Disodium 2-[[5-carbamoyl-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridyl]azo]-4-[[4-chloro-6-[[3-[[2-(sulphonatooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]benzenesulphonate

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:

The supporting QMRF report has been attached.

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3 with log kow as the primary descriptors.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: Disodium 2-[[5-carbamoyl-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl -6-oxo-3-pyridyl]azo]- 4-[[4-chloro-6-[[3-[[2- (sulphona tooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]benzenesulphonate.
- Molecular formula : C26H24ClN9Na2O12S3
- Molecular weight : 832.1576 g/mol
- Smiles notation: CCn1c(c(c(c(c1=O)C (=O)N)C)/N=N/c2cc(ccc2S(=O)(=O)[O-]) Nc3nc(nc(n3)Cl)Nc4cccc(c4)S(=O)(=O)CCOS(=O) (=O)[O-])O. [Na+].[Na+]
- InChI: 1S/C26H26ClN9O12S3.2Na/c1-3-36-22(38)19(21(28)37)13(2)20(23(36)39)35-34-17-12-15(7-8-18(17)50(42,43)44)30-26-32-24(27)31-25(33-26) 29-14-5-4-6-16(11-14)49(40,41)10-9-48-51(45,46)47;;/h4-8,11-12,39H,3,9-10H2,1-2H3,(H2,28,37)(H,42,43,44)(H,45,46,47)(H2,29,30,31,32,33);;/q;2*+1/p-2/b35-34+;;
- Substance type: Organic

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Daphnia magna

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Test temperature:

23 degC

pH:

7.9

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

541 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

other: Intoxication

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 ( not "g") )  )  and "h" )  and "i" )  and "j" )  and ("k" and ( not "l") )  )  and "m" )  and ("n" and ( not "o") )  )  and ("p" and "q" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Non-specific AND Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    AND Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives AND Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives AND SN1 AND SN1 >> Nucleophilic substitution on diazonium ions AND SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Iminium Ion Formation AND SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines by DNA binding by OECD

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 SNAr AND SNAr >> Nucleophilic aromatic substitution AND SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Nucleophilic addition AND Nucleophilic addition >> Addition to carbon-hetero double bonds AND Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones 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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Iminium Ion Formation AND SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Sulfonylureas OR Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR No alert found OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic nitro OR SN2 OR SN2 >> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Halogenated polarised alkenes by DNA binding by OECD

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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: "j"

Referential boundary: The target chemical should be classified as Very fast by Bioaccumulation - metabolism half-lives ONLY

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr AND Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 16 - Sulfur S AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P OR Group 17 - Halogens F by Chemical elements

Domain logical expression index: "m"

Similarity boundary:Target: CCN1C(=O)C(C(N)=O)=C(C)C(=NNc2cc(Nc3nc(Nc4cccc(S(=O)(=O)CCOS(=O)(=O)O{-}.[Na]{+})c4)nc(Cl)n3)ccc2S(=O)(=O)O{-}.[Na]{+})C1=O
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Aliphatic amines (Mucous membrane irritation) Rank C OR Thioalcohols (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.67

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.145

Validity criteria fulfilled:

not specified

Conclusions:

The short term toxicity on Daphnia magna (aquatic invertebrates) was predicted for disodium 2-[[5-carbamoyl-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl -6-oxo-3-pyridyl]azo]- 4-[[4-chloro-6-[[3-[[2- (sulphona tooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]benzenesulphonate using OECD QSAR toolbox version 3.3 and EC50 value was estimated to be 541.0 mg/l on Daphnia magna for 48 hrs duration considering Intoxication effects.

Executive summary:

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, the short term toxicity on aquatic invertebrate was predicted for disodium 2-[[5-carbamoyl-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl -6-oxo-3-pyridyl]azo]- 4-[[4-chloro-6-[[3-[[2- (sulphona tooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]benzenesulphonate (Cas no. 84000-63-5). Effect concentration i.e EC50 value was estimated to be 541.0 mg/l for Daphnia magna for 48 hrs duration. Based on the effective value, the substance was likely to be non toxic to aquatic invertebrates at environmentally relevant concentrations and hence it can be considered to be not classified as per the CLP classification criteria.

