1,3-Benzenedisulfonic acid, 4,4'-[1,2-ethenediylbis[(3-sulfo-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]]bis[6-[[5-(aminocarbonyl)-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridinyl]azo]-, hexasodium salt

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:

key study

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 the QMRF report has been attached

Qualifier:

according to guideline

Guideline:

OECD Guideline 201 (Alga, Growth Inhibition Test)

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.4

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material : hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate}
- Molecular formula : C50H44Cl2N18O24S6.6Na
- Molecular weight : 1544.3016 g/mol
- Smiles notation : CCN1C(=C(C(=C(C1=O)N=NC2=CC(=C(C=C2S(=O)(=O)O)S(=O)(=O)O)NC3=NC(=NC(=N3)NC4=CC(=C(C=C4)C=CC5=C(C=C(C=C5)NC6=NC(=NC(=N6)Cl)NC7=C(C=C(C(=C7)N=NC8=C(C(=C(N(C8=O)CC)[O-])C(=N)[O-])C)S(=O)(=O)O)S(=O)(=O)O)S(=O)(=O)[O-])S(=O)(=O)[O-])Cl)C)C(=N)[O-])[O-].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+]
- InChl : 1S/C50H44Cl2N18O24S6/c1-5-69-41(73)35(39(53)71)19(3)37(43(69)75)67-65-27-15-25(31(97(83,84)85)17-33(27)99(89,90)91)57-49-61-45(51)59-47(63-49)55-23-11-9-21(29(13-23)95(77,78)79)7-8-22-10-12-24(14-30(22)96(80,81)82)56-48-60-46(52)62-50(64-48)58-26-16-28(34(100(92,93)94)18-32(26)98(86,87)88)66-68-38-20(4)36(40(54)72)42(74)70(6-2)44(38)76/h7-18,75-76H,5-6H2,1-4H3,(H2,53,71)(H2,54,72)(H,77,78,79)(H,80,81,82)(H,83,84,85)(H,86,87,88)(H,89,90,91)(H,92,93,94)(H2,55,57,59,61,63)(H2,56,58,60,62,64)/b8-7?,67-65+,68-66+
- 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:

22.5 – 23.2°C

pH:

7.18-8.08

Nominal and measured concentrations:

Estimated

Reference substance (positive control):

not specified

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

107.812 mg/L

Nominal / measured:

estimated

Conc. based on:

not specified

Basis for effect:

growth rate

Remarks on result:

other: Other details not known

The prediction was based on dataset comprised from the following descriptors: EC50
Estimation method: Takes average value from the 5 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" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Iminium Ion Formation AND SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines by DNA binding by OECD

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Nucleophilic addition AND Nucleophilic addition >> Addition to carbon-hetero double bonds AND Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones AND SNAr AND SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds AND SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates AND SNAr AND SNAr >> Nucleophilic aromatic substitution AND SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid moiety AND Acrylamides AND Triazines, Aromatic AND Vinyl/Allyl Alcohols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Iminium Ion Formation AND 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 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 >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR No alert found OR Schiff base formers OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Tertiary (unsaturated) heterocyclic amine  OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Epoxides 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, non cyclic structure by Estrogen Receptor Binding

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 Acid moiety AND Acrylamides AND Triazines, Aromatic AND Vinyl/Allyl Alcohols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Acid moiety AND Acrylamides AND Triazines, Aromatic AND Vinyl/Allyl Alcohols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Acid moiety AND Acrylamides AND Triazines, Aromatic AND Vinyl/Allyl Alcohols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Triazoles (Non-Fused) by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aliphatic alcohol  [-OH] AND Amide   [-C(=O)-N  or -C(=S)-N] AND Aromatic amine   [-NH2  or  -NH-] AND Aromatic chloride   [-CL] AND Aromatic-H AND Azo group   [-N=N-] AND Benzene AND -C=CH  [alkenyl hydrogen] AND -CH2-  [linear] AND Methyl  [-CH3] AND Sulfonic acid / salt -> aromatic attach AND Triazine ring (symmetric) by Bioaccumulation - metabolism alerts

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.177

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.24

Validity criteria fulfilled:

not specified

Conclusions:

Based on the growth rate inhibition of algae, the EC50 value was estimated to be 107.81 mg/l when hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine-4,2-diyl)imino]} bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazenyl]benzene-1,3-disulfonate} exposed to Pseudokirchneriella subcapitata for 72hrs.

