Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-)

Endpoint summary

Description of key information

Acute Oral Toxicity: 

In Acute oral toxicity ,LD50 value was predicted based on OECD QSAR toolbox for target substance Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-)(52953-39-6) was estimated to be 4747.09 mg/kg bw,and for different studies available structurally similar read across substance (4Z)-4-[(1-hydroxynaphthalen-2-yl)hydrazinylidene]-7-nitro-3-oxonaphthalene-1-sulfonic acid (1787-61-7) was considered to be 17590 mg/kg bw for rats and for functionally 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)was considered to be >15000 mg/kg bw for rats.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,Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-)(52953-39-6) cannot be classified for acute oral 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 3.4 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction was done by using OECD QSAR toolbox v3.4,2018

GLP compliance:

not specified

Test type:

other: estimated data

Limit test:

no

Specific details on test material used for the study:

- Name of test material: Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-)
- Molecular formula: C36H21CrN8O11S.2H
- Molecular weight: 827.6847 g/mole
- Smiles : [H+].[H+].Cc1c\2c(n(n1)c3ccccc3)O[Cr-2]45(Oc6ccc(cc6/N=N2)[N+](=O)[O-])Oc7ccc8ccccc8c7/N=N/c9c1ccc(cc1c(cc9O4)S(=O)(=O) O5)[N+](=O)[O-]
-Inchl:1S/C20H13N3O7S.C16H13N5O4.Cr/c24-16-8-5-11-3-1-2-4-13(11)19(16)21-22-20-14-7-6-12(23(26)27)9-15(14)18(10-17(20)25)31(28,29)30;1-10-15(16(23)20(19-10)11-5-3-2-4-6-11)18-17-13-9-12(21(24)25)7-8-14(13)22;/h1-10,24-25H,(H,28,29,30);2-9,22-23H,1H3;/q;;+3/p-3/b22-21+;18-17+;
- Substance type: Organic
- Physical state: Solid

Species:

rat

Strain:

other: Tif: RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

No data available

Doses:

4747.09 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:

4 747.09 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

No data available

Clinical signs:

other: 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" )  and "e" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and "j" )  and "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 AN2 OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems >> Pyrazolone and Pyrazolidine Derivatives OR AN2 >> Schiff base formation with carbonyl compounds (AN2) OR AN2 >> Schiff base formation with carbonyl compounds (AN2) >> Pyrazolone and Pyrazolidine Derivatives OR Schiff base formation OR Schiff base formation >> Schiff base on pyrazolones and pyrazolidinones OR Schiff base formation >> Schiff base on pyrazolones and pyrazolidinones >> Pyrazolones and Pyrazolidinones by Protein binding by OASIS v1.4 ONLY

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 >> Aromatic nitro 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 Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Nitroaromatics OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Nitroaromatics OR SN1 OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Fused-Ring Nitroaromatics by DNA binding by OASIS v.1.4 ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as 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 ONLY

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group 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: "h"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OECD

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Similarity boundary:Target: CC1C2C(N(c3ccccc3)N=1)=O[Cr]134(N2=Nc2cc(N(=O)=O)ccc2O1)N(c1c2ccc(N(=O)=O)cc2c(S(O)(=O)=O)cc1O3)=Nc1c2ccccc2ccc1O4
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "k"

Similarity boundary:Target: CC1C2C(N(c3ccccc3)N=1)=O[Cr]134(N2=Nc2cc(N(=O)=O)ccc2O1)N(c1c2ccc(N(=O)=O)cc2c(S(O)(=O)=O)cc1O3)=Nc1c2ccccc2ccc1O4
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 681 Da

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of Molecular weight which is <= 892 Da

Interpretation of results:

other: not classified

Conclusions:

The LD50 value was estimated to be 4747.09 mg/kg bw,when male and female Tif: RAIf (SPF) rats were orally exposed with Dihydrogen[2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-) (CAS No. 52953-39-6) via gavage.

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 Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-) (CAS No. 52953-39-6).The LD50 was estimated to be 4747.09 mg/kg bw,when male and female Tif: RAIf (SPF) rats were orally exposed with

Dihydrogen[2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-) (CAS No. 52953-39-6) via gavage.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 747.09 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.4

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute Oral Toxicity: 

In different studies,Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-)(52953-39-6) 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 Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-)(52953-39-6) along with the studies available on the structurally similar read across substance (4Z)-4-[(1-hydroxynaphthalen-2-yl)hydrazinylidene]-7-nitro-3-oxonaphthalene-1-sulfonic acid (1787-61-7) and functionally similar read across substanceDisodium 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 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 Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-) (CAS No. 52953-39-6).The LD50 was estimated to be 4747.09 mg/kg bw,when male and female Tif: RAIf (SPF) rats were orally exposed with

Dihydrogen[2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-) (CAS No. 52953-39-6) via gavage.

In experimental study conducted by U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) for the structurally similar read across substance (4Z)-4-[(1-hydroxynaphthalen-2-yl)hydrazinylidene]-7-nitro-3-oxonaphthalene-1-sulfonic acid (1787-61-7).Acute oral toxicity study was done in rats using test material (4Z)-4-[(1-hydroxynaphthalen-2-yl)hydrazinylidene]-7-nitro-3-oxonaphthalene-1-sulfonic acid(1787-61-7).50% mortality was observed at dose 17590 mg/kg bw.Clinical signs like behavioral excitement,gastrointestinal hypermotility, diarrhea and changes in motor activity (specific assay) were observed.Hence,LD50 value was considered to be 17590 mg/kg bw,when rats were treated with (4Z)-4-[(1-hydroxynaphthalen-2-yl)hydrazinylidene]-7-nitro-3-oxonaphthalene-1-sulfonic acid (1787-61-7) orally.

 

The above study was further supported by European Commission (EC) - Scientific Committee on Cosmetology (SCC) (Environment and Quality of Life - Reports (Seventh Series), European Commission (EC) - Scientific Committee on Cosmetology (SCC),1988) for the functionally similar read across substanceDisodium 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 done in rats using test material 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) .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 onDihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-)(52953-39-6) and it’s structurally similar and functionally related 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,Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-)(52953-39-6) cannot be classified for acute oral toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-)(52953-39-6) and it’s structurally and functionally 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,Dihydrogen [2,4-dihydro-4-[(2-hydroxy-5-nitrophenyl)azo]-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)][3-hydroxy-4-[(2-hydroxy-1-naphthyl)azo]-7-nitronaphthalene-1-sulphonato(3-)]chromate(2-)(52953-39-6) cannot be classified for acute oral toxicity.