Registration Dossier

Administrative data

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 studies 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 0.000116 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 studies 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:
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 read across test chemicals.
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
WoE report is based on 3 acute oral toxicity studies as - WoE 2, WoE 3 and WoE 4.
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:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
2. TEST ANIMALS
- Source National Institute of biosciences, Pune.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Female rats of the age of approximately 8 to 12 weeks old were used .
- Weight at study initiation : The weight were within ± 20% of the mean weight of any animal used for dosing. Body weight range was 198.2 to 206.2 grams.
Body weights at the start : Female Mean : 200.93 g (= 100 %); Minimum : 198.2 g (- 1.36 %); Maximum : 206.2 g (+ 2.62 %)
- Fasting period before study: Approximately 16 hours or more.
- Housing: The rats were housed in polycarbonate cages.
- Diet (e.g. ad libitum): Rodent feed supplied by the Nutrivet Life Sciences, Pune, was provided ad libitum from individual feeders.
- Water (e.g. ad libitum): Water was provided ad libitum from individual bottles attached to the cages. All water was from a local source and passed through the reverse osmosis membrane before use.
- Acclimation period: 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Room temperature was maintained at 20.6 to 23.2 degree centigrade
- Humidity (%): Room humidity was maintained at 54.2% to 58.6%.
- Air changes (per hr): The animal room was independently provided with at least ten to fifteen air changes per hour of 100% fresh air that had been passed through the HEPA filters.
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.
3. TEST ANIMALS
- Weight at study initiation: 234-244g (average weight 238g)
- Fasting period before study: The rats were not given any food for 16 hours before administered, 2 hours after the dye was administered,
- Housing: the animals were kept in plastic cages on plane rakes
- Diet (e.g. ad libitum): The animals were fed as the Postural diet ALTROMIN 1324 of the company Altromin GmbH in Lage / Lippe, ad libitum
- Water (e.g. ad libitum): tap water. libitum
4. not specified
Route of administration:
oral: gavage
Vehicle:
other: 2. water 3. Sesame oil 4. not specified
Details on oral exposure:
2. VEHICLE
MAXIMUM DOSE VOLUME APPLIED: The test item was administered in the dose volume of 10 ml/kg body weight.
3. VEHICLE
- Concentration in vehicle: 5000mg/kg bw
4. not specified
Doses:
2. Dose Group I : 300 mg/kg
Dose Group II : 2000 mg/kg
3. 5000 mg/kg bw
4. 3660 mg/kg
No. of animals per sex per dose:
2. Three females were used at each step.
3. 10 female rat
4. not specified
Control animals:
not specified
Details on study design:
2. - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical Observations and General Appearance: Animals were observed for clinical signs, mortality and morbidity, until sacrifice.
Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at immediately (0 to 5 minutes), 5, 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily thereafter for 14 day. Daily observation was done as far as possible at the same time.
Body weights: Individual animal body weights were recorded, before fasting, prior to administration of the test item (fasting body weights), weekly thereafter and at termination on day 14. Weight changes were calculated and recorded.
Gross Pathology: Necropsy was performed on all animals at the end of the study period on day 15. Macroscopic examination of all the orifices, cavities and tissues were made and the findings were recorded. All animals surviving the study period were sacrificed by the carbon dioxide asphyxiation technique.
3. Details on study design
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examination were performed
4. not specified
Statistics:
2. not specified
3. not specified
4. not specified
Preliminary study:
2. not specified
3. not specified
4. not specified
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed
Sex:
not specified
Dose descriptor:
LD50
Effect level:
3 660 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality was observed
Mortality:
2. All animals survived through the study period of 14 days.
3. No animal died on administration of 5000 mg/kg body weight.
4. 50% mortality was observed at 3660 mg/kg bw.
Clinical signs:
2. Group I Step I :Animals treated at the dose level of 300 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days. All animals survived through the study period of 14 days.
Group I Step II :Animals treated at the dose level of 300 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days. All animals survived through the study period of 14 days.
Group II Step I :Animals treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days. All animals survived through the study period of 14 days.
Group II Step II : Animals treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days. All animals survived through the study period of 14 days.
3. The animals showed normal behavior
4. not specified
Body weight:
2. Group I Step I (300 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 5.75% and 14.49% respectively.
Group I Step II (300 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 6.68% and 15.41% respectively.
Group II Step I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 5.60% and 13.64% respectively.
Group II Step II (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 6.35% and 15.17% respectively.
3. The body weight gain at the follow-up was regular.
4. not specified
Gross pathology:
2. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups.
3. not specified
4. not specified
Other findings:
2. not specified
3. After administration of the dye, a dark blue feces and blue urine staining were observed.
4. not specified
Interpretation of results:
other: Not classified
Conclusions:
According to CLP regulation, the test chemical cannot be classified for acute oral toxicity, as the LD50 value is >2000 mg/kg bw.
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 test chemical. The studies are summarized as below –