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 five closest read across substances, toxicity on Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) was predicted for hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine- 4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl) diazenyl]benzene-1,3-disulfonate} (CAS no. 68991 -98 -0). Based on the growth rate inhibition of algae, the EC50 value was estimated to be 107.81 mg/l when hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine- 4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy- 4-methyl- 6-oxo-1,6-dihydropyridin-3-yl) diazenyl]benzene-1,3-disulfonate} exposed to Pseudokirchneriella subcapitata for 72hrs. Based on this value it can be concluded that the substance hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine- 4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl) diazenyl]benzene-1,3-disulfonate} (CAS no. 68991 -98 -0) 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 3.4 with log kow as the primary descriptor and considering the five closest read across substances, toxicity on Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) was predicted for hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine- 4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl) diazenyl]benzene-1,3-disulfonate} (CAS no. 68991 -98 -0). Based on the growth rate inhibition of algae, the EC50 value was estimated to be 107.81 mg/l when hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine- 4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy- 4-methyl- 6-oxo-1,6-dihydropyridin-3-yl) diazenyl]benzene-1,3-disulfonate} exposed to Pseudokirchneriella subcapitata for 72hrs. Based on this value it can be concluded that the substance hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine- 4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl) diazenyl]benzene-1,3-disulfonate} (CAS no. 68991 -98 -0) 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:

107.81 mg/L

Additional information

Based on the various predicted data for the target chemical and experimental data for structurally and functionally similar read across chemicals study have been reviewed to determine the toxic nature of target chemical hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino (6-chloro-1,3,5-triazine- 4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl) diazenyl]benzene-1,3-disulfonate} (CAS no. 68991 -98 -0) on the growth of aquatic algae and cyanobacteria. The studies are as mentioned below:  

 

In the first predicted data for the target chemical using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, toxicity on Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) was predicted for hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino (6-chloro-1,3,5-triazine- 4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl) diazenyl]benzene-1,3-disulfonate} (CAS no. 68991 -98 -0). Based on the growth rate inhibition of algae, the EC50 value was estimated to be 107.81 mg/l when hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine- 4,2-diyl)imino]}bis{6-[(5-carbamoyl-1- ethyl-2-hydroxy- 4-methyl- 6-oxo-1,6-dihydropyridin-3-yl) diazenyl]benzene-1,3-disulfonate} exposed to Pseudokirchneriella subcapitata for 72hrs. Based on this value it can be concluded that the substance hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino(6-chloro-1,3,5-triazine- 4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydropyridin-3-yl) diazenyl]benzene-1,3-disulfonate} (CAS no. 68991 -98 -0) 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 second experimental supporting study for the read across chemical 4-methoxyphenylacetic acid (12225-21-7) from ABITEC report. The effect of test item Aluminium, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-1Hpyrazole-3-carboxylic acid complex, (CAS No. 12225-21-7) was studied on the growth of fresh water green alga Chlorella vulgaris. The study was conducted following OECD guideline 201- Alga, growth inhibition test. The test concentration chosen for the study were 6.25 mg/L,12.5 mg/L,25 mg/L,50 mg/L,100 mg/L,200 mg/L. The test concentrations were prepared using stock solution of the test item using mineral media. The green alga was exposed to the test concentration for a period of 72 hours to observe average specific growth rate and % growth inhibition under the effect of the test item. EC50 calculated graphically through probit analysis was observed to be >200 mg/L. It can be concluded from the value that the Aluminium, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-1Hpyrazole-3-carboxylic acid complex, (CAS No. 12225-21-7) is not toxic to the aquatic algae and can be considered as "not classified" as per the classification criteria for aquatic environment.

 

Based on the predicted data for the target chemical (from OECD QSAR) and for the read across chemical from experimental lab reports (ABITEC report), it can be concluded that the substance

hexasodium 4,4'-{ethene-1,2-diylbis[(3-sulfonato-4,1-phenylene)imino (6-chloro-1,3,5-triazine- 4,2-diyl)imino]}bis{6-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl) diazenyl]benzene-1,3-disulfonate} (CAS no. 68991 -98 -0) is considered to be not toxic to aquatic environment and cannot be classified as toxic as per the criteria mentioned in CLP regulation.