Chromate(1-), [2,4-dihydro-4-[(2-hydroxy-5-methyl-3-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-[4-[[5-(2,2-dimethylpropyl)-2-hydroxy-3-nitrophenyl]azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonamidato(2-)]-, hydrogen

Endpoint summary

Description of key information

Acute oral toxicity: 

Acute oral toxicity dose (LD50) for Chromate(1 -),[2,4-dihydro-4-[(2-hydroxy-5-methyl-3-nitrophenyl)azo]-5-methyl-2-phenyl-3H pyrazol-3-onato(2 -)][3-[4-[[5-(2,2-dimethylpropyl)-2-hydroxy-3 -nitrophenyl]azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonamidato(2-)]-, hydrogen (CAS No.72928-87-1) was predicted based on OECD QSAR toolbox 5413 mg/kg bw and different studies available on structurally similar read across substances 4,4'-(1E,1'E)-(3,3'-dichlorobiphenyl-4,4'-diyl)bis(diazene-2,1-diyl)bis(3-methyl-1-phenyl-1H-pyrazol-5(4H)-one) (CAS no: 3520-72-7) >5000 mg/kg bw and Disodium hydrogen bis[5-chloro-3-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]-2-hydroxybenzenesulphonato(3-)]chromate(3-) (6408-26-0) >15000 mg/kg bw. All these studies concluded that the LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Chromate(1 -),[2,4-dihydro-4-[(2-hydroxy-5-methyl-3-nitrophenyl)azo]-5-methyl-2-phenyl-3H pyrazol-3-onato(2 -)][3-[4-[[5-(2,2-dimethylpropyl)-2-hydroxy-3 -nitrophenyl]azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonamidato(2-)]-, hydrogen cannot be classified for acute oral toxicity.

Acute Inhalation Toxicity:

The acute inhalation toxicity study need not be conducted because exposure of humans via inhalation route is not likely taking into account due to the low vapour pressure of the substance Chromate(1 -),[2,4-dihydro-4-[(2-hydroxy-5-methyl-3-nitrophenyl)azo]-5-methyl-2-phenyl-3H pyrazol-3-onato(2 -)][3-[4-[[5-(2,2-dimethylpropyl)-2-hydroxy-3 -nitrophenyl]azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonamidato(2-)]-, hydrogen (CAS No.72928-87-1), which is reported as 1.58E-31 Pa; High melting point, which is reported as 350˚C; Also considering the particle size distribution of the substance, the majority of the particles were found to be in the size of range 150 micrometer to 53 micrometer which is much larger size range compared to the inhalable particulate matter. Thus, exposure to inhalable dust, mist and vapour of the chemical Chromate(1 -),[2,4-dihydro-4-[(2-hydroxy-5-methyl-3-nitrophenyl)azo]-5-methyl-2-phenyl-3H pyrazol-3-onato(2 -)][3-[4-[[5-(2,2-dimethylpropyl)-2-hydroxy-3 -nitrophenyl]azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonamidato(2-)]-, hydrogen is highly unlikely. Therefore this study is considered for waiver.

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 3.4 and the supporting QMRF report has been attached

Qualifier:

according to

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

Name: Chromate(1-), [2,4-dihydro-4-[(2-hydroxy-5-methyl-3-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-[4-[[5-(2,2-dimethylpropyl)-2-hydroxy-3-nitrophenyl]azo] -4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonamidato(2-)]-, hydrogen
SMILES:Cc1cc(N(=O)=O)c(O)c(N=NC{-}2(.[Cr]{3+}3.C{-}4(C(C)=NN(c5cccc(S(N)(=O)=O)c5)C4=O)N=Nc4cc(CC(C)(C)C)cc(N(=O)=O)c4O{-}.3)C(C)=NN(c3ccccc3)C2=O)c1
InChI:1S/C21H23N6O6S.C17H14N5O4.Cr/c1-12-18(20(29)26(25-12)14-6-5-7-15(10-14)34(22,32)33)24-23-16-8-13(11-21(2,3)4)9-17(19(16)28)27(30)31;1-10-8-13(16(23)14(9-10)22(25)26)18-19-15-11(2)20-21(17(15)24)12-6-4-3-5-7-12;/h5-10,28H,11H2,1-4H3,(H2,22,32,33);3-9,23H,1-2H3;/q2*-1;+3/p-1/b24-23+;19-18+;
Molecular Formula: C38H35CrN11O10S.H
Molecular Weight: 890.831 g/mole

