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

Endpoint summary

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose toxicity was predicted for 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid. The study assumed the use of male and female Sprague Dawley rats in a 28 days toxicity study. Since no significant treatment related effects were observed at the mentioned dose level, hence the No Observed Adverse Effect Level (NOAEL) for 4-[(5-amino-3-methyl-1-phenyl-1H- pyrazol-4-yl)azo]-2,5- dichlorobenzenesulphonic acid is predicted to be 942.666687012 mg/Kg bw/day.

Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose 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 from OECD QSAR Toolbox version 3.3 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.3, 2017

GLP compliance:

not specified

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
- 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/mol
- 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

Species:

rat

Strain:

Fischer 344

Details on species / strain selection:

No data

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data

Route of administration:

oral: unspecified

Details on route of administration:

No data

Vehicle:

not specified

Details on oral exposure:

No data

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

90 days

Frequency of treatment:

Daily

Remarks:

No data

No. of animals per sex per dose:

No data

Control animals:

not specified

Details on study design:

No data

Positive control:

No data

Observations and examinations performed and frequency:

No data

Sacrifice and pathology:

No data

Other examinations:

No data

Statistics:

No data

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Details on results:

No data

Dose descriptor:

NOAEL

Effect level:

942.667 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No significant alterations were noted at the mentioned dose level

Critical effects observed:

not specified

The prediction was based on dataset comprised from the following descriptors: NOAEL
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

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 Aliphatic Amine, primary AND Aryl AND Aryl halide AND Azo AND Overlapping groups AND Pyrazole AND Sulfonic acid by Organic Functional groups (nested)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Alkyl arenes by Organic Functional groups (nested)

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.601

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is <= 9.86

Conclusions:

The No Observed Adverse Effect Level (NOAEL) for 4-[(5-amino-3-methyl-1-phenyl-1H- pyrazol-4-yl)azo]-2,5- dichlorobenzenesulphonic acid is predicted to be 942.666687012 mg/Kg bw/day.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose toxicity was predicted for 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid. The study assumed the use of male and female Sprague Dawley rats in a 28 days toxicity study. Since no significant treatment related effects were observed at the mentioned dose level, hence the No Observed Adverse Effect Level (NOAEL) for 4-[(5-amino-3-methyl-1-phenyl-1H- pyrazol-4-yl)azo]-2,5- dichlorobenzenesulphonic acid is predicted to be 942.666687012 mg/Kg bw/day.

Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

942.667 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Data is from K2 prediction database

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose toxicity: Oral

Prediction model based estimation and data from read across chemicals have been reviewed to determine the toxic nature of

4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid. The studies are as mentioned below:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose toxicity was predicted for 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid. The study assumed the use of male and female Sprague Dawley rats in a 28 days toxicity study. Since no significant treatment related effects were observed at the mentioned dose level, hence the No Observed Adverse Effect Level (NOAEL) for 4-[(5-amino-3-methyl-1-phenyl-1H- pyrazol-4-yl)azo]-2,5- dichlorobenzenesulphonic acid is predicted to be 942.666687012 mg/Kg bw/day.

Maekawa et al (Food and chemical toxicology, 1987) performed 13 week subchronic toxicity study to evaluate the toxic nature of the functionally similar read across chemical tartrazine (RA CAS no 1934 -21 -0). The test compound was administered in drinking water at a dose level of 0(control), 0.3, 0.6, 1.25, 2.5 or 5.0% (w/v) (0, 150, 300, 625, 1250 or 2500 mg/Kg bw). All rats were observed daily and clinical signs and deaths were recorded. Body weights were measured once a week. At the end of the study, all survivors were killed and organs and tissues were taken for gross and microscopical examination. Six of the male rats and all of the female rats given tartrazine at 5% in drinking-water died during the study. None of the rats in any of the other groups died. In all but the highest (5%) dose group, there was < 10% depression of body-weight gain compared with the control group. The absolute organ weights of the thymus, lungs, heart, liver, spleen, kidneys and testes of the males given 5% tartrazine and of the liver in the males and females given 2.5% tartrazine were significantly lower than those of the corresponding control groups. However, the relative organ weights (g/100 g body weight) of the brain, lungs, adrenals, kidneys and testes of males in the 5% dose group were increased, and those of the thymus in the males in the highest dose group and of the liver in the females given 2.5% tartrazine were significantly decreased. Histological examination revealed toxic changes only in rats of both sexes in the highest (5%) dose group. In rats that died during the experimental period, severe atrophy and/or degeneration of the haematopoietic organs such as the thymus, bone marrow, lymph nodes or spleen was observed, although no marked changes were detected in other organs. Based on the results observed, the no observed adverse effect level (NOAEL) for the test compound tartrazine is considered to be 2.5 % (1250 mg/Kg bw) when male and female F344 rats were exposed to the test chemical for 13 weeks.

Based on the data available for the targer chemical and its read across, 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid is not likely to be toxic as per the criteria mentioned n CLP regulation.

Justification for classification or non-classification

Based on the data available for the targer chemical and its read across, 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonic acid (CAS no 12239 -15 -5) is not likely to be toxic as per the criteria mentioned n CLP regulation