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Administrative data

Description of key information

Acute oral toxicity: 

The acute oral toxicity dose (LD50) was considered based on different studies conducted on rats and mice for the test chemical. The LD50 value is 4590 mg/kg bw. The study 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 the low vapour pressure of the test chemical, which is reported to be 3.61 Pa (0.0271 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 LD50 value is >5000 mg/kg bw. The study 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:
other: Refer below principle
Principles of method if other than guideline:
Acute oral toxicity study of the given test chemical in rat.
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Species:
rat
Strain:
Osborne-Mendel
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data
- Females (if applicable) nulliparous and non-pregnant: No data
- Age at study initiation: Young rats were used for the study
- Weight at study initiation: No data
- Fasting period before study: 18 hrs prior to treatment
- Housing: Animals were housed in cages
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

IN-LIFE DATES: From: To: No data
Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 4590 mg/Kg bw
- Amount of vehicle (if gavage): No data
- Justification for choice of vehicle: No data
- Lot/batch no. (if required): No data
- Purity: No data

MAXIMUM DOSE VOLUME APPLIED: No data

DOSAGE PREPARATION (if unusual): No data

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: No data
Doses:
4590 mg/kg bw
No. of animals per sex per dose:
10 rats evenly divided by sex
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were maintained under close observation for recording toxic signs artd time of death. Such observation was continued until animals appeared normal and showed weight gaiu.
- Necropsy of survivors performed: No data
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: No data
Statistics:
LD50'S were computed by the method of Litchfield & Wilcoxon (1949).
Preliminary study:
not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 590 mg/kg bw
Based on:
test mat.
95% CL:
> 3 880 - < 5 400
Mortality:
50% mortality was observed at 4590 mg/kg bw. Death time was 4 hrs - 4 days
Clinical signs:
Depression, tremors
Body weight:
not specified
Gross pathology:
not specified
Other findings:
not specified
Interpretation of results:
other: Not classified
Conclusions:
The acute oral toxicity dose (LD50) value was considered to be 4590 mg/kg bw, when rats were treated with the given test chemical via oral gavage route of exposure.
Executive summary:

Acute oral toxicity study was conducted for the test chemical using male and female Osborne Mendel rats at the dose concentration of 4590 mg/kg bw via oral gavage route of exposure. Groups of 10 young adult Osborne-Mendel rats evenly divided by sex were fasted for approximately 18 hr prior to treatment. Animals had access to water at all times, and the food was replaced in cages as soon as animals received their respective doses. All doses were given by intubation. All animals were maintained under close observation for recording toxic signs artd time of death. Such observations were continued until animals appeared normal and showed weight gain. The test chemical showed depression and tremors and the death time was 4 hrs to 4 days. 50% mortality was observed at 4590 mg/kg bw. Hence, the LD50 value was considered to be 4590 mg/kg bw, when rats was treated with the given test chemical via oral gavage route of exposure.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
4 590 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from publication.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
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: Refer below principle
Principles of method if other than guideline:
WoE report is based on 3 acute dermal toxicity studies as- WoE 2, WoE 3 and WoE 4.
Acute dermal toxicity test was carried out to study the effects of the test chemicals on rodents.
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Species:
other: 1. rabbit 2. rabbit 3. rat
Strain:
other: 1. not specified 2. not specified 3. Wistar
Sex:
male/female
Details on test animals and environmental conditions:
1. not specified
2. not specified
3. TEST ANIMALS
- Source: In-house animals, bred at Animal House
- Females (if applicable) nulliparous and non-pregnant: Yes
- Weight at study initiation: Male:Minimum: 229 g and Maximum: 262 g
(Prior to Treatment) Female:Minimum: 203 g and Maximum: 241 g
- Fasting period before study: The food was withheld prior to dosing and 3-4 hours post dosing but drinking water was provided ad libitum.
- Housing: The animals were housed individually in polycarbonate cages.All cages were provided with corn cobs
- Diet (e.g. ad libitum): All animals were provided conventional laboratory rodent diet ad libitum. Batch No.: 400012.
- Water (e.g. ad libitum): Aqua guard filtered tap water was provided ad libitum via drinking bottles
- Acclimation period:All animals were acclimatized to the test conditions for 5 days prior to administration of the test item.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Room temperature was maintained at 21.10 to 24.40 degree centigrade.
- Humidity (%): Room humidity was maintained at 36.60% to 57.30%.
- Air changes (per hr): More than 12 changes per hour
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.
Type of coverage:
other: 1. Dermal 2. occlusive 3. occlusive
Vehicle:
other: 1. not specified 2. unchanged (no vehicle) 3. unchanged (no vehicle)
Details on dermal exposure:
1. TEST SITE
- Area of exposure: The test chemical was applied to abraded rabbit skin
2. TEST SITE
- Area of exposure: The given test chemical was applied to intact and abraded skin
3. TEST SITE
- Area of exposure: over clipped dorsal area of rat skin. Approx. 10% of body surface area of rat
- % coverage: porous gauze dressing
- Type of wrap if used: The test site was further covered in a suitable manner to retain the gauze dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, At the end of the exposure period, residual test item was removed by using distilled water.
- Time after start of exposure:24hr

