Trisodium 4-[[4-chloro-6-[(4-sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2-[[1-(2,5-dichloro-4-sulphonatophenyl)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-4-yl]azo]benzenesulphonate

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:

other: as mentioned below

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.3 with logKow as the primary descriptor.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): trisodium 2,5-dichloro-4-(4-{[5-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate
- Molecular formula : C25H18Cl3N9O10S3.3Na
- Molecular weight : 872.974 g/mol
- Smiles notation : c1(\N=N\c2c(n(c3cc(c(S([O-])(=O)=O)cc3Cl)Cl)nc2C)O)cc(ccc1S(=O)(=O)[O-])Nc1nc(nc(n1)Cl)Nc1ccc(cc1)S(=O)(=O)[O-].[Na+].[Na+].[Na+]
- InChl : 1S/C25H18Cl3N9O10S3.3Na/c1-11-21(22(38)37(36-11)18-9-16(27)20(10-15(18)26)50(45,46)47)35-34-17-8-13(4-7-19(17)49(42,43)44)30-25-32-23(28)31-24(33-25)29-12-2-5-14(6-3-12)48(39,40)41;;;/h2-10,38H,1H3,(H,39,40,41)(H,42,43,44)(H,45,46,47)(H2,29,30,31,32,33);;;/q;3*+1/p-3
- Substance type:Organic
- Physical state: Solid

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Desmodesmus subspicatus (previous name: Scenedesmus subspicatus)

Test type:

static

Water media type:

freshwater

Total exposure duration:

72 h

Test temperature:

22 °C

pH:

8.1-8.3

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

244.371 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

growth rate

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 ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and "m" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Substituted Triazines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding by OECD ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Schiff base formation OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives >> Pyrazolones and Pyrazolidinones  OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.3 ONLY

Domain logical expression index: "d"

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 SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD 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 >> 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 AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters 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 >> Coumarins OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Radical OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Coumarins OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters 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 >> 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 >> Coumarins OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters 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 by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND Group All Melting Point > 200 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as (!Undefined)Group C Surface Tension > 62 mN/m OR (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR Group All log Kow > 9 OR Group CN Aqueous Solubility < 0.0001 g/L OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN log Kow > 5.5 OR Group CN Melting Point > 180 C OR Group CN Molecular Weight > 290 g/mol OR Group CN Molecular Weight > 540 g/mol OR Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.481

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.721

Validity criteria fulfilled:

not specified

Conclusions:

The median Effective concentration (EC50) value for trisodium 2,5-dichloro-4-(4-{[5-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate on Desmodesmus subspicatus in a 72 hour study was estimated to be 244.37 mg/L on the basis of effects on growth rate.

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, the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance trisodium 2,5 -dichloro-4 -(4 -{[5 -({4 -chloro-6 -[(4 -sulfonatophenyl)amino]-1,3,5 -triazin-2 -yl}amino)-2 -sulfonatophenyl]diazenyl}-3 -methyl-5 -oxo-4,5 -dihydro-1H-pyrazol-1 -yl)benzenesulfonate (CAS no. 50662 -99 -2). EC50 value was estimated to be 244.37 mg/l for Desmodesmus subspicatus for 72 h duration. Based on this value it can be concluded that the substance trisodium 2,5 -dichloro-4 -(4 -{[5 -({4 -chloro-6 -[(4 -sulfonatophenyl)amino]-1,3,5 -triazin-2 -yl}amino)-2 -sulfonatophenyl]diazenyl}-3 -methyl-5 -oxo-4,5 -dihydro-1H-pyrazol-1 -yl)benzenesulfonate 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

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, the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance trisodium 2,5 -dichloro-4 -(4 -{[5 -({4 -chloro-6 -[(4 -sulfonatophenyl)amino]-1,3,5 -triazin-2 -yl}amino)-2 -sulfonatophenyl]diazenyl}-3 -methyl-5 -oxo-4,5 -dihydro-1H-pyrazol-1 -yl)benzenesulfonate (CAS no. 50662 -99 -2) (2017). EC50 value was estimated to be 244.37 mg/l for Desmodesmus subspicatus for 72 h duration. Based on this value it can be concluded that the substance trisodium 2,5 -dichloro-4 -(4 -{[5 -({4 -chloro-6 -[(4 -sulfonatophenyl)amino]-1,3,5 -triazin-2 -yl}amino)-2 -sulfonatophenyl]diazenyl}-3 -methyl-5 -oxo-4,5 -dihydro-1H-pyrazol-1 -yl)benzenesulfonate 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:

