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Description of key information

Acute Oral Toxicity: 

In Acute oral toxicity ,LD50 value was predicted based on OECD QSAR toolbox for target substance trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9) was estimated to be 3730.47 mg/kg bw,and for differentstudies available on the structurally similar read across substance Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate (CAS No. 2519-30-4) was considered to be 5000 mg/kg bw; for Tartrazine (1934-21-0) was considered to be >2000 mg/kg bw; for Disodium 6-hydroxy-5-[(4-sulphonatophenyl)azo]naphthalene-2-sulphonate(2783-94-0) was considered to be >10000 mg/kg bw and >6000 mg/kg bw.All these studies concluded that the LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9) cannot be classified for acute oral toxicity.

Acute Inhalation Toxicity: 

Trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9) has very low vapor pressure (7.62E-028 Pa.).So the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore the acute inhalation toxicity end point was considered for waiver.

Acute Dermal Toxicity:

In Acute dermal toxicity, LD50 value was predicted based on OECD QSAR toolbox for target substance Trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9) was estimated to be 6322.25 mg/kg bw,and for differentstudies available on structurally similar read across substance Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate (CAS No. 2519-30-4) was considered to be >2000 mg/kg bw and for disodium (5E)-5-[2-(2-methoxy-5-methyl-4-sulfonatophenyl)hydrazin-1-ylidene]-6-oxo-5,6-dihydronaphthalene-2-sulfonate (25956-17-6) was considered to be >10000 mg/kg bw. All these studies concluded that the LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9) cannot be classified for acute dermal toxicity.

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 QMRF report has been attached
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Prediction was done by using OECD QSAR toolbox v3.3,2017
GLP compliance:
not specified
Test type:
other: estimated data
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material (IUPAC name): trisodium
2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate
- Molecular formula: C22H17N4Na3O13S4
- Molecular weight: 742.6253 g/mol
-InChl:1S/C22H20N4O13S4.3Na/c1-13-20(22(27)26(25-13)14-5-7-15(8-6-14)40(28,29)12-11-39-43(36,37)38)24-23-18-10-9-16-17(21(18)42(33,34)35)3-2-4-19(16)41(30,31)32;;;/h2-10,20H,11-12H2,1H3,(H,30,31,32)(H,33,34,35)(H,36,37,38);;;/q;3*+1/p-3/b24-23+;;;
- Substance type: Organic
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
No data available
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
No data available
Doses:
2577.06 mg/kg bw
No. of animals per sex per dose:
No data available
Control animals:
not specified
Details on study design:
No data available
Statistics:
No data available
Preliminary study:
No data available
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 577.06 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality was observed
Mortality:
No data available
Clinical signs:
No data available
Body weight:
No data available
Gross pathology:
No data available
Other findings:
No data available

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Naphthalene sulfonic acids, condensates by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Vinyl Sulfones by US-EPA New Chemical Categories

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA 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  by Protein binding by OASIS v1.3 ONLY

Domain logical expression index: "e"

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 by Protein 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

Domain logical expression index: "g"

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 OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Dicarbonyl compounds 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 AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Coumarins OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters 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 metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Amino Anthraquinones OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after metabolic 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 >> Nitro Azoarenes 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 >> p-Substituted Mononitrobenzenes OR SN1 >> Nucleophilic substitution on diazonium ions OR SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives 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 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Coumarins OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters 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.1.3

