Disodium 6-hydroxy-5-[(2-methoxy-4-sulphonato-m-tolyl)azo]naphthalene-2-sulphonate

Endpoint summary

Description of key information

Acute oral toxicity: 

The acute oral toxicity dose (LD50) was considered based on different studies conducted on rats and mice for the given test chemical. The LD50 value is >10000 mg/kg bw. The study concluded that the LD50 value is >2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute oral toxicity.

Acute Inhalation Toxicity:

The acute inhalation toxicity study need not be conducted because exposure to humans via inhalation route is not likely taking into account due to the low vapour pressure of the test chemical, which is reported to be 1.67E-021 Pa. Thus, exposure to inhalable dust, mist and vapour of the chemical is highly unlikely. Therefore this study is considered for waiver. 

 

Acute Dermal toxicity:

The acute dermal toxicity dose (LD50) was considered based on different studies conducted on rats and rabbits for the test chemical. The LD50 value is >10000 mg/kg bw. The study concluded that LD50 value is >2000 mg/kg bw, for acute dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical 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 publication.

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Acute oral toxicity study of the given test chemical was performed in rat.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Remarks:

albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Fasting period before study: The animals were fasted for 3-4 hours prior to dosing.
- Housing: Following dosing, the animals were housed in metal cages suspended above the droppings.
- Diet (e.g. ad libitum): Food, ad libitum.
- Water (e.g. ad libitum): Water, ad libitum.

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 10% W/V solution

Doses:

215, 464, 1000, 2150, 4640, and 10000 mg/kg bw

No. of animals per sex per dose:

Six groups of five male and five female

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were made immediately following dosing, at 1, 4, 24, 48 hours and once daily thereafter up to 14 days.
- Necropsy of survivors performed: yes, following the observation period, the animals were weighed, sacrificed by cerebral concussion and necropsied.

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths at any dose level tested.

Clinical signs:

other: Clinical observations were normal with the exception of red colored feces in both sexes at all dose levels and red-colored urine at the three highest dose levels in the female animals.

Gross pathology:

not specified

Other findings:

not specified

Interpretation of results:

other: Not classified

Conclusions:

Acute oral toxicity dose (LD50) value was considered to be >10000 mg/kg bw, when male and female Sprague-Dawley albino rats were treated with the given test chemical via oral gavage route.

Executive summary:

Acute oral toxicity study was conducted by using the given test chemical in male and female Sprague-Dawley albino rats at the dose concentrations of 215, 464, 1000, 2150, 4640, and 10000 mg/kg bw. Six groups of five male and five female Sprague-Dawley rats each were administered the test substance in a 10% weight/volume solution. The animals were fasted for 3-4 hours prior to dosing. Following dosing, the animals were housed in metal cages suspended above the droppings. Food and water were available ad libitum. Observations were made immediately following dosing, at 1, 4, 24, 48 hours and once daily thereafter up to 14 days. Following the observation period, the animals were weighed, sacrificed by cerebral concussion and necropsied. There were no deaths at any dose level tested. Clinical observations were normal with the exception of red colored feces in both sexes at all dose levels and red-colored urine at the three highest dose levels in the female animals. Under the condition of the study, the LD50 value was considered to be >10000 mg/kg bw, when male and female Sprague-Dawley albino rats were treated with the given test chemical via oral gavage route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

10 000 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:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

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 Publication.

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Acute dermal toxicity study of the given test chemical was performed in rabbit.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Type of coverage:

other: Dermal

Vehicle:

not specified

Details on dermal exposure:

not specified

Duration of exposure:

not specified

Doses:

10000 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:

> 10 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed at 10000 mg/kg bw in treated animals.

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

Interpretation of results:

other: Not classified

Conclusions:

Acute dermal toxicity dose (LD50) value was considered to be >10000 mg/kg bw, when rabbits were treated with the given test chemical by dermal application.

