N-(phenylsulphonyl)benzenesulphonamide

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to aquatic invertebrates

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:

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 : N-(phenylsulphonyl)benzenesulphonamide
- Common name : N-(benzenesulfonyl)benzenesulfonamide
- 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

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Daphnia magna

Details on test organisms:

- Common name: Water flea

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Nominal and measured concentrations:

Estimated data

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

222.387 mg/L

Nominal / measured:

estimated

Conc. based on:

not specified

Basis for effect:

other: Intoxication

Remarks on result:

other: Other details not known

Details on results:

The EC50 was 222.387 mg/l.

The prediction was based on dataset comprised from the following descriptors: EC50
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" )  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 >> 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 >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism via ROS formation (indirect) 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) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Thiols OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers 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 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 >> Nitroaniline Derivatives 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 >> Polynitroarenes 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 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives 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 >> Haloalkanes Containing Heteroatom 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 an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers 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 Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> Activated haloarenes OR High reactive >> Isothiazolinone derivatives OR Low reactive OR Low reactive >> N-substituted aromatic amides by DPRA Cysteine peptide depletion

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Reactive unspecified by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "k"

Similarity boundary:Target: O=S(=O)(c1ccccc1)NS(=O)(=O)c1ccccc1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Aromatic compound AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Heterocyclic compound by Organic functional groups, Norbert Haider (checkmol)

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 Acrylamide by Organic Functional groups

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.15

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.83

Validity criteria fulfilled:

not specified

Conclusions:

Based on the intoxication of daphnia magna due to the exposure of chemical N-(benzenesulfonyl)benzenesulfonamide, the EC50 was 222.387 mg/l.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the six closest read across substances, toxicity on Daphnia magna was predicted for N-(benzenesulfonyl)benzenesulfonamide (2618-96-4). The EC50 value was estimated to be 222.387mg/l when N-(benzenesulfonyl)benzenesulfonamide exposed to Daphnia magna for 48hrs.

Based on this value it can be concluded that the substance N-(benzenesulfonyl)benzenesulfonamideis considered to be not toxic to aquatic environment as per the criteria mentioned in CLP regulation. 

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the six closest read across substances, toxicity on Daphnia magna was predicted for N-(benzenesulfonyl)benzenesulfonamide (2618-96-4). The EC50 value was estimated to be 222.387mg/l when N-(benzenesulfonyl)benzenesulfonamide exposed to Daphnia magna for 48hrs. Based on this value it can be concluded that the substance N-(benzenesulfonyl)benzenesulfonamideis considered to be not toxic to aquatic environment as per the criteria mentioned in CLP regulation. 

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

222.387 mg/L

Additional information

Various predicted data for the target compound N-(benzenesulfonyl)benzenesulfonamide (2618-96-4) and supporting weight of evidence studies for its closest read across substance with log Kow as the primary descriptor and on the basis of structural and functional similarity were reviewed for the toxicity on the invertebrates end point which are summarized as below: 

In a prediction done by SSS (2017), Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the six closest read across substances, toxicity on Daphnia magna was predicted for N-(benzenesulfonyl)benzenesulfonamide (2618-96-4). The EC50 value was estimated to be 222.387 mg/l when N-(benzenesulfonyl)benzenesulfonamide exposed to Daphnia magna for 48hrs. Based on this value it can be concluded that the substance N-(benzenesulfonyl)benzenesulfonamideis considered to be not toxic to aquatic environment as per the criteria mentioned in CLP regulation. 

 

In second prediction using the prediction done by EPI suite, ECOSAR version 1.1, on the basis of similarity of structure to chemicals for which the aquatic toxicity has been previously measured by structure-activity relationships (SARs) program, the LC 50 value for short term toxicity to aquatic invertebrates was predicted. On the basis of this program, the LC 50 value for short term toxicity to aquatic invertebrates was predicted to be 721.924 mg/l for N-(benzenesulfonyl)benzenesulfonamide in 48 hrs. Based on this value it can be concluded that the substance is considered to be not toxic to aquatic environment and cannot be classified as per the criteria mentioned in CLP regulation.  