TEST MATERIAL
- Concentration (if solution): 2000mg/kgbw
- Constant volume or concentration used: yes
Duration of exposure:
1. not specified
2. 24 h
3. 24hr
Doses:
1. 5000 mg/kg
2. 5000 mg/kg
3. 2000mg/kg bw
No. of animals per sex per dose:
1. 10
2. Total = 8
3. Total : 10
male : 5
female: 5
Control animals:
not specified
Details on study design:
1. not specified
2. - Duration of observation period following administration: 14 days
3. - Duration of observation period following administration: 14 days
- Frequency of observations and weighing:daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs:After test item administration, individual animals were frequently observed at 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing). Subsequently, all animals were observed once a day during the 14 day observation period.
Local Signs/Skin Reactions: All animals were observed once daily during days 1-14 (in common with clinical signs).
body weight:All rats were weighed on days 0 (prior to dosing), 7 and 14.
Mortality:Animals were observed twice daily for any mortality during the experimental period
Pathology:At the end of 14 day observation period, all the surviving rats were euthanised by overdose of CO2 and subjected to gross pathology examination, for external and internal observations.
Statistics:
1. not specified
2. not specified
3. No statistical analysis was performed since the study was terminated with limit test
Preliminary study:
1. not specified
2. not specified
3. not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 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
Mortality:
1. No mortality was observed at 5000 mg/kg bw
2. No mortality was observed at 5000 mg/kg bw
3. No mortality was observed at limit dose of 2000 mg/kg body weight of test item during the 14 day observation period
Clinical signs:
1. not specified
2. not specified
3. No systemic or local signs of toxicity were observed at limit dose of 2000 mg/kg body weight of test item during the experimental period
Body weight:
1. not specified
2. not specified
3. The male and female animals were observed with body weight gain compared to day 0 throughout the experiment
Gross pathology:
1. not specified
2. not specified
3. The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality
Other findings:
1. not specified
2. not specified
3. 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 -

 

Acute dermal toxicity study was conducted by using test chemical in 10 rabbits at the dose concentration of 5000 mg/kg bw by dermal application to abraded rabbit skin. Animals were observed for mortality after application of the test chemical. No mortality was observed at 5000 mg/kg bw. Hence, the LD50 value was considered to be >5000 mg/kg bw, when 10 rabbits were treated with the given test chemical by dermal application to abraded rabbit skin.

