N-(phenylsulphonyl)benzenesulphonamide

Endpoint summary

Description of key information

Acute oral toxicity: 

Acute oral toxicity dose (LD50) for N-(phenylsulfonyl) benzenesulfonamide (CAS no: 2618-96-4) was predicted based on OECD QSAR toolbox 3512 mg/kg bw; Danish (Q)SAR Database for rat 4200 mg mg/kg bw and for mice 4000 mg mg/kg bw; and different studies available on structurally similar read across substances Diphenyl acetonitrile (CAS No. 86-29-3) conducted by Sustainability Support Services (Europe) AB >2000 mg/kg body weight and 4-anilino-3-nitro-N-phenylbenzenesulphonamide (5124-25-4) conducted by J-CHECK Japan Chemicals Collaborative Knowledge database >2000 mg/kg bw. All these studies concluded that the LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, N-(phenylsulfonyl) benzenesulfonamide cannot be classified for acute oral toxicity.

Acute Inhalation Toxicity:

N-(phenylsulfonyl) benzenesulfonamide (CAS no: 2618-96-4) has very low vapour pressure (7.79E-07 Pa at 25°C), so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point was considered for waiver.

Acute Dermal toxicity: 

Acute Dermal toxicity dose (LD50) for N-(phenylsulfonyl) benzenesulfonamide (CAS no: 2618-96-4) was predicted based on OECD QSAR toolbox 2656 mg/kg bwand differentstudies available for the structurally similar read across substance Diphenyl acetonitrile (CAS No. 86-29-3) > 2000 mg/kg bw and N,N-dimethyl-2,2-diphenylacetamide (957-51-7)> 6320 mg/kg bw. All these studies concluded that the LD50 value is>2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, N-(phenylsulfonyl) benzenesulfonamide cannot be classified for acute dermal toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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 predicted using OECD QSAR toolbox version 3.4 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

Name: N-(phenylsulphonyl)benzenesulphonamide
SMILES:O=S(=O)(c1ccccc1)NS(=O)(=O)c1ccccc1
InChI: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
Molecular Weight: 297.354 g/mole
Mol. formula: C12H11NO4S2

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

not specified

Doses:

3512 mg/kg

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 512 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

not specified

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average 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 ( 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 >> Quinoneimines 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 Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines 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 Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Sulfonylureas 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 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 >> Aromatic phenylureas 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 Strong binder, OH group 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 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: "k"

Referential boundary: The target chemical should be classified as Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Acylation involving an activated (glucuronidated) ester group OR Acylation >> Acylation involving an activated (glucuronidated) ester group >> Arenecarboxylic Acid Esters OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Azlactones and unsaturated lactone derivatives  OR Acylation >> Direct acylation involving a leaving group >> Carbamates  OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR Acylation >> Direct acylation involving a leaving group >> N-Carbonylsulfonamides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Carbamates  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-type addition to quinoid structures  OR AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides OR AN2 >> Schiff base formation with carbonyl compounds (AN2) OR AN2 >> Schiff base formation with carbonyl compounds (AN2) >> Pyrazolone and Pyrazolidine Derivatives OR No alert found OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Schiff base formation OR Schiff base formation >> Direct acting Schiff base formers OR Schiff base formation >> Direct acting Schiff base formers >> 1,2-Dicarbonyls and 1,3-Dicarbonyls  OR Schiff base formation >> Schiff base on pyrazolones and pyrazolidinones OR Schiff base formation >> Schiff base on pyrazolones and pyrazolidinones >> Pyrazolones and Pyrazolidinones OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds  OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> alpha-Activated haloalkanes  by Protein binding by OASIS v1.4

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 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 17 - Halogens Cl 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 >= 0.918

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.6

Interpretation of results:

other: Not classified

Conclusions:

LD50 was estimated to be 3512 mg/kg bw, when Wistar male and female rats were treated with N-(phenylsulfonyl)benzenesulfonamide (CAS no: 2618-96-4) via oral gavage route.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for N-(phenylsulfonyl)benzenesulfonamide (CAS no: 2618-96-4). The LD50 was estimated to be 3512 mg/kg bw, when Wistar male and female rats were treated with N-(phenylsulfonyl)benzenesulfonamide (CAS no: 2618-96-4) via oral gavage route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 512 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.4.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Quality of whole database:

Waiver

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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 predicted using OECD QSAR toolbox version 3.4 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

