Calcium 3-hydroxy-4-[(4-methyl-2-sulphonatophenyl)azo]-2-naphthoate

Endpoint summary

Description of key information

Acute oral toxicity: 

The acute oral toxicity dose (LD50) for calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl) diazenyl]-2-naphthoate (CAS no. 5281-04-9) was considered based on different experimental studies conducted on rats and mice, the values were considered to be >5000 mg/kg bw in rat and >16000 mg/kg bw in mice; and based on different study available for structurally similar related read across substances, the LD50 values were considered to be >2000 mg/kg bw in rat and 4166.66 mg/kg bw in mice. All these studies concluded that the LD50 value is >2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl) diazenyl]-2-naphthoate cannot be classified for acute oral toxicity.

Acute Inhalation Toxicity:

The acute inhalation toxicity study need not be conducted because exposure of humans via inhalation route is not likely taking into account due to the low vapour pressure of the substance calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl) diazenyl]-2-naphthoate (CAS no. 5281-04-9); and High melting point, which is reported up to 400°C. Thus, exposure to inhalable dust, mist and vapour of the chemical calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl) diazenyl]-2-naphthoate is highly unlikely. Therefore this study is considered for waiver.

Acute Dermal toxicity:

The acute dermal toxicity dose (LD50) for calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl) diazenyl]-2-naphthoate (CAS no. 5281-04-9) was considered based on experimental study conducted on rats, the value was considered to be >2500 mg/kg bw; and based on different study available for structurally similar related read across substances, the LD50 values were considered to be >2000 mg/kg bw in rats. All these studies concluded that the LD50 value is >2000 mg/kg bw, for acute dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl) diazenyl]-2-naphthoate 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:

weight of evidence

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 publication

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Acute Oral toxicity study of calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (CAS no. 5281-04-9) in rats.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

- IUPAC Name: calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate- Common Name: D & C Red no. 7- InChI:1S/C18H14N2O6S.Ca/c1-10-6-7-14(15(8-10)27(24,25)26)19-20-16-12-5-3-2-4-11(12)9-13(17(16)21)18(22)23;/h2-9,21H,1H3,(H,22,23)(H,24,25,26);/q;+2/p-2/b20-19+;- Smiles:c12c(c(c(C(=O)[O-])cc1cccc2)O)\N=N\c1c(cc(C)cc1)S(=O)(=O)[O-].[Ca+2]- Name of test material (as cited in study report):C. I. Pigment 57:1- Molecular formula :C18H12CaN2O6S- Molecular weight :424.445 g/mol- Substance type:organic- Physical state:solid

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: unspecified

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

not specified

Doses:

2000 mg/kg and 5000 mg/kg bw

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days -Other examinations performed: Animals were observed for mortality and clinical signs.

Statistics:

not specified

Preliminary study:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality was observed

Mortality:

No mortality was observed at dose 5000 mg/kg bw

Clinical signs:

other: No signs of toxicity were observed.

Gross pathology:

not specified

Other findings:

not specified

Interpretation of results:

other: Not classified

Conclusions:

The acute oral toxicity dose (LD50) was considered to be >5000 mg/kg bw, when rats were treated with calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate via oral route.

Executive summary:

Acute oral toxicity study was conducted in rats using test material calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (CAS no. 5281-04-9) at the dose concentration of 2000 or 5000 mg/kg bw. Animals were observed for mortality and clinical signs. No mortality was observed at dose 5000 mg/kg bw. No signs of toxicity were observed. Therefore, LD50 was considered to be >5000 mg/kg bw, when rats were treated with calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate via oral route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from publication.

