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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 LD50 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 2.45E-11 mm Hg. 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:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from publication.
Qualifier:
according to guideline
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Acute oral toxicity of the given test chemical in rat.
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
not specified
Route of administration:
oral: unspecified
Vehicle:
water
Details on oral exposure:
not specified
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
Total = 10
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for mortality and clinical signs.
Statistics:
not specified
Preliminary study:
not specified
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed at 5000 mg/kg bw in treated animals.
Clinical signs:
Clinical symptoms were not observed in treated animals.
Body weight:
not specified
Gross pathology:
not specified
Other findings:
not specified
Interpretation of results:
other: Not classified
Conclusions:
The acute oral LD50 value was considered to be >5000 mg/kg bw, when 10 male Wistar rats were treated with the given test chemical via oral route.
Executive summary:

Acute oral toxicity study was conducted by using the given test chemical in 10 male Wistar rats at the dose concentration of 5000 mg/kg bw.

The given test chemical was dissolved or suspended in water and administered via oral route.

Animals were observed for mortality and clinical signs for 14 days. No mortality was observed at 5000 mg/kg bw in treated animals. Clinical symptoms were not observed in treated animals.

Hence, the LD50 value was considered to be >5000 mg/kg bw, when 10 male Wistar rats were treated with the given test chemical via oral route.

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 peer-reviewed journal.

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: 2. rat 3. rat 4. rabbit
Strain:
other: 2. Sprague-Dawley 3. Wistar 4. not specified
Sex:
male/female
Details on test animals or test system 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. TEST ANIMALS
- Source: Institute for Industrial Research & Toxicology, Ghaziabad
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: 200±20g
- Housing:Groups of 2 animals of similar sex in polypropylene cages with stainless steel grill top, facilities for food and water bottle, and bedding of clean paddy husk.
- Diet (e.g. ad libitum): Pelleted feed
- Water (e.g. ad libitum): Fresh and clean water filered through 'Aqua Guard on line water filter', was kept in glass bottles, ad libitum
- Acclimation period: The healthy Wistar albino rats selected for study accliatized to standard laboratory condition for period of one week under close veterinary supervision.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): temperature between 22-25°C
- Humidity (%): relative humidity 40-60%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): illumination cycle set to 12 hours artificial fluorescent light and 12
hours dark.
IN-LIFE DATES: From:18/03/2013 To:28/04/2013
4. not specified
Type of coverage:
other: 2. occlusive 3. occlusive 4. Dermal
Vehicle:
other: 2. water 3. water 4. not specified
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. TEST SITE
- Area of exposure: back skin of total body surface area
- % coverage: 10%
- Type of wrap if used: The test compound held in contact with an impervious dressing secured in place with an adhesive tape.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dressing was removed and the site of application was cleaned with lukewarm water wiping the test compound.
- Time after start of exposure: 24 Hours
4. not specified
Duration of exposure:
2. 24 hours
3. 24 hours
4. not specified
Doses:
2. A single dose of 2000 mg of the test item per kilogram of body weight was administered to ten rats (five males and five females).
3. 2000 mg/kg
4. 8112 mg/kg bw
No. of animals per sex per dose:
2. 10 (5/sex).
3. Total = 20
Group I - 2000 mg/kg - 10 (5 male and Female)
Group II - 2000 mg/kg - 10 (5 male and Female)
4. not specified
Control animals:
not specified
Details on study design:
2. - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical Observations and General Appearance: Animals were observed for clinical signs, mortality, until sacrifice.
Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily thereafter for 14 day. Daily observation was done as far as possible at the same time.
The observations were included general clinical signs, observations of eyes, mucous membranes, respiratory, circulatory system and behavior pattern.

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

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

Gross Pathology: Necropsy was performed on animals surviving at the end of the study. Macroscopic examination of all the orifices, cavities and tissues were made and the findings were recorded. All animals surviving the study period were sacrificed by the carbon dioxide asphyxiation technique (day 15).

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:The body weight of all the animals was observed weekly on day 0 (pre treatment), 7th and 14th (post treatment).Rats were observed for mortality at 30 minutes time interval for first 6 hous on the day of test compund and therafter twice a day for 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: The treated animals were closely observed for clinical signs of in toxication, first 4 hours and every 1 hrs interval for 24 hrs after dosing and thereafter twice a day for 14 days. All the rats were observed at least twice daily with the purpose of recording any symptoms of ill-health or behavioral changes. The organ which showed gross pathological change during necropsy subjected for histopathological study.
4. not specified
Statistics:
2. not specified
3. not specified
4. not specified
Preliminary study:
2. not specified
3. not specified
4. not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed
Sex:
not specified
Dose descriptor:
LD50
Effect level:
8 112 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 at 2000 mg/kg bw
4. 50% mortality was observed at 8112 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. Animals did not produce any clinical signs of intoxication throughout the period of observation.
4. not specified
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. Animals showed normal gain in body weight on day 7th and 14th as compared to control group.
4. not specified
Gross pathology:
2. Gross pathological examination did not reveal any abnormalities in animals from 2000 mg/kg dose group.
3. No significant gross pathological changes related to compound toxicity were observed.
4. not specified
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. Skin and hair coat was observed wet.
4. not specified
Interpretation of results:
other: Not classified
Conclusions:
According to CLP regulation, the test chemical cannot be classified for acute dermal toxicity, as the LD50 value is >2000 mg/kg bw.
Executive summary:

In different studies, the given test chemical has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats and rabbits for test chemical. The studies are summarized as below -

 

The 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. 

