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Description of key information

Acute oral toxicity: 

The acute oral toxicity dose (LD50) was considered based on different studies conducted on rats for the test chemical. The LD50 value is 4100 mg/kg bw. The study concluded that LD50 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 very low vapour pressure of the test chemical. 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 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, 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:
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:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
not specified
Doses:
Range of 3100-5500 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:
male/female
Dose descriptor:
LD50
Effect level:
4 100 mg/kg bw
Based on:
test mat.
95% CL:
3 100 - 5 500
Mortality:
50% mortality was observed at 4100 mg/kg bw in treated animals.
Clinical signs:
not specified
Body weight:
not specified
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 4100 mg/kg bw, with 95% confidence limits of 3100-5500 mg/kg bw, when male and female rats was treated with the given test chemical via oral route.
Executive summary:

Acute oral toxicity study was conducted by using the given test chemical in male and female rats at the dose concentration range of 3100-5500 mg/kg bw.

Animals were observed for mortality. 50% mortality was observed at 4100 mg/kg bw in treated animals.

Hence, the LD50 value was considered to be 4100 mg/kg bw, with 95% confidence limits of 3100-5500 mg/kg bw, when male and female rats was treated with the given test chemical via oral route.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
4 100 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from peer-reviewed journal.

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:
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:
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 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:
Range of 2440-6460 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:
3 970 mg/kg bw
Based on:
test mat.
95% CL:
2 440 - 6 460
Mortality:
50% mortality was observed at 3970 mg/kg bw in treated animals.
Clinical signs:
not specified
Body weight:
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 3970 mg/kg bw, with 95% confidence limits of 2440-6460 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 range of 2440-6460 mg/kg bw.

Animals were observed for mortality. 50% mortality was observed at 3970 mg/kg bw in treated animals.

Hence, the LD50 value was considered to be 3970 mg/kg bw, with 95% confidence limits of 2440-6460 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
2 000 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 for test chemical. The studies are summarized as below -

 

The reported study was mentioned in peer-reviewed journals, handbook and authoritative database to determine the acute oral toxicity dose for the given test chemical. The study was conducted in male and female rats at the dose concentration range of 3100-5500 mg/kg bw. Animals were observed for mortality. 50% mortality was observed at 4100 mg/kg bw in treated animals. Hence, the LD50 value was considered to be 4100 mg/kg bw, with 95% confidence limits of 3100-5500 mg/kg bw, when male and female rats was treated with the given test chemical via oral route.

 

The above study is supported with another study mentioned in study report for the given test chemical. The study was conducted as per OECD No. 423 (Acute Oral toxicity - Acute Toxic Class Method) in female Wistar rats.

Six female Wistar rats were selected for acute oral toxicity study. The animals were fasted for minimum 16-18 hours prior to dosing and for 4 hours post dosing, food was withheld but drinking water provided ad libitum. The time intervals between dosing were determined by the onset, duration and severity of toxic signs.

Three rats of first group were dosed with starting dose of 2000 mg/kg body weight and the animals did not show any mortality so another three animals of the same group were dosed with 2000 mg/kg body weight and no mortality was observed. Hence, further dosing was stopped.

Body weights were re­corded on day 0 (prior to dosing) 7 and 14. Mean body weight of all the animals treated with 2000 mg/kg body weight was observed with gain on day 7 and 14, as compared to day 0. At 2000 mg/kg, all the animals were normal throughout the experimental period. No external and internal gross pathological changes were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice.

Under the conditions of this; acute oral toxicity dose was considered to be >2000 mg/kg bw, when female rats were treated with the given test chemical via oral gavage route.

 

These studies are supported with the data available in report for the test chemical. The acute oral toxicity study was conducted as per OECD No. 423 on 6 female Wistar rats at the concentration of 2000 mg/kg bw.

