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Acute oral toxicity:

Acute oral toxicity dose (LD50) of Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS no: 57741-47-6) was predicted based on OECD QSAR toolbox 6216 mg/kg bw and different studies available on structurally similar read across substances Disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS No. 3567-66-6) >2000 mg/kg bw and Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS no: 3734-67-6) >2000 mg/kg bw. All these studies concluded that the LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate cannot be classified for acute oral toxicity.

Acute Inhalation toxicity:

Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS no: 57741-47-6) has very low vapour pressure (1.559E-19 Pa at 25°C), so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point was considered for waiver.

Acute Dermal toxicity:

Acute Dermal toxicity dose (LD50) for Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS no: 57741-47-6) was predicted based on OECD QSAR toolbox 3204 mg/kg bw and different studies available for the structurally similar read across substances Disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS no: 3567-66-6) >2000 mg/kg bw and Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS no: 3734-67-6) >2000 mg/kg bw. All these studies concluded that the LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate cannot be classified for acute dermal toxicity.

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 the supporting QMRF report has been attached.
Qualifier:: according to guideline
Guideline:: other: estimated data
Principles of method if other than guideline:: Prediction is done using QSAR Toolbox version 3.3
GLP compliance:: not specified
Test type:: other: not specified
Limit test:: no
Specific details on test material used for the study:: Name: Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate
SMILES:Nc1ccc2cc(S(=O)(=O)O{-}.[Na]{+})cc(O)c2c1N=Nc1ccc(Cl)cc1C(F)(F)F
InChI: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-;
Mol. formula: C17H10ClF3N3NaO4S
Molecular Weight: 467.786 g/mole
Species:: rat
Strain:: Wistar
Sex:: male/female
Details on test animals or test system and environmental conditions:: not specified
Route of administration:: oral: gavage
Vehicle:: unchanged (no vehicle)
Details on oral exposure:: not specified
Doses:: 6216 mg/kg
No. of animals per sex per dose:: 10
Control animals:: not specified
Details on study design:: not specified
Statistics:: not specified
Preliminary study:: not specified
Sex:: male/female
Dose descriptor:: LD50
Effect level:: 6 216 mg/kg bw
Based on:: test mat.
Remarks on result:: other: 50% mortality was observed
Mortality:: not specified
Clinical signs:: other: not specified
Gross pathology:: not specified
Other findings:: not specified
Interpretation of results:: other: Not classified
Conclusions:: LD50 was estimated to be 6216 mg/kg bw, when 10 male and female Wistar rats were treated with Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS no: 57741-47-6) via oral gavage route.
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 Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS no: 57741-47-6). The LD50 was estimated to be 6216 mg/kg bw, when 10 male and female Wistar rats were treated with Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate via oral gavage route.

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

6 216 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3.

Reference

Endpoint:: acute toxicity: inhalation
Data waiving:: other justification
Justification for data waiving:: other:

Quality of whole database:

Waiver

Reference

Endpoint:: acute toxicity: dermal
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 the supporting QMRF report has been attached.
Qualifier:: according to guideline
Guideline:: other: estimated data
Principles of method if other than guideline:: Prediction is done using QSAR Toolbox version 3.3.
GLP compliance:: not specified
Test type:: other: not specified
Limit test:: no
Specific details on test material used for the study:: Name: Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate
SMILES:Nc1ccc2cc(S(=O)(=O)O{-}.[Na]{+})cc(O)c2c1N=Nc1ccc(Cl)cc1C(F)(F)F
InChI: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-;
Mol. formula: C17H10ClF3N3NaO4S
Molecular Weight: 467.786 g/mole
Species:: rabbit
Strain:: New Zealand White
Sex:: male/female
Details on test animals or test system and environmental conditions:: not specified
Type of coverage:: occlusive
Vehicle:: unchanged (no vehicle)
Details on dermal exposure:: not specified
Duration of exposure:: 24 hours
Doses:: 3204 mg/kg
No. of animals per sex per dose:: 10
Control animals:: not specified
Details on study design:: not specified
Statistics:: not specified
Preliminary study:: not specified
Sex:: male/female
Dose descriptor:: LD50
Effect level:: 3 204 mg/kg bw
Based on:: test mat.
Remarks on result:: other: 50% mortality was observed
Mortality:: not specified
Clinical signs:: other: not specified
Gross pathology:: not specified
Other findings:: not specified
Interpretation of results:: other: Not classified
Conclusions:: LD50 was estimated to be 3204 mg/kg bw, when 10 male and female New Zealand White rabbits were treated with Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS no: 57741-47-6) for 24 hours by dermal application occlusively.
Executive summary:: In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS no: 57741-47-6). The LD50 was estimated to be 3204 mg/kg bw, when 10 male and female New Zealand White rabbits were treated with Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate for 24 hours by dermal application occlusively.

