Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate

Endpoint summary

Description of key information

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 oral toxicity was predicted for the test compound Sodium 6-amino-5-{[4-chloro-2-(trifluoromethyl)phenyl]diazenyl} -4-hydroxynaphthalene -2-sulfonate (57741-47-6). The study assumed the use of male and female Crj: CD(SD) in chronic study of 90days. No significant alterations were noted at the dose level of 667.080mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for compound Sodium 6-amino-5-{[4-chloro-2-(trifluoromethyl) phenyl]diazenyl}-4-hydroxynaphthalene-2-sulfonate is considered to be 450.2mg/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:

Prediction is done using OECD QSAR Toolbox version 3.3 and the supporting QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.3, 2018.

GLP compliance:

not specified

Limit test:

no

Specific details on test material used for the study:

- Name of test material : Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate
- Molecular formula : C17H10ClF3N3NaO4S
- Molecular weight : 467.786 g/mol
- Smiles notation : c12c(cc(S(=O)(=O)[O-])cc2O)ccc(c1\N=N/c1c(cc(Cl)cc1)C(F)(F)F)N.[Na+]
- InChl : 1S/C17H11ClF3N3O4S.Na/c18-9-2-4-13(11(6-9)17(19,20)21)23-24-16-12(22)3-1-8-5-10(29(26,27)28)7-14(25)15(8)16;/h1-7,25H,22H2,(H,26,27,28);/q;+1/p-1/b24-23-;
- Substance type : Organic
- Physical state : Solid

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

not specified

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

90 days

Frequency of treatment:

not specified

Remarks:

not specified

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Positive control:

not specified

Observations and examinations performed and frequency:

not specified

Sacrifice and pathology:

not specified

Other examinations:

not specified

Statistics:

not specified

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

Dose descriptor:

NOAEL

Effect level:

450.238 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: NO significant effect were observed at this dose .

Remarks on result:

other: No toxic effect were observed a this dose .

Critical effects observed:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

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" or "d" or "e" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and "s" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines AND Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines AND SN1 AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines by DNA binding by OASIS v.1.3

Domain logical expression index: "c"

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 >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group AND Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Acid moiety AND Anilines (Unhindered) AND Phenol Amines AND Phenols AND Salt by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as p-Aminophenols (Renal toxicity) Rank B by Repeated dose (HESS)

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Nitrobenzenes (Hepatotoxicity) Rank C by Repeated dose (HESS)

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Anilines (Hepatotoxicity) Rank C by Repeated dose (HESS)

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Alkyl fluoride AND Alkyl halide AND Amine AND Anion AND Aromatic compound AND Aryl chloride AND Aryl halide AND Azo compound AND Cation AND Halogen derivative AND Hydroxy compound AND Phenol AND Primary amine AND Primary aromatic amine AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Alcohol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Alkyl fluoride AND Alkyl halide AND Amine AND Anion AND Aromatic compound AND Aryl chloride AND Aryl halide AND Azo compound AND Cation AND Halogen derivative AND Hydroxy compound AND Phenol AND Primary amine AND Primary aromatic amine AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Carbonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Alkyl fluoride AND Alkyl halide AND Amine AND Anion AND Aromatic compound AND Aryl chloride AND Aryl halide AND Azo compound AND Cation AND Halogen derivative AND Hydroxy compound AND Phenol AND Primary amine AND Primary aromatic amine AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as No functional group found by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.09

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.86

Conclusions:

The predicted No Observed Adverse Effect Level (NOAEL) for Sodium 6-amino-5-{[4-chloro-2-(trifluoromethyl)phenyl]diazenyl}-4-hydroxynaphthalene-2-sulfonate (57741-47-6) is considered to be 450.2mg/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 oral toxicity was predicted for the test compound Sodium 6-amino-5-{[4-chloro-2-(trifluoromethyl)phenyl]diazenyl}-4-hydroxynaphthalene-2-sulfonate (57741-47-6). The study assumed the use of male and female Crj: CD(SD) in chronic study of 90days. No significant alterations were noted at the dose level of 667.080mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for compound Sodium 6-amino-5-{[4-chloro-2-(trifluoromethyl) phenyl]diazenyl}-4-hydroxynaphthalene-2-sulfonate is considered to be 450.2mg/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

450.2 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

Data is from K2 prediction OECD QSAR toolbox 3.3.

