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 LD50 value is 6500 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 < 0.133 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:
calculation (if not (Q)SAR)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Justification for type of information:
Data is from Danish QSAR
Qualifier:
equivalent or similar to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Prediction is done by using Danish QSAR database
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
Not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
Not specified
Doses:
6500 mg/kg bw
No. of animals per sex per dose:
Not specified
Control animals:
not specified
Details on study design:
Not specified
Statistics:
Not specified
Preliminary study:
Not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
6 500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality was observed
Mortality:
Not specified
Clinical signs:
Not specified
Body weight:
Not specified
Gross pathology:
Not specified
Other findings:
Not specified
Interpretation of results:
other: not classified
Conclusions:
Based on the QSAR prediction done using the Danish (Q)SAR Database, the LD50 value was estimated to be 6500 mg/kg bw, when rats were treated with the given test chemical orally.
Executive summary:

Based on the QSAR prediction done using the Danish (Q)SAR Database, the acute oral toxicity was estimated for the given test chemical. The LD50 was estimated to be 6500 mg/kg bw, with Reliability Index 0.51 (0.5-0.75 = moderate prediction quality), when rats were treated with the given test chemical via oral route.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
6 500 mg/kg bw
Quality of whole database:
Data is Klimisch 2 from Danish QSAR.