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, non cyclic structure OR Non binder, without OH or NH2 group OR Strong binder, NH2 group OR Strong binder, OH group OR Very strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND Group All log Kow < -3.1 AND Group All Melting Point > 200 C AND Group All Molecular Weight > 650 g/mol AND Group CNS log Kow < -2 AND Group CNS Melting Point > 200 C AND Group CNS Melting Point > 50 C AND Group CNS Molecular Weight > 620 g/mol by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as (!Undefined)Group All log Kow < -3.1 OR (!Undefined)Group All log Kow > 9 OR (!Undefined)Group All Melting Point > 200 C OR (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR (!Undefined)Group CNHal Lipid Solubility < 400 g/kg OR Group All Aqueous Solubility < 0.000005 g/L OR Group All Aqueous Solubility < 0.00002 g/L OR Group All log Kow > 9 OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Aqueous Solubility < 0.0005 g/L OR Group C Melting Point > 55 C OR Group C Molecular Weight > 380 g/mol OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN Molecular Weight > 290 g/mol OR Group CNHal Aqueous Solubility < 0.004 g/L OR Group CNHal Aqueous Solubility < 0.1 g/L OR Group CNHal log Kow > 3.8 OR Group CNHal Molecular Weight > 370 g/mol OR Group CNS Aqueous Solubility < 0.006 g/l OR Group CNS log Kow > 1.5 by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Aryl AND Azo AND Fused carbocyclic aromatic AND Naphtalene AND Pyrazolone AND Sulfate AND Sulfone AND Sulfonic acid AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Acetal by Organic Functional groups

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.53

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.725

Interpretation of results:
other: not classified
Conclusions:
The LD50 was estimated to be 2577.06 mg/kg bw,when male and female wistar rats were orally exposed with trisodium
2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9) via gavage.
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 trisodium

2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate(20298-05-9) .The LD50 was estimated to be 2577.06 mg/kg bw,when male and female wistar rats were orally exposed with trisodium

2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate(20298-05-9) via gavage.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 577.06 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from QSAR toolbox 3.3

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Quality of whole database:
Waiver

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:
Data is predicted using OECD QSAR toolbox version 3.3 and QMRF report has been attached
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Prediction was done by using OECD QSAR toolbox v3.3,2017
GLP compliance:
not specified
Test type:
other: estimated data
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material (IUPAC name): trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate
- Molecular formula: C22H17N4Na3O13S4
- Molecular weight: 742.6253 g/mol
-InChl:1S/C22H20N4O13S4.3Na/c1-13-20(22(27)26(25-13)14-5-7-15(8-6-14)40(28,29)12-11-39-43(36,37)38)24-23-18-10-9-16-17(21(18)42(33,34)35)3-2-4-19(16)41(30,31)32;;;/h2-10,20H,11-12H2,1H3,(H,30,31,32)(H,33,34,35)(H,36,37,38);;;/q;3*+1/p-3/b24-23+;;;
- Substance type: Organic
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
No data available
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
No data available
Duration of exposure:
24 hours
Doses:
6322.25 mg/kg bw
No. of animals per sex per dose:
No data available
Control animals:
not specified
Details on study design:
No data available
Statistics:
No data available
Preliminary study:
No data available
Sex:
male/female
Dose descriptor:
LD50
Effect level:
6 322.25 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% Mortality was observed
Mortality:
No data available
Clinical signs:
No data available
Body weight:
No data available
Gross pathology:
No data available
Other findings:
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" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and "m" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Naphthalene sulfonic acids, condensates by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Vinyl Sulfones by US-EPA New Chemical Categories

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA 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  by Protein binding by OASIS v1.3 ONLY

Domain logical expression index: "e"

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 by Protein 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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones 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 AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives 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) >> Specific Imine and Thione Derivatives OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic substitution on diazonium ions OR SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives 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 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters 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 by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Allyl esters (Hepatotoxicity) Rank A OR Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C OR Oxyphenistain (Hepatotoxicity) Alert OR Perhexiline (Hepatotoxicity) Alert OR Tamoxifen (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNS Surface Tension > 62 mN/m AND Group All log Kow < -3.1 AND Group All Melting Point > 200 C AND Group CNS log Kow < 0.5 AND Group CNS log Kow < -2 AND Group CNS Melting Point > 120 C AND Group CNS Melting Point > 50 C AND Group CNS Molecular Weight > 620 g/mol by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as (!Undefined)Group C Surface Tension > 62 mN/m OR (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR Group C Melting Point > 55 C OR Group C Vapour Pressure < 0.0001 Pa OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN Melting Point > 180 C OR Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is >= -7.06

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.77

Interpretation of results:
other: not classified
Conclusions:
The LD50 value was estimated to be 6322.25 mg/kg bw,when male and female wistar rats were semiocclusively exposed with trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9) by dermal application for 24 hours.
Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9) .The LD50 was estimated to be 6322.25 mg/kg bw,when male and female  wistar rats were semiocclusively exposed with trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9) by dermal application for 24 hours.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
6 322.25 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from QSAR toolbox 3.3

