Disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate

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 3.3.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material : disodium [[4-[bis [4- [(sulphonatophenyl) amino] phenyl] methylene] cyclohexa-2, 5-dien-1-ylidene] amino] benzenesulphonate
- Molecular formula : C37H26N3Na2O9S3
- Molecular weight : 800.8182 g/mol
- Smiles notation : c1cc(ccc1C(=C2C=CC(=[NH+]c3ccc (cc3)S(=O) (=O)[O-])C=C2)c4ccc(cc4)Nc5ccc(cc5)S (=O)(=O)[O-])Nc6ccc(cc6)S(=O)(=O)O.[Na+].[Na+]
- InChl : 1S/C37H29N3O9S3.2Na/c41-50(42,43)34-19-13-31(14-20-34)38-28-7-1-25(2-8-28)37(26-3-9-29(10-4-26)39-32-15-21-35(22-16-32)51(44,45 46)27-5-11-30(12-6-27)40-33-17-23-36(24-18-33)52(47,48)49;;/h1-24,38-39H,(H,41,42,43)(H,44,45,46)(H,47,48,49);;/q;2*+1/p-1
- 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

Hardness:

No data

Test temperature:

No data

pH:

No data

Dissolved oxygen:

No data

Salinity:

No data

Conductivity:

No data

Nominal and measured concentrations:

Estimated data

Details on test conditions:

No data

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

161.37 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 161.3 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" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and "i" )  and "j" )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and "s" )  and ("t" and ( not "u") )  )  and ("v" and ( not "w") )  )  and "x" )  and "y" )  and ("z" and "aa" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Alkene OR Ammonium salt OR Aromatic amine OR Aryl OR Sulfonic acid by Organic Functional groups ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkene OR Ammonium salt OR Aromatic amine OR Aryl OR Overlapping groups OR Sulfonic acid by Organic Functional groups (nested) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Nitrogen, two aromatic attach [-N-] OR Aromatic Carbon [C] OR Miscellaneous sulfide (=S) or oxide (=O) OR Nitrogen, hydrogen attach {v+5} OR Nitrogen, two or tree olefinic attach [>N-] OR Olefinic carbon [=CH- or =C<] OR Ortho-substitutes on N=C<, aromatic OR Suflur {v+4} or {v+6} OR Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Amine OR Anion OR Aromatic compound OR Cation OR Secondary amine OR Secondary aromatic amine OR Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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 >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition 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 >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

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"

Referential boundary: The target chemical should be classified as Not Related to an Existing ECOSAR Class by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Surfactants-Cationic OR Triazines, Aromatic OR Vinyl/Allyl Alcohols OR Vinyl/Allyl Ketones by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Not Related to an Existing ECOSAR Class by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Aromatic amine   [-NH2  or  -NH-] AND Aromatic-H AND Benzene AND -C=CH  [alkenyl hydrogen] AND Quaternary amine AND Sulfonic acid / salt -> aromatic attach by Bioaccumulation - metabolism alerts

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as No alert found by Bioaccumulation - metabolism alerts

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aromatic amine   [-NH2  or  -NH-] AND Aromatic-H AND Benzene AND -C=CH  [alkenyl hydrogen] AND Quaternary amine AND Sulfonic acid / salt -> aromatic attach by Bioaccumulation - metabolism alerts

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as -CH2-  [cyclic] by Bioaccumulation - metabolism alerts

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Fast by Bioaccumulation - metabolism half-lives ONLY

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Metals (1a) by DART scheme v.1.0

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr AND 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: "w"

Referential boundary: The target chemical should be classified as Group 17 - Halogens Br by Chemical elements

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Aliphatic Nitrogen, two aromatic attach [-N-] AND Aromatic Carbon [C] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen, hydrogen attach {v+5} AND Nitrogen, two or tree olefinic attach [>N-] AND Olefinic carbon [=CH- or =C<] AND Ortho-substitutes on N=C<, aromatic AND Suflur {v+4} or {v+6} AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Aliphatic Nitrogen, two aromatic attach [-N-] AND Aromatic Carbon [C] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen, hydrogen attach {v+5} AND Nitrogen, two or tree olefinic attach [>N-] AND Olefinic carbon [=CH- or =C<] AND Ortho-substitutes on N=C<, aromatic AND Suflur {v+4} or {v+6} AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.37

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.556

Validity criteria fulfilled:

not specified

Conclusions:

Based on the intoxication of test organism the EC50 value was estimated to be 161 mg/l when Disodium [[4-[bis[4[(sulphonatophenyl)amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate exposed to daphnia magna for 48 hrs.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, toxicity on daphnia magna was predicted disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate (28983-56-4). Based on the intoxication of test organism the EC50 value was estimated to be 161 mg/l when Disodium [[4-[bis[4[(sulphonatophenyl)amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate exposed to daphnia magna for 48 hrs. Based on this value it can be concluded that the substance Disodium [[4-[bis[4-[(sulphonatophenyl) amino]phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]amino] benzene -sulphonate (28983-56-4) is considered to be nontoxic to aquatic environment and cannot classified as per the criteria mentioned in CLP regulation.         