Name: N-(phenylsulphonyl)benzenesulphonamide
SMILES:O=S(=O)(c1ccccc1)NS(=O)(=O)c1ccccc1
InChI: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
Molecular Weight: 297.354 g/mole
Mol. formula: C12H11NO4S2

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

not specified

Duration of exposure:

24 hours

Doses:

2656 mg/kg

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 656 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality observed

Mortality:

not specified

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average 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 "i" )  )

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 OECD

Domain logical expression index: "e"

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 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 by DNA binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "g"

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 OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.455

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.6

Interpretation of results:

other: Not classified

Conclusions:

LD50 was estimated to be 2656 mg/kg bw, when New Zealand White male and female rabbit was treated with N-(phenylsulfonyl) benzenesulfonamide (CAS no: 2618-96-4) for 24 hours by dermal application occlusively.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for N-(phenylsulfonyl) benzenesulfonamide (CAS no: 2618-96-4). The LD50 was estimated to be 2656 mg/kg bw, when New Zealand White male and female rabbit was treated with N-(phenylsulfonyl) benzenesulfonamide for 24 hours by dermal application occlusively.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 656 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.4

Additional information

Acute oral toxicity:

In different studies, N-(phenylsulfonyl) benzenesulfonamide (CAS no: 2618-96-4) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats and mice for N-(phenylsulfonyl) benzenesulfonamide along with the study available on structurally similar read across substances Diphenyl acetonitrile (CAS No. 86-29-3) and 4-anilino-3-nitro-N-phenylbenzenesulphonamide (5124-25-4). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for N-(phenylsulfonyl) benzenesulfonamide (CAS no: 2618-96-4). The LD50 was estimated to be 3512 mg/kg bw, when Wistar male and female rats were treated with N-(phenylsulfonyl) benzenesulfonamide (CAS no: 2618-96-4) via oral gavage route.

In another study based on the QSAR prediction done using the Danish (Q)SAR Database, the acute oral toxicity was estimated for the N-(phenylsulphonyl)benzenesulphonamide (2618-96-4). The LD50 was estimated to be 4200 mg mg/kg bw with Reliability Index 0.69 (0.5-0.75 = moderate prediction quality), when rats were treated with N-(phenylsulphonyl) benzenesulphonamide orally.

The above study is supported by the Danish (Q)SAR Database, the acute oral toxicity was estimated for the N-(phenylsulphonyl)benzenesulphonamide (2618-96-4). The LD50 was estimated to be 4000 mg mg/kg bw with Reliability Index 0.51 (0.5-0.75 = moderate prediction quality), when mice were treated with N-(phenylsulphonyl) benzenesulphonamide orally.

The above study is further supported by Sustainability Support Services (Europe) AB (study no.19162, 2017) was designed and conducted for the structurally similar read across substance Diphenyl acetonitrile (CAS No. 86-29-3) in Sprague Dawley rats. Initially, three female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality after the dosing. No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. As no mortality were observed at 24 hours after the dosing, additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - II). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups. The acute oral LD50 of Diphenyl acetonitrile (CAS No. 86-29-3) was >2000 mg/kg body weight. Thus, it was concluded that the acute toxicity study of Diphenyl acetonitrile (CAS No. 86-29-3), when administered via oral route in Sprague Dawley rats falls into the “Category Unclassified” criteria of CLP.

