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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:
Data is from OECD QSAR toolbox version 3.4 and the QMRF report has been attached.
Qualifier:
according to
Guideline:
other: Estimated data
Principles of method if other than guideline:
Prediction was done using the OECD QSAR toolbox version 3.4.
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid
- Molecular formula: C20H15NO8S2
- Molecular weight: 461.47 g/mol
- Smiles notation: O=S(=O)(O)c1cc(O)c2c(cc(Nc3ccc4c(cc(S(=O)(=O)O)cc4O)c3)cc2)c1
- InChl: 1S/C20H15NO8S2/c22-19-9-15(30(24,25)26)7-11-5-13(1-3-17(11)19)21-14-2-4-18-12(6-14)8-16(10-20(18)23)31(27,28)29/h1-10,21-23H,(H,24,25,26)(H,27,28,29)
- 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
Limit test:
no
Total exposure duration:
48 h
Hardness:
96 mg/L as CaCO3
Test temperature:
24 to 26 °C
pH:
7.8
Dissolved oxygen:
No data available
Salinity:
No data available
Conductivity:
No data available
Nominal and measured concentrations:
No data available
Details on test conditions:
No data available
Reference substance (positive control):
not specified
Key result
Duration:
48 h
Dose descriptor:
EC50
Effect conc.:
332.839 mg/L
Nominal / measured:
estimated
Conc. based on:
test mat.
Basis for effect:
other: Intoxication
Remarks on result:
other: Nontoxic

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Very strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> N-Substituted Aromatic Amines AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Phenols by Protein binding by OASIS v1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Class 2 (less inert compounds) by Acute aquatic toxicity classification by Verhaar (Modified)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid moiety AND Phenols, Poly 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 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones and Trihydroxybenzenes 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 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 >> Quinones and Trihydroxybenzenes OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones and Trihydroxybenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> p-Substituted Mononitrobenzenes OR SN2 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, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom 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 >> Haloalkanes Containing Heteroatom 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 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.4

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 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 >> 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 Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethanolamines (including morpholine) 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 >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas 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 No alert found by Protein binding by OECD

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates OR Acylation >> Direct Acylation Involving a Leaving group >> Azlactone OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halocarbonyls OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-pyridines OR SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Class 2 (less inert compounds) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "o"

Similarity boundary:Target: Oc1cc(S(O)(=O)=O)cc2cc(Nc3ccc4c(c3)cc(S(O)(=O)=O)cc4O)ccc12
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Similarity boundary:Target: Oc1cc(S(O)(=O)=O)cc2cc(Nc3ccc4c(c3)cc(S(O)(=O)=O)cc4O)ccc12
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

Similarity boundary:Target: Oc1cc(S(O)(=O)=O)cc2cc(Nc3ccc4c(c3)cc(S(O)(=O)=O)cc4O)ccc12
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Aromatic alcohol  [-OH] AND Aromatic amine   [-NH2  or  -NH-] AND Aromatic-H AND Sulfonic acid / salt -> aromatic attach by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Carbon with 4 single bonds & no hydrogens by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "t"

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

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.268

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.82

Validity criteria fulfilled:
not specified
Conclusions:
The EC50 value was estimated to be 332.83 mg/l when 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid 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 predicted for 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (87 -03 -6). The EC50 value was estimated to be 332.83 mg/l when 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid exposed to Daphnia magna for 48 hrs.

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 predicted for 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (87 -03 -6). The EC50 value was estimated to be 332.83 mg/l when 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid exposed to Daphnia magna for 48 hrs.

Key value for chemical safety assessment

EC50/LC50 for freshwater invertebrates:
332.83 mg/L

Additional information

Various predicted data for the target compound 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl) amino]naphthalene-2-sulfonic acid (CAS no. 87-03-6) and supporting weight of evidence studies for its closest read across substance with log Kow as the primary descriptor were reviewed for the toxicity on the invertebrates end point which are summarized as below:

 

In a prediction done by SSS (2017), 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 predicted for 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (87 -03 -6). The EC50 value was estimated to be 332.83 mg/l when 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid exposed to Daphnia magna for 48 hrs.

 

In second prediction using the Estimation Programs Interface Suite (EPI suite, 2017), toxicity measured. Based on the prediction done by EPI suite, ECOSAR version 1.1, on the basis of similarity of structure to chemicals for which the aquatic toxicity has been previously measured by structure-activity relationships (SARs) program, the LC 50 value for short term toxicity to aquatic invertebrates was predicted. On the basis of this program, the LC 50 value for short term toxicity to aquatic invertebrates was predicted to be 3537.372 mg/l for 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl) amino]naphthalene-2-sulfonic acid in 48 hrs. Based on this value it can be concluded that the substance 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl) amino]naphthalene-2- sulfonic acid is considered to be not toxic to aquatic environment and cannot be classified as per the criteria mentioned in CLP regulation.

 

Similarly in a supporting weight of evidence study from ECOTOX database 2017 for read across chemical Isopropylamine (75-31-0), toxicity experiment was conducted for evaluating the effect of read across substance. Determination of short term toxicity of Isopropyl amine on the mobility of daphnia magna for 48hrs. Test performed by static system. After the exposure effect concentration was measured on the basis of intoxication were effect measured by the immobility of daphnia magna. Based on the immobilization of daphnia magna due to the exposure with chemical for 48 hrs, the EC50 was 197.6 mg/l. Based on the EC50, it can be concluded that the chemical was nontoxic and can be consider to be not classified as toxic as per the CLP classification criteria.

 

On the basis of above results for target chemical 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl) amino]naphthalene-2-sulfonic acid (CAS no. 87-03-6) (from OECD QSAR toolbox version 3.3 and EPI suite, 2017) and for its read across substance from ECOTOX database it can be concluded that the test substance 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl) amino]naphthalene-2-sulfonic acid is not toxic and can be consider to be not classified as toxic as per the CLP classification criteria.