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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:
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:
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 : [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt
- Molecular weight : 1101.8036 g/mol
- Smiles notation : [Na+].[Na+].[Na+].[Na+].O=N(=Nc1ccc2N=Nc3c4O[Cu-2]5(Oc2c1)OS(=O)(=O)c6ccc4c(c6)cc3S(=O)(=O)O5)c7ccc8N=Nc9c%10O[Cu-2]%11(Oc8c7)OS(=O)(=O)c%12ccc%10c(c%12)cc9S(=O)(=O)O%11
- InChl : 1S/C32H22N6O17S4.2Cu.4Na/c39-25-13-17(1-7-23(25)33-35-29-27(58(50,51)52)11-15-9-19(56(44,45)46)3-5-21(15)31(29)41)37-38(43)18-2-8-24(26(40)14-18)34-36-30-28(59(53,54)55)12-16-10-20(57(47,48)49)4-6-22(16)32(30)42;;;;;;/h1-14,39-42H,(H,44,45,46)(H,47,48,49)(H,50,51,52)(H,53,54,55);;;;;;/q;2*+2;4*+1/p-8/b35-33+,36-34+,38-37+;;;;;;
- Substance type : Organic
- Physical state : Liquid
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:
24 - 263 mg/L CaCO3
Reference substance (positive control):
not specified
Key result
Duration:
48 h
Dose descriptor:
EC50
Effect conc.:
25.518 mg/L
Nominal / measured:
estimated
Conc. based on:
not specified
Basis for effect:
other: Intoxication
Remarks on result:
other: Toxic

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 "m" )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and ("t" and ( not "u") )  )  and ("v" and "w" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] OR Aliphatic Nitrogen, one aromatic attach [-N] OR Aromatic Carbon [C] OR Azo [-N=N-] OR Hydroxy, aromatic attach [-OH] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Oxygen, one aromatic attach [-O-] OR Suflur {v+4} or {v+6} OR Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aryl OR Azo OR Azoxy OR Fused carbocyclic aromatic OR Overlapping groups OR Phenol OR Sulfonic acid by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aryl OR Azo OR Azoxy OR Fused carbocyclic aromatic OR Naphtalene OR Phenol OR Sulfonic acid by Organic Functional groups 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 Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Aminobiphenyl Analogs 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 SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> p-Aminobiphenyl Analogs 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 >> Alkyl phenols 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 >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes 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 by DNA binding by OECD

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 Very strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "k"

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: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Acid moiety AND Phenols, Poly AND Salt by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as No alert found by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aromatic mono-and dialkylamine (Genotox) OR Metals, oxidative stress (Nongenotox) OR Primary aromatic amine,hydroxyl amine and its derived esters (Genotox) OR Structural alert for genotoxic carcinogenicity OR Structural alert for nongenotoxic carcinogenicity by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] AND Azo [-N=N-] AND Hydroxy, aromatic attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] AND Suflur {v+4} or {v+6} AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA)

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] by Organic functional groups (US EPA)

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] AND Azo [-N=N-] AND Hydroxy, aromatic attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] AND Suflur {v+4} or {v+6} AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA)

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Aromatic Nitrogen by Organic functional groups (US EPA)

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.0494

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.691

Validity criteria fulfilled:
not specified
Conclusions:
Based on the intoxication of test organism the EC50 value was estimated to be 25.5 mg/l when [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]] bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt 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 seven closest read across substances, toxicity on daphnia magna was predicted for [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (75173-68-1). Based on the intoxication of test organism the EC50 value was estimated to be 25.5 mg/l when [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]] bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt exposed to daphnia magna for 48 hrs. Based on this value it can be concluded that the substance [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (75173-68-1) is considered to be toxic to aquatic environment and can be classified as chronic category 3 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 seven closest read across substances, toxicity on daphnia magna was predicted for [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (75173-68-1). Based on the intoxication of test organism the EC50 value was estimated to be 25.5 mg/l when [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]] bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt exposed to daphnia magna for 48 hrs. Based on this value it can be concluded that the substance [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (75173-68-1) is considered to be toxic to aquatic environment and can be classified as chronic category 3 as per the criteria mentioned in CLP regulation.    

Key value for chemical safety assessment

EC50/LC50 for freshwater invertebrates:
25.5 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 [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (75173-68-1) on the behavior and growth rate of algae. The studies are as mentioned below:  

 

The first predicted study for the target chemical (100-07-2) done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the seven closest read across substances, toxicity on daphnia magna was predicted for [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (75173-68-1). Based on the intoxication of test organism the EC50 value was estimated to be 25.5 mg/l when [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]] bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt exposed to daphnia magna for 48 hrs. Based on this value it can be concluded that the substance [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (75173-68-1) is considered to be toxic to aquatic environment and can be classified as chronic category 3 as per the criteria mentioned in CLP regulation.    

 

First predicted study was supported by the second experimental weight of evidence study for the structurally closest read across chemical (17095-24-8) from peer reviewed journal (Journal of Hazardous Materials (2014)). Aim of this study was to evaluate the toxic nature of chemical Tetrasodium 4-amino-5-hydroxy-3,6-bis[[4-[[2(sulphonatooxy)ethyl]sulphonyl] phenyl]azo]naphthalene-2,7-disulphonate (Reactive Black 5) on the growth of microcrustacea D. Similis. Neonates of less than 24 h old isolated from Daphnia culture were used for the study. Screw cap tubes, filled with 10 mL solution were used in the study in which 5 test organisms added in each vessel. 4 replicates per concentration was used. After 48 hrs of exposure, the number of immobile organisms was recorded and EC50 was calculated. Based on the immobility of daphnia similis by the chemical Tetrasodium 4-amino-5-hydroxy-3,6-bis[[4-[[2(sulphonatooxy)ethyl] sulphonyl]phenyl]azo]naphthalene-2,7-disulphonate (Reactive Black 5) for 48 hrs, the EC50 was determine to be 36 mg/l. Based on the EC50, chemical was consider as toxic and classified as aquatic chronic 3 as per the CLP classification criteria.

 

Similarly for another read across chemical (633-96-5) from peer reviewed journal (Journal of Hazardous Materials (2014)) short term toxicity was studied. Short term toxicity study to Daphnia similis was carried out for 48 hrs. Neonates of less than 24 h old isolated from Daphnia culture were used for the study. Five test organisms were placed in each screw cap tubes, filled with 10 mL solution, and then incubated at 21±0.3°C in the dark. After 48 h of exposure, the number of immobile organisms was recorded. Jspear software was used to calculate the median 50% immobilization concentration (EC50). Based on immobilization of test organism by test chemical Acid Orange 7, the EC50 value was determine to be 87 mg/l along with confidence interval (p – 0.05) of 76-99 mg/l.

 

Based on the predicted data for the target chemical [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]] bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (75173-68-1) and for the read across chemical from peer reviewed journal (Journal of Hazardous Materials (2014)), it can be concluded that the [μ-[[3,3'-[azoxybis[(2-hydroxy-p-phenylene)azo]]bis[4-hydroxynaphthalene-2,7-disulphonato]](8-)]]dicopper, tetrasodium salt (75173-68-1) is considered to be toxic to aquatic environment (aquatic algae and cyanobacteria) and can be classified as chronic 3 category as per the CLP classification criteria.