 

The reported study was designed and conducted to determine the acute oral toxicity profile of the given test chemical in Sprague Dawley rats.

Initially, three 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, three 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 three 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 three 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 the given test chemical, when administered to 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 the given test chemical falls into the “Category No classified”.

 

The above study is supported with another study mentioned in report for the given test chemical. In an acute oral toxicity study, 10 female SPF Wistar rats strain Hoe: WISKF (SPF 71) weighing 234-244g (average weight 238g) rats were treated at the dose concentration of 5000 mg/kg bw.

The 25% suspension of test material was dissolved in sesame oil and was administered once via oral gavage route. The rats were not given any food for 16 hours before application. 2 hours after the dye was administered, the animals were fed again. The observation time after administration was 14 days. During this time, the animals were kept Weekly weighed, the animals received as feed the ALTROMIN stabilizer 1324 of the company Altromin GmbH in Lage/Lippe and tap water. Food and water were offered ad libitum.

Animals were observed for mortality and clinical signs changes for 14 days. The experimental animals were killed at the end of the follow-up period in anaesthesia, dissected and examined macroscopically.

No animal died on administration of 5000 mg/kg body weight. After the application, the animals showed normal behaviour. The body weight gain at the follow-up was regular. After administration of the dye, a dark blue faeces and blue urine staining were observed.

Under the condition of the study, the LD50 value was considered to be >5000 mg/kg bw, when female rats were treated with the given test chemical orally via gavage.  

 

Both the above studies are further supported with the study mentioned in database and handbook for the test chemical. The acute oral toxicity was conducted in rats at the concentration of 3660 mg/kg bw. 50% mortality was observed in treated rats at 3660 mg/kg bw. Therefore, LD50 was considered to be 3660 mg/kg bw, when rats were treated with the 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. 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
2 000 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from report.

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:
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 read across test chemicals.
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
WoE report is based on 3 acute dermal toxicity studies as- WoE 2, WoE 3 and WoE 4.
Acute dermal 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:
other: 2. rat 3. rabbit 4. rabbit
Strain:
other: 2. Sprague-Dawley 3. not specified 4. not specified
Sex:
male/female
Details on test animals and environmental conditions:
2. TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Age at study initiation: Young adult male and female rats aged between 6 – 9 weeks were used.
- Weight at study initiation: The weight range of approximately 233.1 to 271.0 grams at initiation of dosing were used.
Body weights at the start : Male Mean : 268.48 g (= 100 %); Minimum : 264.2 g (- 1.59 %); Maximum : 271.0 g (+ 0.94 %)
Female Mean: 241.38 g (= 100 %); Minimum : 233.1 g (- 3.43 %); Maximum : 248.3 g (+ 2.87 %)
- Housing: The rats were individually housed in polycarbonate cages with paddy husk as bedding.
- Diet (e.g. ad libitum): Rodent feed supplied by the Nutrivet Life Sciences, Pune, was provided ad libitum from individual feeders.
- Water (e.g. ad libitum): Water was provided ad libitum from individual bottles attached to the cages. All water was from a local source and passed through the reverse osmosis membrane before use.
- Acclimation period : 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Room temperature was maintained at 20.1 to 22.3 degree centigrade.
- Humidity (%): Room humidity was maintained at 55.7% to 59.6%.
- Air changes (per hr): The animal room was independently provided with at least ten to fifteen air changes per hour of 100% fresh air that had been passed through the HEPA filters.
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.
3. not specified
4. not specified
Type of coverage:
other: 2. occlusive 3. Dermal 4. Dermal
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
2. TEST SITE
- Area of exposure: Dorsal surface and sides from scapular to pelvic area.
- % coverage: Approximately 10% of the total body surface area
- Type of wrap if used: Porous gauze dressing and non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Distilled water was used to remove residual test item.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: yes
3. not specified
4. not specified
Duration of exposure:
2. 24 hours
3. not specified
4. not specified
Doses:
2. A single dose of 2000 mg of the test item per kilogram of body weight was administered to ten rats (five males and five females).
3. 2000 mg/kg bw
4. 2000 mg/kg bw
No. of animals per sex per dose:
2. 10 (5/sex).
3. not specified
4. not specified
Control animals:
not specified
Details on study design:
2. - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily
- Necropsy of survivors performed: yes
- Other examinations performed:
Clinical Observations and General Appearance:
Animals were observed for clinical signs, mortality, until sacrifice.
Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily thereafter for 14 day. Daily observation was done as far as possible at the same time.
The observations were included general clinical signs, observations of eyes, mucous membranes, respiratory, circulatory system and behavior pattern.

