Registration Dossier

Administrative data

Description of key information

Skin Irritation:

The dermal irritation potential of 2-amino-5-acetamidobenzene-1-sulfonic acid was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor.

2-amino-5-acetamidobenzene-1-sulfonic acid was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated results, 2-amino-5-acetamidobenzene-1-sulfonic acid can be considered to be not irritating to skin and can be classified under the category “Not Classified” as per CLP regulation.

Eye Irritation:

The ocular irritation potential of 2-amino-5-acetamidobenzene-1-sulfonic acid was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor.

2-amino-5-acetamidobenzene-1-sulfonic acid was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated results, 2-amino-5-acetamidobenzene-1-sulfonic acid can be considered to be not irritating to eyes and can be classified under the category “Not Classified” 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:
(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:
data is from OECD QSAR toolbox v3.4 and the QMRF report has been attached
Reference:
Composition 1
Qualifier:
according to
Guideline:
other: Estimated data
Principles of method if other than guideline:
Prediction was done using OECD QSAR toolbox v3.4
GLP compliance:
not specified
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material: 5-acetamido-2-aminobenzenesulphonic acid
- IUPAC name: 2-amino-5-acetamidobenzene-1-sulfonic acid
- Molecular formula: C8H10N2O4S
- Molecular weight: 230.243 g/mole
- Smiles: O=C(Nc1ccc(N)c(S(=O)(=O)O)c1)C
- Inchl: 1S/C8H10N2O4S/c1-5(11)10-6-2-3-7(9)8(4-6)15(12,13)14/h2-4H,9H2,1H3,(H,10,11)(H,12,13,14)
- Substance type: Organic
- Physical state: Solid crystal powder (white to yellowish grey)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
no data available
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.5gm
Duration of treatment / exposure:
4 hours
Observation period:
1,24,48 and 72 hours
Number of animals:
3
Details on study design:
no data available
Other effects / acceptance of results:
no data available
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
72 h
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No irritation observed

Estimation method: Takes mode value from the 9 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" )  and ("s" and ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and "z" )  )

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 Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines AND SN1 AND SN1 >> Nucleophilic attack after nitrenium ion formation AND SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines by DNA binding by OASIS v.1.4

Domain logical expression index: "c"

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

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Acylation involving an activated (glucuronidated) carboxamide group AND Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides AND Acylation >> Direct acylation involving a leaving group AND Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides AND AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines by Protein binding by OASIS v1.4

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation >> Direct Acylation Involving a Leaving group >> Acyl halides (including benzyl and carbamoyl deriv.) OR Acylation >> Direct Acylation Involving a Leaving group >> Anhydrides OR Acylation >> Direct Acylation Involving a Leaving group >> Azlactone OR Acylation >> Direct Acylation Involving a Leaving group >> Sulphonyl halides OR Acylation >> Ring Opening Acylation OR Acylation >> Ring Opening Acylation >> alpha-Lactams OR Michael addition OR Michael addition >> Acid imides OR Michael addition >> Acid imides >> Acid imides-MA OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - amides OR Michael addition >> Polarised Alkenes >> Polarised alkene - esters OR Michael addition >> Polarised Alkenes >> Polarised alkene - ketones OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinone-imine OR No alert found OR Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> 1-2-Dicarbonyls OR SN2 OR SN2 >> Epoxides and Related Chemicals OR SN2 >> Epoxides and Related Chemicals >> Epoxides OR SN2 >> SN2 reaction at a sulphur atom OR SN2 >> SN2 reaction at a sulphur atom >> Disulfides OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl halides OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halocarbonyls OR SN2 >> SN2 reaction at sp3 carbon atom >> Sulfonates OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes OR SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Pyrrolidones by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR Acylation >> Ring opening acylation reaction OR Acylation >> Ring opening acylation reaction >> Carboxylic Acid Anhydrides OR AN2 OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems >> Pyrazolone and Pyrazolidine Derivatives OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> Carboxylic Acid Amides OR AN2 >> Michael addition to the quinoid type structures >> N-Subsituted Aromatic Amines OR AN2 >> Michael addition to the quinoid type structures >> Substituted Anilines OR AN2 >> Michael addition to the quinoid type structures >> Substituted Phenols OR AN2 >> Michael type addition to activated double bond of pyrimidine bases OR AN2 >> Michael type addition to activated double bond of pyrimidine bases >> Pyrimidines and Purines OR AN2 >> Shiff base formation with carbonyl compounds OR AN2 >> Shiff base formation with carbonyl compounds >> Pyrazolone and Pyrazolidine Derivatives OR AN2 >> Shiff base formation with carbonyl group of pyrimidine or purine bases OR AN2 >> Shiff base formation with carbonyl group of pyrimidine or purine bases >> Pyrimidines and Purines OR Radical mechanism OR Radical mechanism >> ROS generation OR Radical mechanism >> ROS generation >> Sterically Hindered Piperidine Derivatives OR SN2 OR SN2 >> Alkylation by nucleophilic subsitution at sp3-Carbon atom OR SN2 >> Alkylation by nucleophilic subsitution at sp3-Carbon atom >> Alpha-Activated Haloalkanes by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for skin sensitization by OASIS v1.4

