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

Endpoint summary

Description of key information

Acute toxicity: oral

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for disodium 2-{2-[(3Z)-5-carbamoyl-1-ethyl- 4-methyl-2,6- dioxo-1,2,3,6-tetrahydropyridin-3-ylidene]hydrazin-1-yl}-4-{[4-chloro-6-({3-[2-(sulfonatooxy)ethanesulfonyl] phe nyl}amino)-1,3,5-triazin-2-yl]amino}benzene-1-sulfonate. The LD50 was estimated to be 3790 mg/kg bw when Wistar male and female rats were orally exposed with disodium 2-{2-[(3Z)-5-carbamoyl-1-ethyl-4-methyl-2,6- dioxo-1,2,3,6-tetrahydropyridin-3-ylidene]hydrazin-1-yl}-4- {[4-chloro-6-({3- [2-(sulfonatooxy)ethan esulfonyl]phenyl}amino)-1,3,5-triazin-2-yl]amino}benzene-1-sulfonate.

 

Acute toxicity: inhalation

According to column 2 of REACH Annex VIII, the acute toxicity inhalation study need not be conducted because exposure of humans via inhalation route is not likely taking into account the particle size distribution of the substance the majority of the particles were found to be in the size of 106.0 micrometer which is much larger size range compared to the inhalable particulate matter. Thus, exposure to inhalable dust, mist and vapour of the chemical disodium 2-[[5-ca rbamoyl-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-tria zin-2-yl]a mino]benzenesulphonate is highly unlikely. Therefore this study is considered for waiver.

 

Acute toxicity: dermal

The acute toxicity study was predicted using OECD QSAR toolbox version 3.3 (2017) with log kow as the primary descriptor; to evaluate the toxic effects of administration of 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 (CAS No. 84000-63-5) in rabbits by the dermal route. 50% mortality was observed at 40760.10 mg/kg bw in treated rabbit.The acute dermal median lethal dose (LD50) of 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 in rabbit was estimated to be 40760.10 mg/kg bw. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that 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 (CAS No. 84000- 63-5) does not classify as an acute dermal toxicant.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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:

Data is predicted using OECD QSAR toolbox version 3.3 and 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

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

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+]
- Substance type: Organic

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

No data

Doses:

3790 mg/kg bw

No. of animals per sex per dose:

3 males, 2 females

Control animals:

no

Details on study design:

No data

Statistics:

No data

Preliminary study:

No data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 790 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

50% mortality observed at 3790.0 mg.kg bw in treated rats.

Clinical signs:

No data

Body weight:

No data

Gross pathology:

No data

Other findings:

No data

The prediction was based on dataset comprised from the following descriptors: LD50
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 ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and "n" )  and ("o" and ( not "p") )  )  and "q" )  and ("r" and "s" )  )

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 >> Direct Addition of an Acyl Halide OR Acylation >> Direct Addition of an Acyl Halide >> Alkyl carbamyl halides OR Acylation >> Isocyanates and Isothiocyanates OR Acylation >> Isocyanates and Isothiocyanates >> Isocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides OR Michael addition OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Furans OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Thiophenes-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 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary (unsaturated) heterocyclic amine  OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Epoxides OR SN2 >> Episulfonium Ion Formation OR SN2 >> Episulfonium Ion Formation >> Mustards OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Alkali Earth AND Halogens AND Non-Metals by Groups of elements

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Alkaline Earth OR Metalloids OR Transition Metals by Groups of elements

Domain logical expression index: "j"

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: "k"

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: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Aliphatic amines (Mucous membrane irritation) Rank C OR Aliphatic nitriles (Hepatotoxicity) Rank B OR Allyl esters (Hepatotoxicity) Rank A OR Chlorphentermine (Hepatotoxicity) Alert OR Fialuridine (Hepatotoxicity) Alert OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as AhR binders.Polycyclic aromatic hydrocarbons (PAHs) (3b-3) OR Alkyl amide, urea, thiourea, nitroso urea, carbonate, guanidine and carbamate derivatives (21b1) OR Alkyl amide, urea, thiourea, nitroso urea, carbonate, guanidine and carbamate derivatives (21b1) >> Alkylamide or thioamide analogs OR Known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= -16.3

