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

Endpoint summary

Description of key information

Acute Oral Toxicity: 

In Acute oral toxicity ,LD50 value for target substance C.I. Acid Red 151(CAS NO: 6406-56-0) was considered to be 7736 mg/kg bw,and for differentstudies available on the structurally similar read across substance Disodium 6-hydroxy-5-[(4-sulphonatophenyl)azo]naphthalene-2-sulphonate(2783-94-0) was considered to be >6000 mg/kg bw ;for FD & C Red NO. 40 (25956-17-6) was considered to be >10000 mg/kg bw and for Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate (CAS No. 3567-66-6) was considered to be 5000 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, C.I. Acid Red 151(CAS NO: 6406-56-0) cannot be classified for acute oral toxicity.

Acute Inhalation Toxicity: 

Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate (6406-56-0) has very low vapor pressure (5.19E-021 Pa.), 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 the acute inhalation toxicity end point was considered for waiver.

Acute Dermal Toxicity:

In Acute dermal toxicity, LD50 value was predicted based on OECD QSAR toolbox for target substance Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate (6406-56-0) was estimated to be 6184.56 mg/kg bw,and for differentstudies available on structurally similar read across substance Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate (CAS No. 3567-66-6) was considered to be >2000 mg/kg bw and for Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate (CAS No. 2519-30-4) was considered to be >2000 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, Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate (6406-56-0) cannot be classified for acute dermal 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:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data is from authoritative database

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

The acute oral L50 test of C.I. Acid Red 151(CAS NO: 6406-56-0) in ChR-CD male rat.

GLP compliance:

not specified

Test type:

other: no data available

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report):C.I. Acid Red 151
- Molecular formula :C22H15N4O4S.Na
- Molecular weight :455.448 g/mol
- Substance type:Organic
- Physical state:Solid
-Purity70% (22% Active Ingredient;35% 2-Ethoxyethanol;2% ''Merpol" DA;1% Compound 85;5% "Pluronic" L 42;5% NaOH)
- Impurities (identity and concentrations):30%

Species:

rat

Strain:

other: ChR-CD

Sex:

male

Details on test animals or test system and environmental conditions:

Details on test animal:
TEST ANIMALS
- Age at study initiation:young and adult rats were used

Route of administration:

other: Oral (intragastric intubation)

Vehicle:

water

Details on oral exposure:

No data available

Doses:

7500, 8000, 8500 and 9500 mg/kg bw

No. of animals per sex per dose:

Total:40 animals
7500 mg/kg bw: 10 male
8000 mg/kg bw: 10 male
8500 mg/kg bw: 10 male
9500 mg/kg bw: 10 male

Control animals:

not specified

Details on study design:

Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

The LD50 value was calculated from the mortality data using the method of D. J. Finney.

Preliminary study:

no data available

Sex:

male

Dose descriptor:

LD50

Effect level:

7 736 mg/kg bw

95% CL:

7 347 - 7 977

Remarks on result:

other: 50% mortality was observed

Mortality:

At 7500 mg/kg bw – 2/10 rats died
At 8000mg/kg bw – 9/10 rats died.
At 8500 mg/kg bw – 9/10 rats died.
At 9500 mg/kg bw – 10/10 rats died.

Clinical signs:

other: Belly-to-cage posture, eyes half closed, prostration, pallor, stained mouth and compound and/or metabolite(s) in feces after dosing at 9,500 mg/kg. Belly-to-cage posture, eyes half closed, lethargy, prostration, labored breathing, stained nose and mouth,

Gross pathology:

No data available

Other findings:

No data available

Dose(mg/kg)	Average Body Weight (g)	Mortality ratio
7500	267	2/10
8000	256	9/10
8500	266	9/10
9500	244	10/10

Interpretation of results:

other: not classified

Conclusions:

The acute oral LD50 value of C.I. Acid Red 151 is considered to be 7,736 mg/kg (95% Confidence Limits:7347 mg/kg bw -7977 mg/kg bw) in ChR-CD male rats when test material was administered by intragastric intubation following 14 days of observation period.