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Anhydrides (sulphur analogues of anhydrides)  OR Acylation >> Direct acylation involving a leaving group >> Carbamates  OR Acylation >> Direct acylation involving a leaving group >> N-Haloacylamides  OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters  OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> Active cyclic agents  OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR SN2 OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  OR SNVinyl OR SNVinyl >> SNVinyl at a vinylic (sp2) carbon atom OR SNVinyl >> SNVinyl at a vinylic (sp2) carbon atom >> Vinyl type compounds with electron withdrawing groups  by Protein binding alerts for skin sensitization by OASIS v1.4

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 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 12 - Trans.Metals Zn,Cd,Hg OR Group 15 - Phosphorus P OR Group 17 - Halogens Br OR Group 17 - Halogens Cl OR Group 17 - Halogens F OR Group 17 - Halogens F,Cl,Br,I,At OR Group 17 - Halogens I by Chemical elements

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Similarity boundary:Target: CC(=O)Nc1ccc(N)c(S(O)(=O)=O)c1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "r"

Similarity boundary:Target: CC(=O)Nc1ccc(N)c(S(O)(=O)=O)c1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Stable form by Tautomers unstable

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Conjugated ketoamine(scy) - 1,5-H shift OR Enamine form OR Enol form OR Keto form (5-membered heteroarenes) - 1,3-H shift by Tautomers unstable

Domain logical expression index: "u"

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: "v"

Referential boundary: The target chemical should be classified as Perhexiline (Hepatotoxicity) Alert OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank OR Valproic acid (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as No alert found by DNA alerts for CA and MNT by OASIS v.1.1

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> N-Hydroxyethyl Lactams by DNA alerts for CA and MNT by OASIS v.1.1

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.31

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is <= -1.25

Interpretation of results:
other: not irritating
Conclusions:
2-amino-5-acetamidobenzene-1-sulfonic acid was estimated to be not irritating to the skin of New Zealand White rabbits.
Executive summary:

The dermal irritation potential of 2-amino-5-acetamidobenzene-1-sulfonic acid was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor.

2-amino-5-acetamidobenzene-1-sulfonic acid was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated results, 2-amino-5-acetamidobenzene-1-sulfonic acid can be considered to be not irritating to skin and can be classified under the category “Not Classified” as per CLP regulation.

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:
data is from OECD QSAR toolbox v3.4 and the QMRF report has been attached
Reference:
Composition 1
Qualifier:
according to
Guideline:
other: Estimated data
Principles of method if other than guideline:
Prediction was done using OECD QSAR toolbox v3.4
GLP compliance:
not specified
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material: 5-acetamido-2-aminobenzenesulphonic acid
- IUPAC name: 2-amino-5-acetamidobenzene-1-sulfonic acid
- Molecular formula: C8H10N2O4S
- Molecular weight: 230.243 g/mole
- Smiles: O=C(Nc1ccc(N)c(S(=O)(=O)O)c1)C
- Inchl: 1S/C8H10N2O4S/c1-5(11)10-6-2-3-7(9)8(4-6)15(12,13)14/h2-4H,9H2,1H3,(H,10,11)(H,12,13,14)
- Substance type: Organic
- Physical state: Solid crystal powder (white to yellowish grey)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
no data available
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
100 mg
Duration of treatment / exposure:
single exposure
Observation period (in vivo):
1,24,48 and 72, 96 hours and 7 days
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
6
Details on study design:
no data available
Other effects / acceptance of results:
no data available
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 observed