Evaluation of Dermal Reaction:
Dermal reaction was observed daily for study period of 14 days.

Body weights:
Individual animal body weights were recorded pre-test (prior to administration of the test item), day 7 and at termination on day 14.

Gross Pathology:
Necropsy was performed on animals surviving at the end of the study. Macroscopic examination of all the orifices, cavities and tissues were made and the findings were recorded. All animals surviving the study period were sacrificed by the carbon dioxide asphyxiation technique (day 15).
3. not specified
4. not specified
Statistics:
2. not specified
3. not specified
4. not specified
Preliminary study:
2. not specified
3. not specified
4. not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
2. Mortality was not observed during the study period of 14 days.
3. No mortality was observed at 2000 mg/kg bw.
4. No mortality was observed at 2000 mg/kg bw.
Clinical signs:
2. Sex : Male Group I - Animal treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days.
Sex : Female Group I - Animal treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days.
3. not specified
4. The skin after systemic exposure causes dermatitis and other changes in skin and appendages were observed.
Body weight:
2. Sex : Male Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 8.63% and 17.60% respectively.
Sex : Female Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 5.20% and 9.02% respectively.
3. not specified
4. not specified
Gross pathology:
2. Gross pathological examination did not reveal any abnormalities in animals from 2000 mg/kg dose group.
3. not specified
4. Effect observed on kidney, ureter, and bladder were observed.
Other findings:
2. - Other observations: Evaluation of Dermal Reaction
Sex : Male Group I - Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.
Sex : Female Group I - Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.
3. not specified
4. Changes in urine composition was observed.
Interpretation of results:
other: Not classified
Conclusions:
According to CLP regulation, the test chemical cannot be classified for acute dermal toxicity, as the LD50 value is >2000 mg/kg bw.
Executive summary:

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 acute dermal toxicity profile of test chemical was performed in Sprague Dawley rats according to OECD Guideline 402 (Acute Dermal Toxicity).

The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Animals were observed for clinical signs, mortality, until sacrifice. Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily thereafter for 14 day. Daily observation was done as far as possible at the same time. The observations were included general clinical signs, observations of eyes, mucous membranes, respiratory, circulatory system and behaviour pattern. Individual animal body weights were recorded pre-test (prior to administration of the test item), day 7 and at termination on day 14. Necropsy was performed on animals surviving at the end of the study. Macroscopic examination of all the orifices, cavities and tissues were made and the findings were recorded. All animals surviving the study period were sacrificed by the carbon dioxide asphyxiation technique (day 15).

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.

Hence, LD50 was considered to be >2000 mg/kg bw, when male and female Sprague Dawley rats was treated with test chemical by dermal application.

 

The above study is supported with another study available in authoritative database and conducted on rabbits for the test chemical. The acute dermal toxicity study was conducted at the concentration of 2000 mg/kg bw. Animals were observed for mortality. No mortality was observed in treated rabbits at 2000 mg/kg bw. Therefore, LD50 value was considered to be >2000 mg/kg bw, when rabbits were treated with the given test chemical by dermal application to the skin.