 

The above study is supported with another study mentioned in peer-reviewed journals and secondary report for the test chemical. The acute dermal toxicity study was conducted by using test chemical in 8 rabbits at the dose concentration of 5000 mg/kg bw. The given test chemical (neat) was applied to intact and abraded skin for 24 h under occlusion. Observations for mortality and systemic effects were made for 14 days after exposure. No mortality was observed at 5000 mg/kg bw. Hence, the LD50 value was considered to be >5000 mg/kg bw, when 8 rabbits were treated with the given test chemical by dermal application occlusively.

 

Both the above studies are further supported with the study mentioned in report for the test chemical. The acute dermal toxicity study of the given test chemical was performed as per OECD No.402 in Wistar Rats.

Five male and five female healthy young adult rats were randomly selected. Rats free from injury and irritation of skin were selected for the study. Twenty four hours prior to dermal application of test item, approximately 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight of test item was applied by single dermal application and observed for 14 days after treatment.

On test day 0, as such amount of test item, calculated based on density (0.9407) and body weight was applied directly on the intact skin of clipped area of rats; the surgical gauze patch was put on to the intact skin of clipped area. This gauze patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with non-irritating adhesive tape. After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water. The skin reactions were assessed.

The animals were observed daily for mortality and clinical signs, during the acclimatization period. All animals were observed for clinical signs at approximately 1, 2, 3 and 4 hours after treatment on day 0 and once daily during test days 1‑14. Mortality was recorded after application on test day 0 and twice daily during days 1-14 (at least once on the day of sacrifice). Local signs / Skin reactions were observed daily from test days 1-14 (in common with clinical signs). Body weights were re­corded on day 0 (prior to application) and on day 7 and 14. All animals were necropsied and examined macroscopically.

No mortality was observed in any animal till the end of the experimental period. No clinical signs and any skin reaction were observed throughout the experimental period in all treated animals. The male and female animals were observed with body weight gain compared to day 0 throughout the experiment. The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality.

Hence the LD50 value was considered to be >2000 mg/kg body weight, when female wistar rats 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:
5 000 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from publication.

Additional information

Acute oral toxicity:

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

 

Acute oral toxicity study was conducted by using test chemical in rats at the dose concentration of 4590 mg/kg bw via oral route. Observation for mortality was made. 50% mortality was observed at 4590 mg/kg bw. Hence, the LD50 value was considered to be 4590 mg/kg bw, when rats was treated with the given test chemical via oral route.

 

The acute oral toxicity study was also conducted by using test chemical in 10 mice at the dose concentration of 6657 mg/kg bw via oral route. Observation for mortality was made. 50% mortality was observed at 6657 mg/kg bw. Hence, the LD50 value was considered to be 6657 ± 652 mg/kg bw, when 10 mice were treated with the given test chemical via oral route.

 

Yet another acute oral toxicity study was conducted by using test chemical in 10 mice at the dose concentration of 7000 mg/kg bw via oral route. Observation for mortality was made. 50% mortality was observed at 7000 mg/kg bw. Hence, the LD50 value was considered to be 7000 mg/kg bw, when 10 mice were treated with the given test chemical via oral route.

 

These studies are further supported with the study mentioned in peer-reviewed journal for the test chemical. The acute oral toxicity study was conducted by using test chemical in 10 rats at the dose concentration of 5000 mg/kg bw via oral gavage route. Observations for mortality and/or systemic effects were made over a 14-day period. No mortality was observed at 5000 mg/kg bw. Hence, the LD50 value was considered to be >5000 mg/kg bw, when 10 rats were treated with the given test chemical via oral gavage route.

