N-(phenylsulphonyl)benzenesulphonamide

Endpoint summary

Description of key information

Skin irritation

The dermal irritation potential of target chemical N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) was assessedin various experimental studies which were conducted on rabbits and rats for target chemicalN-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) and its structurally similar read across substancesN-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) and its structurally similar read across substancesDiphenyl acetonitrile (CAS No. 86-29-3), Benzenesulphonohydrazide (CAS No: 80-17-1) and 1H-Benzimidazole-5-sulphonic acid, 2 Phenyl-, monosodiumsalt (CAS No: 5997-53-5). The predicted data usingQSAR toolboxhas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) is unable to cause skin irritation and thus considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Eye irritation

An ocular irritation potential of target chemical N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) was assessedin various experimental studies which were conducted on rabbits for target chemicalN-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) and its structurally similar read across substancesBenzenesulphonohydrazide (CAS No: 80-17-1) and 1H-Benzimidazole-5-sulphonic acid, 2 Phenyl-, monosodiumsalt (CAS No: 5997-53-5). The predicted data usingQSAR toolboxhas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) is unable to cause eye damage and thus can be considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

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 version 3.4 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (IUPAC name): N-(benzenesulfonyl)benzenesulfonamide
- Common name: N-(phenylsulphonyl)benzenesulphonamide
- Molecular formula : C12H11NO4S2
- Molecular weight : 297.354 g/mol
- Smiles notation :
O=S(=O)(NS(=O)(=O)c1ccccc1)c1ccccc1
- InChl : 1S/C12H11NO4S2/c14-18(15,11-7-3-1-4-8-11)13-19(16,17)12-9-5-2-6-10-12/h1-10,13H
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

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 skin irritation was observed.

Estimation method: Takes mode value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group AND Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group >> Arenesulfonamides AND AN2 AND AN2 >> Nucleophilic addition at polarized N-functional double bond AND AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulfonamides by Protein binding by OASIS v1.4

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group AND Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group >> Arenesulfonamides AND AN2 AND AN2 >> Nucleophilic addition at polarized N-functional double bond AND AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulfonamides by Protein binding by OASIS v1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Amides by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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 >> Nucleophilic addition reaction with cycloisomerization OR AN2 >> Nucleophilic addition reaction with cycloisomerization >> Hydrazine 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 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 >> N-Hydroxyethyl Lactams 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) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes 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) >> p-Substituted Mononitrobenzenes 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 >> 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 >> Nitro Azoarenes 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 >> p-Substituted Mononitrobenzenes 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 OR SN2 >> Alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides OR SN2 >> Direct nucleophilic attack on diazonium cation OR SN2 >> Direct nucleophilic attack on diazonium cation >> Hydrazine 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 sulfur atom OR SN2 >> SN2 at sulfur atom >> Sulfonyl Halides 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: "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 >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides OR Michael addition 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 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 Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethylenediamines (including piperazine) 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 >> 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 Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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 >> Acetates OR SN2 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 >> alpha-Halocarbonyls by Protein binding by OECD

Domain logical expression index: "l"

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: "m"

Referential boundary: The target chemical should be classified as Group 17 - Halogens F OR Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.975

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.34

Interpretation of results:

other: not irritating

Conclusions:

The chemical N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4)can be considered to be not irritating to skin.

Executive summary:

The dermal irritation potential of N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The chemical N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4)can be considered to be not irritating to skin and can be classified under the category ˋ 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 version 3.4 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (IUPAC name): N-(benzenesulfonyl)benzenesulfonamide
- Common name: N-(phenylsulphonyl)benzenesulphonamide
- Molecular formula : C12H11NO4S2
- Molecular weight : 297.354 g/mol
- Smiles notation :
O=S(=O)(NS(=O)(=O)c1ccccc1)c1ccccc1
- InChl : 1S/C12H11NO4S2/c14-18(15,11-7-3-1-4-8-11)13-19(16,17)12-9-5-2-6-10-12/h1-10,13H
- 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:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

single application

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

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 eye irritation was observed in treated group.