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, toxicity on daphnia magna was predicted disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate (28983-56-4). Based on the intoxication of test organism the EC50 value was estimated to be 161 mg/l when Disodium [[4-[bis[4[(sulphonatophenyl)amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino] benzenesulphonate exposed to daphnia magna for 48 hrs. Based on this value it can be concluded that the substance Disodium [[4-[bis[4-[(sulphonatophenyl) amino]phenyl]methylene] cyclohexa-2,5-dien-1-ylidene]amino] benzene -sulphonate (28983-56-4) is considered to be nontoxic to aquatic environment and cannot classified as per the criteria mentioned in CLP regulation.         

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

161 mg/L

Additional information

Various predicted data for the target compound disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate (28983-56-4) and experimental studies for 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 (2018), using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, toxicity on daphnia magna was predicted disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate (28983-56-4). Based on the intoxication of test organism the EC50 value was estimated to be 161 mg/l when Disodium [[4-[bis[4[(sulphonatophenyl)amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino] benzenesulphonate exposed to daphnia magna for 48 hrs. Based on this value it can be concluded that the substance Disodium [[4-[bis[4-[(sulphonatophenyl) amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino] benzenesulphonate (28983-56-4) is considered to be nontoxic to aquatic environment and cannot classified as per the criteria mentioned in CLP regulation.         

 

First predicted study was supported by the structurally and functionally similar read across chemical (3567-69-9) from ABITEC report 2016 was used. Aim of the study was to assess the effect of chemical disodium 4-hydroxy-3-[(4-sulphonatonaphthyl)azo]naphthalenesulphonate on the mobility of daphnia magna. Test was conducted according to OECD Guideline 202. The stock solution 150 mg/l was prepared by dissolving dark red powder in reconstituted water. Test solutions of required concentration as were prepared by mixing the stock solution of the test sample with reconstituted test water. The test substance was tested at the 0, 0, 10, 45, 67.5, 100, 150 mg/l nominal concentration. Potassium dichromate (K2Cr2O7) were used as a reference positive control. Effects on immobilisation were observed for 48 hours by using nonlinear regression by the software Prism 4.0. After the exposure of chemical for 48 hrs 50 % immobility was observed. Based on the immobility of daphnia magna, the median effective concentration (EC50) for the test substance, disodium 4-hydroxy-3-[(4-sulphonatonaphthyl)azo]naphthalenesulphonate, in Daphnia magna was determined to be 203.2 mg/L for immobilisation effects. This value indicates that the substance is likely to be non-hazardous to aquatic invertebrates and cannot be classified as toxic as per the CLP criteria.

 

Similarly in a third supporting weight of evidence study for read across chemical (915-67-3) from ABITEC lab report study 2016 was conducted. Determination of the inhibition of the mobility of daphnids was carried out with the substance 2,7-Naphthalenedisulfonic acid, 3-hydroxy- 4-[(4-sulfo-1-naphthalenyl), sodium salt; Amaranth dye according to OECD Guideline 202. The limit test was performed at 100 mg/l. Effects on immobilisation were observed for 48 hours. The effective concentration (EC8) for the test substance, 2,7-Naphthalenedisulfonic acid, 3-hydroxy-4- [(4-sulfo-1 -naphthalenyl), sodium salt (Amaranth dye), in Daphnia magna was determined to be 100 mg/L on the basis of mobility inhibition effects in a 48 hour study. This value indicates that the substance is likely to be non-hazardous to aquatic invertebrates and cannot be classified as toxic as per the CLP criteria.

 

On the basis of above results for target chemical disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl] methylene] cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate (28983-56-4) (from OECD QSAR toolbox version 3.3, 2018) and for its read across substance from ABITEC reports it can be concluded that the test substance disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl]methylene] cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate (28983-56-4) is nontoxic to aquatic environment and cannot be classified as per the criteria mentioned in CLP regulation.