Description of key information

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, the short term toxicity on aquatic invertebrate was predicted for disodium 2-[[5-carbamoyl-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl -6-oxo-3-pyridyl]azo]- 4-[[4-chloro-6-[[3-[[2- (sulphona tooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]benzenesulphonate(Cas no. 84000-63-5). Effect concentration i.e EC50 value was estimated to be 541.0 mg/l for Daphnia magna for 48 hrs duration. Based on the effective value, the substance was likely to be non toxic to aquatic invertebrates at environmentally relevant concentrations and hence it can be considered to be not classified as per the CLP classification criteria.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

541 mg/L

Additional information

Four studies including predicted data from validated tools and experimental data from authorative database for short term aquatic invertebrate’s endpoint of test chemical Disodium 2-[[5-carbamoyl-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl -6-oxo-3-pyridyl]azo]- 4-[[4-chloro-6-[[3-[[2- (sulphona tooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]benzenesulphonate (Cas no. 84000-63-5) with relevant read across which is close to target using log Kow as primary descriptor were summarised as follows:

 

First data from prediction using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, wherein the short term toxicity on aquatic invertebrates was estimated for Disodium 2-[[5-carbamoyl-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl -6-oxo-3-pyridyl]azo]- 4-[[4-chloro-6-[[3-[[2- (sulphona tooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]benzenesulphonate (Cas no. 84000-63-5). The median effective concentration i.e EC50 value was estimated to be 541.0 mg/l for Daphnia magna for 48 hrs duration.

Above predicted result of target assist by experimental result of read across chemical Dimethylformamide (Cas no. 68-12-2) J-CHECK authoritative database which indicate Short term toxicity to Daphnia magna (Invertebrates) study was carried out for 48 hrs. according to OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test).The study was based on the effects of the test compound Dimethylformamide (Cas no. 68-12-2) on Daphnia magna in a semi-static fresh water system. Based on Immobilisation effects the 48 hr EC50 value was observed to be > 1000 mg/l. 

And from ECOTOX database for another read across 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetic acid (Cas no. 60-00-4) indicate Short term toxicity to aquatic invertebrates was performed in Daphnia magna (Water Flea) for 48 hrs with <24 h age (Neonate).Test in fresh water media with static condition and at 20 deg.C test temp. During the experiment, the EC50 value for 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetic acid (Cas no. 60-00-4) was determined to be 113 mg/l on the basis of mobility.

Same data source (ECOTOX database) for read across chemical 2-[({[(4,6-dimethoxypyrimidin-2-yl)carbamoyl]amino}sulfonyl)amino]-N,N-dimethylbenzamide (Cas no. 213464-77-8) indicate Short term toxicity to aquatic invertebrates was performed in Americamysis bahia (Opossum Shrimp) for 96 hrs with <24 h age (Neonate).Test in salt water media with static condition. During the experiment, the LC50 value for 2-[({[(4,6-dimethoxypyrimidin-2-yl)carbamoyl]amino}sulfonyl)amino]-N,N-dimethylbenzamide (Cas no. 213464-77-8)was determined to be 122 mg/l on the basis of mortality.

Thus based on the all available effect concentrations which is in the range of 113 mg/l to 1000 mg/l and lethal concentration (LC50) 122 mg/l for target and read across chemicals give the conclusion that test substance disodium 2-[[5-carbamoyl-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl -6-oxo-3-pyridyl]azo]- 4-[[4-chloro-6-[[3-[[2- (sulphona tooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]benzenesulphonate (Cas no. 84000-63-5) was likely to be non toxic to aquatic invertebrates at environmentally relevant concentrations and hence it can be considered to be not classified as per the CLP classification criteria.