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:

experimental study

Adequacy of study:

weight of evidence

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:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

Acute Dermal toxicity study of calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (CAS no. 5281-04-9) in rats.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

- IUPAC Name: calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate- Common Name: D & C Red no. 7- InChI:1S/C18H14N2O6S.Ca/c1-10-6-7-14(15(8-10)27(24,25)26)19-20-16-12-5-3-2-4-11(12)9-13(17(16)21)18(22)23;/h2-9,21H,1H3,(H,22,23)(H,24,25,26);/q;+2/p-2/b20-19+;- Smiles:c12c(c(c(C(=O)[O-])cc1cccc2)O)\N=N\c1c(cc(C)cc1)S(=O)(=O)[O-].[Ca+2]- Name of test material (as cited in study report):C. I. Pigment 57:1- Molecular formula :C18H12CaN2O6S- Molecular weight :424.445 g/mol- Substance type:organic- Physical state:Solid powder, dark red odourless

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Type of coverage:

other: Dermal

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

not specified

Duration of exposure:

not specified

Doses:

2500 mg/kg bw

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality was observed

Mortality:

No mortality was observed at dose 2500 mg/kg bw

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

Interpretation of results:

other: Not classified

Conclusions:

The acute Dermal toxicity dose (LD50) was considered to be >2500 mg/kg bw, when rats were treated with calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (CAS no. 5281-04-9) by dermal application.

Executive summary:

Acute dermal toxicity study was conducted according to OECD directive 402 in rats using test material calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (CAS no. 5281-04-9) at the dose concentration of 2500 mg/kg bw. No mortality was observed at dose2500 mg/kg bw. Therefore, LD50 was considered to be >2500 mg/kg bw, when rats were treated with calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (CAS no. 5281-04-9) by dermal application.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 500 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from authoritative database.

Additional information

Acute oral toxicity:

In different experimental studies calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl) diazenyl]-2-naphthoate (CAS no. 5281-04-9) 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 and mice for calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl) diazenyl]-2-naphthoate along with the study available on structurally similar read across substances. The studies are summarized as below –

The experimental study mentioned in publication (1982), EFSA Journal (2010) and according to EUROPEAN COMMISSION – European Chemicals Bureau (2000), for the target chemical calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (CAS no. 5281-04-9), the acute oral toxicity study was conducted in rats at the dose concentration of 2000 or 5000 mg/kg bw. Animals were observed for mortality and clinical signs. No mortality was observed at dose 5000 mg/kg bw. No signs of toxicity were observed. Therefore, LD50 was considered to be >5000 mg/kg bw, when rats were treated with calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate via oral route.

The above experimental study is supported by the another experimental study mentioned in handbook, Toxicity and Safe Handling of Rubber Chemicals(1999); authoritative database (IFA GESTIS, 2017); EFSA Journal (2010); SIDS Initial Assessment Report (UNEP, 1994);EUROPEAN COMMISSION – European Chemicals Bureau (2000) and SCCNFP, 2004, for the target chemical calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (CAS no. 5281-04-9). Acute oral toxicity study was conducted in rats using test material at the dose concentration of 5000 mg/kg bw. Animals were observed for mortality and clinical signs. No mortality was observed at dose 5000 mg/kg bw. Toxicity symptoms were not observed in treated rats. Therefore, LD50 was considered to be >5000 mg/kg bw, when rats were treated with calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (CAS no. 5281-04-9) via oral route.

These studies are also supported by data available in EFSA Journal (2010) and SCCNFP, 2004, for the target chemical calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (CAS no. 5281-04-9), the acute oral toxicity study was conducted in rats using test material at the dose concentration of 9800 mg/kg bw. No mortality was observed at dose 9800 mg/kg bw. Therefore, LD50 was considered to be >9800 mg/kg bw, when rats were treated with calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (CAS no. 5281-04-9) via oral route.

All the above studies are further supported by the study mentioned in authoritative database (IFA GESTIS, 2017), EFSA Journal (2010) and SIDS Initial Assessment Report (UNEP, 1994), for the target chemical calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (CAS no. 5281-04-9). Acute oral toxicity study was conducted in mice using test material at the dose concentration of 16000 mg/kg bw. No mortality was observed at dose16000 mg/kg bw. Therefore, LD50 was considered to be >16000 mg/kg bw, when mice were treated with calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate via oral route.

All the above experimental studies are supported by the studies available on the structurally and functionally similar read across chemicals. The studies are as follows –

The acute oral toxicity study was designed and conducted for structurally and functionally similar read across chemical in Sprague Dawley rats. Initially, 3 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, 3 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 3 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 3 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 test chemical was >2000 mg/kg body weight. Thus, it was concluded that the acute toxicity study of test chemical, when administered via oral route in Sprague Dawley rats falls into the “Category Not classified” criteria of CLP.