Species:

rat

Strain:

Crj: CD(SD)

Sex:

female

Details on test animals and environmental conditions:

not specified

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

not specified

Doses:

5413 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

female

Dose descriptor:

LD50

Effect level:

5 413 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

not specified

Clinical signs:

not specified

Body weight:

not specified

Gross pathology:

not specified

Other findings:

not specified

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" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "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 m,p - Cresols by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Michael addition AND Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals AND Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols AND SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic azo AND SN1 >> Nitrenium Ion formation >> Aromatic nitro AND SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group AND Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group >> Arenesulfonamides AND AN2 AND AN2 >> Michael addition to activated double bonds in heterocyclic ring systems AND AN2 >> Michael addition to activated double bonds in heterocyclic ring systems >> Pyrazolone and Pyrazolidine Derivatives AND AN2 >> Nucleophilic addition at polarized N-functional double bond AND AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulfonamides AND AN2 >> Schiff base formation with carbonyl compounds (AN2) AND AN2 >> Schiff base formation with carbonyl compounds (AN2) >> Pyrazolone and Pyrazolidine Derivatives AND Schiff base formation AND Schiff base formation >> Schiff base on pyrazolones and pyrazolidinones AND Schiff base formation >> Schiff base on pyrazolones and pyrazolidinones >> Pyrazolones and Pyrazolidinones by Protein binding by OASIS v1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinoneimines OR AN2 >>  Michael-type addition, quinoid structures >> Quinones and Trihydroxybenzenes OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines 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 >> Polarized Haloalkene Derivatives 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 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Haloalkenes with Electron-Withdrawing Groups OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Polarized Haloalkene 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 and Aminoalkylamine Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Nitroaromatics OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> N-Hydroxyethyl Lactams OR Non-covalent interaction >> DNA intercalation >> Organic Azides OR Non-covalent interaction >> DNA intercalation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR Non-covalent interaction >> DNA intercalation >> Quinones and Trihydroxybenzenes 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 >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Organic Azides 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 Nitroaromatics 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) >> N-Hydroxylamines 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) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones and Trihydroxybenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide 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 nitrene formation OR SN1 >> Nucleophilic attack after nitrene formation >> Organic Azides OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Fused-Ring Nitroaromatics 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 >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> p-Substituted Mononitrobenzenes OR SN1 >> Nucleophilic substitution after carbenium ion formation OR SN1 >> Nucleophilic substitution after carbenium ion formation >> Monohaloalkanes OR SN1 >> Nucleophilic substitution on diazonium ion OR SN1 >> Nucleophilic substitution on diazonium ion >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> N-Hydroxylamines OR SN2 >> Acylation >> Specific Acetate Esters 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 by epoxide metabolically formed after E2 reaction OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Monohaloalkanes OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines 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 >> Haloalkenes with Electron-Withdrawing Groups OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polarized Haloalkene Derivatives OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Monohaloalkanes OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates 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 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides 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 >> Haloalkanes Containing Heteroatom 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 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives OR SN2 >> SN2 at sulfur atom OR SN2 >> SN2 at sulfur atom >> Sulfonyl Halides OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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: "i"

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 by Protein binding by OECD

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acylation >> Direct Acylation Involving a Leaving group >> Anhydrides OR Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - esters OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Alkali Earth OR Halogens by Groups of elements

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 Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= 7.43

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 13.2

Interpretation of results:

other: Not classified

Conclusions:

LD50 was estimated to be 5413 mg/kg bw, when 6 female Crj: CD(SD) rats were treated with Chromate(1-), [2,4-dihydro-4-[(2-hydroxy-5-methyl-3-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-[4-[[5-(2,2-dimethylpropyl)-2-hydroxy-3-nitrophenyl]azo] -4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonamidato(2-)]-,hydrogen (CAS no: 72928-87-1) via oral gavage route.