 

Similarly in a supporting weight of evidence study from Chemosphere, 2009, for read across chemical (59-40-5) study were to determine the toxicity of a chemical. Aim of the study was to determine the effect of chemical 4-amino-N-(quinoxalin-2-yl) benzene-1-sulfonamide (Sulfaquinoxaline) when exposed with the test organism daphnia magna. Test was performed according to the OECD Guideline 202 ‘Daphnia sp., Acute Immobilisation Test’. Test conducted on the nominal 50-500 mg/l concentration. Juvenile daphnids <24-h old were used as a test organism. Chemical was solubilized in ADaM medium. The organisms were derived from a single clone of D. magna Straus cultured and maintained in ADaM medium. Daphnia fed on Scenedesmus dimorphus every other day having 8 × 105cells mL/l. Four groups of 5 young daphnids were exposed to each concentration tested or used as controls. EC50 with 95% confidence limits was estimated by probit analysis using SPSS 16.0 software or by Spearman–Karber method. Based on the immobility of daphnia magna Straus due to the chemical contact 4-amino-N-(quinoxalin-2-yl)benzene-1-sulfonamide (Sulfaquinoxaline) for 48 hrs, the EC50 was 131 mg/l with 95 % CI was 119-143 mg/l. Thus chemical was consider as nontoxic and can be consider to be not classified as per the CLP classification criteria.

 

Similarly fourth study was conducted on the read across chemical selected on the basis of structure similarity (68-35-9) from Chemosphere, 2009, Study was conducted to determine the effect of chemical 4-amino-N-pyrimidin-2-ylbenzenesulfonamide (Sulfadiazine) when exposed with the test organism daphnia magna. Test was performed according to the OECD Guideline 202 ‘Daphnia sp., Acute Immobilisation Test’. Test conducted on the nominal 50-500 mg/l concentration. Juvenile daphnids <24-h old were used as a test organism. Chemical was solubilized in ADaM medium. The organisms were derived from a single clone of D. magna Straus cultured and maintained in ADaM medium. Daphnia fed on Scenedesmus dimorphus every other day having 8 × 105cells mL/l. Four groups of 5 young daphnids were exposed to each concentration tested or used as controls. EC50 with 95% confidence limits was estimated by probit analysis using SPSS 16.0 software or by Spearman–Karber method. Based on the immobility of daphnia magna Straus due to the chemical contact 4-amino-N-pyrimidin-2-ylbenzenesulfonamide (Sulfadiazine) for 48 hrs, the EC50 was 212mg/l with 95 % CI was 187-240 mg/l. Thus chemical was consider as nontoxic and can be consider to be not classified as per the CLP classification criteria.

 

In the fifth weight of evidence study for the same read across chemical 4-amino-N-pyrimidin-2-ylbenzenesulfonamide (Sulfadiazine) (68-35-9) from Chemosphere 2000. Short term toxicity to aquatic invertebrates was performed in Daphnia magna for 48 hrs according to the ISO (1989) and OECD (1996) standard procedures. The daphnia magna was culture in beaker with 20 neonates and maintained in specific test conditions. D. magna was cultured in a fully defined medium M7. Stock solutions were prepared by dissolving the appropriate amount of chemical in M7 medium. The pH of the stock solutions was adjusted to 7.5. The test was performed in static condition with 20 neonates less than 24 hrs. The test containers used were 100-ml glass beakers filled with 25 ml of test solution. The test was performed at 21±0.5°C underdark. The mobility of daphnia was observed at 24 and 48 hrs. After the experiment, the EC 50 value for 4-amino-N-pyrimidin-2-ylbenzenesulfonamide for short term toxicity to aquatic invertebrates was determined to be 221 mg/l. Based on the value, the 4-amino-N-pyrimidin-2-ylbenzenesulfonamide was considered to be not toxic to aquatic invertebrates and can be considered as not classified as per the CLP regulations.

 

Study for the target chemical was supported by the weight of evidence study for the read across chemical (122-11-2) from peer reviewed journal Environment International, 2007. Short term toxicity to aquatic invertebrates was performed in Daphnia magna for 48 hrs at 199.2–296.8 mg/l concentration range. The test was performed in 6 liter of glass jar and Stock solutions were prepared with dimethyl sulfoxide, from which test solutions were prepared with appropriate dilution medium for each test species. After the 48 hrs, the EC 50 value for Sulfadimethoxine (122-11-2) for short term toxicity to aquatic invertebrates was determined to be 248.0 mg/l for 48 hrs. Based on the value, the Sulfadimethoxine (122-11-2) was considered to not toxic to aquatic invertebrates and can be considered to be not classified as per the CLP regulations.

 

On the basis of above results for target chemical N-(benzenesulfonyl)benzenesulfonamide (2618-96-4) (from OECD QSAR toolbox version 3.4, and EPIsuite, 2017) and for its read across substance from peer reviewed journal Chemosphere, 2009, Chemosphere, 2000 and Environment International, 2007 it can be concluded that the test substance N-(benzenesulfonyl)benzenesulfonamide (2618-96-4) is not toxic and can be consider to be not classified as toxic as per the CLP classification criteria.