The above study is supported by the study mentioned in publication for the structurally and functionally similar read across chemical. Acute oral toxicity study was conducted in male Sprague-Dawley white mice by using test chemical at the concentrations of 1250 mg/kg, 2500 mg/kg, 3750 mg/kg, 5000 mg/kg, 6250 mg/kg bw. 6 animals/dose were administered the given test chemical via oral gavage route and control animals were received distilled water. The mice were observed for 3 days for the signs and symptoms of toxicity as well as the death rate of each group were recorded. The LD50 of the substances was calculated using the arithmetic method of Karber. 50% mortality was observed at 4166.66 mg/kg bw. The clinical signs such as, loss of appetite, drowsiness, tachycardia, decrease in locomotion and anorexia were distinctive signs observed in the mice before dead. Therefore, LD50 was considered to be 4166.66 mg/kg bw, when male Sprague- Dawley white mice were treated with test chemical for 3 days via oral gavage route.

Thus, based on the above summarised studies on calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl) diazenyl]-2-naphthoate (CAS no. 5281-04-9) and it’s structurally similar 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, calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl) diazenyl]-2-naphthoate cannot be classified for acute oral toxicity.

Acute Inhalation Toxicity:

The acute inhalation toxicity study need not be conducted because exposure of humans via inhalation route is not likely taking into account due to the low vapour pressure of the substance calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl) diazenyl]-2-naphthoate (CAS no. 5281-04-9); and High melting point, which is reported up to 400°C. Thus, exposure to inhalable dust, mist and vapour of the chemical calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl) diazenyl]-2-naphthoate is highly unlikely. Therefore this study is considered for waiver. 

Even if, the acute inhalation toxicity study was mentioned in authoritative database for the target chemical calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (CAS no. 5281-04-9). The study was conducted according to OECD directive 403 in rats at the dose concentration of 1510 mg/m³. No mortality was observed at dose 1510 mg/m³. Therefore, LC50 was considered to be >1510 mg/m³, when rats were treated with calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (CAS no. 5281-04-9) by inhalation route. 

Though, the study is available for the acute inhalation toxicity, the details on possible symptoms or findings were not provided. Thus, due to the inconclusive result the substance calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (CAS no. 5281-04-9) is consider as waiver for the acute inhalation.

Acute Dermal Toxicity:

In different studies calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl) diazenyl]-2-naphthoate (CAS no. 5281-04-9) 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 rats for calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl) diazenyl]-2-naphthoate along with the study available on structurally similar read across substances. The studies are summarized as below –

The experimental study mentioned in authoritative database (IFA GESTIS, 2017) and EUROPEAN COMMISSION – European Chemicals Bureau (IUCLID Dataset, 2000), for the target chemical calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (CAS no. 5281-04-9). The acute dermal toxicity study was conducted according to OECD directive 402 in rats using test material at the dose concentration of 2500 mg/kg bw. No mortality was observed at dose2500 mg/kg bw. Therefore, LD50 was considered to be >2500 mg/kg bw, when rats were treated with calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate (CAS no. 5281-04-9) by dermal application.

The above experimental study is supported by study available for the structurally and functionally similar read across chemical. The acute dermal toxicity study was designed and conducted for test chemical 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 test chemical, when administered to male and female Sprague Dawley rats was found to be >2000 mg/kg body weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that test chemical does not exhibit acute toxicity by the dermal route.

These studies are further supported by the study available for structurally and functionally similar read across chemical. The acute dermal toxicity study was designed and conducted for test chemical 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 test chemical, when administered to male and female Sprague Dawley rats was considered to be >2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that test chemical does not classify as an acute dermal toxicant. CLP Classification: “Not classified”.

Thus, based on the above summarised study on calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl) diazenyl]-2-naphthoate (CAS no. 5281-04-9) and it’s structurally similar 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, calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl) diazenyl]-2-naphthoate cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above experimental studies on calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl) diazenyl]-2-naphthoate (CAS no. 5281-04-9) and it’s structurally and functionally similar 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, calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl) diazenyl]-2-naphthoate cannot be classified for acute oral and dermal toxicity. For Acute Inhalation toxicity wavier were added so, not possible to classify.