 

Both the above studies are further supported with the study mentioned in authoritative database. The reported study was designed and conducted to determine the acute dermal toxicity profile of the given test chemical.In this study, rabbits were treated by dermal application at the dose concentration of 2000 mg/kg bw.

Animals were observed for mortality. No mortality was observed in treated rabbits at 2000 mg/kg bw. Clinical signs like the skin after systemic exposure cause dermatitis and other changes in skin and appendages were observed. Also effect on kidney, ureter, and bladder and changes in urine composition were noted.

Therefore, the LD50 value was considered to be >2000 mg/kg bw, when rabbits 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.

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 report.

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 designed and conducted to determine the acute oral toxicity profile of the given test chemical in Sprague Dawley rats.

Initially, three 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, three 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 three 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 three 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 the given test chemical, when administered to 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 the given test chemical falls into the “Category No classified”.

 

The above study is supported with another study mentioned in report for the given test chemical. In an acute oral toxicity study, 10 female SPF Wistar rats strain Hoe: WISKF (SPF 71) weighing 234-244g (average weight 238g) rats were treated at the dose concentration of 5000 mg/kg bw.

The 25% suspension of test material was dissolved in sesame oil and was administered once via oral gavage route. The rats were not given any food for 16 hours before application. 2 hours after the dye was administered, the animals were fed again. The observation time after administration was 14 days. During this time, the animals were kept Weekly weighed, the animals received as feed the ALTROMIN stabilizer 1324 of the company Altromin GmbH in Lage/Lippe and tap water. Food and water were offered ad libitum.

Animals were observed for mortality and clinical signs changes for 14 days. The experimental animals were killed at the end of the follow-up period in anaesthesia, dissected and examined macroscopically.

No animal died on administration of 5000 mg/kg body weight. After the application, the animals showed normal behaviour. The body weight gain at the follow-up was regular. After administration of the dye, a dark blue faeces and blue urine staining were observed.

Under the condition of the study, the LD50 value was considered to be >5000 mg/kg bw, when female rats were treated with the given test chemical orally via gavage.  

 

Both the above studies are further supported with the study mentioned in database and handbook for the test chemical. The acute oral toxicity was conducted in rats at the concentration of 3660 mg/kg bw. 50% mortality was observed in treated rats at 3660 mg/kg bw. Therefore, LD50 was considered to be 3660 mg/kg bw, when rats were treated with the 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. 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 0.000116 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 acute dermal toxicity profile of test chemical was performed in Sprague Dawley rats according to OECD Guideline 402 (Acute Dermal Toxicity).

The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Animals were observed for clinical signs, mortality, until sacrifice. Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily thereafter for 14 day. Daily observation was done as far as possible at the same time. The observations were included general clinical signs, observations of eyes, mucous membranes, respiratory, circulatory system and behaviour pattern. Individual animal body weights were recorded pre-test (prior to administration of the test item), day 7 and at termination on day 14. Necropsy was performed on animals surviving at the end of the study. Macroscopic examination of all the orifices, cavities and tissues were made and the findings were recorded. All animals surviving the study period were sacrificed by the carbon dioxide asphyxiation technique (day 15).

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.

Hence, LD50 was considered to be >2000mg/kg bw, when male and female Sprague Dawley rats was treated with test chemical by dermal application.

 

The above study is supported with another study available in authoritative database and conducted on rabbits for the test chemical. The acute dermal toxicity study was conducted at the concentration of 2000 mg/kg bw. Animals were observed for mortality. No mortality was observed in treated rabbits at2000 mg/kg bw. Therefore, LD50 value was considered to be >2000 mg/kg bw, when rabbits were treated with the given test chemical by dermal application to the skin.

 

Both the above studies are further supported with the study mentioned in authoritative database. The reported study was designed and conducted to determine the acute dermal toxicity profile of the given test chemical.In this study, rabbits were treated by dermal application at the dose concentration of 2000 mg/kg bw.

Animals were observed for mortality. No mortality was observed in treated rabbits at 2000 mg/kg bw. Clinical signs like the skin after systemic exposure cause dermatitis and other changes in skin and appendages were observed. Also effect on kidney, ureter, and bladder and changes in urine composition were noted.

Therefore, the LD50 value was considered to be >2000 mg/kg bw, when rabbits 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.