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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 750 mg/kg bw. The study concluded that the LD50 value is between 300-2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical can be classified in “Category 4” 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 1.12E-08 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:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
1. not specified
2. not specified
3. not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
1. not specified
2. not specified
3. not specified
Doses:
1. 750 mg/kg
2. 690 mg/kg
3. 950 mg/kg
No. of animals per sex per dose:
1. not specified
2. not specified
3. not specified
Control animals:
not specified
Details on study design:
1. not specified
2. not specified
3. not specified
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:
750 mg/kg bw
Based on:
test mat.
Sex:
not specified
Dose descriptor:
LD50
Effect level:
690 mg/kg bw
Based on:
test mat.
Sex:
not specified
Dose descriptor:
LD50
Effect level:
950 mg/kg bw
Based on:
test mat.
Mortality:
1. 50% mortality was observed at 750 mg/kg bw.
2. 50% mortality was observed at 690 mg/kg bw.
3. 50% mortality was observed at 950 mg/kg bw.
Clinical signs:
1. not specified
2. not specified
3. not specified
Body weight:
1. not specified
2. not specified
3. not specified
Gross pathology:
1. not specified
2. not specified
3. not specified
Other findings:
1. not specified
2. not specified
3. not specified
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
According to CLP regulation, the given test chemical can be classified in "Category 4" for acute oral toxicity, as the LD50 value is between 300-2000 mg/kg bw.
Executive summary:

In different studies, the given test chemical has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents,

i.e. most commonly in rats for test chemical. The studies are summarized as below –

 

The reported study was mentioned in authoritative database to determine acute oral toxicity dose for the given test chemical. The study was conducted in rats at the dose concentration of 750 mg/kg bw. Animals were observed for mortality.50% mortality was observed at 750 mg/kg bw. Hence, the LD50 value was considered to be 750 mg/kg bw, when rats was treated with the given test chemical via oral route.

 

The above study is supported with another study mentioned in authoritative database for the given test chemical in rats at the concentration of 690 mg/kg bw. Animals were observed for mortality. 50% mortality was observed at 690 mg/kg bw. Hence, the LD50 value was considered to be 690 mg/kg bw, when rats was treated with the given test chemical via oral route.

 

Both the above studies are further supported with the study mentioned in database for the test chemical. The acute oral toxicity study of the given test chemical was conducted in rats at the concentration of 950 mg/kg bw. Animals were observed for mortality. 50% mortality was observed at 950 mg/kg bw. Hence, the LD50 value was considered to be 950 mg/kg bw, when rats was 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 between 300-2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, the given test chemical can be classified in “Category 4” for acute oral toxicity.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
750 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from database.

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
Qualifier:
according to guideline
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: 1. rat 2. rabbit
Strain:
other: 1. Sprague-Dawley 2. not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
1. 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 215.5 to 252.9 grams at initiation of dosing.
Body weights at the start : Male Mean : 246.62 g (= 100 %); Minimum : 241.8 g (- 1.95 %); Maximum : 252.9 g (+ 2.55 %)
Female Mean: 219.46 g (= 100 %); Minimum : 215.5 g (- 1.80 %); Maximum : 222.8 g (+ 1.52 %)
- 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): 19.9 to 21.7 degree centigrade.
- Humidity (%): 55.0% to 58.4%
- 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: 22-05-2017 to 07-08-2017
2. not specified
Type of coverage:
other: 1. occlusive 2. Dermal
Vehicle:
other: 1. water 2. not specified
Details on dermal exposure:
1. 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
2. not specified
Duration of exposure:
1. 24 hours
2. not specified
Doses:
1. 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).
2. 18000 mg/kg bw
No. of animals per sex per dose:
1. 10 (5/sex).
2. not specified
Control animals:
not specified
Details on study design:
1. - 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.
2. not specified
Statistics:
1. not specified
2. not specified
Preliminary study:
1. not specified
2. not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
not specified
Dose descriptor:
LD50
Effect level:
18 000 mg/kg bw
Based on:
test mat.
Mortality:
1. 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.
2. 50% mortality was observed at the dose concentration of 18000 mg/kg bw.
Clinical signs:
1. 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.
2. not specified
Body weight:
1. Sex : Male Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 9.16% and 18.12% respectively.
Sex : Female Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 5.37% and 9.61% respectively.
2. not specified
Gross pathology:
1. Gross pathological examination did not reveal any abnormalities in animals from 2000 mg/kg dose group.
2. not specified
Other findings:
1. - 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.
2. 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 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 conducted on rabbits for the test chemical. The reported study was designed and conducted to determine the acute dermal toxicity dose at the dose concentration of 18000 mg/kg bw. Animals were observed for the mortality. 50% mortality was observed at the dose concentration of 18000 mg/kg bw. Hence, based on this value it can be concluded that the substance is not hazardous to rabbit and cannot be classified under acute dermal toxic category.

 

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 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 authoritative database to determine acute oral toxicity dose for the given test chemical. The study was conducted in rats at the dose concentration of 750 mg/kg bw. Animals were observed for mortality.50% mortality was observed at 750 mg/kg bw. Hence, the LD50 value was considered to be 750 mg/kg bw, when rats was treated with the given test chemical via oral route.

 

The above study is supported with another study mentioned in authoritative database for the given test chemical in rats at the concentration of 690 mg/kg bw. Animals were observed for mortality. 50% mortality was observed at 690 mg/kg bw. Hence, the LD50 value was considered to be 690 mg/kg bw, when rats was treated with the given test chemical via oral route.

 

Both the above studies are further supported with the study mentioned in database for the test chemical. The acute oral toxicity study of the given test chemical was conducted in rats at the concentration of 950 mg/kg bw. Animals were observed for mortality. 50% mortality was observed at 950 mg/kg bw. Hence, the LD50 value was considered to be 950 mg/kg bw, when rats was 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 between 300-2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, the given test chemical can be classified in “Category 4” 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 1.12E-08 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 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 conducted on rabbits for the test chemical. The reported study was designed and conducted to determine the acute dermal toxicity dose at the dose concentration of 18000 mg/kg bw. Animals were observed for the mortality. 50% mortality was observed at the dose concentration of 18000 mg/kg bw. Hence, based on this value it can be concluded that the substance is not hazardous to rabbit and cannot be classified under acute dermal toxic category.

 

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 between 300-2000 mg/kg bw, for acute oral toxicity and the LD50 value is >2000 mg/kg bw, for acute dermal toxicity. Thus, comparing this value and range with the criteria of CLP regulation, the given test chemical can be classified in “Category 4” for acute oral toxicity and cannot be classified for acute dermal toxicity. For acute inhalation toxicity wavier was added so, not possible to classify.