Disodium [5-chloro-3-[[4,5-dihydro-3-methyl-5-oxo-1-(3-sulphophenyl)-1H-pyrazol-4-yl]azo]-2-hydroxybenzene-1-sulphonato(4-)]hydroxychromate(2-)

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 the test material (IUPAC Name): Disodium [5-chloro-3-[[4,5-dihydro-3-methyl-5-oxo-1-(3-sulphophenyl)-1H-pyrazol-4-yl]azo]-2-hydroxybenzene-1-sulphonato(4-)]hydroxychromate(2-)
- Common Name: Acid Red 183
- Molecular formula: C16H13ClCrN4O9S2
- Molecular weight: 599.835 g/mol
- Smiles notation: N1(c2cc(ccc2)S(=O)(=O)[O-])C([C@@-](\N=N\c2c(c(cc(c2)Cl)S(=O)(=O)[O-])[O-])C(=N1)C)=O.[Cr].[Na+].[Na+].[OH-]
- InChl: 1S/C16H12ClN4O8S2.Cr.2Na.H2O/c1-8-14(19-18-12-5-9(17)6-13(15(12)22)31(27,28)29)16(23)21(20-8)10-3-2-4-11(7-10)30(24,25)26;;;;/h2-7,22H,1H3,(H,24,25,26)(H,27,28,29);;;;1H2/q-1;;2*+1;/p-4/b19-18+;;;;
- 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:

136.4 mg/l

Test temperature:

20 °C +/- 1°C

pH:

5.9-6.16

Dissolved oxygen:

> 8mg/l

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

157.93 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 157.929, based on the intoxication.

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

Domain logical expression index: "a"

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

Domain logical expression index: "b"

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

Domain logical expression index: "c"

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 >> Schiff base formation with carbonyl compounds (AN2) AND AN2 >> Schiff base formation with carbonyl compounds (AN2) >> Pyrazolone and Pyrazolidine Derivatives AND Schiff base formation AND Schiff base formation >> Schiff base on pyrazolones and pyrazolidinones AND Schiff base formation >> Schiff base on pyrazolones and pyrazolidinones >> Pyrazolones and Pyrazolidinones by Protein binding by OASIS v1.4

Domain logical expression index: "d"

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: "e"

Referential boundary: The target chemical should be classified as Acid moiety AND Amides AND Hydrazines AND Phenol Amines AND Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acid moiety AND Amides AND Hydrazines AND Phenol Amines AND Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones and Trihydroxybenzenes 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 Non-covalent interaction >> DNA intercalation >> Quinones and Trihydroxybenzenes 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 Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones and Trihydroxybenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines 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 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 >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes 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 >> 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.1.4

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aryl AND Aryl halide AND Fused unsaturated heterocycles AND Pyrazolone AND Sulfonic acid AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Alcohol OR Aldehyde OR Alkene OR Alkoxy OR Alkyl arenes OR Allyl by Organic Functional groups

Domain logical expression index: "s"

Similarity boundary:Target: CC1C2C(N(c3cccc(S(O)(=O)=O)c3)N=1)=O[Cr]1(O)N2=Nc2cc(Cl)cc(S(O)(=O)=O)c2O1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "t"

Similarity boundary:Target: CC1C2C(N(c3cccc(S(O)(=O)=O)c3)N=1)=O[Cr]1(O)N2=Nc2cc(Cl)cc(S(O)(=O)=O)c2O1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of Water Solubility which is >= 29.4 mg/L

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of Water Solubility which is <= 1.45E004 mg/L

Validity criteria fulfilled:

not specified

Conclusions:

Based on the intoxicationof daphnia magna due to the Disodium [5-chloro-3-[[4,5-dihydro-3-methyl-5-oxo-1-(3-sulphophenyl)-1H-pyrazol-4-yl]azo]-2-hydroxybenzene-1-sulphonato(4-)]hydroxychromate(2-) the EC50 was estimated to be 157.929 mg/l.

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 five closest read across substances, toxicity on daphnia magna was predicted for Disodium [5-chloro-3-[[4,5-dihydro-3-methyl-5-oxo-1-(3-sulphophenyl)-1H-pyrazol-4-yl]azo]-2-hydroxybenzene-1-sulphonato(4-)]hydroxychromate(2-) (6408-31-7). Based on the intoxication of test organism the EC50 value was estimated to be 157.929 mg/l when Disodium [5-chloro-3-[[4,5-dihydro-3-methyl-5-oxo-1-(3-sulphophenyl)-1H-pyrazol-4-yl]azo]-2-hydroxybenzene-1 -sulphonato(4-)]hydroxychromate(2-) exposed to daphnia magna for 48 hrs.      

