4-[(2,4-dimethylphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one

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 3.3.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (IUPAC name): 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one
- Common name: Solvent Yellow 18
- Molecular formula: C18H18N4O
- Molecular weight: 306.367 g/mol
- Smiles notation: O=C1N(N=C(C)[C@@H]1\N=N\c1c(cc(cc1)C)C)c1ccccc1
- InChl: 1S/C18H18N4O/c1-12-9-10-16(13(2)11-12)19-20-17-14(3)21-22(18(17)23)15-7-5-4-6-8-15/h4-11,17H,1-3H3/b20-19+
- 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

Hardness:

250 mg/L expressed as CaCO3

Test temperature:

19.6 - 20.4°C

pH:

7.8 - 7.9

Dissolved oxygen:

8.2 - 8.5 mg/l

Nominal and measured concentrations:

Estimated data

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

109.468 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: Other details not known

Details on results:

The EC50 was 109.46 mg/l for the exposure period of 48 hrs.

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" or "e" or "f" or "g" )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and "l" )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and "q" )  and ("r" and ( not "s") )  )  and ("t" and ( not "u") )  )  and ("v" and ( not "w") )  )  and ("x" and "y" )  )

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 >> Aromatic azo AND SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding by OECD

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Schiff base formation AND Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives AND Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives >> Pyrazolones and Pyrazolidinones  by Protein binding by OASIS v1.3

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 SN2 AND SN2 >> SN2 reaction at sp3 carbon atom AND SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo by Protein binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Amides AND Hydrazines by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Amides OR Hydrazines by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "f"

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 SN2 AND SN2 >> SN2 reaction at sp3 carbon atom AND SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo by Protein binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Amides AND Hydrazines by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "i"

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 AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide 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) >> Hydrazine 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  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives 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 >> 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 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.1.3

Domain logical expression index: "j"

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 SN2 AND SN2 >> SN2 reaction at sp3 carbon atom AND SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo by Protein binding by OECD

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Acylation >> Direct Acylation Involving a Leaving group >> Azlactone OR Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - ketones OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinone-imine OR No alert found by Protein binding by OECD

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 Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Group 17 - Halogens F by Chemical elements

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Alkyl arenes AND Aryl AND Azo AND Pyrazolone AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Alkoxy by Organic Functional groups

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Amide, aliphatic attach [-C(=O)N] AND Amino, aliphatic attach [-N<] AND Amino-carbonyl compound [NCC(=O)-C] AND Aromatic Carbon [C] AND Azo [-N=N-] AND Azomethine, aliphatic attach [-N=C] AND Carbonyl, aliphatic attach [-C(=O)-] AND Hydrazine [>N-N<] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen, two or tree olefinic attach [>N-] AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Carbonyl, one aromatic attach [-C(=O)-] by Organic functional groups (US EPA)

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael addition to activated double bonds in heterocyclic ring systems AND AN2 >> Michael addition to activated double bonds in heterocyclic ring systems >> Pyrazolone and Pyrazolidine Derivatives AND AN2 >> Shiff base formation with carbonyl compounds AND AN2 >> Shiff base formation with carbonyl compounds >> Pyrazolone and Pyrazolidine Derivatives by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as AN2 >> Michael-type addition to quinoid structures >> Carboxylic Acid Amines by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is >= 4.84

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is <= 7.54

Validity criteria fulfilled:

not specified

Conclusions:

Based on the immobility of daphnia magna due to the 4-[(E)-2-(2,4-dimethylphenyl) diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one, the EC50 was 109.46 mg/l.

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 five closest read across substances, toxicity on test organism Daphnia magna predicted for 4-[(E)-2-(2,4-dimethylphenyl) diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (6407-78-9). The EC50 value was estimated to be109.46 mg/l when 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one exposed to daphnia magna for 48 hrs. Based on this value it can be concluded that the substance 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5- dihydro-1H- pyrazol-5-one (6407-78-9) is 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 3.3 with log kow as the primary descriptor and considering the five closest read across substances, toxicity on test organism Daphnia magna predicted for 4-[(E)-2-(2,4-dimethylphenyl) diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (6407-78-9). The EC50 value was estimated to be109.46 mg/l when 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one exposed to daphnia magna for 48 hrs. Based on this value it can be concluded that the substance 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5- dihydro-1H- pyrazol-5-one (6407-78-9) is 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:

109.46 mg/L

Additional information

Various predicted data for the target compound 4-[(E)-2-(2,4-dimethylphenyl) diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (6407-78-9) and experimental data for supporting weight of evidence studies for its closest read across substance with log Kow as the primary descriptor and on the basis of structural and functional similarity study 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 3.3 with log kow as the primary descriptor and considering the five closest read across substances, toxicity on test organism Daphnia magna predicted for 4-[(E)-2-(2,4-dimethylphenyl) diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (6407-78-9). The EC50 value was estimated to be109.46 mg/l when 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one exposed to daphnia magna for 48 hrs. Based on this value it can be concluded that the substance 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5- dihydro-1H- pyrazol-5-one (6407-78-9) is considered to be not toxic to aquatic environment and not classified as per the criteria mentioned in CLP regulation. 

 

First predicted study was supported by the structurally similar read across chemical (85-83-6) study were to determine the toxicity of a chemical. Determination of the inhibition of the mobility of daphnids was carried out with the substance 1-(2-Methyl-4-(2-methylphenylazo)phenylazo)-2-naphthol. Test was conducted according to OECD Guideline 202. The stock solution 2 g/L was prepared by dissolving brown powder in acetone. Test solutions of required concentration as were prepared by mixing the stock solution of the test sample with reconstituted test water. The test substance was tested at the concentrations 0, 0, 0.6, 1.2, 2.5, 5, 10 mg/l nominal concentrations. Effects on immobilisation were observed for 48 hours. The median effective concentration (EC50) for the test substance, 1-(2-Methyl-4-(2-methylphenylazo)phenylazo)-2-naphthol, in Daphnia magna was determined to be 3.9 mg/L. This value indicates that the substance is likely to be hazardous to aquatic algae and can be classified as aquatic chronic 2 as per the CLP criteria. But as the chemical was readily biodegradable in water so on the basis of biodegradability, it can be concluded that the chemical 1-(2-Methyl-4-(2-methylphenylazo) phenylazo)-2-naphthol was nontoxic and can be consider to be not classified as per the CLP classification criteria.

 

Similarly in the third weight of evidence study for the functionally similar read across chemical (12225-21-7) from ABITEC report 2017. 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 No12225-21-7) is likely to be non-hazardous to aquatic invertebrates and can be classified as "not classified" as per the CLP criteria.

 

On the basis of above results for target chemical 4-[(E)-2-(2,4-dimethylphenyl) diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (6407-78-9) (from OECD QSAR toolbox version 3.3) and for its read across substance from ABITEC 2017, it can be concluded that the test substance 4-[(E)-2-(2,4-dimethylphenyl) diazen-1-yl]-3-methyl-1-phenyl- 4,5-dihydro-1H-pyrazol-5-one (6407-78-9) is nontoxic to aquatic environment and cannot be classified as per the criteria mentioned in CLP regulation.