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

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:

no guideline available

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):

Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum)

Test type:

static

Water media type:

freshwater

Total exposure duration:

72 h

Test temperature:

23 deg.C

Reference substance (positive control):

not specified

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

376.64 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" or "e" )  and ("f" and ( not "g") )  )  and "h" )  and ("i" and ( not "j") )  )  and "k" )  and "l" )  and ("m" and ( not "n") )  )  and "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 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 >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR No alert found OR Schiff base formers OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Tertiary (unsaturated) heterocyclic amine  by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as No Data by Ultimate biodeg

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as > 100 days by Ultimate biodeg

Domain logical expression index: "k"

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: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Does NOT Biodegrade Fast by Biodeg probability (Biowin 2) ONLY

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= -8.13

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.132

Validity criteria fulfilled:

not specified

Conclusions:

Using OECD QSAR toolbox version 3.3 the median Effective concentration (EC50) value for test chemical disodium 2-[(5-carbamoyl-1- ethyl-2-hyd roxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazenyl]-4-({4-chloro-6-[(3-{[2-(sulfonatooxy)ethyl] sulfonyl}phenyl)amino]-1,3, 5-triazin-2-yl} amino) benz enesulfonate on Pseudokirchneriella subcapitata in a 72 hour study was estimated to be 376.64 mg/L on the basis of effects on growth rate.

Executive summary:

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 disodium 2-[(5-carbamoyl-1-ethyl-2-hydroxy-4 -methyl-6-oxo- 1,6-dihydropyridin- 3-yl)diazenyl]-4-({4-chloro-6-[(3-{[2-(sulfonatooxy)ethyl] sulfonyl}phenyl)amino]-1,3,5-triazin-2-yl}amino)benzenesulfonate (CAS no. 84000-63-5). EC50 value was estimated to be 376.64 mg/l for Pseudokirchneriella subcapitata for 72 h duration. Based on this value it can be concluded that the substance is likely to be non toxic at environmentally relevant concentrations and 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 five closest read across substances, the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance disodium 2-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3 -yl)diazenyl]-4-({4-chloro-6-[(3-{[2-(sulfonatooxy)ethyl] sulfonyl}phenyl)amino]-1,3,5-triazin-2-yl}amino)benzenesulfonate (CAS No. 84000-63-5). EC50 value was estimated to be 376.64 mg/l for Pseudokirchneriella subcapitata for 72 h duration. Based on this value it can be concluded that the substance is likely to be non toxic at environmentally relevant concentrations and can be considered to be not classified as per the CLP classification criteria.

Key value for chemical safety assessment

EC50 for freshwater algae:

376.64 mg/L

Additional information

Two studies including predicted data from validated tool and experimental data from authorative database for toxicity to aquatic algae endpoint of test chemical disodium 2-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazenyl]-4-({4-chloro-6-[(3-{[2-(sulfonatooxy)ethyl] (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, which indicate the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance disodium 2-[(5-carbamoyl-1-ethyl-2- hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazenyl]-4-({4-chloro-6-[(3-{[2-(sulfonatooxy)ethyl] (Cas no. 84000-63-5).The EC50 value was estimated to be 376.64 mg/l for Pseudokirchneriella subcapitata for 72 h duration. 

And read across 2-(2-dimethylaminoethyloxy)ethanol (Cas no. 1704-62-7) suggest In aquatic toxicity study the 50 percent reduction in growth rate (ErC50)of chemical 2-(2-dimethylaminoethyloxy)ethanol with nominal concentration in static test condition in test species Pseudokirchneriella subcapitata was observed to be160 mg/l for 72hrs exposure period. (OECD HPV Chemical Programme, SIDS Dossier, CoCAM 6, 30 - 03 October, 2014)

Thus based on the effects from both studies give the conclusion that test substance disodium 2-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo- 1,6-dihydro pyridin-3-yl)diazenyl]-4-({4-chloro-6-[(3-{[2-(sulfonatooxy)ethyl] (CAS No. 84000-63-5) was likely to be non toxic to aquatic algae at environmentally relevant concentrations and can be considered to be not classified as per the CLP classification criteria.