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
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. Albino 4. albino rabbits
Sex:
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: Young adult female rats aged between 8 – 10 weeks were used.
- Weight at study initiation: The weight ranges of approximately 219.1 to 232.4 grams at initiation of dosing were used.
Body weights at the start :
Female
Mean : 225.52 g (= 100 %)
Minimum : 219.1 g (- 2.85 %)
Maximum : 232.4 g (+ 3.05 %)
Total No. of animals : 5
- Fasting period before study: No data
- 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): 19.3 to 21.8 degree centigrade.
- Humidity (%):55.4% to 59.2%.
- 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: 17-02-2018 to 12-03-2018
3. TEST ANIMALS
Housing: The animals were housed individually
Diet (e.g. ad libitum):ad libitum
Water (e.g. ad libitum): ad libitum
4. not specified
Type of coverage:
other: 2. semiocclusive 3. occlusive 4. occlusive
Vehicle:
other: 2. water 3. not specified 4. unchanged (no vehicle)
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 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: No data
- For solids, paste formed: Yes
3. TEST SITE
- Area of exposure: the closely clipped, intact abdominal skin
- Type of wrap if used: The exposed area was covered with an occlusive binding of dental damming
REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the exposure, the binding was removed, and the remaining material, if any, was cleaned from the skin.
- Time after start of exposure:24 hour
4. TEST SITE
- Area of exposure: Test chemcial was applied full-strength to the clipped intact abdominal skin.
- Type of wrap if used: Each exposed area was covered with an occlusive binding of dental damming that remained in place for 24 h.
Duration of exposure:
2. 24 hours
3. 24 hours
4. 24 h
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. 0.10, 0.316, 1.00, and 3.16 ml/kg were administered volumetrically.
4. 0.10, 0.316, 1.00, and 3.16 ml/kg
No. of animals per sex per dose:
2. 2000 mg/kg bw:2 female rats
3. groups of 4 (sex not mentioned)
4. 16
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: 7 days
- Frequency of observations and weighing: Observations for signs of toxicity were made frequently on the day of application and once daily afterward for a total of 7 days.
Necropsy of survivors performed: yes/no: Yes, Gross necropsies were performed at the end of the experiments.
4. - Duration of observation period following administration: 7 days
- Other examinations performed: Observations for signs of toxicity were made for a total of 7 days post application.
Statistics:
2. No data
3. The results have been converted to gravimetric expressions by use of the specific gravity.
4. not specified
Preliminary study:
2. Dose Range Finding Study: A single dose of 200 mg/kg body weight of the test item was administered to 1 female animal. No death or clinical signs of toxicity was observed during first 48 hours, hence, additional 1 female animal was administered at the dose of 1000 mg/kg body weight. Administration of 1000 mg/kg body weight did not reveal any clinical signs of toxicity or death during first 48 hours, hence, additional 1 female animal was administered at the dose of 2000 mg/kg body weight. Administration of 2000 mg/kg body weight did not reveal any clinical signs of toxicity or death during first 48 hours.
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
Remarks:
2
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 2 600 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Dose reported is the highest dose tested
Remarks:
3
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 2 600 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed at 2600 mg/kg bw
Remarks:
4
Mortality:
2. Sex : Female Dose Range Finding Study: Group I : Animal treated at the dose level of 200 mg/kg body weight survived through the study period of 14 days.
Group I : Animal treated at the dose level of 1000 mg/kg body weight survived through the study period of 14 days.
Group I : Animal treated at the dose level of 2000 mg/kg body weight survived through the study period of 14 days.
Main Study: Group II : Animals treated at the dose level of 2000 mg/kg body weight survived through the study period of 14 days.
3. No Mortality observed at 2600 mg/kg bw.
4. No mortality was observed at 2600 mg/kg bw
Clinical signs:
2. Sex : Female Dose Range Finding Study: Group I : Animal treated at the dose level of 200 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days.
Group I : Animal treated at the dose level of 1000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days.
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.
Main Study: Group 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.
3. No signs of toxicity observed
4. One of the 4 animals in the 3.16 ml/kg group had decreased activity and labored respiration.
Body weight:
2. Sex : Female Dose Range Finding Study: Group I (200 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 3.28% and 7.25% respectively.
Group I (1000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 2.97% and 5.75% respectively.
Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 3.27% and 5.51% respectively.
Main Study: Group II (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 2.43% and 6.67% respectively.
3. No data
4. not specified
Gross pathology:
2. Gross pathological examination did not reveal any abnormalities in animals from 200 mg/kg, 1000 mg/kg and 2000 mg/kg dose groups from dose range finding study and main study sacrificed terminally.
3. No data
4. not specified
Other findings:
2. - Other observations: Evaluation of Dermal Reaction
Sex : Female Dose Range Finding Study: Group I : Animal treated at the dose level of 200 mg/kg body weight did not result in any skin reaction during the study period of 14 days.
Group I : Animal treated at the dose level of 1000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.
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.
Main Study: Group II : Animals 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. On observation of the binders after 24 hours of skin contact, percutaneous absorption was evident with all the alcohols even though the median lethal dose was not achieved.
4. 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 mentioned in study report and conducted to determine acute dermal toxicity dose by using the given test chemical according to OECD Guideline 402 (Acute Dermal Toxicity) in female Sprague Dawley rats. In the dose range finding study a single dose of 200 mg/kg body weight of the test item was administered to 1 female animal. No death or clinical signs of toxicity was observed during first 48 hours, hence, additional 1 female animal was administered with the dose of 1000 mg/kg body weight. Administration of 1000 mg/kg body weight did not reveal any clinical signs of toxicity or death during first 48 hours, hence, additional 1 female animal was administered at the dose of 2000 mg/kg body weight. Administration of 2000 mg/kg body weight did not reveal any clinical signs of toxicity or death during first 48 hours. As the dose range finding study revealed no mortality or clinical signs at the maximum dose of 2000 mg/kg, the main study was initiated with two additional animals. The animals were administered with a dose of 2000 mg/kg body weight in sequential manner at 48 hours intervals. Animals from dose range finding study treated at the dose levels of 200 mg/kg, 1000 mg/kg and 2000 mg/kg and animals from main study treated at the dose level of 2000 mg/kg exhibited normal body weight gain and revealed no clinical signs of toxicity or mortality during the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment. Thus, the acute dermal LD50 value was considered to be >2000 mg/kg body weight, when female Sprague Dawley rats were treated with the given test chemical by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).

