Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate

Endpoint summary

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose toxicity was predicted for Sodium 4 -(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate. The study assumed the use of male and female Sprage Dawley rats in a chronic toxicity study. Since no significant treatment related effects were observed at the mentioned dose level, hence the No Observed Adverse Effect Level (NOAEL) for Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate is predicted to be 574.166687012 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 3.4 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Toxicity of FD & C Red No. 40 (ALLURA RED) was assessed in Sprague Dawley rats in life time study
Prediction is done using OECD QSAR Toolbox version 3.4, 2017

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of the test material: Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate
- IUPAC name: Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate
- Molecular formula: C22H15N4O4SNa
- Molecular weight: 455.448 g/mol
- Substance type: Organic

Species:

rat

Strain:

Sprague-Dawley

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:

Males: 118 weeks
Females: 121 weeks

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:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Details on results:

No data

Dose descriptor:

NOAEL

Effect level:

574.167 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 6 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 ( not "i") )  )  and "j" )  and ("k" and ( not "l") )  )  and ("m" and "n" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic azo by DNA binding by OECD

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acid moiety AND Phenols AND Salt by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "d"

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

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 >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Radical 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) >> Nitro Azoarenes OR SN1 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 reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes by DNA binding by OASIS v.1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Lysine peptide depletion

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> Activated 1,3,5-triazine derivatives by DPRA Lysine peptide depletion

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, without OH or NH2 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 Not categorized by Repeated dose (HESS)

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Amiodarone (Hepatotoxicity) Alert OR p-Alkylphenols (Hepatotoxicity) Rank A OR Phenols (Mucous membrane irritation) Rank C OR Tamoxifen (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.559

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 8.75

Conclusions:

Since no significant treatment related effects were observed at the mentioned dose level, hence the No Observed Adverse Effect Level (NOAEL) for Sodium 4-(4-(2-hydroxy naphthalenylazo) phenylazo) benzenesulphonate is predicted to be 574.166687012 mg/Kg bw/day.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose toxicity was predicted for Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate. The study assumed the use of male and female Sprage Dawley rats in a chronic toxicity study. Since no significant treatment related effects were observed at the mentioned dose level, hence the No Observed Adverse Effect Level (NOAEL) for Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate is predicted to be 574.166687012 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

574.167 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

Data is from K 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 for the target chemical and data from read across chemicals have been reviewed to determine the toxic nature of Sodium 4 -(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate upon repeated exposure by oral route. The studies are as mentioned below:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose toxicity was predicted for Sodium 4 -(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate. The study assumed the use of male and female Sprage Dawley rats in a chronic toxicity study. Since no significant treatment related effects were observed at the mentioned dose level, hence the No Observed Adverse Effect Level (NOAEL) for Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate is predicted to be 574.166687012 mg/Kg bw/day.

The predicted data is further supported by the data available from the read across chemicals as mentioned below:

Sub-chronic oral toxicity study was performed by Prasad and Rastogi (Toxicology letters, 1983) to determine the oral toxic nature of 60 -70% strctrally and functionally similar reda across chemical sodium 3-[(4-anilinophenyl)diazenyl]benzenesulfonate (metanil yellow; RA CAS no 587 -98 -4; IUPAC name: Sodium 3-(p-anilinophenylazo)benzenesulphonate) upon repeated exposure for 180 days. The test compound was force fed to male and female albino mice by oral intubation at a dose levels of 0, 100, 500 or 3000 mg/Kg bw. The animals were observed for general condition, changes in hematological parameters and gross pathology. General condition was unaffected at dose levels of 100 and 500 mg/Kg bw except at 3000 mgKg bw. No change was observed by the 100 and 500 mg/Kg bw but feeding of this colour at the rate of 3000 mg/kg body weight led to certain changes in the haematological values. Total erythrocyte count (TEC) and Hb had decreased whereas ESR, MCV, and mean corpuscular haemoglobin (MCH) had increased. These facts suggested the occurrence of normochromic macrocytic anaemia. Differential leukocyte count (DLC) showed marked increase in the number of lymphocytes and monocytes and decrease in the number of neutrophils and eosinophils. Heinz bodies were observed in 80-90% erythrocytes. Other haematological values like total leukocyte count (TLC), platelet count (PC), PCV, MCHC, bleeding time (BT) and coagulation time (CT) were normal at 3000 mg/Kg bw. Hence, the No Observed Adverse Effect level (NOAEL) for the test compound metanil yellow is 500 mg/Kg bw.

Toxicity of 50 -60% structrally and functionally similar read across chemical FD & C Red No. 40 (Allura red AC; RA CAS no 25956 -17 -6; IUPAC name: disodium 6-hydroxy-5-[(2-methoxy-3-methyl- 4-sulfonato phenyl) diazenyl]naphthalene-2-sulfonate) was assessed by Borzelleca et al (Food and chemical toxicology, 1989) in Sprague Dawley rats in life time study. 30 Sprague Dawley rats per sex per dose group were fed FD & C Red No. 40 (Allura Red AC) in diet at dose concentration ofMales: 0.37, 1.39 or 5.19% (0, 180, 701,2829 mg/kg bw/day), Females: 0.37, 1.39 or 5.19% (0, 228, 901, 3604 mg/kg bw/day), 1 wk before mating, throughout the 3-wk breeding period, and during the gestation and lactation periods. No significant compound related adverse effect were observed on mortality, clinical signs, body weight (except for a reduction in body weight in high-dose females at the end of the study), food consumption, hematology, clinical chemistry, gross and .The no adverse-effect level (NOAEL) in this study were 5.19% (2829 mg/kg/day) for male rats, and 1.39% (901 mg/kg/day) for female rats.

Based on the data available for the target chemical and its read across, Sodium 4 -(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate is not likely to be toxic as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the data available for the target chemical and its read across, Sodium 4 -(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate (CAS no 6406 -56 -0) is not likely to be toxic as per the criteria mentioned in CLP regulation.