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 6.87

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 3790 mg/kg bw when Wistar male and female rats were orally exposed with disodium 2-{2-[(3Z)-5-carbamoyl-1 -ethyl-4- methyl-2,6-dioxo-1,2,3,6-tetrahydropyridin-3-ylidene]hydrazin-1-yl}-4-{[4-chloro-6-({3-[2-(sulfonatooxy)ethanesulfonyl]phenyl}amino)-1,3,5-triazin-2-yl]amino}benzene-1-sulfonate.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for disodium 2-{2-[(3Z)-5-carbamoyl-1-ethyl-4-methyl-2,6-dioxo-1,2,3,6-tetrahydropyridin-3-ylidene]hydrazin-1-yl}-4-{[4-chloro-6-({3-[2-(sulfonatooxy)ethanesulfonyl]phenyl}amino)-1,3,5-triazin-2-yl]amino}benzene-1-sulfonate. The LD50 was estimated to be 3790 mg/kg bw when Wistar male and female rats were orally exposed with disodium 2-{2-[(3Z)-5-carbamoyl-1-ethyl-4-methyl-2,6- dioxo-1,2,3,6-tetrahydropyridin-3-ylidene]hydrazin-1-yl}-4-{[4-chloro-6-({3-[2-(sulfonatooxy)ethanesulfonyl]phenyl}amino)-1,3,5-triazin-2-yl]amino}benzene-1-sulfonate.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 790 mg/kg bw

Quality of whole database:

The data is Klimicsh 2 and from OECD QSAR toolbox version 3.3 (2017).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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:

Prediction is done using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached.

Qualifier:

no guideline available

Principles of method if other than guideline:

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

GLP compliance:

not specified

Test type:

other: No data

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+]
- Substance type: Organic

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Type of coverage:

not specified

Vehicle:

not specified

Doses:

40760.10 mg/kg bw

Control animals:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

40 760.1 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality observed.

Mortality:

50% mortality observed at 40760.10 mg/kg bw in treated rabbit.

Clinical signs:

No data available

Body weight:

No data available

Gross pathology:

No data available

The prediction was based on dataset comprised from the following descriptors: LD50
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" or "g" or "h" or "i" )  and ("j" and ( not "k") )  )  and "l" )  and ("m" and ( not "n") )  )  and "o" )  and ("p" and ( not "q") )  )  and "r" )  and ("s" and "t" )  )

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 Imides (Acute toxicity) OR Substituted Triazines (Acute toxicity) OR Vinyl Sulfones by US-EPA New Chemical Categories ONLY

Domain logical expression index: "c"

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: "d"

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: "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 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: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acid moiety OR Acrylamides OR Hydrazines OR Imides OR Salt OR Triazines, Aromatic by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "i"

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

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: "k"

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 >> 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 SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (original) 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 Aliphatic nitriles (Hepatotoxicity) Rank B OR Chlorphentermine (Hepatotoxicity) Alert OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aliphatic Nitrogen, two aromatic attach [-N-] AND Alpha-oxoamide [C(C(=O))C(=O)N] AND Amino Triazine/Pyrazine/Pyrimidine  AND Amino, aliphatic attach [-N<] AND Amino-carbonyl compound [NCC(=O)-C] AND Aromatic Carbon [C] AND Aromatic Nitrogen AND Carbonyl, olefinic attach [-C(=O)-] AND Chlorine, aromatic attach [-Cl] AND Chlorine, olefinic attach [-Cl] AND Hydrazine [>N-N<] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen, two or tree olefinic attach [>N-] AND Olefinic carbon [=CH- or =C<] AND Suflur {v+4} or {v+6} AND Sulfate, linear [-O-SO2-O-] AND Sulfite, linear [-OS(=O)O-] AND Sulfonate, aromatic attach [-SO2-O] AND Sym-Triazine ring  by Organic functional groups (US EPA) ONLY

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Alkali Earth AND Halogens AND Non-Metals by Groups of elements

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Transition Metals by Groups of elements

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Does NOT Biodegrade Fast by Biodeg probability (Biowin 7) ONLY

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is >= -5.45

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is <= -1.31

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The acute toxicity study was predicted using OECD QSAR toolbox version 3.3 (2017) with log kow as the primary descriptor; to evaluate the toxic effects of administration of 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) in rabbits by the dermal route. 50% morta lity was observed at 40760.10 mg/kg bw in treated rabbit.The acute dermal median lethal dose (LD50) of 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]am ino]ben zenesulphonate in rabbit was estimated to be 40760.10 mg/kg bw.

