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Description of key information

The skin sensitization potential of 2-amino-5-acetamidobenzene-1-sulfonic acid (96-78-6) was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances of 2-amino-5-acetamidobenzene-1-sulfonic acid (96-78-6) was predicted to be not sensitizing to the skin of female Pirbright-Hartley guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
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: As mentioned below
Principles of method if other than guideline:
Prediction was done using OECD QSAR toolbox v3.4, 2017
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
No data available
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:
guinea pig
Strain:
Pirbright-Hartley
Sex:
female
Details on test animals and environmental conditions:
No data available
No. of animals per dose:
Total :15
Test group:10
control group:5
Details on study design:
No data available
Challenge controls:
No data available
Positive control substance(s):
not specified
Statistics:
No data available
Positive control results:
No data available
Reading:
1st reading
Group:
test group
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No skin sensitization reaction was observed
Remarks on result:
no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
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 ( not "i") )  )  and ("j" and ( not "k") )  )  and "l" )  and ("m" and "n" )  )

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 No alert found by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Addition of an Acyl Halide OR Acylation >> Direct Addition of an Acyl Halide >> Alkyl carbamyl halides OR Michael addition OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Furans OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethanolamines (including morpholine) OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding by OECD

Domain logical expression index: "h"

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: "i"

Referential boundary: The target chemical should be classified as Acylation >> Direct Acylation Involving a Leaving group >> Anhydrides OR Acylation >> Direct Acylation Involving a Leaving group >> Azlactone OR Michael addition OR Michael addition >> Acid imides OR Michael addition >> Acid imides >> Acid imides-MA 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 >> Allyl acetates and related chemicals by Protein binding by OECD

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Moderately reactive (GSH) OR Moderately reactive (GSH) >> Substituted 1-Alken-3-ones (MA) by Protein binding potency

Domain logical expression index: "l"

Similarity boundary:Target: CC(=O)Nc1ccc(N)c(S(O)(=O)=O)c1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.46

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.0235

Interpretation of results:
other: not sensitising
Conclusions:
The skin sensitization potential of 2-amino-5-acetamidobenzene-1-sulfonic acid (96-78-6) was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances of 2-amino-5-acetamidobenzene-1-sulfonic acid (96-78-6) was predicted to be not sensitizing to the skin of female Pirbright-Hartley guinea pig.
Executive summary:

The skin sensitization potential of2-amino-5-acetamidobenzene-1-sulfonic acid (96-78-6) was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances of 2-amino-5-acetamidobenzene-1-sulfonic acid (96-78-6) was predicted to be not sensitizing to the skin of female Pirbright-Hartley guinea pig.

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

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

Skin sensitization 

In different studies, 2-amino-5-acetamidobenzene-1-sulfonic acid (96-78-6) has been investigated for potential of skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pig and human for target chemical 2-amino-5-acetamidobenzene-1-sulfonic acid (96-78-6) and its structurally similar read across substances2,4-diaminoanisole sulphate(39156-41-7)and4-ethoxy-m-phenylenediamine (5862-77-1) the predicted data using the OECD QSAR toolbox has also been compared with the experimental data of read across.

The skin sensitization potential of 2-amino-5-acetamidobenzene-1-sulfonic acid (96-78-6) was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances of 2-amino-5-acetamidobenzene-1-sulfonic acid (96-78-6) was predicted to be not sensitizing to the skin of female Pirbright-Hartley guinea pig.

The experimental study conducted by DFG, German Research Foundation (The MAK Collection for Occupational Health and Safety, volume 6 Page No 149, 1985) to evaluate the skin sensitizing potential of 2,4-diaminoanisole sulphate(39156-41-7) in guinea pig . The skin sensitizing study of 2,4-diaminoanisole sulphate(39156-41-7) was carried out in guinea pig by Magnusson and Kligman method in group of 10.Test material dissolved in water .intradermal induction was given as both undiluted and diluted 1:1 with Freund's adjuvant and5 % w/v water solution of test compound on interscapular area. While epicutaneous induction0.4 ml of a 50 % (w/v) aqueous solutionof test material on same skin site (clipped free of fur) on an occlusive patch after 7 days. An interval of 14 days animals were challenged by25 % (w/v) solution of test material by topical application under occlusive patch on left flank.After one week second challenged given at dose5 % test material solution on right flank. Delayed contact hypersensitivity was seen in one animal. After the first challenge treatment, equivocal reactions were observed in two animals. Therefore, based on the results obtained, the2,4-diaminoanisole sulphate(39156-41-7)was considered to be not sensitizing to guinea pig.

Also it is further supported by experimental study conducted by European Commission (Ec) - Scientific Committee on Cosmetology (Scc) (Reports of the Scientific Committee on Cosmetology (Ninth Series), Page No 19, 2000) to evaluate the skin sensitizing potential of read across substance 4-ethoxy-m-phenylenediamine (5862-77-1) in guinea pig . The skin sensitizing study of 4-ethoxy-m-phenylenediamine was carried out in guinea pig in group of 10.Test material dissolved in water .intradermal induction was given by three pairs simultaneously intradermal injections of Freund’s complete adjuvant (FCA, 1:1 in water), 0.1 % water solution of test compound and a 1:1 mixture of the above solution in shoulder area. After 7 days 0.4 ml of a 50 % suspension of test substance in Paraffin perliquidum was topically applied in a filter paper, under occlusion, on the same area for 48 hours An interval of 14 days animals were challenged by 0.1 ml of a 10 % water solution of test material by topical application under occlusive patch for 48 hours on left flank. Cutaneous reactions were evaluated at 24, 48, 72 hours. After challenge no skin reactions were observed 8 out of 9(It has been reported that one animal died from lung infection).Therefore, based on the results obtained, the 4-ethoxy-m-phenylenediamine (5862-77-1) was considered to be not sensitizing to guinea pig.

Thus based on the above predictions on 2-amino-5-acetamidobenzene-1-sulfonic acid (96-78-6) as well as its read across and applying weight of evidence, it can be concluded that 2-amino-5-acetamidobenzene-1-sulfonic acid (96-78-6) is not a skin sensitizer. Thus comparing the above studies with the criteria of CLP regulation, 2-amino-5-acetamidobenzene-1-sulfonic acid (96-78-6) can be considered as not classified for skin sensitization.

Justification for classification or non-classification

Thus comparing the above studies with the criteria of CLP regulation, 2-amino-5-acetamidobenzene-1-sulfonic acid (96-78-6) can be considered as not classified for skin sensitization.