244.37 mg/L

Additional information

1 predicted data for the target chemical trisodium 2,5 -dichloro-4 -(4 -{[5 -({4 -chloro-6 -[(4 -sulfonatophenyl)amino]-1,3,5 -triazin-2 -yl}amino)-2 -sulfonatophenyl]diazenyl}-3 -methyl-5 -oxo-4,5 -dihydro-1H-pyrazol-1 -yl)benzenesulfonate (CAS no. 50662 -99 -2) which is supported further by total 2 weight of evidence studies (from peer reviewed journal and authoritative database) for its closest read across substance with log Kow as the primary descriptor were reviewed for the toxicity to aquatic algae and cyanobacteria end point which are summarized as below:

 

Short term toxicity on aquatic algae and cyanobacteria of target chemical trisodium 2,5 -dichloro-4 -(4 -{[5 -({4 -chloro-6 -[(4 -sulfonatophenyl)amino]-1,3,5 -triazin-2 -yl}amino)-2 -sulfonatophenyl]diazenyl}-3 -methyl-5 -oxo-4,5 -dihydro-1H-pyrazol-1 -yl)benzenesulfonate (CAS no. 50662 -99 -2) is predicted using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances (2017). EC50 value was estimated to be 244.37 mg/l for Desmodesmus subspicatus for 72 h duration.

 

In a supporting weight of evidence study of read across chemical 4 -amino-3,5,6 -trichloropyridine-2 -carboxylic acid (CAS no. 1918 -02 -1) from peer reviewed journal (V. M. Thomas et. al; 1973), short term toxicity to Chlorella pyrenoidosa study was carried out for 48 hrs. Paper disc agar diffusion method was used for determining the sensitivity of the test organism to 4 -amino-3,5,6 -trichloropyridine-2 -carboxylic acid. The study was based on the effects of the read across compound 4 -amino-3,5,6 -trichloropyridine-2 -carboxylic acid on green algae in a static fresh water system. Chlorella pyrenoidosa was used as a test organism. Test chemical conc. used for the study was 1000 mg/l (1 mg/l). Test solution of appropriate conc. was prepared using the ethanol as a solvent. Chlorella seeded agar plates were prepared using the buffered medium. Sterile paper discs (6 mm) containing 20µl of test solution with the appropriate solvent was used. Growth inhibition of test organism was determined by measuring the diameter of inhibition zone around the paper discs. Based on effect on growth inhibition of the test organism Chlorella pyrenoidosa, the 48 hr EC0 value was determined to be 1000 mg/l, respectively.

 

Another short term toxicity study to Pseudokirchneriella subcapitata (green algae) of the same read across chemical 4 -amino-3,5,6 -trichloropyridine-2 -carboxylic acid (CAS no. 1918 -02 -1) was carried out for 24 hrs (HSDB authoritative database, 2016). The study was based on the effects of the read across compound 4 -amino-3,5,6 -trichloropyridine-2 -carboxylic acid on green algae in a static fresh water system at a pH 7.7. Based on effect on physiology and photosynthesis of the test organism Pseudokirchneriella subcapitata (green algae), the 24 hr EC50 value was determined to be 115 mg/l.

 

Thus, based on the overall reported results for target chemical trisodium 2,5 -dichloro-4 -(4 -{[5 -({4 -chloro-6 -[(4 -sulfonatophenyl)amino]-1,3,5 -triazin-2 -yl}amino)-2 -sulfonatophenyl]diazenyl}-3 -methyl-5 -oxo-4,5 -dihydro-1H-pyrazol-1 -yl)benzenesulfonate (OECD QSAR toolbox version 3.3, 2017) and for its read across substance (from peer reviewed journal and authoritative database), it can be concluded that the test substance trisodium 2,5 -dichloro-4 -(4 -{[5 -({4 -chloro-6 -[(4 -sulfonatophenyl)amino]-1,3,5 -triazin-2 -yl}amino)-2 -sulfonatophenyl]diazenyl}-3 -methyl-5 -oxo-4,5 -dihydro-1H-pyrazol-1 -yl)benzenesulfonate can be considered as non-toxic to aquatic environment and thus can be considered to be not classified as per the CLP classification criteria.