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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 >5000 mg/kg bw. The study 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 3.79E-10 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 test chemicals.
Reason / purpose for cross-reference:
read-across source
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 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:
other: 1. Sprague-Dawley 2. Sprague-Dawley 3. not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
1. TEST ANIMALS
- Weight at study initiation: Mean body weight was 180 and 220 g for male dose groups 5000 and 2150, respectively, and 170 g for the two female dose groups.
- Fasting period before study: 15 - 20 h before application
2. TEST ANIMALS
- Weight at study initiation: males 102-139 g, females 89-121 g
- Fasting period before study: Food was withheld 17-24 hours prior to dosing.
3. not specified
Route of administration:
other: 1. oral: gavage 2. oral: unspecified 3. oral: unspecified
Vehicle:
other: 1. CMC (carboxymethyl cellulose) 2. water 3. 50% aqueous concentration
Details on oral exposure:
1. VEHICLE
MAXIMUM DOSE VOLUME APPLIED: The substance was applied as a single oral dose as a 10 mL suspension.
2. not specified
3. not specified
Doses:
1. 2150, 5000 mg/kg b.w.
2. 0, 5000, 6300, 8000, 10000 and 12500 mg/kg bw
3. 6500 mg/kg bw
No. of animals per sex per dose:
1. 5 (sex/dose)
2. 5/sex/dose group
3. not specified
Control animals:
other: 1. not specified 2. yes, water control 3. not specified
Details on study design:
1. - Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes, the post-exposure period was 14 days after which the animals were sacrificed and subjected to a gross-pathological examination.
2. - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were observed for mortality and signs of toxicity. Body weights at dosing and after 1 and 2 weeks were observed.
- Necropsy of survivors performed: yes, Necropsy on all animals that died and selected survivors on day 15.
3. not specified
Statistics:
1. not specified
2. Statistical method: Reed and Muench, 1938.
3. not specified
Preliminary study:
1. not specified
2. not specified
3. not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
7 200 mg/kg bw
Based on:
test mat.
Sex:
not specified
Dose descriptor:
LD50
Effect level:
6 500 mg/kg bw
Based on:
test mat.
95% CL:
5 700 - 7 300
Mortality:
1. No mortality was observed at 5000 mg/kg bw.
2. 50% mortality was observed at 7200 mg/kg bw in treated animals.
3. 50% mortality was observed at 6500 mg/kg bw in treated animals.
Clinical signs:
1. Staggering was the only clinical symptom noted at the dose level of 5000 mg/kg b.w.
2. On day 1 lethargy, diarrhoea, ptosis, lachrymation and piloerection were observed among animals.
3. not specified
Body weight:
1. Males, 5000 mg/kg: beginning of the study 180 g, after 13 d 274 g; 2150 mg/kg: beginning of the study 220 g, after 13 d 250 g
Females, 5000 mg/kg: beginning of the study 170 g, after 13 d 205 g; 2150 mg/kg: beginning of the study 170 g, after 13 d 212 g
2. No treatment related effects was observed.
3. not specified
Gross pathology:
1. Gross pathology did not reveal any abnormal findings. Both sexes showed comparable results.
2. Findings in the animals that died included slight pulmonary inflammation, gastrointestinal inflammation and hemorrhage and mild liver changes.
3. not specified
Other findings:
1. not specified
2. not specified
3. not specified
Interpretation of results:
other: Not classified
Conclusions:
According to CLP regulation, the given 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 –

 

Acute oral toxicity study was conducted according to OECD Guideline 401 (Acute Oral Toxicity) by using test chemical in 20 male and female Sprague-Dawley rats at the dose concentration of 2150 and 5000 mg/kg bw.

The substance was applied as a single oral dose as a 10 mL suspension in CMC (carboxymethyl cellulose). The post-exposure period was 14 days after which the animals were sacrificed and subjected to a gross-pathological examination.

No mortality was observed at 5000 mg/kg bw. Staggering was the only clinical symptom noted at the dose level of 5000 mg/kg b.w. Body weight changes was observed. Gross pathology did not reveal any abnormal findings. Both sexes showed comparable results.

Therefore, LD50 was considered to be >5000 mg/kg bw, when 20 male and female Sprague-Dawley rats were treated with test chemical via oral gavage route.

 

The above study is supported with another study mentioned in publication and secondary source for the given test chemical and was conducted in group of 5 male and female Sprague Dawley rats at the dose concentrations of 0, 5000, 6300, 8000, 10000 and 12500 mg/kg bw.

The given test chemical was dissolved in distilled water and administered via oral route. Control group received water only. The rats were observed for mortality and signs of toxicity. Body weights at dosing and after 1 and 2 weeks were observed. Necropsy on all animals that died and selected survivors on day 15. Statistical method - Reed and Muench, 1938 was used to calculate LD50 value.

50% mortality was observed at 7200 mg/kg bw in treated animals. On day 1 lethargy, diarrhoea, ptosis, lachrymation and piloerection were observed among animals. No treatment related effects was observed in body weight. Findings in the animals that died included slight pulmonary inflammation, gastrointestinal inflammation and hemorrhage and mild liver changes.

