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 given test chemical. The LD50 value is 13900 mg/kg bw. The value 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 low vapour pressure of the test chemical, which is reported to be 0.00351 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 given 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 of read across substances
Justification for type of information:
Data for the target chemical is summarized based on the structurally similar read across 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:
other: 2. not specified 3. not specified 4. Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
2. not specified
3. not specified
4. 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 at the commencement of its dosing.
- Weight at study initiation: Body weight range was 198.9 to 215.1 grams.
Body weights at the start : Female Mean: 205.26 g (= 100 %); Minimum : 198.9 g (- 3.10 %); Maximum : 215.1 g (+ 4.79 %)
- Identification: Each female rat was individually identified by the picric acid marking.
- 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): 20.1 to 21.9 degree centigrade.
- Humidity (%): 56.3% to 59.8%.
- 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: 14-07-2017 to 02-08-2017
Route of administration:
other: 2. oral: unspecified 3. oral: unspecified 4. oral: gavage
Vehicle:
other: 2. not specified 3. not specified 4. 1% aqueous Tween 80
Details on oral exposure:
2. not specified
3. not specified
4. VEHICLE
- Concentration in vehicle: 300 mg/kg, 300 mg/kg, 2000 mg/kg and 2000 mg/kg

- Justification for choice of vehicle:
1) One of the widely used suspending agent in the toxicological evaluations,
2) Test item was insoluble in water. Uniformly dispersed suspension of the test item was possible in 1% aqueous Tween 80.
3) Extremely safe with LD50 = 38 g/kg body weight.

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg body weight.
Doses:
2. 13900 mg/kg bw
3. 14200 mg/kg bw
4. Dose Group I : 300 mg/kg
Dose Group I : 300 mg/kg
Dose Group II : 2000 mg/kg
Dose Group II : 2000 mg/kg
No. of animals per sex per dose:
2. not specified
3. not specified
4. Three females were used at each step.
Control animals:
not specified
Details on study design:
2. not specified
3. not specified
4. - 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.
The observations were included general clinical signs, observations of eyes, mucous membranes, respiratory, circulatory system and behavior pattern.

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.

Histopathology:
No gross abnormalities were observed in animals sacrificed terminally hence, no histopathology was performed.
Statistics:
2. not specified
3. not specified
4. not specified
Preliminary study:
2. not specified
3. not specified
4. not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
13 900 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% Mortality was observed at dose 13900 mg/kg bw.
Remarks:
2
Sex:
not specified
Dose descriptor:
LD50
Effect level:
14 200 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% Mortality was observed in treated rats at 14200 mg/kg bw
Remarks:
3
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed
Remarks:
3
Mortality:
2. 50% Mortality was observed at dose 13900 mg/kg bw.
3. 50% Mortality was observed in treated rats at 14200 mg/kg bw
4. Group I Step I : Animals treated at the dose level of 300 mg/kg body weight: 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: 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: 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: All animals survived through the study period of 14 days.
Clinical signs:
2. not specified
3. not specified
4. 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.
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.
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.
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.
Body weight:
2. not specified
3. not specified
4. Group I Step I (300 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 6.40% and 14.01% respectively.
Group I Step II (300 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 6.46% and 12.23% respectively.
Group II Step I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 6.19% and 12.06% respectively.
Group II Step II (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 6.08% and 11.58% respectively.
Gross pathology:
2. not specified
3. not specified
4. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups.
Other findings:
2. not specified
3. not specified
4. not specified
Interpretation of results:
other: not classified
Conclusions:
According to CLP regulation, the LD50 value is 13900 mg/kg bw. The value 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.
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 reported study was mentioned in authoritative database and conducted to determine acute oral toxicity dose by using the given test chemical in rats at the dose concentration of 13900 mg/kg bw via oral route. Animals were observed for mortality. 50% Mortality was observed at dose 13900 mg/kg bw. Hence, the lethal concentration (LD50) value for acute oral toxicity test was considered to be 13900 mg/kg bw, when rats were treated with the given test chemical orally.

 

The above study is supported with another study mentioned in handbook and authoritative database for the given test chemical. The acute oral toxicity study was conducted in rats at the dose concentration of 14200 mg/kg bw via oral route. Animals were observed for mortality. 50% Mortality was observed at dose 14200 mg/kg bw. Hence, the lethal concentration (LD50) value for acute oral toxicity test was considered to be 14200 mg/kg bw, when rats were treated with the given test chemical orally.

 

These studies are further supported with the data mentioned in study report and 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, 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. Under the condition of the study, the acute oral LD50 value of the given test chemical was considered to be >2000 mg/kg body weight.  Thus, it was concluded that the acute toxicity study of the given test chemical, when administered via oral route in Sprague Dawley rats falls into the “Category Not classified” criteria of CLP.

