Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: 

The acute oral toxicity dose (LD50) was considered based on different studies conducted on rats for the given test chemical. The studies 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 0.00479 mmHg. 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:
experimental study
Adequacy of study:
key study
Study period:
09.10.2017 to 20.11.2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Data is from study report.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Principles of method if other than guideline:
The purpose of the study was to access the toxicological profile of test item to a single administration via oral route to Sprague-Dawley rats.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Female rats of the age of approximately 8 to 12 weeks old were used at the commencement of its dosing
- Weight at study initiation: Body weight range was 197.0 to 206.4 grams.
Body weights at the start : Female Mean: 201.73 g (= 100 %); Minimum : 197.0 g (- 2.35 %); Maximum : 206.4 g (+ 2.31 %)
- Identification: Each female rat was individually identified by the picric acid marking.
- Fasting period before study: Approximately 16 hours or more.
- Housing: The rats were housed in polycarbonate cages.
- Diet (e.g. ad libitum): Rodent feed supplied by the Nutrivet Life Sciences, Pune, was provided ad libitum from individual feeders.
- Water (e.g. ad libitum): Water was provided ad libitum from individual bottles attached to the cages. All water was from a local source and passed through the reverse osmosis membrane before use.
- Acclimation period: 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 to 22.0 degree centigrade.
- Humidity (%): 54.4% to 59.8%.
- Air changes (per hr): Ten to fifteen air changes per hour.
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.

IN-LIFE DATES: 24-10-2017 to 12-11-2017
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 300 mg/kg, 300 mg/kg, 2000 mg/kg and 2000 mg/kg

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg body weight.

DOSAGE PREPARATION (if unusual): The dose of 300 mg/kg of the test item was prepared by dilution of the test item in corn oil to obtain 30 mg/ml strength of solution. The formulation was prepared fresh on the day of dosing. The test item was administered in the dose volume of 10 ml/kg body weight.
Doses:
Group I:
Step I: 300 mg/kg bw
Step II: 300 mg/kg bw
Group II:
Step I: 2000 mg/kg bw
Step II: 2000 mg/kg bw
No. of animals per sex per dose:
Total:12 females (3/dose)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical Observations and General Appearance: Animals were observed for clinical signs, mortality and morbidity, until sacrifice. Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at immediately (0 to 5 minutes), 5, 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily thereafter for 14 day. Daily observation was done as far as possible at the same time. The observations were included general clinical signs, observations of eyes, mucous membranes, respiratory, circulatory system and behavior pattern.

Body weights: Individual animal body weights were recorded, before fasting, prior to administration of the test item (fasting body weights), weekly thereafter and at termination on day 14. Weight changes were calculated and recorded.

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

Histopathology: No gross abnormalities were observed in animals sacrificed terminally hence, no histopathology was performed.
Statistics:
not specified
Preliminary study:
not specified
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Group I Step I : Animals treated at the dose level of 300 mg/kg body weigh survived through the study period of 14 days.
Group I Step II : Animals treated at the dose level of 300 mg/kg body weight survived through the study period of 14 days.
Group II Step I : Animals treated at the dose level of 2000 mg/kg body weight survived through the study period of 14 days.
Group II Step II : Animals treated at the dose level of 2000 mg/kg body weight survived through the study period of 14 days.
Clinical signs:
Group I Step I : Animals treated at the dose level of 300 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days.
Group I Step II : Animals treated at the dose level of 300 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days.
Group II Step I : Animals treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days.
Group II Step II : Animals treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days.
Body weight:
Group I Step I (300 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 6.22% and 13.55% respectively.
Group I Step II (300 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 7.33% and 14.87% respectively.
Group II Step I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 6.62% and 14.92% respectively.
Group II Step II (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 6.95% and 15.81% respectively.
Gross pathology:
Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups.
Other findings:
not specified

Table No. I

Summary of Clinical Signs of Toxicity and Mortality

Test System : Sprague Dawley Rat

Sex : Female

Group I :   

Step

No.

Dose mg/kg

Observed Signs

Total Number of

Animals

Animal Nos.

