4,4'-dihydroxy-7,7'-iminodi(naphthalene-2-sulphonic acid)

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:

The supporting 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 with logKow as the primary descriptor.

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):

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

Details on test organisms:

No data available

Test type:

static

Water media type:

freshwater

Total exposure duration:

72 h

Hardness:

24 mg/L as CaCO3

Test temperature:

21 °C

pH:

7.3 - 8.0

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:

72 h

Dose descriptor:

EC50

Effect conc.:

177.022 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

growth rate

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

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 >> 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 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) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 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 >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids 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, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines 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 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 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 >> Hydroquinones OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes by DNA binding by OECD

Domain logical expression index: "i"

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: "j"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Known precedent reproductive and developmental toxic potential OR Non-steroid nucleus derived estrogen receptor (ER) and androgen receptor (AR) OR Non-steroid nucleus derived estrogen receptor (ER) and androgen receptor (AR) >> 4-alkylphenol-like derivatives (2b-3) OR Polyhalogenated benzene derivatives (8c) OR Steroid derivatives OR Steroid nucleus derived ER and AR binders OR Steroid nucleus derived ER and AR binders >> Estradiol-like compounds (2a-1) by DART scheme v.1.0

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"

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: "o"

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: "p"

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

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Oxyphenistain (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Chlorphentermine (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.348

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.58

Validity criteria fulfilled:

not specified

Conclusions:

The median Effective concentration (EC50) value for 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid on Pseudokirchneriella subcapitata in a 72 hour study was estimated to be 177.0217 mg/L on the basis of effects on growth rate.

Executive summary:

Using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the six closest read across substances, the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS no. 87-03-6). EC50 value was estimated to be 177.0217 mg/l for Pseudokirchneriella subcapitata for 72 h duration. 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 non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

Description of key information

Using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the six closest read across substances, the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS no. 87-03-6). EC50 value was estimated to be 177.0217 mg/l for Pseudokirchneriella subcapitata for 72 h duration. 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 non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

Key value for chemical safety assessment

EC50 for freshwater algae:

177.022 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 end point which are summarized as below:

 

In a prediction done by SSS (2017) Using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the six closest read across substances, the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid (CAS no. 87-03-6). EC50 value was estimated to be 177.0217 mg/l for Pseudokirchneriella subcapitata for 72 h duration. 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 non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

 

In second prediction using the Estimation Programs Interface Suite (EPI suite, 2017), toxicity measured. Based on the prediction done using the EPI Suite ECOSAR version 1.10, the short term toxicity on green algae was predicted for test substance 4-hydroxy-7-[(5-hydroxy-7 -sulfo- naphthalen-2-yl)amino]naphthalene-2-sulfonic acid (87-03 -6). On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene-2-sulfonic acid is estimated to be 1547.719 mg/l for green algae for 96 hrs duration. Based on this value, it can be concluded that the test chemical 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)amino]naphthalene -2-sulfonic acid can be considered as non-toxic to green algae at environmentally relevant concentrations and can be considered not-classified as toxic as per the CLP classification criteria.

 

Similarly in a supporting weight of evidence study from ECOTOX database 2017 for read across chemical Isopropylamine (75-31-0), Determination of short term toxicity of Isopropyl amine on the population of green algae (Pseudokirchneriella Subcapitata) for 4 days of exposure. Test performed by static system where 8.0 E+4 CELLS/ML was present in the vessel and exposed with the chemical for 96 hrs. (4 days). After the exposure inhibitory concentration was measured on the basis of changes in the population. Based on the changes in population of green algae (Pseudokirchneriella Subcapitata) due to the exposure with chemical for 96 hrs, the IC50 was 118.4 mg/l. Based on the IC50, 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.

 

Similarly in a supporting weight of evidence study from ECOTOX database 2017, for the read across chemical Butan-1-amine (CAS no. 109-73-9), toxicity experiment was conducted for evaluating the effect of read across substance. Short term toxicity study of chemical Butan-1-amine on green algae Chlorococcales was studied for 1 day. Study was conducted by static system for 24 hrs. Based on the Physiology and Assimilation efficiency of green algae (Chlorococcales), the EC10 was 1000 mg/l after the exposure of 1 day. Thus based on the EC10, it can be concluded that test chemical Butan-1-amine is not toxic and can be consider to be not classified 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 per the CLP classification criteria.