 

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:
13 900 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from handbook or collection of data.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
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:
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 2 acute dermal toxicity studies as- WoE 2 and WoE 3.
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
Strain:
other: 2. Sprague-Dawley 3. New Zealand Albino
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 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. not specified
Type of coverage:
other: 2. occlusive 3. dermal
Vehicle:
other: 2. Distilled water 3. corn oil
Details on dermal exposure:
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. VEHICLE
- Concentration in vehicle: 40% solution-suspension in corn oil
Duration of exposure:
2. 24 hours
3. 24 hours
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. 3160, 5010 and 7940 mg/kg bw
No. of animals per sex per dose:
2. 10 (5/sex).
3. Total: 3 animals
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).

Histopathology: No gross abnormalities were observed in animals sacrificed terminally hence, no histopathology was performed.
3. - Duration of observation period following administration: 9 days
- Frequency of observations and weighing: Animals were observed for mortality and sign of intoxication.
- Necropsy of survivors performed: yes
Statistics:
2. not specified
3. not specified
Preliminary study:
2. not specified
3. not specified
Sex:
male/female
Dose descriptor:
LD50
Remarks:
2
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Remarks:
3
Effect level:
> 5 010 mg/kg bw
Based on:
test mat.
Mortality:
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. No mortality was observed in treated rabbits 5010 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. Clinical signs like increased weakness, collapse, death, reduced appetite and activity (2 - 3 days in survivors) 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 8.58% 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. not specified
Gross pathology:
2. Gross pathological examination did not reveal any abnormalities in animals from 2000 mg/kg dose group.
3. In necropsy examination, lung hyperomia, liver & kidney discolouration, enlarged gall bladder, gastrointestinal inflammation 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
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 the given test chemical. The studies are summarized as below -

The reported study was designed and conducted to determine the acute dermal toxicity profile of the given test chemical 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 the given 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 the given test chemical does not classify as an acute dermal toxicant. CLP Classification: “Not classified”.

 

The above study is supported with another study mentioned in secondary source and conducted to determine the acute dermal toxicity dose of the given test chemical in 2 male and 1 female New Zealand Albino rabbits at the dose concentration of 3160, 5010 and 7940 mg/kg bw via dermal route. The given test chemical was applied as a 40 % solution-suspension in corn oil. Animals were observed for mortality and sign of intoxication. Necropsy of survivors performed. No mortality was observed in treated rabbits 5010 mg/kg bw. Clinical signs like increased weakness, collapse, death, reduced appetite and activity (2 - 3 days in survivors) were observed. In necropsy examination, lung hyperaemia, liver & kidney discolouration, enlarged gall bladder, gastrointestinal inflammations were observed. Therefore, the acute dermal LD50 value was considered to be >5010 mg/kg bw, when 2 male and 1 female New Zealand Albino 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
Value:
2 000 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from handbook or collection of data.

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 reported study was mentioned in authoritative database and conducted to determine acute oral toxicity dose by using the given test chemical in rats at the dose concentration of 13900 mg/kg bw via oral route. Animals were observed for mortality. 50% Mortality was observed at dose 13900 mg/kg bw. Hence, the lethal concentration (LD50) value for acute oral toxicity test was considered to be 13900 mg/kg bw, when rats were treated with the given test chemical orally.

 

The above study is supported with another study mentioned in handbook and authoritative database for the given test chemical. The acute oral toxicity study was conducted in rats at the dose concentration of 14200 mg/kg bw via oral route. Animals were observed for mortality. 50% Mortality was observed at dose 14200 mg/kg bw. Hence, the lethal concentration (LD50) value for acute oral toxicity test was considered to be 14200 mg/kg bw, when rats were treated with the given test chemical orally.

 

These studies are further supported with the data mentioned in study report and 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, 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. Under the condition of the study, the acute oral LD50 value of the given test chemical was considered to be >2000 mg/kg body weight.  Thus, it was concluded that the acute toxicity study of the given test chemical, when administered via oral route in Sprague Dawley rats falls into the “Category Not classified” criteria of CLP.

 

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.

 

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 low vapour pressure of the test chemical, which is reported to be 0.00351 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 the given test chemical. The studies are summarized as below -

The reported study was designed and conducted to determine the acute dermal toxicity profile of the given test chemical 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 the given 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 the given test chemical does not classify as an acute dermal toxicant. CLP Classification: “Not classified”.

 

The above study is supported with another study mentioned in secondary source and conducted to determine the acute dermal toxicity dose of the given test chemical in 2 male and 1 female New Zealand Albino rabbits at the dose concentration of 3160, 5010 and 7940 mg/kg bw via dermal route. The given test chemical was applied as a 40 % solution-suspension in corn oil. Animals were observed for mortality and sign of intoxication. Necropsy of survivors performed. No mortality was observed in treated rabbits 5010 mg/kg bw. Clinical signs like increased weakness, collapse, death, reduced appetite and activity (2 - 3 days in survivors) were observed. In necropsy examination, lung hyperaemia, liver & kidney discolouration, enlarged gall bladder, gastrointestinal inflammations were observed. Therefore, the acute dermal LD50 value was considered to be >5010 mg/kg bw, when 2 male and 1 female New Zealand Albino 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.