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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 given test chemical. The study concluded that the LD50 value is >5000 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.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
experimental data from various test chemicals
Justification for type of information:
Data is summarized based on the available information from various test chemicals.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
other: as mentioned below
Principles of method if other than guideline:
WoE report is based on 2 acute oral toxicity studies as- WoE 2 and WoE 3.
Acute oral toxicity test was carried out to study the effects of the test chemicals on rodents.
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
2. - Fasting period before study: Fasting was done.
3. not specified
Route of administration:
other: 2. oral: gavage 3. oral: unspecified
Vehicle:
other: 2. water 3. unchanged (no vehicle)
Details on oral exposure:
2. MAXIMUM DOSE VOLUME APPLIED: 10 mg/kg body weight.
3. not specified
Doses:
2. 0, 2000 and 5000 mg/kg bw
3. 4500 mg/kg
No. of animals per sex per dose:
2. 20 males and 10 females
-2000 mg/kg: 10 males
- 5000 mg/kg: 10 males and 10 females
3. not specified
Control animals:
other: 2. yes 3. not specified
Details on study design:
2. - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 14 days following the single administration of the test item
- Necropsy of survivors performed: yes
- Other -examinations performed: Clinical signs, mortality and body weight
3. not specified
Statistics:
No data
Preliminary study:
2. Based on a previous study (not available) indicating that LD50 was greater than 1000 mg/kg in male rats, the first dose of the test item to be tested in male rats was 2000 mg/kg. The other tested dose-level administered was 5000 mg/kg (1 group of females, 1 group of males).
3. not specified
Sex:
male
Dose descriptor:
LD50
Remarks:
2
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality occurred
Sex:
female
Dose descriptor:
LD50
Remarks:
2
Effect level:
> 2 000 - < 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 3 out of 10 males and 6 out 10 females died on day 2
Sex:
not specified
Dose descriptor:
LD50
Remarks:
3
Effect level:
4 500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality was observed
Mortality:
2. - At 2000 mg/kg , no mortality occurred.
- At 5000 mg/kg, 3 out of 10 males and 6 out 10 females died on day 2.
- In the negative control groups, no deaths occurred.
3. 50% mortality was observed at 4500 mg/kg bw
Clinical signs:
2. - In males exposed to 2000 mg/kg, mild depression and piloerection were observed from day 1 (1 hour after dosing) to day 2.
- In males and females exposed to 5000 mg/kg, mild depression and piloerection were observed from day 1 (immediately after dosing) to day 3.
- There were no clinical signs in the negative control groups.
3. not specified
Body weight:
2. At 2000 and 5000 mg/kg, body weight gain was similar to controls.
3. not specified
Gross pathology:
2. At necropsy, red lungs and stomachs filled with a clear watery fluid were reported in those animals.
3. not specified
Other findings:
not specified
Interpretation of results:
other: Not classified
Conclusions:
The test chemical cannot be classified for acute oral toxicity, as the LD50 value is >5000 mg/kg bw according to CLP regulation.
Executive summary:

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 the given test chemical. The studies are summarized as below -

 

The acute oral toxicity study was conducted for the given test chemical according to methods similar to OPPTS 870.1100 and OECD 401 guidelines in male and female rats. The test chemical was prepared in water and was administered by gavage under a dosage-volume of 10 mL/kg bw to groups of 10 fasted rats. Based on a previous study (not available) indicating that LD50 was greater than 1000 mg/kg in male rats, the first dose of the test chemical to be tested in male rats was 2000 mg/kg. The other tested dose-level administered was 5000 mg/kg (1 group of females, 1 group of males). Negative control groups receiving water only were included in the study. Clinical signs, mortality and body weight were checked for a period of 14 days following the single administration of the test item. All animals were subjected to necropsy. At the dose-level of 2000 mg/kg, no mortality occurred. Mild depression and piloerection were observed from day 1 (1 hour after dosing) to day 2. Body weight gain was similar to controls and no apparent abnormalities were observed at necropsy. At the dose- level of 5000 mg/kg, 3 out 10 males and 6 out 10 females were found dead on day 2. At necropsy, red lungs and stomachs filled with a clear watery fluid were reported in those animals. In the surviving animals, mild depression and piloerection were observed from day 1 (immediately after dosing) to day 3. Body weight gain was similar to controls and no apparent abnormalities were observed at necropsy. Under the experimental conditions of this study, acute oral LD50 of test chemical in male rats was determined to be >5000 mg/kg and in female rats was observed in between 2000-5000 mg/kg bw.

 

The above study is supported with the data available in authoritative database for the given test chemical. The reported study was designed and conducted to determine the acute oral toxicity profile in rat at the concentration of 4500 mg/kg bw. Animals were observed for mortality. 50% mortality was observed at 4500 mg/kg bw. Therefore, the LD50 was considered to be 4500 mg/kg bw, when rats were treated with test chemical via oral route.

  

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.

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 handbook or collection of data.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

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 the given test chemical. The studies are summarized as below -

 

The acute oral toxicity study was conducted for the given test chemical according to methods similar to OPPTS 870.1100 and OECD 401 guidelines in male and female rats. The test chemical was prepared in water and was administered by gavage under a dosage-volume of 10 mL/kg bw to groups of 10 fasted rats. Based on a previous study (not available) indicating that LD50 was greater than 1000 mg/kg in male rats, the first dose of the test chemical to be tested in male rats was 2000 mg/kg. The other tested dose-level administered was 5000 mg/kg (1 group of females, 1 group of males). Negative control groups receiving water only were included in the study. Clinical signs, mortality and body weight were checked for a period of 14 days following the single administration of the test item. All animals were subjected to necropsy. At the dose-level of 2000 mg/kg, no mortality occurred. Mild depression and piloerection were observed from day 1 (1 hour after dosing) to day 2. Body weight gain was similar to controls and no apparent abnormalities were observed at necropsy. At the dose- level of 5000 mg/kg, 3 out 10 males and 6 out 10 females were found dead on day 2. At necropsy, red lungs and stomachs filled with a clear watery fluid were reported in those animals. In the surviving animals, mild depression and piloerection were observed from day 1 (immediately after dosing) to day 3. Body weight gain was similar to controls and no apparent abnormalities were observed at necropsy. Under the experimental conditions of this study, acute oral LD50 of test chemical in male rats was determined to be >5000 mg/kg and in female rats was observed in between 2000-5000 mg/kg bw.

 

The above study is supported with the data available in authoritative database for the given test chemical. The reported study was designed and conducted to determine the acute oral toxicity profile in rat at the concentration of 4500 mg/kg bw. Animals were observed for mortality. 50% mortality was observed at 4500 mg/kg bw. Therefore, the LD50 was considered to be 4500 mg/kg bw, when rats were treated with test chemical via oral route.

  

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.

 

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 toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute oral toxicity.