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Short-term toxicity to aquatic invertebrates

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Reference
Endpoint:
short-term toxicity to aquatic invertebrates
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:
QMRF report has been attached
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: Estimated data
Principles of method if other than guideline:
Prediction is done using OECD QSAR Toolbox version 3.4
GLP compliance:
not specified
Test material information:
Composition 1
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):
Daphnia magna
Details on test organisms:
- Common name: Water flea
Test type:
static
Water media type:
freshwater
Total exposure duration:
48 h
Test temperature:
19 - 21 °C
pH:
8.0 - 8.2
Dissolved oxygen:
8.7 - 9.1 mg/l
Nominal and measured concentrations:
Estimated
Reference substance (positive control):
not specified
Key result
Duration:
48 h
Dose descriptor:
EC50
Effect conc.:
418.388 mg/L
Nominal / measured:
nominal
Conc. based on:
test mat.
Basis for effect:
other: Intoxication
Remarks on result:
other: Other details not known
Details on results:
The EC50 was 418.3 mg/l

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 ( not "j") )  )  and "k" )  and ("l" and ( not "m") )  )  and ("n" and "o" )  )

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 No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Polarized Haloalkene 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 AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Haloalkenes with Electron-Withdrawing Groups OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Polarized Haloalkene Derivatives 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 Non-covalent interaction >> DNA intercalation >> Quinolone Derivatives OR Radical OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Five-Membered Aromatic Nitroheterocycles OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Conjugated Nitro Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N,N-Dialkyldithiocarbamate Derivatives 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 reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Conjugated Nitro Compounds 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, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Haloalkenes with Electron-Withdrawing Groups OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polarized Haloalkene Derivatives OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline 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 an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

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: "h"

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 >> Benzylamines-Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Sulfonylureas 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 >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR No alert found OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2 >> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Halogenated polarised alkenes by DNA binding by OECD

Domain logical expression index: "i"

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: "j"

Referential boundary: The target chemical should be classified as No alert found OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals by Protein binding by OECD

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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: "m"

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

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.158

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.57

Validity criteria fulfilled:
not specified
Conclusions:
Based on the intoxication of test organism the EC50 value was estimated to be 418.3 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} (CAS no. 68991-98-0) exposed to daphnia magna for 48 hrs.
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 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 intoxication of test organism the EC50 value was estimated to be 418.3 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 daphnia magna for 48 hrs. 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} (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 six closest read across substances, toxicity on daphnia magna was predicted 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 intoxication of test organism the EC50 value was estimated to be 418.3 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 daphnia magna for 48 hrs. 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} (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/LC50 for freshwater invertebrates:
418.3 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 mobility of aquatic invertebrates. 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 six closest read across substances, toxicity on daphnia magna was predicted 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 intoxication of test organism the EC50 value was estimated to be 418.3 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 daphnia magna for 48 hrs. 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} (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. Determination of the inhibition of the mobility of daphnids was carried out with the substance Aluminium,4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-1H-pyrazole- 3-carboxylic acid complex (CAS No12225-21-7) according to OECD Guideline 202. The test substance was tested at the concentrations 0, 50, 70, 100, 140, 200 mg/L. Effects on immobilisation were observed for 48 hours. The median effective concentration (EC50) for the test substance Aluminium, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-1H-pyrazole-3-carboxylic acid complex (CAS No12225-21-7) in Daphnia magna was determined to be 360.4 mg/L for immobilisation effects. This value indicates that the Aluminium,4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-1H-pyrazole -3- carboxylic acid complex (CAS No 12225-21-7) is likely to be non-hazardous to aquatic invertebrates and can be classified as "not classified" as per the CLP criteria.

 

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 (aquatic invertebrates) and cannot be classified as toxic as per the criteria mentioned in CLP regulation.