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 report and performed as per OECD Guideline 402 (Acute Dermal Toxicity) by using the given test chemical in wistar albino rats.

In limit test, healthy wistar albino rats of body weight 200±20 gm were selected for study after acclimatization. Approximate 10% back skin of total body surface area was prepared 24 hrs prior to application of test compound. Test drug was applied dermally at the dose of 2000 mg/kg bw for each animal. The treated animals were observed for clinical signs of intoxication. The body weight of all the animals was observed weekly on day 0 (pre treatment), 7th and 14th (post treatment). The Necropsy was performed on all at the termination of the study.

After 72 hrs, a confirmatory test was conducted in same species of animals to confirm the limit test of the test compound. Rats were observed for mortality at 30 minutes time interval for first 6 hours on the day of test compound and thereafter twice a day for 14 days. All the rats were observed at least twice daily with the purpose of recording any symptoms of ill-health or behavioural changes. The organ which showed gross pathological change during necropsy subjected for histopathological study.

No mortality was observed at 2000 mg/kg bw. Animals did not produce any clinical signs of intoxication throughout the period of observation. Animals showed normal gain in body weight on day 7th and 14th as compared to control group. No significant gross pathological changes related to compound toxicity were observed. Skin and hair coat was observed wet.

Under the condition of the study, the acute dermal LD50 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 test chemical, when applied by dermal route in wistar albino rats falls into the “Category Not classified" according to criteria of CLP.

 

Both the above studies are further supported with the study mentioned in authoritative database for the test chemical. The acute dermal toxicity study was conducted in rabbits at the dose concentration of 8112mg/kg bw. Animals were observed for mortality. 50% mortality was observed at 8112 mg/kg bw. Hence, LD50 value was considered to be 8112 mg/kg bw, when rabbits were treated with 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, 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.

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 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 mentioned in peer-reviewed journal, authoritative database and secondary report to determine the acute oral toxicity dose for the given test chemical. The study was conducted in 10 male Wistar rats at the dose concentration of 5000 mg/kg bw.

The given test chemical was dissolved or suspended in water and administered via oral route. Animals were observed for mortality and clinical signs for 14 days. No mortality was observed at 5000 mg/kg bw in treated animals. Clinical symptoms were not observed in treated animals.

Hence, the LD50 value was considered to be >5000 mg/kg bw, when 10 male Wistar rats were treated with the given test chemical via oral route.

 

The above study is supported with another study mentioned in authoritative database and secondary source for the given test chemical. The study was conducted to evaluate the acute toxic effects in 10 female Wistar rats by the oral route at the dose concentration of 15000 mg/kg bw.

Animals were observed for mortality and clinical signs for 14 days. No mortality was observed at 15000 mg/kg bw in treated animals. No clinical signs of toxicity were observed.

Hence, the LD50 value was considered to be >15000 mg/kg bw, when 10 female Wistar rats were treated with the given test chemical via oral route.

 

These studies are supported with the data available in publication, authoritative databases and secondary report for the test chemical. The acute oral toxicity study was conducted in 10 male Wistar rats at the dose concentration of 5000 mg/kg bw.

The given test chemical was dissolved or suspended in water and administered via oral route. Animals were observed for mortality and clinical signs for 14 days. No mortality was observed at 5000 mg/kg bw in treated animals. Clinical symptoms were not observed in treated animals.

Hence, the LD50 value was considered to be >5000 mg/kg bw, when 10 male Wistar rats were treated with the given test chemical via oral route.

 

All the above studies are further supported with the study available in study report and designed and conducted to determine the acute oral toxicity profile of the given test chemical as per OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method) 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 was considered to be >2000 mg/kg bw for the test chemical. 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. 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 2.45E-11 mm Hg. 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 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. 

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 report and performed as per OECD Guideline 402 (Acute Dermal Toxicity) by using the given test chemical in wistar albino rats.

In limit test, healthy wistar albino rats of body weight 200±20 gm were selected for study after acclimatization. Approximate 10% back skin of total body surface area was prepared 24 hrs prior to application of test compound. Test drug was applied dermally at the dose of 2000 mg/kg bw for each animal. The treated animals were observed for clinical signs of intoxication. The body weight of all the animals was observed weekly on day 0 (pre treatment), 7th and 14th (post treatment). The Necropsy was performed on all at the termination of the study.

After 72 hrs, a confirmatory test was conducted in same species of animals to confirm the limit test of the test compound. Rats were observed for mortality at 30 minutes time interval for first 6 hours on the day of test compound and thereafter twice a day for 14 days. All the rats were observed at least twice daily with the purpose of recording any symptoms of ill-health or behavioural changes. The organ which showed gross pathological change during necropsy subjected for histopathological study.

No mortality was observed at 2000 mg/kg bw. Animals did not produce any clinical signs of intoxication throughout the period of observation. Animals showed normal gain in body weight on day 7th and 14th as compared to control group. No significant gross pathological changes related to compound toxicity were observed. Skin and hair coat was observed wet.

Under the condition of the study, the acute dermal LD50 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 test chemical, when applied by dermal route in wistar albino rats falls into the “Category Not classified" according to criteria of CLP.

 

Both the above studies are further supported with the study mentioned in authoritative database for the test chemical. The acute dermal toxicity study was conducted in rabbits at the dose concentration of 8112mg/kg bw. Animals were observed for mortality. 50% mortality was observed at 8112 mg/kg bw. Hence, LD50 value was considered to be 8112 mg/kg bw, when rabbits were treated with 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, 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.

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.