Executive summary:

The acute toxicity study was predicted using OECD QSAR toolbox version 3.3 (2017) with log kow as the primary descriptor; to evaluate the toxic effects of administration of 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 (CAS No. 84000-63-5) in rabbits by the dermal route. 50% mortality was observed at 40760.10 mg/kg bw in treated rabbit.The acute dermal median lethal dose (LD50) of 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 in rabbit was estimated to be 40760.10 mg/kg bw. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that 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 (CAS No. 84000- 63-5) does not classify as an acute dermal toxicant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

40 760.1 mg/kg bw

Quality of whole database:

The data is Klimicsh 2 and from OECD QSAR toolbox version 3.3 (2017).

Additional information

Acute toxicity: oral

In different studies, disodium 2-{2-[(3Z)-5-carbamoyl-1-ethyl-4-methyl-2,6-dioxo-1,2,3,6-tetrahydropyridin-3-ylidene]hydrazin-1-yl}-4-{[4-chloro-6-({3-[2-(sulfonatooxy)ethanesulfonyl]phenyl}amino)-1,3,5-triazin-2-yl]amino}benzene-1-sulfonate has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for disodium 2-{2-[(3Z)-5-carbamoyl-1-ethyl-4-methyl-2,6-dioxo-1,2,3,6-tetrahydropyridin-3-ylidene]hydrazin-1-yl}-4-{[4-chloro-6-({3-[2-(sulfonatooxy)ethanesulfonyl]phenyl}amino)-1,3,5-triazin-2-yl]amino}benzene-1-sulfonate along with the study available on structurally similar read across substance Imidurea (CAS no 39236-46-9). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for disodium 2-{2-[(3Z)-5-carbamoyl-1-ethyl-4-methyl-2,6-dioxo-1,2,3,6-tetrahydropyridin-3-ylidene]hydrazin-1-yl}-4-{[4-chloro-6-({3-[2-(sulfonatooxy)ethanesulfonyl]phenyl}amino)-1,3,5-triazin-2-yl]amino}benzene-1-sulfonate. The LD50 was estimated to be 3790 mg/kg bw when Wistar male and female rats were orally exposed with disodium 2-{2-[(3Z)-5-carbamoyl-1-ethyl-4-methyl-2,6-dioxo-1,2,3,6-tetrahydropyridin-3-ylidene]hydrazin-1-yl}-4-{[4-chloro-6-({3-[2-(sulfonatooxy)ethanesulfonyl]phenyl}amino)-1,3,5-triazin-2-yl]amino}benzene-1-sulfonate.

In another experimental study summarized by U.S. National Library of Medicine (ChemIDplus A Toxnet Database, 2017) on structurally similar read across substance Imidurea (CAS no 39236-46-9), mice and rats were treated with Imidurea in the concentration of 7200 and 11300 mg/kg bw orally. 50 % mortality was observed in treated mice and rat at 7200 and 11300 mg/kg bw and Gastrointestinal: Ulceration or Bleeding From Duodenum and Stomach, Hypermotility and Diarrhea were observed in treated mice and Gastrointestinal Hypermotility, Diarrhea, Ulceration or Bleeding from Stomach and Duodenum was observed in treated rats. Therefore, LD50 was considered to be 7200 and 11300 mg/kg bw when mice and rat were treated with Imidurea orally.

Thus, based on the above studies and predictions on disodium 2-{2-[(3Z)-5-carbamoyl-1-ethyl-4-methyl-2,6-dioxo-1,2,3,6-tetrahydropyridin-3-ylidene]hydrazin-1-yl}-4-{[4-chloro-6-({3-[2-(sulfonatooxy)ethanesulfonyl]phenyl}amino)-1,3,5-triazin-2-yl]amino}benzene-1-sulfonate and its read across substances and by applying weight of evidance, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, disodium 2-{2-[(3Z)-5-carbamoyl-1-ethyl-4-methyl-2,6-dioxo-1,2,3,6-tetrahydropyridin-3-ylidene]hydrazin-1-yl}-4-{[4-chloro-6-({3-[2-(sulfonatooxy)ethanesulfonyl]phenyl}amino)-1,3,5-triazin-2-yl]amino}benzene-1-sulfonate can be 'Not classified' for acute oral toxicity.

