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Description of key information

Acute oral toxicity: 

Acute oral toxicity dose (LD50) for target chemical was considered based on different experimental studies conducted on rats. The LD50 values were considered to be >5000 mg/kg bw; 3755 mg/kg bw, with 95% confidence limit of 2715-5193 mg/kg bw; and >3200 mg/kg bw. Thus, comparing these values with the criteria of CLP regulation, test chemical cannot be classified for acute oral toxicity.

Acute Inhalation toxicity:

The acute Inhalation toxicity dose (LC50) for test chemical was considered based on experimental study conducted on rats. The LC50 value was considered to be >3.66 mg/L air (>3600 mg/m3). The study concluded that the LC50 value is between 1-5 mg/L, for acute inhalation toxicity. Thus, comparing this value with the criteria of CLP regulation, test chemical can be classified in “Category 4” for acute inhalation toxicity.

Acute Dermal toxicity:

The acute dermal toxicity dose (LD50) for target chemical was considered based on experimental study conducted on rats, the value was considered to be >2500 mg/kg bw, for acute dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, 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
Study period:
June 1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Data is from study report.
Qualifier:
according to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
The acute oral toxicity study was conducted in rats by using test chemical
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 6-7 weeks
- Weight at study initiation: 190 g. (male) and 151 g. (female)
- Fasting period before study: 18 hours
- Housing: Rats were caged singly and kept in a room maintained at a constant temperature
- Diet (e.g. ad libitum): A commercial pelleted diet (Oakes Special Diet with added Vit. E) was fed, ad libitum
- Water (e.g. ad libitum): Water was available at all times.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±2°C.
- Photoperiod (hrs dark / hrs light): Animals were subjected to 12 hours artificial light and 12 hours darkness in each 24 hour period.
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 25% w/v suspension
- Amount of vehicle (if gavage): 20 ml/kg

DOSAGE PREPARATION (if unusual):25% w/v suspension of the compound in a 50% aqueous solution of polyethylene glycol was administered
Doses:
20 ml/kg (Equivalent to 5g/kg. compound)
No. of animals per sex per dose:
Total = 10 (5 male and 5 female)
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Deaths and clinical symptoms were recorded.
- Necropsy of survivors performed: yes, at the end of the observation period surviving animals were killed by exsanguination under ether anaesthesia and an autopsy performed.
Statistics:
not specified
Preliminary study:
not specified
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other:
Remarks:
Mortality observed
Mortality:
Two male died at 164 and 175 hours respectively after administration of the compound.
Clinical signs:
One male animal showed severe respiratory distress.
Body weight:
not specified
Gross pathology:
At autopsy no changes in organs or tissues caused by the administration of the test compound were seen.
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 male and female Sprague-Dawley rats were treated with test chemical via oral gavage route.
Executive summary:

The acute oral toxicity study was conducted by using test chemical in 10 male and female Sprague-Dawley rats at the dose concentration of 5000 mg/kg bw. A 25% w/v suspension of the compound in a 50% aqueous solution of polyethylene glycol (vehicle) was administered as a single dose by gavage to rats which had been fasted for 18 hours, at a dose rate of 20ml/kg. (Equivalent to 5g/kg. compound).  After administration of the compound, the animals were observed for 14 days. Deaths and clinical symptoms were recorded. At the end of the observation period surviving animals were killed by exsanguination under ether anaesthesia and an autopsy performed. Two male died at 164 and 175 hours respectively after administration of the compound. One male animal showed severe respiratory distress.At autopsy no changes in organs or tissues caused by the administration of the test compound were seen. Therefore, LD50 value was considered to be >5000 mg/kg bw, when male and female Sprague-Dawley rats were treated with test chemical via oral gavage route. This toxicity value does not fall in the range of classification within the EU CLP regulation and thus the substance is not considered to be classified in the toxic category.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from experimental study report.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Data is from study report.
Qualifier:
according to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
The acute inhalation toxicity study was conducted in rats by using test chemical
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:
inhalation: dust
Type of inhalation exposure:
not specified
Vehicle:
air
Remark on MMAD/GSD:
not specified
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: desiccator
- Source and rate of air: 200 ltr./air hours
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
8 h
Remarks on duration:
not specified
Concentrations:
3.66 mg/L
No. of animals per sex per dose:
Total = 12
Control animals:
not specified
Details on study design:
- Necropsy of survivors performed: yes, after a week the animals were killed and dissected
Statistics:
not specified
Preliminary study:
not specified
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 3.66 mg/L air
Based on:
test mat.
Exp. duration:
8 h
Remarks on result:
other: No mortality was observed
Mortality:
No mortality was obseved at 3.66 mg/L air concentration in treated rats.
Clinical signs:
Red colored fur was observed.
Body weight:
not specified
Gross pathology:
not specified
Other findings:
not specified
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute inhalation toxicity dose (LC50) value was considered to be >3.66 mg/L air, when 12 male and female rats were treated with test chemical via inhalation route by dust form for 8 hours exposure.
Executive summary:

