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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:
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-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen-1-yl]-5-oxo-1-(4-sulfophenyl)- 4,5-dihydro -1H-pyrazole-3-carboxylic acid
- Molecular formula: C25H18ClN9O12S3
- Molecular weight: 768.1192 g/mol
- Smiles notation: C1=CC(=CC(=C1)S(=O)(=O)O)NC2=NC(=NC(=N2)NC3=CC(=C(C=C3)S(=O)(=O)O)N=NC4C(=NN(C4=O)C5=CC=C(C=C5)S(=O)(=O)O)C(=O)O)Cl
- InChl: 1S/C25H18ClN9O12S3/c26-23-29-24(27-12-2-1-3-16(10-12)49(42,43)44)31-25(30-23)28-13-4-9-18(50(45,46)47)17(11-13)32-33-19-20(22(37)38)34-35(21(19)36)14-5-7-15(8-6-14)48(39,40)41/h1-11,19H,(H,37,38)(H,39,40,41)(H,42,43,44)(H,45,46,47)(H2,27,28,29,30,31)/b33-32+
- 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:
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.:
257.161 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 257.1 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" or "e" )  and "f" )  and "g" )  and "h" )  and "i" )  and "j" )  and "k" )  and "l" )  and ("m" and "n" )  )

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 Acid moiety OR Amides OR Hydrazines OR Triazines, Aromatic by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "c"

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: "d"

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: "e"

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

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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  AND SNAr AND SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds AND 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: "h"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Reactive unspecified by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acid moiety AND Amides AND Hydrazines AND Triazines, Aromatic by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Acid moiety AND Amides AND Hydrazines AND Triazines, Aromatic by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Acid moiety AND Amides AND Hydrazines AND Triazines, Aromatic by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.718

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.53

Validity criteria fulfilled:
not specified
Conclusions:
Based on the intoxication of daphnia magna due to the exposure of chemical 4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen -1-yl]-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid, the EC50 was 257.1 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 six closest read across substances, toxicity on daphnia magna was predicted for 4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen-1-yl]-5-oxo-1- (4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (93858-24-5). Based on the immobility of test organism the EC50 value was estimated to be 257.1 mg/l when 4-[(E)-2-(5- {[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen -1-yl]-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid exposed to daphnia magna for 48 hrs.        

Based on this EC50 value it can be concluded that the substance4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl) diazen -1-yl]-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid is considered to be nontoxic to aquatic environment and cannot 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 six closest read across substances, toxicity on daphnia magna was predicted for 4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen-1-yl]-5-oxo-1- (4-sulfophenyl)-4,5- dihydro-1H-pyrazole-3-carboxylic acid (93858-24-5). Based on the immobility of test organism the EC50 value was estimated to be 257.1 mg/l when 4-[(E)-2-(5- {[(2Z,4E)-6-chloro-4- [(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen -1-yl]-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid exposed to daphnia magna for 48 hrs. Based on this EC50 value it can be concluded that the substance 4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}- 2-sulfophenyl) diazen -1-yl]-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid is considered to be nontoxic to aquatic environment and cannot classified as per the criteria mentioned in CLP regulation.         

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates
Effect concentration:
257.1 mg/L

Additional information

Various predicted data for the target compound 4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen-1-yl]-5-oxo-1- (4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (93858-24-5) 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 (2018), based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, toxicity on daphnia magna was predicted for 4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen-1-yl]-5-oxo-1- (4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (93858-24-5). Based on the immobility of test organism the EC50 value was estimated to be 257.1 mg/l when 4-[(E)-2-(5- {[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen -1-yl]-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid exposed to daphnia magna for 48 hrs. Based on this EC50 value it can be concluded that the substance4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl) diazen -1-yl]-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid is considered to be nontoxic to aquatic environment and cannot classified as per the criteria mentioned in CLP regulation.         

 

In second prediction using 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 programe, the LC 50 value for short term toxicity to aquatic invertebrates was predicted to be 2475.6 mg/l for 4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl) imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen-1-yl]-5-oxo-1 -(4-sulfophenyl)- 4,5-dihydro-1H-pyrazole-3-carboxylic acid in 48 hrs. Based on this value it can be concluded that the substance 4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen-1-yl]-5-oxo-1 -(4-sulfophenyl)- 4,5-dihydro-1H-pyrazole-3-carboxylic acid is considered to be not toxic to aquatic environment and cannot be classified as per the criteria mentioned in CLP regulation.