Based on this value it can be concluded that the substance Disodium [5-chloro-3-[[4,5-dihydro-3-methyl-5-oxo-1-(3-sulphophenyl)-1H-pyrazol-4-yl]azo]-2-hydroxybenzene-1-sulphonato(4-)] hydroxychromate(2-) is considered to be not toxic to aquatic environment 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 five closest read across substances, toxicity on daphnia magna was predicted for Disodium [5-chloro-3-[[4,5-dihydro-3-methyl-5-oxo-1-(3-sulphophenyl)-1H-pyrazol-4-yl]azo]-2-hydroxybenzene-1-sulphonato(4-)]hydroxychromate(2-) (6408-31-7). Based on the intoxication of test organism the EC50 value was estimated to be 157.929 mg/l when Disodium [5-chloro-3-[[4,5-dihydro-3-methyl-5-oxo-1-(3-sulphophenyl)-1H-pyrazol-4-yl]azo]-2-hydroxybenzene-1 -sulphonato(4-)]hydroxychromate(2-) exposed to daphnia magna for 48 hrs.  

Based on this value it can be concluded that the substance Disodium [5-chloro-3-[[4,5-dihydro-3-methyl-5-oxo-1-(3-sulphophenyl)-1H-pyrazol-4-yl]azo]-2-hydroxybenzene-1-sulphonato(4-)] hydroxychromate(2-) is considered to be not toxic to aquatic environment as per the criteria mentioned in CLP regulation.   

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

157.929 mg/L

Additional information

Various predicted data for the target compound Disodium [5-chloro-3-[[4,5-dihydro-3-methyl-5-oxo-1-(3-sulphophenyl)-1H-pyrazol-4-yl]azo]-2-hydroxybenzene-1-sulphonato(4-)]hydroxychromate(2-) (6408-31-7) 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 (2017), Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, toxicity on daphnia magna was predicted for Disodium [5-chloro-3-[[4,5-dihydro-3-methyl-5-oxo-1-(3-sulphophenyl)-1H-pyrazol-4-yl]azo]-2-hydroxybenzene-1-sulphonato(4-)]hydroxychromate(2-) (6408-31-7). Based on the intoxication of test organism the EC50 value was estimated to be 157.929 mg/l when Disodium [5-chloro-3-[[4,5-dihydro-3-methyl-5-oxo-1-(3-sulphophenyl)-1H-pyrazol-4-yl]azo]-2-hydroxybenzene-1 -sulphonato(4-)]hydroxychromate(2-) exposed to daphnia magna for 48 hrs. Based on this value it can be concluded that the substance Disodium [5-chloro-3-[[4,5-dihydro-3-methyl-5-oxo-1-(3-sulphophenyl)-1H-pyrazol-4-yl]azo]-2-hydroxybenzene-1-sulphonato(4-)] hydroxychromate(2-) is considered to be not toxic to aquatic environment 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 program, the LC 50 value for short term toxicity to aquatic invertebrates was predicted to be 892.348 mg/l for Disodium [5-chloro-3-[[4,5-dihydro-3-methyl-5-oxo-1- (3-sulphophenyl)-1H-pyrazol-4-yl]azo]-2-hydroxybenzene-1-sulphonato(4-)]hydroxychromate(2-) in 48 hrs. Based on this value it can be concluded that the substance is considered to be not toxic to aquatic environment and cannot be classified as per the criteria mentioned in CLP regulation.

 

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 found 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 Disodium [5-chloro-3-[[4,5-dihydro-3-methyl-5-oxo-1-(3-sulphophenyl)-1H-pyrazol-4-yl]azo]-2-hydroxybenzene-1-sulphonato(4-)]hydroxychromate(2-) (6408-31-7) (from OECD QSAR toolbox version 3.4, and EPIsuite, 2017) and for its read across substance from peer reviewed journal Ecotoxicology and Environmental Safety, 1999 and The Journal of Toxicological Sciences, 1977, it can be concluded that the test substance Disodium [5-chloro-3-[[4,5-dihydro-3-methyl-5-oxo-1-(3-sulphophenyl)-1H-pyrazol-4-yl]azo]-2-hydroxybenzene-1-sulphonato(4-)]hydroxychromate(2-) is not toxic and can be consider to be not classified as toxic as per the CLP classification criteria.