This study is also supported by Ministry of Health, Labour and Welfare, Ministry of the Environment and National Institute of Technology and Evaluation (J-CHECK Japan Chemicals Collaborative Knowledge database, 2010), for the structurally similar read across substance 4-anilino-3-nitro-N-phenylbenzenesulphonamide (5124-25-4). Acute oral toxicity study was conducted in 20 Sprague-Dawley (Crj: CD (SD) IGS, SPF) male and female rat at the concentration of 0 and 2000 mg/kg bw. The test substance (lot number 936, purity 68%, impurities, moisture: 32%; Obtained from -Mitsui BASF Dye Co., Ltd. (Osaka))was dissolved in a 0.5% sodium carboxymethyl cellulose solution to prepare a 20 w/v% suspension, which was stored under refrigeration, sealing and shielding until the next day administration. The dosing volume was 10 mL per 1 kg of body weight; the animals were fasted from the day before administration. Mortality and general condition were observed for 14 days, observations were carried out continuously for 1 hour from immediately after administration on the administration day, and thereafter at about 1 hour interval up to 6 hours after administration. Once a day from observation 2nd to 15th day; and weighing: Body weights were measured for all cases immediately before administration, observation days 1, 4, 8, 11 and 15.Necropsy was performed by sacrificing all the cases under pentobarbital sodium anaesthesia on the observation day 15 and exsanguinations. At the time of autopsy, the brain, pituitary, eyeball, thyroid, heart, trachea, lung, liver, kidney, thymus, spleen, adrenal gland, gastrointestinal tract, mammary gland, bladder, mandibular lymph node, mesenteric lymph node, femoral bone marrow , Pancreas, sub maxillary gland, tongue, oesophagus, aorta, Harder's gland and skin. Of these, the major organ / tissue of one male (brain, heart, lung, liver, kidney, spleen, and gastrointestinal tract) were fixed with 0.1 mol phosphate buffered 10% formalin solution. No changes were noted in autopsy findings, so no histological examination was performed. Animals were observed for clinical signs. There were no deaths in both males and females. On the administration day, all sexes excreted yellow urine, and early ones were observed from observation for 3 hours after administration. In observation 6 hours after administration, yellowish faeces were observed in one male and three females. On the second day of observation, all cases of urine colour tone returned to normal. Regarding the colour of faeces, in all cases, normal colour and those showing yellow colour were mixed. No change in general condition was observed in all cases after day 3 of observation. Changes that excretions showed transient yellowing are considered to be due to the colour tone of the administered specimen. A steady increase in body weight shift was observed. At necropsy conducted on observation day 15, macroscopic abnormal findings were not observed in all organs and tissues of both sexes. From the above results, no apparent toxicity change due to administration of Disperse Yellow 42 was observed. Hence, LD50 was considered to be >2000 mg/kg bw, when Male and female Sprague-Dawley rats were treated with 4-anilino-3-nitro-N-phenylbenzenesulphonamide via oral gavage route.

Thus, based on the above studies on N-(phenylsulfonyl) benzenesulfonamide (CAS no: 2618-96-4) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, N-(phenylsulfonyl) benzenesulfonamide cannot be classified for acute oral toxicity.

Acute Inhalation Toxicity:

N-(phenylsulfonyl) benzenesulfonamide (CAS no: 2618-96-4) has very low vapour pressure (7.79E-07 Pa at 25°C), so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point was considered for waiver.

Acute Dermal toxicity:

In different studies, N-(phenylsulfonyl) benzenesulfonamide (CAS no: 2618-96-4) has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rabbits and rats for N-(phenylsulfonyl) benzenesulfonamide along with the study available on the structurally similar read across substance Diphenyl acetonitrile (CAS No. 86-29-3) and N,N-dimethyl-2,2-diphenylacetamide (957-51-7). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for N-(phenylsulfonyl) benzenesulfonamide (CAS no: 2618-96-4). The LD50 was estimated to be 2656 mg/kg bw, when New Zealand White male and female rabbit was treated with N-(phenylsulfonyl) benzenesulfonamide for 24 hours by dermal application occlusively.

This study is supported by Sustainability Support Services (Europe) AB (study no. 19162, 2017) was designed and conducted for the structurally similar read across substance Diphenyl acetonitrile (CAS No. 86-29-3) in Sprague Dawley rats. The test item 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. 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. It was concluded that the acute dermal median lethal dose (LD50) of Diphenyl acetonitrile (CAS No. 86-29-3), when administered to male and female Sprague Dawley rats was found to be > 2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that Diphenyl acetonitrile (CAS No. 86-29-3) does not classify as an acute dermal toxicant. CLP Classification: “Unclassified”.

The above study is further supported by U.S. National Library of Medicine (ChemIDplus, 2017) and IFA GESTIS (GESTIS SUBSTANCE Database, 2017), for the functionally similar read across substance N,N-dimethyl-2,2-diphenylacetamide (957-51-7).Acute Dermal toxicity study was conducted in rats at the concentration of 6320 mg/kg bw. No Mortality observed at 6320 mg/kg. Therefore, LD50 was considered to be > 6320 mg/kg bw, when rats were treated with N,N-dimethyl-2,2-diphenylacetamide by dermal application to the skin.

Thus, based on the above studies on N-(phenylsulfonyl) benzenesulfonamide (CAS no: 2618-96-4) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, N-(phenylsulfonyl) benzenesulfonamide cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on N-(phenylsulfonyl) benzenesulfonamide (CAS no: 2618-96-4) and it’s read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw for acute oral and dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, N-(phenylsulfonyl) benzenesulfonamide cannot be classified for acute oral and dermal toxicity. For Acute Inhalation toxicity wavier were added so, not possible to classify.