The acute inhalation toxicity study was conducted by using test chemical in 12 male and female rats at the dose concentration of 3.66 mg/L via inhalation route by dust form. The desiccator was used as inhalation chamber for animals in which source and rate of air was 200 ltr./air hours. The duration of exposure was 8 hours. Necropsy of survivors performed. After a week the animals were killed and dissected. No mortality was obseved at 3.66 mg/L air concentration in treated rats. Red colored fur was observed. Therefore, LC50 value was considered to be >3.66 mg/L air, when 12 male and female rats were treated with test chemical via inhalation route by dust form for 8 hours exposure.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
3 600 mg/m³
Quality of whole database:
Data is Klimisch 2 and from study report.

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
Study period:
March 1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Data is from study report.
Qualifier:
according to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
The acute dermal toxicity study was conducted in rats by using test chemical
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Remarks:
SPF
Sex:
male/female
Details on test animals and environmental conditions:
not specifiedTEST ANIMALS
- Weight at study initiation: Male - 146 g; Female - 122 g
Type of coverage:
not specified
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: Back p.c
- % coverage: 50%
VEHICLE
- Concentration (if solution): 50% solution in distilled water
Duration of exposure:
24 hours
Doses:
2500 mg/kg
No. of animals per sex per dose:
5 male and 5 female
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were obsrved for mortality and clinical signs.
- Necropsy of survivors performed: yes, animals were killed after 14 days and necropsied with carbon dioxide
Statistics:
not specified
Preliminary study:
not specified
Sex:
male/female
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 2500 mg/kg bw.
Clinical signs:
During and after application of the 14 days the animals are found blithe. At 24 hour, redness did not recognize in 10/10 animals. On 8 day, red substance residues observed in 10/10 animals.
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 >2500 mg/kg bw, when 10 male and female Sprague-Dawley SPF rats were treated with test chemical by dermal application based on which it can be concluded that it is non toxic via dermal route.
Executive summary:

The acute dermal toxicity study was conducted by using test chemical in 10 male and female Sprague-Dawley SPF rats at the dose concentration of 2500 mg/kg bw. The given test chemical was dissolved as 50% solution in distilled water and applied on 50% area of back skin of rats. Animals were obsrved for mortality and clinical signs for 14 days. Animals were killed after 14 days and necropsied with carbon dioxide. No mortality was observed at 2500 mg/kg bw. During and after application of the 14 days the animals are found blithe. At 24 hour, redness did not recognize in 10/10 animals. On 8 day, red substance residues observed in 10/10 animals. Therefore, LD50 value was considered to be >2500 mg/kg bw, when 10 male and female Sprague-Dawley SPF rats were treated with test chemical by dermal application based on which it can be concluded that it is non toxic via dermal route.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 500 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from study report.

Additional information

 Acute oral toxicity:

 

In different experimental studies, 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 acute oral toxicity study was conducted by using test chemical in 10 male and female Sprague-Dawley rats at the dose concentration of 5000 mg/kg bw. A 25% w/v suspension of the compound in a 50% aqueous solution of polyethylene glycol (vehicle) was administered as a single dose by gavage to rats which had been fasted for 18 hours, at a dose rate of 20ml/kg (Equivalent to 5g/kg compound).  After administration of the compound, the animals were observed for 14 days. Deaths and clinical symptoms were recorded. At the end of the observation period surviving animals were killed by exsanguinations under ether anaesthesia and an autopsy performed. Two male died at 164 and 175 hours respectively after administration of the compound. One male animal showed severe respiratory distress. At autopsy no changes in organs or tissues caused by the administration of the test compound were seen. Therefore, LD50 value was considered to be >5000 mg/kg bw, when male and female Sprague-Dawley rats were treated with test chemical via oral gavage route. This toxicity value does not fall in the range of classification within the EU CLP regulation and thus the substance is not considered to be classified in the toxic category.