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

Mode of Action Analysis / Human Relevance Framework

Repeated dose toxicity: via oral route

Various experimental studies were reviewed to determine the toxic nature of target substance Sodium 6-amino-5-{[4-chloro-2-(trifluoromethyl)phenyl]diazenyl}-4- hydroxynaphthalene-2-sulfonate (57741-47-6)upon repeated exposure by oral route. 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 oral toxicity was predicted for the test compound Sodium 6-amino-5-{[4-chloro-2-(trifluoromethyl)phenyl]diazenyl}-4-hydroxynaphthalene-2-sulfonate (57741-47-6). The study assumed the use of male and female Crj: CD(SD) in chronic study of 90days. No significant alterations were noted at the dose level of 667.080mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for compound Sodium 6-amino-5-{[4-chloro-2-(trifluoromethyl) phenyl]diazenyl}-4-hydroxynaphthalene-2-sulfonate is considered to be 450.2mg/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.

Another chronic toxicity study for Read across was performed by Ministry of Health, Labour and Welfare", Scientific Committee on Cosmetology (Environment, Consumer Protection and Nuclear Safety, 1988) to determine the oral toxic nature of D&C Red 33; IUPAC name disodium 5-amino-4-hydroxy-3-(phenyldiazenyl)naphthalene-2,7-disulfonate (3567-66-6). The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on mutation from the analogue substance. In a chronic repeated dose toxicity study, dogs were treated with Disodium salt of 8-amino-2-phenylazo-1-naphtoL-3, 6-disulphonic acid in the concentration of 750 mg/kg bw/day orally in diet. Histopathological changes in the Liver, kidneys and thyroid were observed in 750 mg/kg/day treated dogs No other effect in clinical sign, mortality ,morbidity were observed at this dose. Therefore, NOAEL was considered to be 750 mg/kg bw/day when dogs were treated with Disodium salt of 8-amino-2-phenyLazo-1-naphtoL-3, 6-disuLphonic acid orally for 90 days.  

Repeated inhalation study:

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance Sodium 6-amino-5-{[4-chloro-2-(trifluoromethyl)phenyl]diazenyl}-4-hydroxynaphthalene-2-sulfonate (57741-47-6) ,which is reported as 1.5598E-19Pa at 25 C. Also considering the particle size distribution of the substance the majority of the particles was found to be in the size of 150 micron to 25 micron which is much larger size range compared to the inhalable particulate matter. Thus, exposure to inhalable dust, mist and vapour of the chemical Sodium 6-amino-5-{[4-chloro-2-(trifluoromethyl)phenyl]diazenyl}-4-hydroxynaphthalene-2-sulfonate is highly unlikely. Therefore this study is considered for waiver.

Repeated dermal study

The acute toxicity value for Sodium 6-amino-5-{[4-chloro-2-(trifluoromethyl)phenyl]diazenyl}-4-hydroxynaphthalene-2-sulfonate (57741-47-6) (as provided in section 7.2.3) is 3204mg/kg body weight. Also, given the use of the chemical; repeated exposure by the dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected that Sodium 6-amino-5-{[4-chloro-2-(trifluoromethyl)phenyl]diazenyl}-4-hydroxynaphthalene-2-sulfonate shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that Sodium 6-amino-5-{[4-chloro-2-(trifluoromethyl)phenyl]diazenyl}-4-hydroxynaphthalene-2-sulfonate shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

Based on the data available for the target chemical and its prediction, Sodium 6-amino-5-{[4-chloro-2-(trifluoromethyl)phenyl]diazenyl}-4-hydroxynaphthalene-2-sulfonate (57741-47-6) does not exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.

Additional information

Based on the data available for the target chemical and its prediction, Sodium 6-amino-5-{[4-chloro-2-(trifluoromethyl)phenyl]diazenyl}-4-hydroxynaphthalene-2-sulfonate (57741-47-6) does not exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.