Additional information

Acute Oral Toxicity: 

In different studies, Trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9) has been investigated for acute oral toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for Trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9) along with the study available on the structurally similar read across substance Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate (CAS No. 2519-30-4); Tartrazine (1934-21-0) and Disodium 6-hydroxy-5-[(4-sulphonatophenyl)azo]naphthalene-2-sulphonate(2783-94-0). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

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 trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate(20298-05-9) .The LD50 was estimated to be 2577.06 mg/kg bw,when male and female wistar rats were orally exposed with trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate(20298-05-9) via gavage.

The experimental study was further supported by Sustainability Support Services (Europe) AB (study number: 18817, 2016-10-25) for the structurally similar Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate (CAS No. 2519-30-4). Acute oral toxicity study was done in female Sprague Dawley rats using test material Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate (CAS No. 2519-30-4).Distilled water was used as vehicle.Initially, three female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality after the dosing. No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg resulted in diarrhoea (black colour stools) in all animals with onset at 2 hours and no mortality after the dosing. As no mortality were observed at 24 hours after the dosing, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - II). Administration of the test item at 2000 mg/kg resulted in diarrhoea (black colour stools) in all animals with onset at 4 hours and no mortality after the dosing. All animals from 300 mg/kg and 2000 mg/kg dose groups survived through the study period of 14 days. Staining of the stool is attributed to the black colour of the test item. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups.Hence,LD50 value was considered to be5000 mg/kg bw,when female Sprague Dawley rats were treated with Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate (CAS No. 2519-30-4)orally via gavage following 14 days of observation period according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).

The above study was further supported by Yu F. Sasaki et. al. (Mutation Research 519 (2002) 103–119) for the structurally similar Tartrazine (1934-21-0).Acute oral toxicity test has been performed to study the lethargic dose of chemical tartrazine(1934 -21 -0). Mice were exposed to test chemical tartrazine at limit dose of 2000 mg/kg to 4 to 5 animals by oral route.No mortality was observed at dose of 2000 mg/kg .Hence, The LD50 value of chemical tartrazine(1934 -21 -0) was considered to be >2000 mg/kg bw in acute oral toxicity test conducted on mice.

The acute toxicity study was conducted to evaluate the toxic effects of administration of disodium 6-hydroxy-5-[(4-sulphonatophenyl)azo]naphthalene- 2-sulphonate (Sunset Yellow FCF) to male and female Carworth Farm E strain rats by the oral route for observation period of 7 days.Single doses of aqueous solutions of Sunset Yellow FCF (5 ml/kg) were administered to groups of five males and five females of Carworth Farm E strain rat species by the oral route.The lethal dose (LD50) of disodium 6-hydroxy-5-[(4-sulphonatophenyl)azo]naphthalene-2-sulphonate (Sunset Yellow FCF) in rat was found to be 10000 mg/kg of body weight. No macroscopic changes were seen after treatment.Test material which was 85% pure and supplied through the Food Colours Committee of the Association of British Chemical Manufacturers was dissolved in water (Vehicle) and given via gavage route. The animals were fasted for 18 hr before treatment and observed for 7 days after treatment.No Mortality was observed at dose10000 mg/kg bw. Slight diarrhoea lasted for 24 hr after dosing.The faeces and urine were coloured orange. Autopsies were carried out on those animals which died and on selected survivors. There were no macroscopic changes were seen after treatment.Therefore, LD50 was considered to be >10000 mg/kg bw, when Carworth Farm E strain male and female rats were treated with Disodium 6-hydroxy-5-[(4 sulphonatophenyl)azo]naphthalene-2-sulphonate (2783-94-0) orally.