Estimation method: Takes mode value from the 7 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 ( not "j") )  )  and "k" )  and "l" )  and "m" )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and "t" )  and ("u" and ( not "v") )  )  and ("w" and "x" )  )

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 Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines AND SN1 AND SN1 >> Nucleophilic attack after nitrenium ion formation AND SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines by DNA binding by OASIS v.1.4

Domain logical expression index: "c"

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

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Acylation involving an activated (glucuronidated) carboxamide group AND Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides AND Acylation >> Direct acylation involving a leaving group AND Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides AND AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines by Protein binding by OASIS v1.4

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation >> Direct Acylation Involving a Leaving group >> Acyl halides (including benzyl and carbamoyl deriv.) OR Acylation >> Direct Acylation Involving a Leaving group >> Anhydrides OR Acylation >> Direct Acylation Involving a Leaving group >> Azlactone OR Acylation >> Direct Acylation Involving a Leaving group >> Sulphonyl halides OR Acylation >> Ring Opening Acylation OR Acylation >> Ring Opening Acylation >> alpha-Lactams OR Michael addition OR Michael addition >> Acid imides OR Michael addition >> Acid imides >> Acid imides-MA OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - amides OR Michael addition >> Polarised Alkenes >> Polarised alkene - esters OR Michael addition >> Polarised Alkenes >> Polarised alkene - ketones OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinone-imine OR No alert found OR SN2 OR SN2 >> SN2 reaction at a sulphur atom OR SN2 >> SN2 reaction at a sulphur atom >> Disulfides OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl halides OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halocarbonyls OR SN2 >> SN2 reaction at sp3 carbon atom >> Sulfonates OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes OR SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Similarity boundary:Target: CC(=O)Nc1ccc(N)c(S(O)(=O)=O)c1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Similarity boundary:Target: CC(=O)Nc1ccc(N)c(S(O)(=O)=O)c1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Similarity boundary:Target: CC(=O)Nc1ccc(N)c(S(O)(=O)=O)c1
Threshold=60%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR Acylation >> Ring opening acylation reaction OR Acylation >> Ring opening acylation reaction >> Carboxylic Acid Anhydrides OR AN2 OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> Carboxylic Acid Amides OR AN2 >> Michael type addition to activated double bond of pyrimidine bases OR AN2 >> Michael type addition to activated double bond of pyrimidine bases >> Pyrimidines and Purines OR AN2 >> Shiff base formation with carbonyl group of pyrimidine or purine bases OR AN2 >> Shiff base formation with carbonyl group of pyrimidine or purine bases >> Pyrimidines and Purines OR Radical mechanism OR Radical mechanism >> ROS generation OR Radical mechanism >> ROS generation >> Sterically Hindered Piperidine Derivatives by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Pyrrolidones by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as No alert found by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as alpha,beta-unsaturated aliphatic alkoxy group (Genotox) OR alpha,beta-unsaturated carbonyls (Genotox) OR Benzenesulfonic ethers, methylation (Nongenotox) OR Imidazole, benzimidazole (Nongenotox) OR N-methylol derivatives (Genotox) OR Primary aromatic amine,hydroxyl amine and its derived esters (Genotox) OR Structural alert for genotoxic carcinogenicity OR Structural alert for nongenotoxic carcinogenicity OR Structural alerts for both genotoxic and nongenotoxic carcinogenicity OR Substituted n-alkylcarboxylic acids (Nongenotox) by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines by DNA binding by OECD

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.14

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.267

Interpretation of results:
other: not irritating
Conclusions:
2-amino-5-acetamidobenzene-1-sulfonic acid was estimated to be not irritating to the eyes of New Zealand White rabbits.
Executive summary:

The ocular irritation potential of 2-amino-5-acetamidobenzene-1-sulfonic acid was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor.

