4-hydroxy-6-(methylamino)naphthalene-2-sulphonic acid

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

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

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 (IUPAC name): 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid
- Molecular formula: C11H11NO4S
- Molecular weight: 253.2769 g/mol
- Smiles notation: CNc1ccc2cc(cc(c2c1)O)S(=O)(=O)O
- InChl: 1S/C11H11NO4S/c1-12-8-3-2-7-4-9(17(14,15)16)6-11(13)10(7)5-8/h2-6,12-13H,1H3,(H,14,15,16)
- Substance type: Organic
- Physical state: Solid

Analytical monitoring:

not specified

Details on sampling:

No data available

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

Post exposure observation period:

No data available

Hardness:

No data available

Test temperature:

No data available

pH:

No data available

Dissolved oxygen:

No data available

Salinity:

No data available

Conductivity:

No data available

Nominal and measured concentrations:

Estimated data

Details on test conditions:

No data available

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

308.738 mg/L

Nominal / measured:

estimated

Conc. based on:

not specified

Basis for effect:

other: Intoxication

Remarks on result:

other: Other details not known

Details on results:

The EC50 was 308.738 mg/l

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 "m" )  and ("n" and "o" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Secondary aromatic amine by DNA binding by OECD

Domain logical expression index: "b"

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

Domain logical expression index: "c"

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: "d"

Referential boundary: The target chemical should be classified as Acid moiety AND Phenols 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 on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones 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 >> 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) >> Nitroarenes with Other Active Groups 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 reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups 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, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones 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 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 Protein binding by OECD

Domain logical expression index: "h"

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 >> Ring Opening Acylation OR Acylation >> Ring Opening Acylation >> alpha-Lactams 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 by Protein binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as High (Class III) AND Low (Class I) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No Data by Ultimate biodeg

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as > 100 days OR 1 to 10 days by Ultimate biodeg

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"

Similarity boundary:Target: CNc1ccc2cc(S(O)(=O)=O)cc(O)c2c1
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.93

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.39

Validity criteria fulfilled:

not specified

Conclusions:

The EC50 was estimated to be 308.738 mg/l based on the intoxication of daphnia magna due to the exposure with chemical 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid.

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 for4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (6259-53-6). Based on the intoxication of test organism the EC50 value was estimated to be 308.738 mg/l when 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid exposed to daphnia magna for 48 hrs. Based on this value it can be concluded that the substance 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acidis considered to be not toxic to aquatic environment and not 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 for 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (6259-53-6). Based on the intoxication of test organism the EC50 value was estimated to be 308.738 mg/l when 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid exposed to daphnia magna for 48 hrs. Based on this value it can be concluded that the substance 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acidis considered to be not toxic to aquatic environment and not classified as per the criteria mentioned in CLP regulation.     

 

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

308.73 mg/L

Additional information

Various predicted data for the target compound 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (6259-53-6) and supporting weight of evidence studies for its closest read across substance with structural similarity and 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 was predicted for 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (6259-53-6). Based on the intoxication of test organism the EC50 value was estimated to be 308.738 mg/l when 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid exposed to daphnia magna for 48 hrs. Based on this value it can be concluded that the substance 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acidis considered to be not toxic to aquatic environment and not classified as per the criteria mentioned in CLP regulation.     

 

 

Similarly in a supporting weight of evidence study from ABITEC report for (130-23-4) study were to determine the toxicity of a chemical 4-amino-5-hydroxynaphthalene-1,7-disulphonic acid on the growth of water flea daphnia magna. Determination of the inhibition of the mobility of daphnids was carried out with the substance 4-amino-5-hydroxynaphthalene-1,7-disulphonic acid according to OECD Guideline 202. The test substance was tested at the concentrations of 0 for 3 controls and 5, 10, 25, 100, 200 mg/L for test chemical. Effects on immobilisation were observed for 48 hours. The median effective concentration (EC50) for the test substance, 4-amino-5-hydroxynaphthalene-1,7-disulphonic acid, in Daphnia magna was determined to be 500 mg/L for immobilisation effects. This value indicates that the substance 4-amino-5-hydroxynaphthalene-1,7-disulphonic acid is likely to be non-hazardous to aquatic invertebrates and cannot be classified as toxic as per the CLP criteria.

 

Similarly in a third supporting weight of evidence study from Chemosphere, 1994 for the structural similar read across chemical (121-57-3) toxicological profile for the sulfonic acids were study. Total 24hrs of exposure was provided to the daphnia magna. From the study the EC50 value for short term toxicity to aquatic invertebrates for Sulfanilic acid (121-57-3) in 24 hrs was determined to be 109.13 mg/l. Based on the result, Sulfanilic acid (121-57-3) was considered as not classified as per the CLP regulations.

 

Further study for the read across chemical (98-40-8) supports the classification of target chemical. Study for the read across chemical was taken from Chemosphere 1994. Study was conducted to determine the toxic nature of chemical 2-(Ethylamino) toluene-4-sulphonic acid on the mobility of daphnia magna. The EC50 value for short term toxicity to aquatic invertebrates daphnia magna for 2-(Ethylamino)toluene-4-sulphonic acid in 24 hrs and 48hrs was determined to be 170 mg/l and 154 mg/l. Based on the EC50 value, it can be concluded that the chemical 2-(Ethylamino) toluene-4-sulphonic acid was nontoxic and can be consider to be not classified as per the CLP classification criteria.

 

Similarly fifth study was conducted on the read across chemical selected on the basis of structure similarity 2-Naphthalenecarboxylic acid, 3-hydroxy-4-[(4-methyl-2-sulfophenyl) azo]-, calcium salt (D & C Red no. 7) (5281-04-9) from the OECD SIDS Initial Assessment Report. Detection of the effect of D & C Red no. 7 on the growth of daphnia magna by following standard OECD guideline. The test was performed in static system by following the OECD guideline. Daphnia magna exposed with the chemical for 24hrs. Based on the immobilization of daphnia magna by the chemical 2-Naphthalenecarboxylic acid, 3-hydroxy-4-[(4-methyl-2-sulfophenyl) azo]-, calcium salt (D & C Red no. 7) for 24hrs, the EC50 was 280 mg/l.

 

On the basis of above results for target 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (6259-53-6) (from OECD QSAR toolbox version 3.4) and for its read across substance from ABITEC report, peer reviewed journal Chemosphere 1994 and SIDS report, it can be concluded that the test substance 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (6259-53-6) is not toxic and can be consider to be not classified as toxic as per the CLP classification criteria.