 

 

The above study is further supported by I.F. Gaunt et. al. (Food and Cosmetics Toxicology. Vol. 5, pp. 747-754 (1967)) ; U.S. National Library of Medicine (HSDB (Hazardous Substances Data Bank); US national Library of Medicine,2017) and U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) for the structurally similar Disodium 6-hydroxy-5-[(4-sulphonatophenyl)azo]naphthalene-2-sulphonate(2783-94-0). Acute oral toxicity study was done in 10 male and female lCI Alderley Park strain mice using test material Disodium 6-hydroxy-5-[(4 sulphonatophenyl)azo]naphthalene-2-sulphonate(2783-94-0) which was 85% pure.The animals were fasted for 18 hr before treatment and observed for 7 days after treatment.No Mortality was observed at dose 6000 mg/kg bw. Slight diarrhoea lasted for 24 hr after dosing.The faeces and urine were coloured orange. Autopsies were carried out on those animals which died and on selected survivors.Hence,LD50 value was considered to be>6000 mg/kg bw when mice were treated with Disodium 6-hydroxy-5-[(4 sulphonatophenyl)azo]naphthalene-2-sulphonate(2783-94-0) orally.

Thus, based on the above studies on trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate(20298-05-9) and it’s structurally similar read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate(20298-05-9) cannot be classified for acute oral toxicity.

Acute Inhalation Toxicity: 

Trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9) has very low vapor pressure (7.62E-028 Pa.).So the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore the acute inhalation toxicity end point was considered for waiver.

Acute Dermal Toxicity:

In different studies, Trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9) has been investigated for acute dermal toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rabbits for Trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9) along with the study available on structurally similar read across substance Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate (CAS No. 2519-30-4) and disodium (5E)-5-[2-(2-methoxy-5-methyl-4-sulfonatophenyl)hydrazin-1-ylidene]-6-oxo-5,6-dihydronaphthalene-2-sulfonate (25956-17-6).The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9) .The LD50 was estimated to be 6322.25 mg/kg bw,when male and female  wistar rats were semiocclusively exposed with trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9) by dermal application for 24 hours.

The above study was further supported by Sustainability Support Services (Europe) AB (study number: 18818, 2016-10-24) for the structurally similar read across substance Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate (CAS No. 2519-30-4). In acute dermal toxicity study,male and female Sprague Dawley rats were treated with Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate (CAS No. 2519-30-4)in the concentration of 2000 mg/kg bw by dermal application.Distilled water was used as vehicle. 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.Hence,The LD50 value was considered to be >2000 mg/kg bw,when male and female Sprague Dawley rats were semiocclusively treated with Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate (CAS No. 2519-30-4)by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).

Also these results are further supported by World Health Organization(Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additives Ser 15: Allura Red AC (1980)); U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017); U.S. National Library of Medicine (HSDB (Hazardous Substances Data Bank); US national Library of Medicine,2017) and Richard J. Lewis (Sax's Dangerous Properties of Industrial Materials, 12th Edition, 5 Volume Set,2012) for the structurally similar read across substance disodium (5E)-5-[2-(2-methoxy-5-methyl-4-sulfonatophenyl)hydrazin-1-ylidene]-6-oxo-5,6-dihydronaphthalene-2-sulfonate (25956-17-6). In acute dermal toxicity study,rabbits were treated with disodium (5E)-5-[2-(2-methoxy-5-methyl-4-sulfonatophenyl)hydrazin-1-ylidene]-6-oxo-5,6-dihydronaphthalene-2-sulfonate (25956-17-6) in the concentration of 10000 mg/kg bw by dermal application.No mortality was observed in treated rabbits at dose 10000 mg/kg bw.Therefore, LD50 value was considered to be >10000 mg/kg bw,when rabbits were treated with disodium (5E)-5-[2-(2-methoxy-5-methyl-4-sulfonatophenyl)hydrazin-1-ylidene]-6-oxo-5,6-dihydronaphthalene-2-sulfonate (25956-17-6)  by dermal application. 

Thus, based on the above studies on Trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9) and it’s structurally similar read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9) cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on Trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9)  and it’s structurally similar read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Trisodium 2-[(E)-2-(3-methyl-5-oxo-1-{4-[2-(sulfonatooxy)ethanesulfonyl]phenyl}-4,5-dihydro-1H-pyrazol-4-yl)diazen-1-yl]naphthalene-1,5-disulfonate (20298-05-9) cannot be classified for acute oral and dermal toxicity. For Acute inhalation toxicity wavier was added so, not possible to classify.