Period of signs in days

From - to

Mortality

I

300

No clinical signs observed

3

1,2,3

Day 0 - Day 14

0/3

 

Group I :

Step

No.

Dose mg/kg

Observed Signs

Total Number of

Animals

Animal Nos.

Period of signs in days

From - to

Mortality

II

300

No clinical signs observed

3

4,5,6

Day 0 - Day 14

0/3

 

Group II :

Step

No.

Dose mg/kg

Observed Signs

Total Number of

Animals

Animal Nos.

Period of signs in days

From - to

Mortality

I

2000

No clinical signs observed

3

7,8,9

Day 0 - Day 14

0/3

 

Group II :

Step

No.

Dose mg/kg

Observed Signs

Total Number of

Animals

Animal Nos.

Period of signs in days

From - to

Mortality

II

2000

No clinical signs observed

3

10,11,

12

Day 0 - Day 14

0/3

 

Table No.II

Mean Body Weight and Percent Body Weight Gain (g)

Test System : Sprague Dawley Rat

Sex : Female

Group I :

Step

No.

Dose

(mg/kg body weight)

 

Before Fasting Body weight

Body weight Day 7

% body weight gain

day 0-7

Body weight Day 14

% body weight gain

day 7- 14

% body weight gain

day 0- 14

I

300

Mean

201.97

214.53

6.22

229.33

6.90

13.55

± SD

3.03

2.70

0.28

3.56

0.37

0.10

 

 

Group I :

Step

No.

Dose

(mg/kg body weight)

 

Before Fasting Body weight

Body weight Day 7

% body weight gain

day 0-7

Body weight Day 14

% body weight gain

day 7- 14

% body weight gain

day 0- 14

II

300

Mean

202.10

216.90

7.33

232.13

7.03

14.87

± SD

4.40

4.12

0.44

3.55

0.48

0.96

 

 

Group II :

Step

No.

Dose

(mg/kg body weight)

 

Before Fasting Body weight

Body weight Day 7

% body weight gain

day 0-7

Body weight Day 14

% body weight gain

day 7- 14

% body weight gain

day 0- 14

I

2000

Mean

201.00

214.30

6.62

231.00

7.79

14.92

± SD

3.95

4.33

0.31

5.12

0.51

0.88

 

 

Group II :

Step

No.

Dose

(mg/kg body weight)

 

Before Fasting Body weight

Body weight Day 7

% body weight gain

day 0-7

Body weight Day 14

% body weight gain

day 7- 14

% body weight gain

day 0- 14

II

2000

Mean

201.87

215.90

6.95

233.80

8.29

15.81

± SD

2.67

3.65

0.42

4.75

0.37

0.85

 

 

Table No.III

Summary of Gross Pathological Findings

Test System : Sprague Dawley Rat

Sex : Female

Group I :

 

Step

No.

Dose

mg/kg

Animal Numbers

Animal Fate

Gross Pathological Findings

I

300

1 - 3

TS

No abnormality detected

 

       

 Group I :

Step

No.

Dose

mg/kg

Animal Numbers

Animal Fate

Gross Pathological Findings

II

300

4 - 6

TS

No abnormality detected

 

 Group II :

Step No.

Dose

mg/kg

Animal Numbers

Animal Fate

Gross Pathological Findings

I

2000

7 - 9

TS

No abnormality detected

 

             

 Group II :

Step No.

Dose

mg/kg

Animal Numbers

Animal Fate

Gross Pathological Findings

II

2000

10 - 12

TS

No abnormality detected

               

TS = Terminal Sacrifice

Interpretation of results:
other: Not classified
Conclusions:
Under the condition of the study, the acute oral LD50 value was considered to be >2000 mg/kg body weight, when Sprague Dawley rats were treated with the given test chemical via oral route. Thus, it falls into the “Category Not classified” as per the criteria of CLP.
Executive summary:

The reported study was designed and conducted to determine the acute oral toxicity profile as per OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method) by using the given test chemical in Sprague Dawley rats. Initially, three female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality after the dosing. No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. As no mortality were observed at 24 hours after the dosing, additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - II). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups.