Executive summary:

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for Chromate(1-), [2,4-dihydro-4-[(2-hydroxy-5-methyl-3-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-[4-[[5-(2,2-dimethylpropyl)-2-hydroxy-3-nitrophenyl]azo] -4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonamidato(2-)]-,hydrogen (CAS no: 72928-87-1). The LD50 was estimated to be 5413 mg/kg bw, when 6 female Crj: CD(SD) rats were treated with Chromate(1-), [2,4-dihydro-4-[(2-hydroxy-5-methyl-3-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-[4-[[5-(2,2-dimethylpropyl)-

2-hydroxy-3-nitrophenyl]azo] -4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonamidato(2-)]-,hydrogen via oral gavage route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 413 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.4.

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

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

In different studies, Chromate(1 -),[2,4-dihydro-4-[(2-hydroxy-5-methyl-3-nitrophenyl)azo]-5-methyl-2-phenyl-3H pyrazol-3-onato(2 -)][3-[4-[[5-(2,2-dimethylpropyl)-2-hydroxy-3 -nitrophenyl]azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonamidato(2-)]-, hydrogen (CAS No.72928-87-1) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for Chromate(1 -),[2,4-dihydro-4-[(2-hydroxy-5-methyl-3-nitrophenyl)azo]-5-methyl-2-phenyl-3H pyrazol-3-onato(2 -)][3-[4-[[5-(2,2-dimethylpropyl)-2-hydroxy-3 -nitrophenyl]azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonamidato(2-)]-, hydrogen along with the study available on structurally similar read across substances 4,4'-(1E,1'E)-(3,3'-dichlorobiphenyl-4,4'-diyl)bis(diazene-2,1-diyl)bis(3-methyl-1-phenyl-1H-pyrazol-5(4H)-one) (3520-72-7) and Disodium hydrogen bis[5-chloro-3-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]-2-hydroxybenzenesulphonato(3-)]chromate(3-) (6408-26-0). 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 (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for Chromate(1-), [2,4-dihydro-4-[(2-hydroxy-5-methyl-3-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-[4-[[5-(2,2-dimethylpropyl)-2-hydroxy-3-nitrophenyl]azo] -4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonamidato(2-)]-,hydrogen (CAS no: 72928-87-1). The LD50 was estimated to be 5413 mg/kg bw, when 6 female Crj: CD(SD) rats were treated with Chromate(1-), [2,4-dihydro-4-[(2-hydroxy-5-methyl-3-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-[4-[[5-(2,2-dimethylpropyl)-2-hydroxy-3-nitrophenyl]azo] -4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonamidato(2-)]-,hydrogen via oral gavage route.

The above study is supported by U.S. National Library of Medicine (ChemIDplus, 2017), for the structurally similar read across substance 4,4'-(1E,1'E)-(3,3'-dichlorobiphenyl-4,4'-diyl)bis(diazene-2,1-diyl)bis(3-methyl-1-phenyl-1H-pyrazol-5(4H)-one) (3520-72-7).Acute oral toxicity study was conducted in rats at the concentration of 5000 mg/kg bw. No Mortality was observed at dose 5000 mg/kg bw. Hence, LD50 value was considered to be >5000 mg/kg bw, when rats were treated with4,4'-(1E,1'E)-(3,3'-dichlorobiphenyl-4,4'-diyl)bis(diazene-2,1-diyl)bis(3-methyl-1-phenyl-1H-pyrazol-5(4H)-one) via oral route.