The animals were fasted for minimum 16-18 hours prior to dosing and for 3-4 hours post dosing, with food withheld but drinking water provided ad libitum. The time intervals between dosing were determined by the onset, duration and severity of toxic signs. Three rats of first group were dosed with starting dose of 2000 mg/kg body weight and the animals did not show any mortality so another three animals of the same group were dosed with 2000 mg/kg body weight and no mortality was observed. Hence, further dosing was stopped. Body weights were re­corded on day 0 (prior to dosing) 7 and 14.

Body weight gain was observed in all the animals treated with 2000 mg/kg body weight, during the 14 day observation period, as compared to day 0. At 2000 mg/kg, animal nos. 1, 2, 3, 5 and 6 were observed normal throughout the experimental period, whereas animal no. 4 was observed normal at 30 minutes, 1, 2, 3 and 4 hours, with mild ataxia from day 1 to 4, with mild tremors on day 1, with mild chromodacryorrhea from day 2 to 6 and with moderate to mild lethargy from day 3 to 9 post dosing followed by normal observation till day 14. No external and internal gross pathological changes were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice. No mortality was observed in the animals treated with 2000 mg/kg dose throughout the 14 days observation period post dosing.

Therefore, the LD50 was considered to be >2000 mg/kg bw, when female Wistar rats were treated with the given test chemical orally.

 

All the above studies are further supported with the study available in study report and designed and conducted to determine the acute oral toxicity profile of the given test chemical as per OECD No. 423 for the given test chemical in six female Wistar rats.

The animals were fasted for minimum 16-18 hours prior to dosing and for 4 hours post dosing, food was withheld but drinking water provided ad libitum. The time intervals between dosing were determined by the onset, duration and severity of toxic signs. Three rats of first group were dosed with starting dose of 2000 mg/kg body weight and the animals did not show any mortality so another three animals of the same group were dosed with 2000 mg/kg body weight and no mortality was observed. Hence, further dosing was stopped.

Body weights were recorded on day 0 (prior to dosing) 7 and 14. Mean body weight of all the animals treated with 2000 mg/kg body weight was observed with gain on day 7 and 14, as compared to day 0. At 2000 mg/kg, all the animals were normal throughout the experimental period. No external and internal gross pathological changes were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice. No mortality was observed at dose 2000mg/kg bw in treated rats.

Hence, the LD50 was considered to be >2000mg/kg bw, when rats were treated with the given test chemical orally.

 

Thus, based on the above summarised studies on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw. 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 very low vapour pressure of the test chemical. 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 mentioned in publication, handbook and authoritative database and designed and conducted to determine the acute dermal toxicity profile of the given test chemical in rabbits at the dose concentration range of 2440-6460 mg/kg bw. Animals were observed for mortality. 50% mortality was observed at 3970 mg/kg bw in treated animals. Hence, the LD50 value was considered to be 3970 mg/kg bw, with 95% confidence limits of 2440-6460 mg/kg bw, when rabbits were treated with the given test chemical by dermal application.

 

The above study is supported with another study mentioned in report and performed as per OECD No. 402 in Wistar rats.

Five male and five female healthy young adult rats were randomly selected and used for conducting acute dermal toxicity study. Rats free from injury and irritation of skin were selected for the study. Approximately, twenty four hours prior to dermal application of test item, greater than 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight based on the test item density (1.05513) and latest body weight was applied by single dermal application and observed for 14 days after treatment.

On test day 0, calculated volume of test item was applied directly on the intact skin of clipped area of rats; the porous gauze dressing was put on to the intact skin of clipped area. This porous gauze dressing was covered with a non-irritating tape. After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water. The skin reactions were assessed.

The animals were observed daily for mortality and clinical signs, during the acclimatization period and post dosing till the termination. All animals were observed for clinical signs at approximately 1, 2, 3 and 4 hours after treatment on day 0 and once daily during test days 1‑14. Mortality was recorded after application on test day 0 and twice daily during days 1-14 (at least once on the day of sacrifice). Local signs / Skin reactions were observed daily from test days 1-14 (in common with clinical signs). Body weights were re­corded on day 0 (prior to application) and on day 7 and 14. All animals were necropsied and examined macroscopically.