 

The above study is supported with another study mentioned in publication and conducted to determine the acute dermal toxicity profile of the given test chemical in groups of 4 albino rabbits at the dose concentration of 0.10, 0.316, 1.00, and 3.16 ml/kg bw administered volumetrically. The animals were housed individually with feed and water freely available. No mechanical restraints were used. The test chemical was applied full-strength to the closely clipped, intact abdominal skin of albino rabbits. The exposed area was covered with an occlusive binding of dental damming for 24 hours. After the exposure, the binding was removed, and the remaining material, if any, was cleaned from the skin. Observations for signs of toxicity were made frequently on the day of application and once daily afterward for a total of 7 days. Gross necropsies were performed at the end of the experiments. The results have been converted to gravimetric expressions by use of the specific gravity. No Mortality observed at 2600 mg/kg bw. No signs of toxicity observed. On observation of the binders after 24 hours of skin contact, percutaneous absorption was evident with the chemical even though the median lethal dose was not achieved. Therefore, LD50 was considered to be >2600 mg/kg bw, when groups of 4 albino rabbits were treated with test chemical by dermal application occlusively to the closely clipped, intact abdominal skin for 24 hours.

 

These studies are further supported with the data available in publication and the study was conducted by using the given test chemical in 16 albino rabbits at the concentration of 0.10, 0.316, 1.00, and 3.16 ml/kg bw. The test chemical was applied full-strength to the clipped intact abdominal skin of rabbits. The animals were divided equally into 4 treatment groups: 0.10, 0.316, 1.00, and 3.16 ml/kg doses. Each exposed area was covered with an occlusive binding of dental damming that remained in place for 24 h. Observations for signs of toxicity were made for a total of 7 days post application. No mortality was observed at 2600 mg/kg bw. One of the 4 animals in the 3.16 ml/kg group had decreased activity and labored respiration. Therefore, LD50 was considered to be >2600 mg/kg bw, when 16 albino rabbits were treated with test chemical by dermal application occlusively to the clipped intact abdominal skin.

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 study 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 based on the QSAR prediction done using the Danish (Q)SAR Database to determine the acute oral toxicity dose for the given test chemical. The LD50 was estimated to be 6500 mg/kg bw, with Reliability Index 0.51 (0.5-0.75 = moderate prediction quality), when rats were treated with the given test chemical via oral route.

 

The above prediction study is supported with another study mentioned in report for the given test chemical. The acute oral toxicity study was performed according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method) in female 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 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. Thus, the acute oral LD50 value was considered to be >2000 mg/kg body weight, when female Sprague Dawley rats were treated with the given test chemical orally via gavage according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).

 

These studies are supported with the data mentioned in publication for the given test chemical. The acute oral toxicity study was conducted in groups of 5 male Sprague-Dawley rats at the concentration ranging from 0.032 to 10.0 ml/kg body weight. The given test chemical was dissolved in a corn oil suspension or in undiluted form. The animals had been fasted for 3 to 4 hours prior to the study and were group-housed, with water and feed freely available after dosing. Observations for signs of toxicity were made frequently on the day of administration and daily thereafter for a period of 7 to 14 days. Gross necropsy examinations were performed on all animals that died or were killed. The mortality data were analyzed by the moving average of Horn or the method of Litchfield and Wilcoxon. The results have been converted to weight units by means of the specific gravity. LD50 was estimated, since mortality pattern was not suitable for analysis. 50% Mortality observed at 4750 mg/kg bw.The principal signs of effect were central nervous system depression and labored respiration. The depression included inactivity, ataxia, limb sprawling, depressed righting and placement reflexes, prostration, and coma. Gross necropsy revealed some evidence of gastrointestinal irritation. Therefore, the acute oral toxicity dose (LD50) was considered to be 4750 mg/kg bw, when groups of 5 male Sprague-Dawley rats were treated with the test chemical via oral gavage route.

 

This study is supported with the data available in publication for the given test chemical. The acute oral toxicity study was conducted in 10 fasted Harlan Wistar rats at oral dose 7 ml/kg of a formulation containing 2.0% Cetyl Alcohol. Animals were observed for clinical signs of toxicity. No mortality was observed at 7000 mg/kg bw. No signs of toxicity were noted. Therefore, LD50 was considered to be >7000 mg/kg bw, when 10 male Harlan Wistar rats were treated with the test chemical via oral gavage route.