 

 

Similarly in the third weight of evidence study for the read across chemical (70616-89-6) from ABITEC study was carried out. Short term toxicity of trisodium 2-({6-[(4-amino-6-chloro-1,3,5-triazin-2-yl)(methyl)amino]-1-hydroxy-3-sulfonato-2-naphthyl}diazenyl)naphthalene-1,5-disulfonate to aquatic invertebrates was performed according to the OECD guideline in a static system for the total exposure period of 48 hr. The stock solution 250 mg/l was prepared by dissolving redbrown powder in reconstituted water. Test solutions of required concentration as were prepared by mixing the stock solution of the test sample with reconstituted test water. Chemical was tested at 0 , 45, 67, 100, 150, 225 mg/l nominal concentrations. Effects on immobilisation were observed for 48 hours. With the test substance one positive control Potassium dichromate (K2Cr2O7) was also run simultaneously. After the exposure of chemical, effect concentration EC50 was calculated using nonlinear regression by the software Prism 4.0. The median effective concentration (EC50) for the test substance trisodium2-({6-[(4-amino-6-chloro-1,3,5-triazin-2-yl)(methyl)amino]-1-hydroxy-3-sulfonato-2-naphthyl}diazenyl) naphthalene-1,5-disulfonate, in Daphnia magna was determined to be 229 mg/l. On the basis of mobility inhibition effects in a 48 hour study. Based on the EC50 value, indicates that the substance is likely to be non-hazardous to aquatic invertebrates and cannot be classified as per the CLP criteria.

 

Similarly in a supporting weight of evidence study from Ecotoxicology and Environmental Safety, 1999 for read across chemical (1934-21-0) study were to determine the toxicity of a chemical Trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate (Tartrazine; Food yellow 4) on the growth of water flea Ceriodaphnia cf. dubia. Stock solutions were made by dissolving the appropriate amount in 1 or 2 L of the water described previously and then gently stirred for 12 h in the dark at 23 ± 1°C using Teflon magnetic stirrers. Light was excluded during the stirring to minimize photodegradation of the chemicals. Stock solutions were diluted to the appropriate concentrations immediately prior to the commencement of a test. Test was conducted on the < 24hrs old water flea. 250-ml glass beakers which held 200 ml of the test solution or control solution having headspace of 50 ml were used. The absence of visible movement by the cladocera within 15 s of gentle agitation of the test solution was observed at 5706.55 mg/l. Based on the immobilization of Ceriodaphnia cf. dubia due to the exposure of chemical Trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo) pyrazole-3-carboxylate, the EC50 was 5706.55 mg/l. Thus based on the EC50, the chemical was consider as nontoxic and can be consider to be not classified.

 

Similarly fourth study was conducted on the read across chemical selected on the basis of structure similarity (1934-21-0) from The Journal of Toxicological Sciences, 1977. Short term toxicity study to Artemia Salina was carried out for 24-48 hrs. The test chemical conc. used for the study was 5343.68 mg/l and 534.368 mg/l, respectively. A. salina eggs (encysted dried gastrulae) were commercially obtained, and were stored at -20°C, Eggs used in experiments were washed and stored at room temperature in a desiccator over anhydrous granular CaCl, . Larvae were obtained by incubating eggs in petri dishes containing muslin-filtered sea water at 30°C for 24 hours. The larvae were separated from shells, dead larvae and unhatched eggs by their phototactic movements toward a light source. Food dyes of various concentrations were placed in a petri dish, and sea water containing 20 to 30 larvae was added. After this was incubated at 30°C for 24 hours and 48 hours, larvae surviving were measured by direct count. The same method was tested from 5 to 6 times for each concentration, and the death rate was calculated. The study was performed under static conditions for 24 – 48 hrs at 30°C. Death was assumed to have occurred when there was no movement. The death rate was defined as the average of the percentage of deaths observed for 24 hours and 48 hours. Based on death rate or mortality of test organism, the LC83.8 value was determine to be 5343.68 mg/l. The chemical was considered as not classified according to the CLP regulation.

 

On the basis of above results for target chemical 4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen-1-yl]-5-oxo-1- (4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid (93858-24-5) (from OECD QSAR toolbox version 3.3, and EPIsuite, 2017) and for its read across substance from ABITEC report, peer reviewed journal Ecotoxicology and Environmental Safety, 1999 and The Journal of Toxicological Sciences, 1977, it can be concluded that the test substance 4-[(E)-2-(5-{[(2Z,4E)-6-chloro-4-[(3-sulfophenyl)imino]-1,2,3,4-tetrahydro-1,3,5-triazin-2-ylidene]amino}-2-sulfophenyl)diazen-1-yl]-5-oxo-1- (4-sulfophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid is not toxic and can be consider to be not classified as toxic as per the CLP classification criteria.