No mortality was observed in any animal till the end of the experimental period. At 2000 mg/kg, all the animals were observed normal throughout the experimental period. Mean body weight was observed with gain on day 7 and 14 of male and female animals, as compared to day 0. The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality.

Hence, the LD50 value was considered to be >2000 mg/kg bw, when male and female wistar rats were occlusively treated with test chemical by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).

These studies are supported with the study mentioned in study report by using the given test chemical as per OECD No.402 in 10 male and female healthy young adult Wistar rats which were randomly selected and used for conducting acute dermal toxicity study at the concentration of 2000 mg/kg bw.

Rats free from injury and irritation of skin were selected for the study. 24 hours prior to dermal application of test item, approximately 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight of test item was applied by single dermal application and observed for 14 days after treatment. On test day 0, as such amount of test item, calculated based on density (1.0016) and body weight was applied directly on the intact skin of clipped area of rats; the surgical gauze patch was put on to the intact skin of clipped area. This porous gauze dressing was covered with a non-irritating adhesive tape. The porous gauze dressing was wrapped around the abdomen and anchored with non-irritating adhesive tape. After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water. The skin reactions were assessed.

The animals were observed daily for mortality and clinical signs, during the acclimatization period. All animals were observed for clinical signs at approximately 1, 2, 3 and 4 hours after treatment on day 0 and once daily during test days 1‑14. Mortality was recorded after application on test day 0 and twice daily during days 1-14 (at least once on the day of sacrifice). Local signs / Skin reactions were observed daily from test days 1-14 (in common with clinical signs). Body weights were re­corded on day 0 (prior to application) and on day 7 and 14. All animals were necropsied and examined macroscopically.

No mortality was observed in any animal till the end of the experimental period. No clinical signs and any skin reaction were observed throughout the experimental period in all treated animals. The male and female animals were observed with body weight gain throughout the experiment, except on day 7 male animals were observed with decline in mean body weight gain as compared to day 0. The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality.

Therefore, the LD50 was considered to be >2000mg/kg bw, when rats were treated with the given test chemical by dermal application.

 

All the above studies are further supported with the study mentioned in report for the test chemical and was performed as per OECD No. 402 in Wistar Rats.

Five male and five female healthy young adult rats were randomly selected and used for conducting acute dermal toxicity study. Rats free from injury and irritation of skin were selected for the study. Approximately, twenty four hours prior to dermal application of test item, greater than 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight based on the test item density (1.07513) and latest body weight was applied by single dermal application and observed for 14 days after treatment.

On test day 0, calculated volume of test item was applied directly on the intact skin of clipped area of rats; the porous gauze dressing was put on to the intact skin of clipped area. This porous gauze dressing was covered with a non-irritating tape. After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water. The skin reactions were assessed.

The animals were observed daily for mortality and clinical signs, during the acclimatization period and post dosing till the termination. All animals were observed for clinical signs at approximately 1, 2, 3 and 4 hours after treatment on day 0 and once daily during test days 1-14. Mortality was recorded after application on test day 0 and twice daily during days 1-14 (at least once on the day of sacrifice). Local signs / Skin reactions were observed daily from test days 1-14 (in common with clinical signs). Body weights were re­corded on day 0 (prior to application) and on day 7 and 14. All animals were necropsied and examined macroscopically.

No mortality was observed in any animal till the end of the experimental period. At 2000 mg/kg, all the animals were observed normal throughout the experimental period. Mean body weight was observed with gain on day 7 and 14 of male and female animals, as compared to day 0. The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality.

Hence, the LD50 was considered to be >2000mg/kg bw, when rats were treated with the given test chemical by dermal application.

 

Thus, based on the above summarised studies on 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 on 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 wavier was added so, not possible to classify.