Under the condition of this, the LD50 value was considered to be 7200 mg/kg bw, when group of 5 male and female Sprague Dawley rats were treated with the given test chemical via oral route.

 

Both the above studies are further supported with the study mentioned in publication and secondary database for the test chemical. The acute oral toxicity study was conducted using the given test chemical in rats at the dose concentration of 6500 mg/kg bw.

The given test chemical was administered as 50% aqueous concentration via oral route. Animals were observed for mortality. 50% mortality was observed at 6500 mg/kg bw in treated animals.

Hence, the LD50 value was considered to be 6500 mg/kg bw, with 95% confidence interval of 5700 - 7300 mg/kg bw, when rats were treated with the given 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
Value:
5 000 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from study 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 test chemicals.
Reason / purpose for cross-reference:
read-across source
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 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: 1. rabbit 2. rat 3. rat
Strain:
other: 1. not specified 2. Sprague-Dawley 3. Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
1. not specified
2. TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Age at study initiation: Young adult male and female rats aged between 8 – 12 weeks were used.
- Weight at study initiation: The weight range of approximately 221.7 to 255.3 grams at initiation of dosing.
Body weights at the start : Male Mean : 249.20 g (= 100 %); Minimum : 243.9 g (- 2.13 %); Maximum : 255.3 g (+ 2.45 %)
Female Mean : 225.60 g (= 100 %); Minimum : 221.7 g (- 1.73 %); Maximum : 230.5 g (+ 2.17 %)
- Identification: Each rat was individually identified by the cage number.
- 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): 20.1 to 22.5 degree centigrade.
- Humidity (%): 53.2% to 58.8%
- Air changes (per hr): Ten to fifteen air changes per hour.
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.

IN-LIFE DATES: 20-07-2017 to 04-08-2017
3. 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 240.7 to 273.1 grams at initiation of dosing were used.
Body weights at the start : Male Mean: 270.52 g (= 100 %); Minimum : 268.2 g (- 0.86 %); Maximum : 273.1 g (+ 0.95 %)
Female Mean : 244.46 g (= 100 %); Minimum : 240.7 g (- 1.54 %); Maximum : 252.5 g (+ 3.29 %)
- 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): 20.1 to 22.3 degree centigrade.
- Humidity (%): 55.7% to 59.6%.
- Air changes (per hr): Ten to fifteen air changes per hour.
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.

IN-LIFE DATES: 30-09-2016 to 15-10-2016
Type of coverage:
other: 1. Dermal 2. occlusive 3. occlusive
Vehicle:
other: 1. not specified 2. water 3. water
Details on dermal exposure:
1. not specified
2. TEST SITE
- Area of exposure: Trunk (dorsal surface and sides from scapular to pelvic area)
- % coverage: Approximately 10% of the 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
- For solids, paste formed: Yes
3. TEST SITE
- Area of exposure: Trunk (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
- For solids, paste formed: Yes
Duration of exposure:
1. not specified
2. 24 hours
3. 24 hours
Doses:
1. 2000 mg/kg bw
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. 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).
No. of animals per sex per dose:
1. not specified
2. 10 (5/sex).
3. 10 (5/sex).
Control animals:
not specified
Details on study design:
1. not specified
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).
Histopathology: No gross abnormalities were observed in animals sacrificed terminally hence, no histopathology was performed.
3. - 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).
Histopathology: No gross abnormalities were observed in animals sacrificed terminally hence, no histopathology was performed.
Statistics:
1. not specified
2. not specified
3. not specified
Preliminary study:
1. not specified
2. not specified
3. not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
1. No mortality was observed at 2000 mg/kg bw in treated animals.
2. Sex : Male Group I - Animal treated at the dose level of 2000 mg/kg body weight: All animals survived through the study period of 14 days.
Sex : Female Group I - Animal treated at the dose level of 2000 mg/kg body weight: All animals survived through the study period of 14 days.
3. Sex : Male Group I - Animal treated at the dose level of 2000 mg/kg: All animals survived through the study period of 14 days.
Sex : Female Group I – Animal treated at the dose level of 2000 mg/kg: All animals survived through the study period of 14 days.
Clinical signs:
1. not specified
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. 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.
Body weight:
1. not specified
2. Sex : Male Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 8.58% and 18.09% respectively.
Sex : Female Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 5.54% and 9.72% respectively.
3. Sex : Male Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 10.12% and 18.53% respectively.
Sex : Female Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 4.97% and 9.07% respectively.
Gross pathology:
1. not specified
2. Gross pathological examination did not reveal any abnormalities in animals from 2000 mg/kg dose group.
3. Gross pathological examination did not reveal any abnormalities in animals from 2000 mg/kg dose group.
Other findings:
1. not specified
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. - 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.
Interpretation of results:
other: Not classified
Conclusions:
According to CLP regulation, the given 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 study was mentioned in publication and secondary database and conducted in rabbits by using the given test chemical at the dose concentration of 2000 mg/kg bw. Animals were observed for mortality. No mortality was observed at 2000 mg/kg bw in treated animals. Hence, the LD50 value was considered to be >2000 mg/kg bw, when rabbits were treated with the given test chemical by dermal application.