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

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group AND Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group >> Arenesulfonamides AND AN2 AND AN2 >> Nucleophilic addition at polarized N-functional double bond AND AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulfonamides by Protein binding by OASIS v1.4

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group AND Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group >> Arenesulfonamides AND AN2 AND AN2 >> Nucleophilic addition at polarized N-functional double bond AND AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulfonamides by Protein binding by OASIS v1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Amides by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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 >> Nucleophilic addition reaction with cycloisomerization OR AN2 >> Nucleophilic addition reaction with cycloisomerization >> Hydrazine 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 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 >> N-Hydroxyethyl Lactams 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) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes 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) >> p-Substituted Mononitrobenzenes 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 >> 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 >> Nitro Azoarenes 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 >> p-Substituted Mononitrobenzenes 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 OR SN2 >> Alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides OR SN2 >> Direct nucleophilic attack on diazonium cation OR SN2 >> Direct nucleophilic attack on diazonium cation >> Hydrazine 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 sulfur atom OR SN2 >> SN2 at sulfur atom >> Sulfonyl Halides 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: "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 >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides OR Michael addition 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 Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethylenediamines (including piperazine) 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 >> 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 Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (extension) ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND Group All Melting Point > 200 C AND Group CNS Melting Point > 200 C AND Group CNS Melting Point > 50 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR (!Undefined)Group CNHal Lipid Solubility < 400 g/kg OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN Molecular Weight > 290 g/mol OR Group CNS log Kow > 1.5 by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aryl by Organic Functional groups

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Sulfone by Organic Functional groups

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.879

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.01

Interpretation of results:

other: not irritating

Conclusions:

The chemical N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) can be considered to be not irritating to eye.

Executive summary:

The ocular irritation potential of N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The chemical N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) can be considered to be not irritating to eye and can be classified under the category ˋ 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:

Various studieshas been investigated for the test chemical N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits and rats for target chemicalN-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) and its structurally similar read across substancesDiphenyl acetonitrile (CAS No. 86-29-3), Benzenesulphonohydrazide (CAS No: 80-17-1) and 1H-Benzimidazole-5-sulphonic acid, 2 Phenyl-, monosodiumsalt (CAS No: 5997-53-5).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for test chemical N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) .The chemical N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) is estimated to be not irritating to skin of New Zealand White rabbits.

 

This result was supported by the experimental study conducted in an OECD GLP laboratory (Sustainability Support Services (Europe) AB has the letter of access) for the structurally similar read across substance Diphenyl acetonitrile (CAS No. 86-29-3) in Sprague Dawley rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures.. Ten rats (5 male and 5 female) were used for conducting dermal irritation/ corrosion study. The animals were kept in their cages for at least 5 days prior to administration for acclimatization to the laboratory condition and after acclimatization period, animals were randomly selected. Approximately 24 hours before application, the hair of each rat was closely clipped from the trunk (dorsal surface and sides from scapular to pelvic area) with an electric clipper, so as to expose at least 10% of the body surface area. The test item was applied directly onto the exposed skin of the animal, taking care to spread the test item evenly over the entire area of approximately 10% of the total body surface area or as much of the area as can reasonably be covered. The test item was held in contact with the skin using a porous gauze dressing and non- irritating tape around the animal to cover the exposure site for first 24 hours exposure period. Elizabethan collar was placed on each animal for first 24 hours after application of the test item. These collars prevent ingestion of test item. Following 24 hours of exposure, the wrapping was removed and the test site wiped free of excess test item. Distilled water was used to remove residual test item.  The test item Diphenyl acetonitrile (CAS No. 86-29-3) was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Also, the erythema and edema score of rats was calculated as 0. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment.  Hence, it was concluded that Diphenyl acetonitrile (CAS No. 86-29-3) was Non-Irritating to the skin of Sprague Dawley rats under the experimental conditions tested and Classified as “Category- Not Classified” as per CLP Classification.