2-amino-5-acetamidobenzene-1-sulfonic acid was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated results, 2-amino-5-acetamidobenzene-1-sulfonic acid can be considered to be not irritating to eyes and can be classified under the category “Not Classified” as per CLP regulation

 

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation:

In different studies,2-amino-5-acetamidobenzene-1-sulfonic acidhas been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical and its structurally and functionally similar read across substances, 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid[ CAS: 40306-75-0], 7-Amino-4-hydroxy-2-naphthalenesulfonic acid [CAS: 87-02-5] and 6-Amino-4-hydroxy-2-naphthalene-6-sulfonic acid [CAS: 90-51-7]. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the dermal irritation potential was estimated for2-amino-5-acetamidobenzene-1-sulfonic acid. 2-amino-5-acetamidobenzene-1-sulfonic acid was estimated to be not irritating to the skin of New Zealand White rabbits.

Skin irritation effects were also estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for 2-amino-5-acetamidobenzene-1-sulfonic acid. Based on estimation, No severe skin irritation effects were known when 2-amino-5-acetamidobenzene-1-sulfonic acid was exposed to rabbit skin.

 

Both the estimated results are in agreement with each other, indicating the possibility of 2-amino-5-acetamidobenzene-1-sulfonic acid being not irritating to skin.

These results are further supported by the experimental study conducted in SSS sponsored lab(Sustainability Support Services (Europe) AB has letter of access, 2012), for the structurally and functionally similar read across substance, 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid [CAS: 40306-75-0].The study was performed according to OECD 404. 3 female New Zealand White rabbits were used for the study. The animals were prepared 24 hrs prior to application of test product. The furs from the dorsal area of trunk of animals were removed with electric clippers exposing an area measuring approximately 6 cm2 of body surface area of animal. The care was taken such that abrasion penetrated the Stratum corneum only and not dermis. 0.5 gm of the test compound was applied on a small area 6 square cms of the intact test site. Each site of application was covered with an impervious dressing which was secured with an adhesive tape. The animals were housed individually and restrained by the use of plastic collars. After patch removal [4 hours later] the unabsorbed test chemical was removed and the test site was washed with lukewarm water. The intact skin site of application was observed for erythema and edema at 1, 24,48 and 72 hours till 14 days after application and scored according to Draize method.

3-acetamido-5-amino-4-hydroxybenzenesulphonic acid did not produce erythema or edema throughout the observation period of 14 days. The dermal irritation index was calculated to be 0.00. 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid did not produce any clinical signs of toxicity throughout the study.

Based on the score and observations, 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid can be considered not irritating to skin and can be classified under the category 'Not Classified'.

These results are further supported by the experimental study summarized in Chemosphere. Vol. 28, No. 12, pp. 2203.2236, 1994; for the structurally and functionally similar read across substance,7-Amino-4-hydroxy-2-naphthalenesulfonic acid [CAS: 87-02-5]. 500 mg 7-amino-4-hydroxy-2-naphthalenesulfonic acid (I acid) was applied to the inner surface of the ears of 2 rabbits.

7-amino-4-hydroxy-2-naphthalenesulfonic acid (I acid)was applied under an adhesive dressing for 24 hours to the skin of male and Female New Zealand white rabbits. 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 signs of irritation were observed after 7 days.

Hence,7-amino-4-hydroxy-2-naphthalenesulfonic acid can be considered not irritating to rabbit skin.

Above results are also supported by the experimental study summarized in Chemosphere. Vol. 28, No. 12, pp. 2203.2236, 1994; for the structurally and functionally similar read across substance,6-Amino-4-hydroxy-2-naphthalene-6-sulfonic acid [CAS: 90-51-7]. 500 mg 6-Amino-4-hydroxy-2-naphthalene-6-sulfonic acid was applied to the inner surface of the ears of 2 rabbits. 6-Amino-4-hydroxy-2-naphthalene-6-sulfonic acid was applied under an adhesive dressing for 24 hours to the skin of male and Female New Zealand white rabbits. 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, 6-Amino-4-hydroxy-2-naphthalene-6-sulfonic acid can be considered not-irritating to rabbit skin.