Executive summary:

Acute dermal toxicity study was conducted by using the given test chemical in rabbits at the dose concentration of 10000 mg/kg bw.

Animals were observed for mortality. No mortality was observed at 10000 mg/kg bw in treated animals.

Hence, the LD50 value was considered to be >10000 mg/kg bw, when rabbits were treated with the given test chemical by dermal application.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

10 000 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from publication.

Additional information

Acute oral toxicity:

In different studies, the given test chemical 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 the given test chemical. The studies are summarized as below –

 

The reported study was conducted to determine acute oral toxicity dose by using the given test chemical in male and female Sprague-Dawley albino rats at the dose concentrations of 215, 464, 1000, 2150, 4640, and 10000 mg/kg bw. Six groups of five male and five female Sprague-Dawley rats each were administered the test substance in a 10% weight/volume solution. The animals were fasted for 3-4 hours prior to dosing. Following dosing, the animals were housed in metal cages suspended above the droppings. Food and water were available ad libitum. Observations were made immediately following dosing, at 1, 4, 24, 48 hours and once daily thereafter up to 14 days. Following the observation period, the animals were weighed, sacrificed by cerebral concussion and necropsied. There were no deaths at any dose level tested. Clinical observations were normal with the exception of red colored feces in both sexes at all dose levels and red-colored urine at the three highest dose levels in the female animals. Under the condition of the study, the LD50 value was considered to be >10000 mg/kg bw, when male and female Sprague-Dawley albino rats were treated with the given test chemical via oral gavage route.

 

The above study is supported with another study for the given test chemical. The acute oral toxicity study was conducted in four to five mice at the dose concentration of 2000 mg/kg bw. The given test chemical was dissolved in saline and administered via oral route. Animals were observed for mortality. There were no deaths observed at 2000 mg/kg bw. Hence, the LD50 value was considered to be >2000 mg/kg bw, when four to five mice were treated with the given test chemical via oral route.

 

These studies are supported with the data available in study report and the acute oral toxicity study was designed and conducted as per OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method) for the test 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. Under the condition of the study, 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.

 

All the above studies are further supported with the data available in study report for the given test chemical and conducted 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 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 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 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 test chemical, when administered to Sprague Dawley rats was considered to be >2000 mg/kg body weight and falls into the “Category Not classified” criteria of CLP.

 

Thus, based on the above summarised studies on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute oral toxicity.

 

Acute Inhalation Toxicity:

The acute inhalation toxicity study need not be conducted because exposure to humans via inhalation route is not likely taking into account due to the low vapour pressure of the test chemical, which is reported to be 1.67E-021 Pa. Thus, exposure to inhalable dust, mist and vapour of the chemical is highly unlikely. Therefore this study is considered for waiver. 

 

Acute Dermal Toxicity:

In different studies, the given test chemical 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 and rabbits for test chemical. The studies are summarized as below -

 

The reported study was conducted to determine acute dermal toxicity dose by using the given test chemical in rabbits at the dose concentration of 10000 mg/kg bw. Animals were observed for mortality. No mortality was observed at 10000 mg/kg bw in treated animals. Hence, the LD50 value was considered to be >10000 mg/kg bw, when rabbits were treated with the given test chemical by dermal application.

 

The above study is supported with the data available in study report and conducted by using the given 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”.

 

These studies are supported with the data mentioned in report for the given test chemical. The study was designed and conducted to determine the acute dermal toxicity dose tested 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 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.

 

All the above studies are further supported with the data available in study report and the study was designed and conducted to determine the acute dermal toxicity profile of 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 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.

 

Thus, based on the above summarised studies for test chemical, it can be concluded that LD50 value is >2000 mg/kg bw, for acute dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute dermal toxicity.

 

Justification for classification or non-classification

Based on the above studies for the test chemical, it can be concluded that LD50 value is >2000 mg/kg bw, for acute oral and acute dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute oral and acute dermal toxicity. For acute inhalation toxicity waiver was added so, not possible to classify.