 

 

The next skin irritation study was carried out by IFA GESTIS (IFA GESTIS, GESTIS SUBSTANCE Database, 2017) for read across chemical Benzenesulphonohydrazide (CAS No: 80-17-1) in rabbits.TheBenzenesulphonohydrazidewas applied onto the skin of each rabbit fixed with a plaster dressing for 24 hours and observed for skin reactions.No irritation was registered including the post-observation period of 7 days. Therefore the chemicalBenzenesulphonohydrazide (CAS No: 80-17-1) was considered to be not irritating to the eye of rabbits.

 

The above results were further supported by the experimental study conducted by OPINION ON PHENYLBENZIMIDAZOLE SUFONIC ACID AND ITS SALTS {OPINION ON PHENYLBENZIMIDAZOLE SUFONIC ACID AND ITS SALTS- HEALTH AND CONSUMER PROTECTION GENERAL- SCCP/1056/ 19 December 2006} on New Zealand rabbits for read across chemical 1H-Benzimidazole-5-sulphonic acid, 2 Phenyl-, monosodiumsalt (CAS No: 5997-53-5). The 0.5ml of 30% aqueous solution applied to Left side of back of 6 rabbits on intact and abraded skin (3 rabbits/ site) for 24 hours under occlusive condition and observed for skin reaction. No abnormalities were recorded over a 7 day observation period. Hence the chemical 1H-Benzimidazole-5-sulphonic acid, 2 Phenyl-, monosodiumsalt (CAS No: 5997-53-5) was considered to be not irritating to the skin of New Zealand rabbit.

 

Thus based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) is unable to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

 

Eye irritation:

In different studies,the test chemical N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) has been investigated for potential for ocular irritationto a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemicalBenzenesulphonohydrazide (CAS No: 80-17-1) and 1H-Benzimidazole-5-sulphonic acid, 2 Phenyl-, monosodiumsalt (CAS No: 5997-53-5).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the eye irritation potential was estimated for test chemicalN-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) .The chemical N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) is estimated to be not irritating to eye of New Zealand White rabbits.

 

The IFA GESTIS (IFA GESTIS, GESTIS SUBSTANCE Database, 2017) conducted an eye irritation study for read across chemical Benzenesulphonohydrazide (CAS No: 80-17-1) in rabbits.When 500 mg ofBenzenesulphonohydrazidechemical was installed into the conjunctival sac of each rabbit, no irritation was observed in treated rabbits within 7 days. Therefore the chemicalBenzenesulphonohydrazide (CAS No: 80-17-1) was considered to be not irritating to the eye of rabbits.

 

The above results were further supported by the experimental study conducted by OPINION ON PHENYLBENZIMIDAZOLE SUFONIC ACID AND ITS SALTS {OPINION ON PHENYLBENZIMIDAZOLE SUFONIC ACID AND ITS SALTS- HEALTH AND CONSUMER PROTECTION GENERAL- SCCP/1056/ 19 December 2006} on New Zealand rabbits for read across chemical 1H-Benzimidazole-5-sulphonic acid, 2 Phenyl-, monosodiumsalt (CAS No: 5997-53-5). About 0.1ml of 30% aqueous solution was instilled into conjunctival sac of left eye while the other untreated right eye served as control.No abnormalities were recorded over a 7 day observation period. Hence the chemical 1H-Benzimidazole-5-sulphonic acid, 2 Phenyl-, monosodiumsalt (CAS No: 5997-53-5) was considered to be not irritating to the eyes of New Zealand rabbits.

 

Thus on the basis of available data for thetarget chemicalN-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) and its structurally similar read across substancesBenzenesulphonohydrazide (CAS No: 80-17-1) and 1H-Benzimidazole-5-sulphonic acid, 2 Phenyl-, monosodiumsalt (CAS No: 5997-53-5),it can be concluded thatchemical N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) is unable to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Justification for classification or non-classification

The skin and eye irritation potential of test chemical N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemical 4-aminobenzene-1,2-dicarbonitrile is unlikely to cause skin and eye irritation. Hence N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) can be classified under the category “Not Classified” for skin and eye as per CLP.