Based on the available data for the target as well as read across substances and applying the weight of evidence approach,2-amino-5-acetamidobenzene-1-sulfonic acid was not irritating to skin.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”

 

Eye Irritation:

In different studies,2-amino-5-acetamidobenzene-1-sulfonic acidhas been investigated for potential for ocular irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical and its structurally and functionally similar read across substances, 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid[ CAS: 40306-75-0], 7-Amino-4-hydroxy-2-naphthalenesulfonic acid [CAS: 87-02-5] and 6-Amino-4-hydroxy-2-naphthalene-6-sulfonic acid [CAS: 90-51-7]. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the ocular irritation potential was estimated for2-amino-5-acetamidobenzene-1-sulfonic acid. 2-amino-5-acetamidobenzene-1-sulfonic acid was estimated to be not irritating to the eyes of New Zealand White rabbits.

This result is supported by the experimental study conducted in SSS sponsored lab (Sustainability Support Services (Europe) AB has letter of access, 2012), for the structurally and functionally similar read across substance, 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid [CAS: 40306-75-0].The study was performed according to OECD 404. 3 female New Zealand White rabbits were used for the study. 0.1 gm of the test chemical was moistened with water was instilled in the conjunctival sac of rabbits after gently pulling the lower lid away from the eyeball. The other eye which remained untreated served as a control. The ocular lesions were evaluated at 1, 24, 48 and 72 hours after the treatment. The grades of ocular reactions (conjunctiva, cornea and iris) were recorded at each observation. To determine the reversibility of the effect the animals were observed normally for 21 days. Any other lesions in the eye viz pannus, staining were observed and scored accordingly. Examination of reactions was facilitated by use of biomicroscope and hand slit lamp. Individual animal weights before and during the study was observed. The overall irritation index of 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid was 1.25 after 72 hours.

Also 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid did not produce any clinical signs of toxicity throughout the examination period of 21 days. Hence, under the test conditions, 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid can be concluded to be not irritating to New Zealand White rabbit eyes.

These results are further supported by the experimental study summarized in Chemosphere. Vol. 28, No. 12, pp. 2203.2236, 1994; for the structurally and functionally similar read across substance,7-Amino-4-hydroxy-2-naphthalenesulfonic acid [CAS: 87-02-5].50 mg 7-amino-4-hydroxy-2-naphthalenesulfonic acid (I acid) was instilled into the conjunctival sac of 2 animals and animals were observed for 7 days. No eye 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 non-irritant to rabbit eyes.

Above results are also supported by the experimental study summarized in BG Chemie InfoCenter, TOXIKOLOGISCHE BEWERTUNGEN; TOXICOLOGICAL EVALUATION last updated: 06/2000;for the structurally and functionally similar read across substance,6-Amino-4-hydroxy-2-naphthalene-6-sulfonic acid [CAS: 90-51-7]. 50 mg (the test chemical was dry and ground, made into paste with water) 6-Amino-4-hydroxy-2-naphthalene-6-sulfonic acid was instilled into the eyes of 2 New Zealand White rabbits. The rabbits were observed for signs of irritation till 7 days. Slight reddening was seen in 1 rabbits after 1 hour after application which got completely cleared up by 3 days.

Since the effects were fully reversible, 6-Amino-4-hydroxy-2-naphthalene-6-sulfonic acid was considered to be not irritating to rabbit eyes.

Based on the available data for the target as well as read across substances and applying the weight of evidence approach,2-amino-5-acetamidobenzene-1-sulfonic acid was not irritating to eyes.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

Justification for classification or non-classification

Available data for 2-amino-5-acetamidobenzene-1-sulfonic acid suggests that it is not likely to cause any irritation to eyes and skin.

2-amino-5-acetamidobenzene-1-sulfonic acid can be classified under the category “Not Classified” as per CLP regulation.