4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid

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 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid (12239-15-5) was estimated to be 3878.13 mg/kg bw,and for differentstudies available on the structurally similar read across substance 3-methyl-1-phenylpyrazol-5-ylamine(1131-18-6) was considered to be 2500 mg/kg bw and for functionally similar read across substanceBarium bis[2-chloro-5-[(2-hydroxy-1-naphthyl)azo]toluene-4-sulphonate] (5160-02-1) 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, 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid (12239-15-5) 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 3.3 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 v3.3,2017

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: 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid / Acid Yellow 49
- IUPAC name: 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid
- Molecular formula: C16H13Cl2N5O3S
- Molecular weight: 426.283 g/mole
- Smiles :n1(c2ccccc2)c(c(\N=N\c2c(cc(S(O)(=O)=O)c(c2)Cl)Cl)c(n1)C)N
- Inchl: 1S/C16H13Cl2N5O3S/c1-9-15(16(19)23(22-9)10-5-3-2-4-6-10)21-20-13-7-12(18)14(8-11(13)17)27(24,25)26/h2-8H,19H2,1H3,(H,24,25,26)/b21-20+
- Substance type: Organic
- Physical state: Solid powder (yellow)

Species:

rat

Strain:

Fischer 344

Sex:

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:

3878.13 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:

female

Dose descriptor:

LD50

Effect level:

3 878.13 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 7 nearest neighbours
Domain  logical expression:Result: In Domain

(((("a" or "b" or "c" )  and ("d" and ( not "e") )  )  and "f" )  and ("g" and "h" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Acid moiety OR Anilines (Unhindered) OR Pyrazoles/Pyrroles by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes by Protein binding by OECD 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 >> Primary (unsaturated) heterocyclic amine 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 No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "e"

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 Primary Aromatic Amines OR Radical OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives 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) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers 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 >> 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 >> Nitroaniline Derivatives 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 >> Polynitroarenes OR SN2 OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers 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: "f"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine AND SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding by OECD ONLY

Domain logical expression index: "g"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.536

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is <= 5.24

Interpretation of results:

other: not classified

Conclusions:

The LD50 value was estimated to be 3878.13 mg/kg bw,when female Fischer 344 rats were orally exposed with 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid (12239-15-5) 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 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid (12239-15-5).The LD50 was estimated to be 3878.13 mg/kg bw,when female Fischer 344 rats were orally exposed with 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid (12239-15-5) via gavage.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 878.13 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3

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, 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid (12239-15-5) 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 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid (12239-15-5) along with the study available on the structurally similar read across substance 3-methyl-1-phenylpyrazol-5-ylamine(1131-18-6) and on the functionally similar read across substanceBarium bis[2-chloro-5-[(2-hydroxy-1-naphthyl)azo]toluene-4-sulphonate] (5160-02-1).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 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid (12239-15-5).The LD50 was estimated to be 3878.13 mg/kg bw,when female Fischer 344 rats were orally exposed with 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid (12239-15-5) via gavage.

The above study was further supported by U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) and RTECS database (RTECS (Registry of Toxic Effects of Chemical Substances),2017) for the structurally similar read across substance 3-methyl-1-phenylpyrazol-5-ylamine(1131-18-6). In a acute oral toxicity study, rats were treated with 3-methyl-1-phenyl-1H-pyrazol-5-amine (1131-18-6) in the concentration of 2500 mg/kg bw orally. 50 % mortality was observed in treated rats at 2500 mg/kg bw. Changes in motor activity were observed. Therefore, LD50 was considered to be 2500 mg/kg bw,when rat were treated with 3-methyl-1-phenyl-1H-pyrazol-5-amine (1131-18-6) orally.

This is further supported by RTECS (RTECS (registry of toxic effect of chemical substance data base ), 2017); EUROPEAN COMMISSION – European Chemicals Bureau (IUCLID DATASET, EUROPEAN COMMISSION – European Chemicals Bureau, 18–FEB–2000) and United Nations Environmental Programme (UNEP) (SIDS Initial Assessment Report for barium bis[2-chloro-5-[(hydroxy-1-naphthyl)azo]toluene-4-sulphonate], United Nations Environmental Programme (UNEP),1999) for the functionally similar read across substanceBarium bis[2-chloro-5-[(2-hydroxy-1-naphthyl)azo]toluene-4-sulphonate] (5160-02-1).Acute oral toxicity study was done in rats using test material Barium bis[2-chloro-5-[(2-hydroxy-1-naphthyl)azo]toluene-4-sulphonate] (5160-02-1).No mortality was observed at dose 10000 mg/kg bw in treated rats.Hence,LD50 value was considered to be >10000 mg/kg bw,when rats were treated with Barium bis[2-chloro-5-[(2-hydroxy-1-naphthyl)azo]toluene-4-sulphonate] (5160-02-1)orally.

Thus, based on the above studies on 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid (12239-15-5) and it’s structurally similar read across substances 3-methyl-1-phenylpyrazol-5-ylamine(1131-18-6) and the functionally similar read across substanceBarium bis[2-chloro-5-[(2-hydroxy-1-naphthyl)azo]toluene-4-sulphonate] (5160-02-1), it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 1,4-dimethyl-5-[[4-[methylbenzylamino]phenyl]azo]-1H-1,2,4-triazolium acetate (84000-82-8) cannot be classified for acute oral toxicity.

Justification for classification or non-classification

Based on the above experimental studies and prediction on 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid (12239-15-5) and it’s structurally similar read across substances 3-methyl-1-phenylpyrazol-5-ylamine(1131-18-6) and the functionally similar read across substance Barium bis[2-chloro-5-[(2-hydroxy-1-naphthyl)azo]toluene-4-sulphonate] (5160-02-1), it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid (12239-15-5) cannot be classified for acute oral toxicity.