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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 and mice for the test chemical. The LD50 value is >5000 mg/kg bw. The study 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 0.22 Pa (0.0016 mm Hg). 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 >5000 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 in rat.
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
not specified
Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
not specified
Doses:
5000 mg/kg
No. of animals per sex per dose:
Total = 10
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Other examinations performed: Observations for mortality and systemic effects were made over a 14-day period.
Statistics:
not specified
Preliminary study:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed at 5000 mg/kg bw
Clinical signs:
not specified
Body weight:
not specified
Gross pathology:
not specified
Other findings:
not specified
Interpretation of results:
other: Not classified
Conclusions:
The acute oral toxicity dose (LD50) value was considered to be >5000 mg/kg bw, when 10 rats were treated with the given test chemical via oral gavage route.
Executive summary:

Acute oral toxicity study was conducted by using test chemical in 10 rats at the dose concentration of 5000 mg/kg bw. Observations for mortality and systemic effects were made over a 14-day period.No mortality was observed at 5000 mg/kg bw.

Hence, the LD50 value was considered to be >5000 mg/kg bw, when 10 rats were treated with the given test chemical via oral gavage 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:
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 dermal toxicity study of the given test chemical 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:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: The given test chemical was applied to intact and abraded skin
Duration of exposure:
24 h
Doses:
5000 mg/kg
No. of animals per sex per dose:
Total = 8
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
Statistics:
not specified
Preliminary study:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed at 5000 mg/kg bw
Clinical signs:
not specified
Body weight:
not specified
Gross pathology:
not specified
Other findings:
not specified
Interpretation of results:
other: Not classified
Conclusions:
The acute dermal toxicity dose (LD50) value was considered to be >5000 mg/kg bw, when 8 rabbits were treated with the given test chemical by dermal application occlusively.
Executive summary:

Acute dermal toxicity study was conducted by using test chemical in 8 rabbits at the dose concentration of 5000 mg/kg bw.

The given test chemical (neat) was applied to intact and abraded skin for 24 h under occlusion.

Observations for mortality and systemic effects were made for 14 days after exposure.

No mortality was observed at 5000 mg/kg bw.

Hence, the LD50 value was considered to be >5000 mg/kg bw, when 8 rabbits were treated with the given test chemical by dermal application occlusively.

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.

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 test chemical. The studies are summarized as below:

 

Acute oral toxicity study was conducted by using test chemical in 10 rats at the dose concentration of 5000 mg/kg bw. Observations for mortality and systemic effects were made over a 14-day period.No mortality was observed at 5000 mg/kg bw. Hence, the LD50 value was considered to be >5000 mg/kg bw, when 10 rats were treated with the given test chemical via oral gavage route.

 

Another study is supported with the above study mentioned in secondary reports for the test chemical. The acute oral toxicity study was conducted by using test chemical in 10 rats at the dose concentration of 5000 mg/kg bw. Animals were observed for mortality. One animal died at an unspecified time. Hence, the LD50 value was considered to be >5000 mg/kg bw, when 10 rats were treated with the given test chemical via oral gavage route.

 

The above studies are supported with the study mentioned in various publications and secondary reports for the test chemical. The acute oral toxicity study was conducted by using test chemical in 10 male and female CF-1 mice at the dose concentration of 8714 mg/kg bw.

In an acute range-finding toxicity test, 4–5 week old white mice received a single oral (gavage) administration of the test chemical at dose levels of 2, 5 and 10 g/kg. The animals were observed for signs of toxicity over a 7 day period. No deaths occurred at 2 and 5 g/kg. One animal died (1/2) at 10 g/kg. The acute LD50 was reported to be approximately 10 g/kg.

From the range finding study, the dose limit was determined and the LD50 was calculated by the method of Miller and Tainter (Proc. Soc. Exptl. Biol. Med. 57:261, 1944) for this study. Mortality was observed over a 72 h period.

Hence, the LD50 value was considered to be 8714 mg/kg bw, with 95% Confidence Limit of ±252 mg/kg bw, when 10 male and female CF-1 mice were treated with the given test chemical via oral gavage route.

 

These studies are further supported with the study mentioned in peer-reviewed journals for the test chemical. The acute oral toxicity study was conducted by using test chemical in rats at the dose concentration of 4590 mg/kg bw via oral route. Observation for mortality was made. 50% mortality was observed at 4590 mg/kg bw. Hence, the LD50 value was considered to be 4590 mg/kg bw, when rats was treated with the given test chemical via oral route.

 

All the above studies are supported with the study mentioned in study report for the test chemical. The acute oral toxicity study of the given test chemical was performed as per OECD 423 guideline in 6 female wistar rats.

The test material dissolved in corn oil. The volume was made up to 10 ml to achieve the appropriate concentrations. The dosing solution was prepared fresh, prior to dose administration and given in dose concentration 2000 mg/kg bw by oral gavage route. 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 surviving 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, 4, 5 and 6 were observed normal at 30 minutes, 1 hour, on day 1 to 14 post dosing and moderate to mild lethargy was observed at 2, 3 and 4 hours post dosing. Animal nos. 2 and 3 were observed normal at 30 minutes, 1 hour, on day 1 to 14 post dosing and mild lethargy was observed at 2, 3 and 4 hours post dosing. No external and internal gross pathological changes were seen in the animals treated with 2000 mg/kg body weight during terminal sacrifice.

Hence, the LD50 value was considered to be >2000 mg/kg body weight, when female wistar 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 the low vapour pressure of the test chemical, which is reported to be 0.22 Pa (0.0016 mm Hg). 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 -

 

Acute dermal toxicity study was conducted by using test chemical in 8 rabbits at the dose concentration of 5000 mg/kg bw. The given test chemical (neat) was applied to intact and abraded skin for 24 h under occlusion. Observations for mortality and systemic effects were made for 14 days after exposure. No mortality was observed at 5000 mg/kg bw.

Hence, the LD50 value was considered to be >5000 mg/kg bw, when 8 rabbits were treated with the given test chemical by dermal application occlusively.

 

The above study is supported with another study mentioned in secondary reports for the test chemical. The acute dermal toxicity study was conducted by using test chemical in rabbits at the dose concentrations of 2500 and 5000 mg/kg bw.

Observations for mortality and systemic effects were made. 6 out of 10 animals died in the 5000 mg/kg group. Clinical symptoms were observed such as, At 5000 mg/kg - Diarrhea in 2 animals, anorexia and lethargy in 1 animal was observed, also, severe redness and moderate edema was observed; At 2500 mg/kg - moderate to severe redness in 4 animals and severe edema was observed.

Under the condition of this, the LD50 value was considered to be 5000 mg/kg bw, when rabbits were treated with the given test chemical by dermal application.

  

These studies are supported with the study mentioned in publication for the test chemical. The acute dermal toxicity study was conducted by using test chemical in 10 rabbits at the dose concentration of 5000 mg/kg bw by dermal application to abraded rabbit skin.

Animals were observed for mortality after application of the test chemical. No mortality was observed at 5000 mg/kg bw.

Hence, the LD50 value was considered to be >5000 mg/kg bw, when 10 rabbits were treated with the given test chemical by dermal application to abraded rabbit skin.

 

All the above studies are further supported with the study mentioned in report for the test chemical. The acute dermal toxicity study of the given test chemical was performed as per OECD No.402 in Wistar Rats.

Five male and five female healthy young adult rats were randomly selected. Rats free from injury and irritation of skin were selected for the study. Twenty four 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 (0.9407) 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 gauze patch was covered with a semi-occlusive dressing. The 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 compared to day 0 throughout the experiment. 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 body weight, when female wistar 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. 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.