Acute toxicity: inhalation

According to column 2 of REACH Annex VIII, the acute toxicity inhalation study need not be conducted because exposure of humans via inhalation route is not likely taking into account the particle size distribution of the substance the majority of the particles were found to be in the size of 106.0 micrometer which is much larger size range compared to the inhalable particulate matter. Thus, exposure to inhalable dust, mist and vapour of the 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-(sulphonatooxy)ethyl] sulphonyl] phenyl]amino]-1,3,5-triazin-2-yl]amino]benzenesulphonate is highly unlikely. Therefore this study is considered for waiver.

Acute toxicity: dermal

In different studies, 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 (CAS No. 84000- 63-5) has been reviewed for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rabbits 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-(sulphonatooxy)ethyl] sulphonyl] phenyl]amino]-1,3,5-triazin-2-yl]amino]benzenesulphona te along with the study available on structurally similar read across substances disodium 6-hydroxy-5 -[(2-methoxy-4-sulphonato-m-tolyl)azo] naphthalene-2- sulphonate (ALLURA RED AC) (CAS No. 25956-17-6) and Disodium 3-[(2,4-dimethyl-5- sulphon atophenyl)azo]-4-hydroxynaphthalene-1-sulphonate (CAS: 4548-53-2). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.  

 

The acute toxicity study was predicted using OECD QSAR toolbox version 3.3 (2017) with log kow as the primary descriptor; to evaluate the toxic effects of administration of 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 (CAS No. 84000-63-5) in rabbits by the dermal route. 50% mortality was observed at 40760.10 mg/kg bw in treated rabbit.The acute dermal median lethal dose (LD50) of 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 in rabbit was estimated to be 40760.10 mg/kg bw.  

 

This is supported by the acute dermal toxicity study of structurally similar read across substance disodium 6-hydroxy-5 -[(2-methoxy-4-sulphonato-m-tolyl)azo] naphthalene-2- sulphonate (ALLURA RED AC) (CAS No. 25956-17-6) conducted by J.F. Borzelleca et al. (Food and Chemical Toxicology Volume 27, Issue 11, 1989, Pages 701–705). The acute dermal median lethal dose (LD50) of disodium 6-hydroxy -5-[(2-methoxy-4-sulphonato-m-tolyl)azo]naphthalene-2-sulphonate (ALLURA RED AC) in rabbit was observed to be >10000 mg/kg of body weight.  

 

Moreover, the study now reported was designed and conducted by Sustainability Support Services (Europe) AB (2017) to determine the acute dermal toxicity profile of Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl) azo]-4-hydroxynaphthalene-1-sulphonate in Sprague Dawley rats by following OECD guideline 402.

The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days.   

Animals exhibited normal body weight gain through the study period of 14 days.

Gross pathological examination did not reveal any abnormalities attributable to the treatment.

It was concluded that the acute dermal median lethal dose (LD50) of Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4-hydroxynaphthalene-1- sulpho nate supplied by Sustainability Support Services (Europe) AB, Sweden, when administered to male and female Sprague Dawley rats was found to be greater than 2000 mg/kg body weight.  

 

So, based on the above mentioned studies for target 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-(sulphonatooxy)ethyl] sulphonyl] phenyl]amino]-1,3,5-triazin-2-yl]amino]benzenesulphonate (CAS No. 84000- 63-5) and to its read across substance, the median lethal dose (LD50) value was found to be in the range of > 2000 mg/kg b.wt. to >10,000.0 mg/kg b.wt. Thus, on the basis of these LD50 value and according to CLP criteria for acute toxicity rating for the chemicals, it infers that 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 (CAS No. 84000- 63-5) does not classify as an acute dermal toxicant.

Justification for classification or non-classification

Based on the above mentioned studies ondisodium 2-[[5-carbamoyl-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridyl] azo]-4-[[4-chloro-6-[[3-[[2-(sulphon atooxy)ethyl]sulphonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]benzenesulphonate(CAS No. – 84000-63-5), it can be found that LD50 (oral and dermal) value is greater than 2000 mg/kg b.wt. Thus, by comparing these studies with the criteria of CLP regulation, it infers that the test substancedisodium 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]benzene sulphonate(CAS No. – 84000-63-5) does not classify as an acute toxicant (by oral and dermal route).