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 204 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3.

Acute oral toxicity:

In different studies, Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS no: 57741-47-6) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate along with the study available on structurally similar read across substances Disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS No. 3567-66-6) and Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS no: 3734-67-6). 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 Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS no: 57741-47-6). The LD50 was estimated to be 6216 mg/kg bw, when 10 male and female Wistar rats were treated with Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate via oral gavage route.

The above study is supported by Sustainability Support Services (Europe) AB (study no.18819, 2016) was designed and conducted for the structurally similar read across substance Disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS No. 3567-66-6) in Sprague Dawley rats. Initially, three female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality after the dosing. No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg resulted in diarrhoea (reddish colour stools) in all animals with onset at 2 hours and no mortality after the dosing. As no mortality were observed at 24 hours after the dosing, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - II). Administration of the test item at 2000 mg/kg resulted in diarrhoea (reddish colour stools) in all animals with onset at 2 hours and no mortality after the dosing. All animals from 300 mg/kg and 2000 mg/kg dose groups survived through the study period of 14 days. Staining of the stool is attributed to the reddish colour of the test item. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups. The acute oral LD50 of Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate (CAS No. 3567-66-6) was >2000 mg/kg body weight. Thus, it was concluded that the acute toxicity study of Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate, when administered via oral route in Sprague Dawley rats falls into the “Category Unclassified” criteria of CLP.

This study is further supported by Sustainability Support Services (Europe) AB (study no.18825, 2014) was designed and conducted for the structurally similar read across substance Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS no: 3734-67-6) in Sprague Dawley rats. Initially, three female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality after the dosing. No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. As no mortality were observed at 24 hours after the dosing, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - II). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups. It was concluded that the acute oral median lethal dose (LD50) of Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate supplied by Sustainability Support Services (Europe) AB, Sweden, when administered to Sprague Dawley rats was found to be >2000 mg/kg body weight and falls into the “Category Unclassified” criteria of CLP.

Thus, based on the above studies on Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS no: 57741-47-6) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate cannot be classified for acute oral toxicity.

Acute Inhalation toxicity:

Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS no: 57741-47-6) has very low vapour pressure (1.559E-19 Pa at 25°C), so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point was considered for waiver.

Acute Dermal toxicity:

In different studies, Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS no: 57741-47-6) has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rabbits and rats for Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate along with the study available on the structurally similar read across substances Disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS no: 3567-66-6) and Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS no: 3734-67-6). 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 dermal toxicity was estimated for Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS no: 57741-47-6). The LD50 was estimated to be 3204 mg/kg bw, when 10 male and female New Zealand White rabbits were treated with Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate for 24 hours by dermal application occlusively.

This study is supported by Sustainability Support Services (Europe) AB (study no.18820, 2016) was designed and conducted for the structurally similar read across substance Disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS no: 3567-66-6) in Sprague Dawley rats. The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment. It was concluded that the acute dermal median lethal dose (LD50) of Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disul phonate, when administered to male and female Sprague Dawley rats was found to be >2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate does not classify as an acute dermal toxicant. CLP Classification: “Unclassified”.

The above study is further supported by Sustainability Support Services (Europe) AB (study no.18826, 2016) was designed and conducted for the structurally similar read across substance Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS no: 3734-67-6) in Sprague Dawley rats. The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment. It was concluded that the acute dermal median lethal dose (LD50) of Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate supplied by Sustainability Support Services (Europe) AB, Sweden, when administered to male and female Sprague Dawley rats was found to be >2000 mg/kg body weight.

Thus, based on the above studies on Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS no: 57741-47-6) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate cannot be classified for acute dermal toxicity.

Based on the above studies and prediction on Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate (CAS no: 57741-47-6) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw for acute oral and dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, Sodium 6-amino-5-[[4-chloro-2-(trifluoromethyl)phenyl]azo]-4-hydroxynaphthalene-2-sulphonate cannot be classified for acute oral and dermal toxicity. For Acute Inhalation toxicity wavier was added so, not possible to classify.