 hours

Observation period:

7 days

Number of animals:

3

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

7 d

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No irritation was observed in test animals after 7 days.

Estimation method: Takes mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

(((((("a" or "b" or "c" or "d" or "e") and("f" and(not "g")) ) and "h") and "i") and("j" and(not "k")) ) and("l" and "m") )

Domain logical expression index: "a"

Referential boundary:The target chemical should be classified as Anilines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary:The target chemical should be classified as Aniline AND Aryl AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "c"

Referential boundary:The target chemical should be classified as Aniline AND Aryl AND Overlapping groups AND Sulfonic acid by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary:The target chemical should be classified as Aliphatic Nitrogen, one aromatic attach [-N] AND Aliphatic Nitrogen, two aromatic attach [-N-] AND Aromatic Carbon [C] AND Hydroxy, sulfur attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen, two or tree olefinic attach [>N-] AND Olefinic carbon [=CH- or =C<] AND Suflur {v+4} or {v+6} AND Sulfinic acid [-S(=O)OH] AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary:The target chemical should be classified as Amine AND Aromatic compound AND Primary amine AND Primary aromatic amine AND Secondary amine AND Secondary aromatic amine AND Sulfonic acid AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary:The target chemical should be classified as Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "g"

Referential boundary:The target chemical should be classified as Moderate binder, NH2 group OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Non binder, without OH or NH2 group OR Strong binder, OH group OR Very strong binder, OH group OR Weak binder, NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary:The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "i"

Referential boundary:The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "j"

Referential boundary:The target chemical should be classified as Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C by Repeated dose (HESS)

Domain logical expression index: "k"

Referential boundary:The target chemical should be classified as 4,4'-Methylenedianilines/benzidines (Hepatobiliary toxicity) Rank B  OR Allyl esters (Hepatotoxicity) Rank A OR Nitrophenols/ Halophenols (Energy metabolism dysfuntion) Rank B OR Not categorized OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.99

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.787

Interpretation of results:

other: not irritating

Conclusions:

The substance Benzenesulfonic acid, 5-amino-2-(phenylamino)- is estimated to be not irritating to skin of rabbit.

Executive summary:

The skin irritation potential forBenzenesulfonic acid, 5-amino-2-(phenylamino)-is estimated using OECD QSAR toolbox version 3.4

The test substanceBenzenesulfonic acid, 5-amino-2-(phenylamino)-is estimated to be not irritating to skin of rabbit.

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:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Prediction was done using OECD QSAR toolbox v3.4

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.4

GLP compliance:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): 5-amino-2-anilinobenzenesulfonic acid
- Molecular formula : C12H12N2O3S
- Molecular weight: 264.304 g/mol
SMILES:Nc1ccc(Nc2ccccc2)c(S(O)(=O)=O)c1
- Substance type:Organic
- Physical state:Solid

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

39 mg

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

3

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Estimation method: Takes mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((("a" or "b" or "c" or "d" or "e") and("f" and(not "g")) ) and("h" and(not "i")) ) and("j" and(not "k")) ) and("l" and(not "m")) ) and("n" and(not "o")) ) and "p") and("q" and "r") )

Domain logical expression index: "a"

Referential boundary:The target chemical should be classified as Anilines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary:The target chemical should be classified as Aniline AND Aryl AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "c"

Referential boundary:The target chemical should be classified as Aniline AND Aryl AND Overlapping groups AND Sulfonic acid by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary:The target chemical should be classified as Aliphatic Nitrogen, one aromatic attach [-N] AND Aliphatic Nitrogen, two aromatic attach [-N-] AND Aromatic Carbon [C] AND Hydroxy, sulfur attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen, two or tree olefinic attach [>N-] AND Olefinic carbon [=CH- or =C<] AND Suflur {v+4} or {v+6} AND Sulfinic acid [-S(=O)OH] AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary:The target chemical should be classified as Amine AND Aromatic compound AND Primary amine AND Primary aromatic amine AND Secondary amine AND Secondary aromatic amine AND Sulfonic acid AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary:The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Referential boundary:The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones and Trihydroxybenzenes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Polarized Haloalkene Derivatives OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Haloalkenes with Electron-Withdrawing Groups OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Polarized Haloalkene Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones and Trihydroxybenzenes OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Diazenes and Azoxyalkanes OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones and Trihydroxybenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Direct nucleophilic attack on diazonium cation (DNA alkylation) OR SN1 >> Direct nucleophilic attack on diazonium cation (DNA alkylation) >> Diazenes and Azoxyalkanes OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Amino Anthraquinones OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN1 >> Nucleophilic substitution on diazonium ion OR SN1 >> Nucleophilic substitution on diazonium ion >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Haloalkenes with Electron-Withdrawing Groups OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polarized Haloalkene Derivatives OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.4

Domain logical expression index: "h"

Referential boundary:The target chemical should be classified as Not possible to classify according to these rules by DPRA Lysine peptide depletion

Domain logical expression index: "i"

Referential boundary:The target chemical should be classified as High reactive OR High reactive >> Activated 1,3,5-triazine derivatives by DPRA Lysine peptide depletion

Domain logical expression index: "j"

Referential boundary:The target chemical should be classified as Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "k"

Referential boundary:The target chemical should be classified as Moderate binder, NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Very strong binder, OH group OR Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "l"

Referential boundary:The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "m"

Referential boundary:The target chemical should be classified as Alkali Earth OR Halogens by Groups of elements

Domain logical expression index: "n"

Referential boundary:The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "o"

Referential boundary:The target chemical should be classified as Group 15 - Phosphorus P by Chemical elements

Domain logical expression index: "p"

Similarity boundary:Target: Nc1ccc(Nc2ccccc2)c(S(O)(=O)=O)c1
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.42

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.88

Interpretation of results:

other: not irritating

Conclusions:

5-amino-2-anilinobenzenesulfonic acid was estimated to be not irritating to eyes of rabbits.