 

All the above studies are further supported with the data mentioned in publication and the study was conducted according to the Protocol stated in Title 16 Part 1500.3 (b)(G)(i)(A) of the Code of Federal Regulations by using the given test chemical in a group of 10 or more laboratory white rats at the dose concentration of 5000 mg/kg bw. The given test chemical was prepared with the moisturizing lotion containing 0.8% test chemical and administered via oral route. No mortality was observed at 5000 mg/kg bw. Therefore, LD50 was considered to be >5000 mg/kg bw, when group of 10 or more laboratory white 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 low vapour pressure of the test chemical, which is reported to be < 0.133 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 mentioned in study report and conducted to determine acute dermal toxicity dose by using the given test chemical according to OECD Guideline 402 (Acute Dermal Toxicity) in female Sprague Dawley rats. In the dose range finding study a single dose of 200 mg/kg body weight of the test item was administered to 1 female animal. No death or clinical signs of toxicity was observed during first 48 hours, hence, additional 1 female animal was administered with the dose of 1000 mg/kg body weight. Administration of 1000 mg/kg body weight did not reveal any clinical signs of toxicity or death during first 48 hours, hence, additional 1 female animal was administered at the dose of 2000 mg/kg body weight. Administration of 2000 mg/kg body weight did not reveal any clinical signs of toxicity or death during first 48 hours. As the dose range finding study revealed no mortality or clinical signs at the maximum dose of 2000 mg/kg, the main study was initiated with two additional animals. The animals were administered with a dose of 2000 mg/kg body weight in sequential manner at 48 hours intervals. Animals from dose range finding study treated at the dose levels of 200 mg/kg, 1000 mg/kg and 2000 mg/kg and animals from main study treated at the dose level of 2000 mg/kg exhibited normal body weight gain and revealed no clinical signs of toxicity or mortality during the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment. Thus, the acute dermal LD50 value was considered to be >2000 mg/kg body weight, when female Sprague Dawley rats were treated with the given test chemical by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).

 

The above study is supported with another study mentioned in publication and conducted to determine the acute dermal toxicity profile of the given test chemical in groups of 4 albino rabbits at the dose concentration of 0.10, 0.316, 1.00, and 3.16 ml/kg bw administered volumetrically. The animals were housed individually with feed and water freely available. No mechanical restraints were used. The test chemical was applied full-strength to the closely clipped, intact abdominal skin of albino rabbits. The exposed area was covered with an occlusive binding of dental damming for 24 hours. After the exposure, the binding was removed, and the remaining material, if any, was cleaned from the skin. Observations for signs of toxicity were made frequently on the day of application and once daily afterward for a total of 7 days. Gross necropsies were performed at the end of the experiments. The results have been converted to gravimetric expressions by use of the specific gravity. No Mortality observed at 2600 mg/kg bw. No signs of toxicity observed. On observation of the binders after 24 hours of skin contact, percutaneous absorption was evident with the chemical even though the median lethal dose was not achieved. Therefore, LD50 was considered to be >2600 mg/kg bw, when groups of 4 albino rabbits were treated with test chemical by dermal application occlusively to the closely clipped, intact abdominal skin for 24 hours.

 

These studies are further supported with the data available in publication and the study was conducted by using the given test chemical in 16 albino rabbits at the concentration of 0.10, 0.316, 1.00, and 3.16 ml/kg bw. The test chemical was applied full-strength to the clipped intact abdominal skin of rabbits. The animals were divided equally into 4 treatment groups: 0.10, 0.316, 1.00, and 3.16 ml/kg doses. Each exposed area was covered with an occlusive binding of dental damming that remained in place for 24 h. Observations for signs of toxicity were made for a total of 7 days post application. No mortality was observed at 2600 mg/kg bw. One of the 4 animals in the 3.16 ml/kg group had decreased activity and labored respiration. Therefore, LD50 was considered to be >2600 mg/kg bw, when 16 albino rabbits were treated with test chemical by dermal application occlusively to the clipped intact abdominal skin.

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.