 

The above study is supported with another study conducted on rats for the test chemical.The reported study was designed and conducted to determine the acute dermal toxicity profile of test chemical as per OECD Guideline 402 (Acute Dermal Toxicity) in Sprague Dawley rats.

The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. 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. 

It was concluded that the acute dermal median lethal dose (LD50) of test chemical, when administered to male and female Sprague Dawley rats was considered to be >2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that test chemical does not classify as an acute dermal toxicant. CLP Classification: “Not classified”.

 

Both the above studies are further supported with the study mentioned in report. The reported study was designed and conducted to determine the acute dermal toxicity profile of the given test chemical as per OECD Guideline 402 (Acute Dermal Toxicity) in Sprague Dawley rats.

The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. 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.

Under the condition of this, it was concluded that the acute dermal median lethal dose (LD50) of test chemical, when administered to male and female Sprague Dawley rats was considered to be >2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that est chemical does not classify as an acute dermal toxicant. CLP Classification: “Not classified”.

 

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
Value:
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 –

 

Acute oral toxicity study was conducted according to OECD Guideline 401 (Acute Oral Toxicity) by using test chemical in 20 male and female Sprague-Dawley rats at the dose concentration of 2150 and 5000 mg/kg bw.

The substance was applied as a single oral dose as a 10 mL suspension in CMC (carboxymethyl cellulose). The post-exposure period was 14 days after which the animals were sacrificed and subjected to a gross-pathological examination.

No mortality was observed at 5000 mg/kg bw. Staggering was the only clinical symptom noted at the dose level of 5000 mg/kg b.w. Body weight changes was observed. Gross pathology did not reveal any abnormal findings. Both sexes showed comparable results.

Therefore, LD50 was considered to be >5000 mg/kg bw, when 20 male and female Sprague-Dawley rats were treated with test chemical via oral gavage route.

 

The above study is supported with another study mentioned in publication and secondary source for the given test chemical and was conducted in group of 5 male and female Sprague Dawley rats at the dose concentrations of 0, 5000, 6300, 8000, 10000 and 12500 mg/kg bw.

The given test chemical was dissolved in distilled water and administered via oral route. Control group received water only. The rats were observed for mortality and signs of toxicity. Body weights at dosing and after 1 and 2 weeks were observed. Necropsy on all animals that died and selected survivors on day 15. Statistical method - Reed and Muench, 1938 was used to calculate LD50 value.

50% mortality was observed at 7200 mg/kg bw in treated animals. On day 1 lethargy, diarrhoea, ptosis, lachrymation and piloerection were observed among animals. No treatment related effects was observed in body weight. Findings in the animals that died included slight pulmonary inflammation, gastrointestinal inflammation and hemorrhage and mild liver changes.

Under the condition of this, the LD50 value was considered to be 7200 mg/kg bw, when group of 5 male and female Sprague Dawley rats were treated with the given test chemical via oral route.

 

Both the above studies are further supported with the study mentioned in publication and secondary database for the test chemical. The acute oral toxicity study was conducted using the given test chemical in rats at the dose concentration of 6500 mg/kg bw.

The given test chemical was administered as 50% aqueous concentration via oral route. Animals were observed for mortality. 50% mortality was observed at 6500 mg/kg bw in treated animals.

Hence, the LD50 value was considered to be 6500 mg/kg bw, with 95% confidence interval of 5700 - 7300 mg/kg bw, when rats were treated with the given 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 3.79E-10 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 study was mentioned in publication and secondary database and conducted in rabbits by using the given test chemical at the dose concentration of 2000 mg/kg bw. Animals were observed for mortality. No mortality was observed at 2000 mg/kg bw in treated animals. Hence, the LD50 value was considered to be >2000 mg/kg bw, when rabbits were treated with the given test chemical by dermal application.

 

The above study is supported with another study conducted on rats for the test chemical.The reported study was designed and conducted to determine the acute dermal toxicity profile of test chemical as per OECD Guideline 402 (Acute Dermal Toxicity) in Sprague Dawley rats.

The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. 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. 

It was concluded that the acute dermal median lethal dose (LD50) of test chemical, when administered to male and female Sprague Dawley rats was considered to be >2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that test chemical does not classify as an acute dermal toxicant. CLP Classification: “Not classified”.

 

Both the above studies are further supported with the study mentioned in report. The reported study was designed and conducted to determine the acute dermal toxicity profile of the given test chemical as per OECD Guideline 402 (Acute Dermal Toxicity) in Sprague Dawley rats.

The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. 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.

Under the condition of this, it was concluded that the acute dermal median lethal dose (LD50) of test chemical, when administered to male and female Sprague Dawley rats was considered to be >2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that est chemical does not classify as an acute dermal toxicant. CLP Classification: “Not classified”.

 

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.