This study is also supported by European Commission (EC) - Scientific Committee on Cosmetology (SCC, 1988), for the structurally similar read across substance Disodium hydrogen bis[5-chloro-3-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]-2-hydroxybenzenesulphonato(3-)]chromate(3-) (6408-26-0). Acute oral toxicity study was conducted in rats at the concentration of 15000 mg/kg bw. No Mortality was observed at dose 15000 mg/kg bw. Hence,LD50 value was considered to be >15000 mg/kg bw, when rats were treated with Disodium hydrogen bis[5-chloro-3-[(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)azo]-2-hydroxybenzenesulphonato(3-)]chromate(3 -) (6408-26-0) orally.

Thus, based on the above studies on Chromate(1 -),[2,4-dihydro-4-[(2-hydroxy-5-methyl-3-nitrophenyl)azo]-5-methyl-2-phenyl-3H pyrazol-3-onato(2 -)][3-[4-[[5-(2,2-dimethylpropyl)-2-hydroxy-3 -nitrophenyl]azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonamidato(2-)]-, hydrogen (CAS No.72928-87-1) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Chromate(1 -),[2,4-dihydro-4-[(2-hydroxy-5-methyl-3-nitrophenyl)azo]-5-methyl-2-phenyl-3H pyrazol-3-onato(2 -)][3-[4-[[5-(2,2-dimethylpropyl)-2-hydroxy-3 -nitrophenyl]azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonamidato(2-)]-, hydrogen cannot be classified for acute oral toxicity.

Acute Inhalation Toxicity:

The acute inhalation toxicity study need not be conducted because exposure of humans via inhalation route is not likely taking into account due to the low vapour pressure of the substance Chromate(1 -),[2,4-dihydro-4-[(2-hydroxy-5-methyl-3-nitrophenyl)azo]-5-methyl-2-phenyl-3H pyrazol-3-onato(2 -)][3-[4-[[5-(2,2-dimethylpropyl)-2-hydroxy-3 -nitrophenyl]azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonamidato(2-)]-, hydrogen (CAS No.72928-87-1), which is reported as 1.58E-31 Pa; High melting point, which is reported as 350˚C; Also considering the particle size distribution of the substance, the majority of the particles were found to be in the size of range 150 micrometer to 53 micrometer which is much larger size range compared to the inhalable particulate matter. Thus, exposure to inhalable dust, mist and vapour of the chemical Chromate(1 -),[2,4-dihydro-4-[(2-hydroxy-5-methyl-3-nitrophenyl)azo]-5-methyl-2-phenyl-3H pyrazol-3-onato(2 -)][3-[4-[[5-(2,2-dimethylpropyl)-2-hydroxy-3 -nitrophenyl]azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonamidato(2-)]-, hydrogen is highly unlikely. Therefore this study is considered for waiver.

Justification for classification or non-classification

Based on the above studies and prediction on Chromate(1 -),[2,4-dihydro-4-[(2-hydroxy-5-methyl-3-nitrophenyl)azo]-5-methyl-2-phenyl-3H pyrazol-3-onato(2 -)][3-[4-[[5-(2,2-dimethylpropyl)-2-hydroxy-3 -nitrophenyl]azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonamidato(2-)]-, hydrogen (CAS No.72928-87-1) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, Chromate(1 -),[2,4-dihydro-4-[(2-hydroxy-5-methyl-3-nitrophenyl)azo]-5-methyl-2-phenyl-3H pyrazol-3-onato(2 -)][3-[4-[[5-(2,2-dimethylpropyl)-2-hydroxy-3 -nitrophenyl]azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonamidato(2-)]-, hydrogen cannot be classified for acute oral toxicity.For Acute Inhalation toxicity wavier were added so, not possible to classify.