Executive summary:

 Acute oral toxicity (LD50) test ofC.I. Acid Red 151was conducted in ChR-CD male rat.Test substancewas administered 7500, 8000, 8500 and 9500 mg/kg by intragastric intubation to four groups of ten rat. After 14 days observation.Mortality observed were 2/10 at dose 7500 mg/kg; 9/10 at 8000 and 8500 mg/kg and all animals died at dose 9500 mg/kg bw. clinical signs were observed at different doses which are as follows:Belly-to-cage posture, eyes half closed, prostration, pallor, stained mouth and compound and/or metabolite(s) in feces after dosing at 9,500 mg/kg.Belly-to-cage posture, eyes half closed, lethargy, prostration, labored breathing, stained nose and mouth, stained and wet perineal &rea and weight loss after dosing at 8,500 mg/kg.Belly-to-cage posture, eyes half closed, lethargy, prostration, chromodacryorrhea, irregular breathing, labored creathing, stained nose and mouth, stained and wet perineal area and weight loss after dosing at 8,000 mg/kg. Therefore,the acute oral L50 value ofC.I. Acid Red 151(95% Confidence Limits:7347 mg/kg bw -7977 mg/kg bw) is considered to be7,736 mg/kg in male ChR-CD rat.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

7 736 mg/kg bw

Quality of whole database:

Data is Klimisch 2

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Quality of whole database:

Waiver

Acute toxicity: via dermal route

Link to relevant study records

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 3.4 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 v3.4,2017

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 (IUPAC name): Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate
- Common name: Acid Red 151
- Molecular formula: C22H15N4O4S.Na
- Molecular weight: 455.448 g/mol
- Smiles notation: c12c(\N=N\c3ccc(\N=N\c4ccc(S(O)(=O)=O)cc4)cc3)c(ccc1cccc2)O.[Na+]
- InChl: 1S/C22H16N4O4S.Na/c27-21-14-5-15-3-1-2-4-20(15)22(21)26-25-17-8-6-16(7-9-17)23-24-18-10-12-19(13-11-18)31(28,29)30;/h1-14,27H,(H,28,29,30);/q;+1/b24-23+,26-25+;
- Substance type: Organic

Species:

rabbit

Strain:

other: albino

Sex:

male

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

No data available

Duration of exposure:

24 hours

Doses:

6184.56 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:

male

Dose descriptor:

LD50

Effect level:

6 184.56 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 5 nearest neighbours
Domain  logical expression:Result: In Domain

((("a" or "b" or "c" )  and "d" )  and ("e" and "f" )  )

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 High (Class III) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "e"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.715

Domain logical expression index: "f"

Parametric boundary:The target chemical should have a value of log Kow which is <= 5.76

Interpretation of results:

other: not classified

Conclusions:

The LD50 value was estimated to be 6184.56 mg/kg bw,when male albino rabbits were semiocclusively exposed with Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate (6406-56-0) by dermal application for 24 hours.

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 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate (6406-56-0).The LD50 was estimated to be 6184.56 mg/kg bw,when male albino rabbits were semiocclusively exposed with Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate (6406-56-0)by dermal application for 24 hours.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

6 184.56 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.4

Additional information

Acute Oral Toxicity: 

In different studies, Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate (6406-56-0) 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 Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate (6406-56-0) along with the study available on the structurally similar read across substance Disodium 6-hydroxy-5-[(4-sulphonatophenyl)azo]naphthalene-2-sulphonate(2783-94-0);FD & C Red NO. 40 (25956-17-6) and Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate (CAS No. 3567-66-6).The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

 

In experimental study conducted by U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017); RTECS (RTECS (registry of toxic effect of chemical substance data base ), 2017) and NTRL(NTRL NO: OTS0571003, 09/03/92) for the structurally similar read across substance Disodium 6-hydroxy-5-[(4-sulphonatophenyl)azo]naphthalene-2-sulphonate(2783-94-0). Acute oral toxicity (LD50) test of C.I. Acid Red 151 was conducted in ChR-CD male rat.Test substance was administered 7500, 8000, 8500 and 9500 mg/kg by intragastric intubation to four groups of ten rat. After 14 days observation.Mortality observed were 2/10 at dose 7500 mg/kg; 9/10 at 8000 and 8500 mg/kg and all animals died at dose 9500 mg/kg bw. clinical signs were observed at different doses which are as follows:Belly-to-cage posture, eyes half closed, prostration, pallor, stained mouth and compound and/or metabolite(s) in feces after dosing at 9,500 mg/kg.Belly-to-cage posture, eyes half closed, lethargy, prostration, labored breathing, stained nose and mouth, stained and wet perineal &rea and weight loss after dosing at 8,500 mg/kg.Belly-to-cage posture, eyes half closed, lethargy, prostration, chromodacryorrhea, irregular breathing, labored creathing, stained nose and mouth, stained and wet perineal area and weight loss after dosing at 8,000 mg/kg. Therefore,the acute oral L50 value of C.I. Acid Red 151(95% Confidence Limits:7347 mg/kg bw -7977 mg/kg bw) is considered to be7,736 mg/kg in male ChR-CD rat.

