N-(phenylsulphonyl)benzenesulphonamide

Endpoint summary

Description of key information

The skin sensitization potential of target chemical N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) was assessedin various experimental studies which were conducted on guinea pigs for target chemicalN-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) and its structurally similar read across substanceEnsulizole(CAS No: -27503 -81 -7 )and functionally similar read across substanceDapsone (CAS No: 80-08-0). 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 sensitization and thus can be considered as not sensitizing. 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 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 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

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

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:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

No data available

Route:

intradermal and epicutaneous

Vehicle:

not specified

Concentration / amount:

No data available

Day(s)/duration:

No data available

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

not specified

Concentration / amount:

No data available

Day(s)/duration:

72 hours

Adequacy of challenge:

not specified

No. of animals per dose:

20

Details on study design:

No data available

Reading:

1st reading

Hours after challenge:

72

Group:

test chemical

Dose level:

No data available

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No skin sensitization was observed in treated group.

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

No skin sensitization was observed in treated group.

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 6 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 >> Quinones and Trihydroxybenzenes 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) >> Nitroarenes with Other Active Groups 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 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 >> Nitroarenes with Other Active Groups 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 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 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 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, 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 Non-Metals by Groups of elements

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR Amineptine (Hepatotoxicity) Alert OR Perhexiline (Hepatotoxicity) Alert OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.974

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.75

Interpretation of results:

other: Not sensitizing

Conclusions:

The chemical N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4)was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs.

Executive summary:

The skin sensitization potential of N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4)was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The chemical N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4)was estimated to be not sensitizing to the skin of Dunkin-Hartley guinea pigs. Based on the estimated result N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) failed to induce skin sanitization effects and hence is considered to be not sensitizing to Dunkin-Hartley guinea pigs and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Various studieshas been investigated for the test chemical N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs for target chemical N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) and its structurally similar read across substanceEnsulizole(CAS No: -27503 -81 -7 )and functionally similar read across substanceDapsone (CAS No: 80-08-0).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

The skin sensitization potential of N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) was estimated to be not sensitizing to the skin of guinea pigs. Based on the estimated result N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs.

 

 

The National Technical Reports library (NTRL, 1991) conducted a preliminary dose-range finding study onfunctionally similar read across substanceDapsone (CAS No: 80-08-0) in which four animals (two males and two females) were exposed to one concentration (as received) of Dapsone (CAS No: 80-08-0) at four skin sites. Based upon the results of the dose-range finding study, the dose chosen for induction was 100 %. Dapsone was dermally applied to twenty guinea pigs (ten males and ten females for a total of three six-hour insult periods at a 100 % concentration. An additional group of ten guinea pigs (five males and five females) was treated with 1-chloro-2,4-dinitrobenzene at 0.3% concentration for a total of three six-hour insult periods. Fourteen days after the last induction period, all animals were challenged at a naive site. A positive response was elicited in the animals receiving the positive control article, 1-chloro-2,4-dinitrobenzene (DNCB). Redness and edema scores in all animals at 24 and 48 h recorded after each treatment and at 24 and 48 h after the challenge. No positive responses were observed in guinea pig receiving dapsone at a 100 % concentration at 24 or 48 hours after the challenge. Dapsone did not cause hypersensitivity in guinea pigs. Hence Dapsone (CAS No: 80-08-0) is not sensitizer to the skin of Guinea pig.

 

 

The above results were further supported by guinea pig maximization study carried out by the HEALTH AND CONSUMER PROTECTION DIRECTORATE GENERAL (2016) onstructurally similar read across substance Ensulizole(CAS No: -27503 -81 -7 ) in Dunkin Hartley guinea pigs. In induction phase 20 test and 10 negative controls were used. Animals were induced with intradermal injections of 0.1ml Freund’s complete adjuvant in water, HR 92/103089 1% w/v in arachis oil, and Freund’s + HR 92/103089 1% w/v in arachis oil (1:1) into three separate sites.After 1 week, a single topical application of 0.2 – 0.3 ml HR 92/103089 50% w/w in arachis oil under occlusion for 48 hours was applied. On day 21 animals were challenged with 0.1-0.2 ml HR 92/103089 25 and 10% w/w in arachis oil. Since there was no evidence of any skin reaction, the chemical Ensulizole can be concluded as not sensitizing to guinea pigs.

 

 

Thus on the basis of available data for thetarget chemical lN-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) and its structurally similar read across substanceEnsulizole(CAS No: -27503 -81 -7 )and functionally similar read across substanceDapsone (CAS No: 80-08-0),it can be concluded thatchemicalN-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) is unable to cause skin sensitization and considered as non-skin sensitizer. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test substance N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) and its structurally similar read across substanceEnsulizole(CAS No: -27503 -81 -7 )and functionally similar read across substanceDapsone (CAS No: 80-08-0) were observed in various studies. From the results obtained from these studies it is concluded that the chemical N-(benzenesulfonyl)benzenesulfonamide (CAS No: 2618-96-4) is not likely to cause skin sensitization and hence can be classified under the category “Not Classified” as CLP regulation.