 

Another acute oral toxicity study of the given test chemical was performed as per OECD 423 guideline in 6 female wistar rats. The test material dissolved in corn oil. The volume was made up to 10 ml to achieve the appropriate concentrations. The dosing solution was prepared fresh, prior to dose administration and given in dose concentration 2000 mg/kg bw by oral gavage route. The animals were fasted for minimum 16-18 hours prior to dosing and for 3-4 hours post dosing, with food withheld but drinking water provided ad libitum. The time intervals between dosing were determined by the onset, duration and severity of toxic signs. Three rats of first group were dosed with starting dose of 2000 mg/kg body weight and the animals did not show any mortality so another three animals of the same group were dosed with 2000 mg/kg body weight and no mortality was observed. Hence, further dosing was stopped. Body weights were re­corded on day 0 (prior to dosing) 7 and 14. Body weight gain was observed in all surviving animals treated with 2000 mg/kg body weight, during the 14 day observation period, as compared to day 0. At 2000 mg/kg, animal nos. 1, 4, 5 and 6 were observed normal at 30 minutes, 1 hour, on day 1 to 14 post dosing and moderate to mild lethargy was observed at 2, 3 and 4 hours post dosing. Animal nos. 2 and 3 were observed normal at 30 minutes, 1 hour, on day 1 to 14 post dosing and mild lethargy was observed at 2, 3 and 4 hours post dosing. No external and internal gross pathological changes were seen in the animals treated with 2000 mg/kg body weight during terminal sacrifice. Hence, the LD50 value was considered to be >2000 mg/kg body weight, when female wistar rats were treated with the given test chemical orally.

 

Thus, based on the above summarised studies on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute oral toxicity.

 

Acute Inhalation Toxicity:

The acute inhalation toxicity study need not be conducted because exposure to humans via inhalation route is not likely taking into account due to the low vapour pressure of the test chemical, which is reported to be 3.61 Pa (0.0271 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 -

 

Acute dermal toxicity study was conducted by using test chemical in 10 rabbits at the dose concentration of 5000 mg/kg bw by dermal application to abraded rabbit skin. Animals were observed for mortality after application of the test chemical. No mortality was observed at 5000 mg/kg bw. Hence, the LD50 value was considered to be >5000 mg/kg bw, when 10 rabbits were treated with the given test chemical by dermal application to abraded rabbit skin.

 

Acute dermal toxicity study was also conducted by using test chemical in 8 rabbits at the dose concentration of 5000 mg/kg bw. The given test chemical (neat) was applied to intact and abraded skin for 24 h under occlusion. Observations for mortality and systemic effects were made for 14 days after exposure. No mortality was observed at 5000 mg/kg bw. Hence, the LD50 value was considered to be >5000 mg/kg bw, when 8 rabbits were treated with the given test chemical by dermal application occlusively.

 

The above studies are further supported with the study mentioned in report for the test chemical. The acute dermal toxicity study of the given test chemical was performed as per OECD No.402 in Wistar Rats. Five male and five female healthy young adult rats were randomly selected. Rats free from injury and irritation of skin were selected for the study. Twenty four hours prior to dermal application of test item, approximately 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight of test item was applied by single dermal application and observed for 14 days after treatment. On test day 0, as such amount of test item, calculated based on density (0.9407) and body weight was applied directly on the intact skin of clipped area of rats; the surgical gauze patch was put on to the intact skin of clipped area. This gauze patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with non-irritating adhesive tape. After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water. The skin reactions were assessed. The animals were observed daily for mortality and clinical signs, during the acclimatization period. All animals were observed for clinical signs at approximately 1, 2, 3 and 4 hours after treatment on day 0 and once daily during test days 1‑14. Mortality was recorded after application on test day 0 and twice daily during days 1-14 (at least once on the day of sacrifice). Local signs / Skin reactions were observed daily from test days 1-14 (in common with clinical signs). Body weights were re­corded on day 0 (prior to application) and on day 7 and 14. All animals were necropsied and examined macroscopically. No mortality was observed in any animal till the end of the experimental period. No clinical signs and any skin reaction were observed throughout the experimental period in all treated animals. The male and female animals were observed with body weight gain compared to day 0 throughout the experiment. The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality. Hence the LD50 value was considered to be >2000 mg/kg body weight, when female wistar rats 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.