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

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Endpoint:

toxicity to aquatic algae and cyanobacteria

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 OECD 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):

Raphidocelis subcapitata (previous names: Pseudokirchneriella subcapitata, Selenastrum capricornutum)

Test type:

static

Water media type:

freshwater

Total exposure duration:

72 h

Test temperature:

22.7 - 23.1 °C

pH:

7.02 - 8.15

Nominal and measured concentrations:

Estimated data

Reference substance (positive control):

not specified

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

208.073 mg/L

Nominal / measured:

estimated

Conc. based on:

not specified

Basis for effect:

growth rate

Remarks on result:

other: Other details not known

Details on results:

The EC50 was 208 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 ( not "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 ( not "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 OECD

Domain logical expression index: "f"

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 SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

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 by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) OR Highly reactive (GSH) >> 3-Alken-2-ones (MA) by Protein binding potency

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 Not Related to an Existing ECOSAR Class by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "p"

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

Domain logical expression index: "q"

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: "r"

Referential boundary: The target chemical should be classified as Surfactants-Cationic by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Alkali Earth AND Non-Metals by Groups of elements

Domain logical expression index: "u"

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

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Alkali Earth AND Non-Metals by Groups of elements

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Metalloids OR Metals by Groups of elements

Domain logical expression index: "x"

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

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Aliphatic nitriles (Hepatotoxicity) Rank B by Repeated dose (HESS)

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.33

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.506

Validity criteria fulfilled:

not specified

Conclusions:

Based on the growth rate inhibition of algae Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum), due to the effect of chemical disodium [[4-[bis [4- [(sulphonatophenyl) amino] phenyl] methylene] cyclohexa-2, 5-dien-1-ylidene] amino] benzenesulphonate, the EC50 was 208 mg/l.

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 six closest read across substances, toxicity on Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) was predicted for disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate (28983-56-4). Based on the growth rate inhibition of algae, the EC50 value was estimated to be 208 mg/l when disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate exposed to Pseudokirchneriella subcapitata for 72hrs. 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.          

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 six closest read across substances, toxicity on Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) was predicted for disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate (28983-56-4). Based on the growth rate inhibition of algae, the EC50 value was estimated to be 208 mg/l when disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate exposed to Pseudokirchneriella subcapitata for 72hrs. 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.    

 

Key value for chemical safety assessment

EC50 for freshwater algae:

208 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 aquatic algae and cyanobacteria end point which are summarized as below: 

In a prediction done by SSS (2018), Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, toxicity on Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) was predicted for disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate (28983-56-4). Based on the growth rate inhibition of algae, the EC50 value was estimated to be 208 mg/l when disodium [[4-[bis[4-[(sulphonatophenyl)amino]phenyl] methylene]cyclohexa-2,5-dien-1-ylidene]amino]benzenesulphonate exposed to Pseudokirchneriella subcapitata for 72hrs. 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. Freshwater algal growth inhibition test was carried out on Desmodesmus subspicatus with the substance Disodium 4-hydroxy- 3-[(4-sulphonatonaphthyl) azo]naphthalenesulphonate according to OECD Guideline 201. The test substance was dissolved in OECD growth medium and tested at the concentrations 0, 2.6, 5.6, 12.0, 27.0, 59.0 and 130 mg/L. Effects on the growth rate of the organism were studied. The median effective concentration (ErC50) for the test substance, Disodium 4-hydroxy-3-[(4-sulphonatonaphthyl)azo] naphthalenesulphonate, in Desmodesmus subspicatus was determined to be 265.1 mg/L. Based on this ErC50 value and after comparing with CLP criteria for aquatic classification of the substance it is concluded that the substance Disodium 4-hydroxy-3-[(4-sulphonatonaphthyl) azo] naphthalenesulphonate does not exhibit toxicity to aquatic algae (Desmodesmus subspicatus).

      

Similarly in a third supporting weight of evidence study for read across chemical (915-67-3) from ABITEC lab report study 2016 was conducted. Freshwater algal growth inhibition test was carried out on Desmodesmus subspicatus with the substance 2,7-Naphthalenedi- sulfonic acid, 3-hydroxy-4-[(4-sulfo- 1-naphthal - enyl), sodium salt (Amaranth dye) according to OECD Guideline 201. The stock solution (200 g/L) was prepared by dissolving brown powder in OECD growth medium. Test solutions of required concentration were prepared by mixing the stock solution of the test sample with OECD growth medium and inoculum culture. The test substance was dissolved in OECD growth medium and tested at the concentrations 0, 12.5, 25, 50, 100, 200 mg/L. Effects on the growth rate of the organism were studied. The median effective concentration (ErC50) for the test substance, 2,7-Naphthalenedisulfonic acid, 3-hydroxy-4-[(4-sulfo-1- -naphthalenyl), sodium salt, in Desmodesmus subspicatus was determined to be 356.2 mg/L. This value indicates that the substance is likely to be non-hazardous to aquatic algae 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 (algae and cyanobacteria) and cannot be classified as per the criteria mentioned in CLP regulation.