 

The above experimental study is supported with the study conducted on rats and mentioned in experimental study report for the target chemical. The acute oral toxicity study was conducted by using test chemical in 40 male and female Tif. RAI rats at the dose concentration of 1670, 2780, 3590, 6000 mg/kg bw. The given test chemical was weighed into an Erlenmeyer flask on a Mettler balance. It was suspended at 20% with carboxymethyl-cellulose 2%. Before treatment the suspension was homogeneously dispersed with an Ultra- Turrax and during treatment it was kept stable with a magnetic stirrer. Animals were observed for mortality and clinical signs. The surviving animals were killed and autopsied after an observation period of 14 days. The LD50 was calculated by probit analysis method (Goulden A., Methods of Statistical Analysis, John Wiley and Sons, 1960, 3rd printing, pages 404-408). Mortality was observed as, At 1670 mg/kg - 1 male on day 7 and 1 male on day 14 died. At 2780 mg/kg - 1 male and 3 females on day 7 and 1 male and 3 females on day 14 died. At 3590 mg/kg - 2 males and 3 females on day 7 and 2 males and 3 females on day 14 died. At 6000 mg/kg - 2 males and 5 females on day 7 and 2 males and 5 females on dya 14 died. Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmus, curved position and ruffled fur. These symptoms became more accentuated as the dose was increased. The surviving animals had recovered within 7 days. No substance related gross organ changes were seen. Therefore, LD50 value was considered to be 3755 mg/kg bw, with 95% confidence limit of 2715-5193 mg/kg bw, when 40 male and female Tif. RAI rats were treated with test chemical via oral gavage route. This toxicity value does not fall in the range of classification within the EU CLP regulation and thus the substance is not considered to be classified in the toxic category.

 

These studies are further supported with the study mentioned in study report and conducted in rats for the target chemical. The acute oral toxicity study was conducted by using test chemical in 10 male and female Gassner rats at the dose concentration of 3200 mg/kg bw. The given test chemical was dissolved as 16% solution in CMC (carboxymethyl cellulose) and administered via oral route. Animals were observed for mortality and clinical signs. 2 males on day 7 and 1 female and 2 males on day 14 were died. All animals showed immediately after the application no later symptom. Sometime later crouch, spasmodically breathing and slight apathy was seen. Therefore, LD50 value was considered to be >3200 mg/kg bw, when 10 male and female Gassner rats were treated with test chemical via oral  route. This toxicity value does not fall in the range of classification within the EU CLP regulation and thus is not considered to be classified in the toxic category.

 

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, test chemical cannot be classified for acute oral toxicity.

 

Acute Inhalation Toxicity:

 

The acute inhalation toxicity study was conducted by using test in 12 male and female rats at the dose concentration of 3.66 mg/L via inhalation route by dust form. The desiccator was used as inhalation chamber for animals in which source and rate of air was 200 ltr./air hours. The duration of exposure was 8 hours. Necropsy of survivors performed. After a week the animals were killed and dissected. No mortality was obseved at 3.66 mg/L air concentration in treated rats. Red colored fur was observed. Therefore, LC50 value was considered to be >3.66 mg/L air, when 12 male and female rats were treated with test chemical via inhalation route by dust form for 8 hours exposure. Thus, based on the above summarised study, it can be concluded that LC50 value is between 1-5 mg/L. Thus, comparing this value with the criteria of CLP regulation, test chemical can be classified in “Category 4” for acute inhalation toxicity.

 

Acute Dermal Toxicity:

 

The acute dermal toxicity study was conducted by using test in 10 male and female Sprague-Dawley SPF rats at the dose concentration of 2500 mg/kg bw. The given test chemical was dissolved as 50% solution in distilled water and applied on 50% area of back skin of rats. Animals were obsrved for mortality and clinical signs for 14 days. Animals were killed after 14 days and necropsied with carbon dioxide. No mortality was observed at 2500 mg/kg bw. During and after application of the 14 days the animals are found blithe. At 24 hour, redness did not recognize in 10/10 animals. On 8 day, red substance residues observed in 10/10 animals. Therefore, LD50 value was considered to be >2500 mg/kg bw, when 10 male and female Sprague-Dawley SPF rats were treated with test chemical by dermal application based on which it can be concluded that it is non toxic via dermal route.

Justification for classification or non-classification

Based on the above experimental studies on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw, for acute oral and acute dermal toxicity; and LC50 value is between 1-5 mg/L, for acute inhalation toxicity. Thus, comparing these values with the criteria of CLP regulation, test chemical cannot be classified for acute oral and acute dermal toxicity while it can be classified in “Category 4” for acute inhalation toxicity.