The above experimental study was further supported by I. F. GAUNT et. al. (Fd Cosmet. ToxicoL Vol. 5, pp. 747-754,1967) and U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) for the structurally similar read across substance FD & C Red NO. 40 (25956-17-6). In a acute oral toxicity study,rats were treated with FD & C Red NO. 40 in the concentration of 10000 mg/kg bw orally. No mortality was observed in treated rats at 10000 mg/kg bw. Therefore,LD50 was considered to be > 10000 mg/kg bw when rats were treated with FD & C Red NO. 40 orally.

This study is further supported by Sustainability Support Services (Europe) AB (study number: 18819, 2016-10-25) for the structurally similar read across substance Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate (CAS No. 3567-66-6).The acute oral toxicity profile of Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate was performed in 12 female Sprague Dawley rats. The test material was dissloved in distilled water and given by oral gavage route.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. Hence,The LD50 value was considered to be 5000 mg/kg body weight,when female Sprague Dawley rats were treated with Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate (CAS No. 3567-66-6) orally according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).

Thus, based on the above studies on Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate (6406-56-0) and it’s structurally similar read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate (6406-56-0) cannot be classified for acute oral toxicity.

Acute Inhalation Toxicity: 

Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate (6406-56-0) has very low vapor pressure (5.19E-021 Pa.), 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 the acute inhalation toxicity end point was considered for waiver.

Acute Dermal Toxicity:

In different studies, Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate (6406-56-0) has been investigated for acute dermal 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 rabbits for Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate (6406-56-0) along with the study available on the structurally similar read across substance Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate (CAS No. 3567-66-6) and Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate (CAS No. 2519-30-4).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 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate(6406-56-0).The LD50 was estimated to be 6184.56 mg/kg bw,when male albino rabbits were semiocclusively exposed with Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate(6406-56-0) by dermal application for 24 hours.

The above study was further supported by Sustainability Support Services (Europe) AB (study number: 18820, 2016-10-24) for the structurally similar read across substance Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate (CAS No. 3567-66-6).The acute dermal toxicity profile of Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate (3567-66-6) in Sprague Dawley rats. Water was used as vehicle.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. Hence,the LD50 value was considered to be >2000 mg/kg bw,when male and female Sprague-Dawley rats were semiocclusively treated with Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate (3567-66-6)by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).

Also these experimental results are further supported by Sustainability Support Services (Europe) AB (study number: 18818, 2016-10-24) for the structurally similar read across substance Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate (CAS No. 2519-30-4).The acute dermal toxicity profile of Tetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulpho natophenylazo)-7-sulphonato-1-naphthyl azo))naphthalene-4,6-disulphonate(CAS No. 2519-30-4) in Sprague Dawley rats.Distilled water was used as vehicle.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.The LD50 value was considered to be >2000 mg/kg bw,when male and female Sprague Dawley rats were semiocclusively treated withTetra sodium 1-acetamido-2-hydroxy-3-(4-((4-sulphonatophenylazo)-7-sulphonato-1-naphthylazo))naphthalene-4,6-disulphonate (CAS No. 2519-30-4)by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).

Thus, based on the above studies on Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate(6406-56-0) and it’s structurally similar read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate(6406-56-0) cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate(6406-56-0) and it’s structurally similar read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Sodium 4-(4-(2-hydroxynaphthalenylazo)phenylazo)benzenesulphonate(6406-56-0) cannot be classified for acute oral and dermal toxicity. For Acute inhalation toxicity wavier was added so, not possible to classify.