Executive summary:

The ocular irritation potential of 5-amino-2-anilinobenzenesulfonic acid was estimated using OECD QSAR toolbox v3.4.

5-amino-2-anilinobenzenesulfonic acid was estimated to be not irritating to eyes of rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation:

The skin irritation potential for Benzenesulfonic acid, 5-amino-2-(phenylamino)- is estimated using OECD QSAR toolbox version 3.4

The test substance Benzenesulfonic acid, 5-amino-2-(phenylamino)- is estimated to be not irritating to skin of rabbit.

The skin irritation test was performed (BG Chemie InfoCenter, 2000) in 2 New Zealand White rabbits (male and female) to assess the skin irritation potency of the similar substance 87-02-5 for the observation period of 7 days. In this skin irritation study, approx. 500 mg 7-amino-4-hydroxy-2-naphthalenesulfonic acid was applied to the inner surface of the ears of 2 rabbits. The test chemical was applied under an adhesive dressing for 24 hours. At the end of the exposure period, the test substance was washed off with water and soap/vegetable oil. The observation period was 7 days. No skin irritation was observed after 7 days. Hence the test chemical 7-Amino-4-hydroxy-2-naphthalenesulfonic acid (CAS No: 87-02-5) can be considered as non-irritant to rabbit skin.

A skin irritation test was performed (BG Chemie InfoCenter, 2000) in 2 New Zealand White rabbits to assess the skin irritation potency of the similar substance 90-51-7 for the observation period of 7 days. In this study, approx. 500 mg 6-amino-4-hydroxy-2-naphthalenesulfonic acid (gamma acid, dry and ground, made into a paste with water) was applied to the inner surface of the ears of rabbits under an adhesive dressing for 24 hours. At the end of the exposure period, the test substance was washed off with water and soap and observations were made for 7 days. Since no known irritation effects were observed during the 7 days observation period, the test chemical, 6-Amino-4-hydroxy-2-naphthalenesulfonic acid (CAS No: 90-51-7) was considered as not irritating to rabbits skin.

Based on the available information for the target as well as various read across substances and applying the weight of evidence approach, Benzenesulfonic acid, 5-amino-2-(phenylamino) can be considered to be not irritating to skin.

 

Eye Irritation:

The ocular irritation potential of 5-amino-2-anilinobenzenesulfonic acid was estimated using OECD QSAR toolbox v3.4.

5-amino-2-anilinobenzenesulfonic acid was estimated to be not irritating to eyes of rabbits.

Eye irritation test of the similar substance 90-51-7 was conducted (BG Chemie InfoCenter, 2000) in rabbits. 50 mg of test chemical was instilled into the conjunctival sac of 2 rabbits. One hour after application, slight reddening was observed, which cleared up completely after 3 days. Hence, the substance 6-Amino-4-hydroxy-2-naphthalene-6-sulfonic acid was considered to be not irritating to rabbit eyes.

Various studies were summarized by BG Chemie InfoCenter, 2000 to evaluate the irritation potential of the similar substance 87-02-5

In an eye irritation study in rabbits, 50 mg 7-amino-4-hydroxy-2-naphthalenesulfonic acid (I acid) was instilled into the conjunctival sac of 2 animals New Zealand white rabbits were used for the study. The animals were observed for 24 hours Mild eye irritation was observed after 24 hours. Hence the test chemical can be considered non-irritant to rabbit eyes

In an another eye irritation study in rabbits, 50 mg 7-amino-4-hydroxy-2-naphthalenesulfonic acid (I acid) was instilled into the conjunctival sac of 2 animals. New Zealand white rabbits were used for the study. The animals were observed for 7 days. No eye irritation was observed after 7 days. Hence 7 -amino-4 -hydroxy-2 -naphthalenesulfonic acid can be considered non-irritant to rabbit eyes.

Therefore, results from both the studies indicates that the similar substance 7 -amino-4 -hydroxy-2 -naphthalenesulfonic acid (CAS: 87-02-5) was not irritating to rabbit eyes.

An ocular irritation test was conducted in albino rabbits to determine the irritation potential of the similar substance 3567-66-6. 0.2 ml of a 10% aqueous solution (20 mg) or suspension of D&C Red 33 was applied twice daily, five times weekly, for four weeks to the conjunctival sac of one eye of each of a group of six or more albino rabbits (40 applications). One hour after each application, the eyes were examined for evidence of staining and the irritation was scored according to Draize method. D&C Red 33 caused intense colouring of the iris, lasting for 2 to 7 days. The overall irritation score after 20 days was 0.0.

Based on the scores, it can be considered that D&C Red 33 was not irritating to rabbit eyes

Based on the information for the target and various read across chemicals and applying the weight of evidence approach, 5-amino-2-anilinobenzenesulfonic acid was not irritating to eyes.

Justification for selection of skin irritation / corrosion endpoint:

data is from OECD QSAR toolbox v 3.4

Justification for selection of eye irritation endpoint:

Data is from OECD QSAR toolbox v 3.4

Justification for classification or non-classification

Available studies for 5-amino-2-anilinobenzenesulfonic acid indicate that it was not likely to cause irritation to eyes and skin. Hence 5-amino-2-anilinobenzenesulfonic acid can be evaluated as Non-Irritant to eyes, skin.