Under the condition of the study, the acute oral LD50 value was considered to be >2000 mg/kg body weight, when Sprague Dawley rats were treated with the given test chemical via oral route. Thus, it falls into the “Category Not classified” as per the criteria of CLP.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Data is Klimisch 1 and from study report.

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:
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:
experimental study
Adequacy of study:
key study
Study period:
09.10.2017 to 28.12.2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Data is from study report.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
This study was designed to determine the dermal LD50 of the test item (up to 2000 mg/kg bw) or to establish a non-lethal dose level of 2000 mg/kg.
GLP compliance:
yes
Test type:
other: Acute dermal toxicity
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Young adult (8 to 10 weeks old) female rats were used.
- Weight at study initiation: The weight range of approximately 22.8 to 242.1 grams at initiation of dosing.
Body weights at the start : Female - Mean: 232.68 g (= 100 %); Minimum : 222.8 g (- 4.25 %); Maximum : 242.1 g (+ 4.04 %)
- 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 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): 19.2 to 21.8 degree centigrade.
- Humidity (%): 56.0% to 59.1%.
- 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: 31-10-2017 to 28-12-2017
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: the trunk (dorsal surface and sides from scapular to pelvic area)
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: The test item was held in contact with the skin using a porous gauze dressing and non irritating tape around the animal to cover the exposure site. Elizabethan collar was placed on each animal for first 24 hours after application of the test item. These collars prevent ingestion of test item.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The wrapping was removed and the test site wiped free of excess test item. Distilled water was used to remove residual test item.
- Time after start of exposure: 24 hours
Duration of exposure:
24 hours
Doses:
Dose range finding study:
Group I: 200, 1000 and 2000 mg/kg bw
Main study:
Group II: 2000 mg/kg bw
No. of animals per sex per dose:
Total: 5 females
Group I: 3 females, 1female/dose
Group II: 2 females/ dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily
- Necropsy of survivors performed: yes, 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).
- 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 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.
Histopathology: No gross abnormalities were observed in animals sacrificed terminally hence, no histopathology was performed.
Statistics:
not specified
Preliminary study:
Dose range finding study: A single dose of 200 mg/kg bw of the test item was administered to 1 female animal. No death or clinical signs of toxicity was observed during first 48 hours, hence, addtional 1 female animal was administered at the dosr 1000 mg/kg bw. Administration of 1000 mg/kg bw 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 bw. Administration of 2000 mg/kg bw did not reveal any clinical signs of toxicity or death during first 48 hours.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Dose Range Finding Study: All animals survived through the study period of 14 days at 200 mg/kg, 1000 mg/kg and 2000 mg/kg body weight .
Main Study: Group II : All animals survived through the study period of 14 days.
Clinical signs:
Dose Range Finding Study: Animals treated at the dose level of 200 mg/kg, 1000 mg/kg and 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.
Body weight:
Dose Range Finding Study: Group I (200 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 6.51% and 11.18% respectively.
Group I (1000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 5.46% and 7.43% respectively.
Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 5.22% and 9.19% respectively.
Main Study: Group II (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 4.77% and 8.31% respectively.
Gross pathology:
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.
Other findings:
Evaluation of Dermal Reaction -
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.

Table No. I

Summary of Clinical Signs of Toxicity and Mortality

 

Laboratory Test Item Code :TAS/122/065

Test System : Sprague Dawley Rat

Sex : Female

Dose Finding Study:

Group

 No.

Dose mg/kg

                            Observed Signs

Total Number of

Animals

 

Animal Nos.

Period of signs in days

 From - to

 

Mortality

I

200

No clinical signs observed

1

1

Day 0 - Day 14

0/1

 

Group

 No.

Dose mg/kg

                            Observed Signs

Total Number of

Animals

 

Animal Nos.

Period of signs in days

 From - to

 

Mortality

I

1000

No clinical signs observed

1

2

Day 0 - Day 14

0/1

 

Group

 No.

Dose mg/kg

                            Observed Signs

Total Number of

Animals

 

Animal Nos.

Period of signs in days

 From - to

 

Mortality

I

2000

No clinical signs observed

1

3

Day 0 - Day 14

0/1

 

Main Study:

Group

 No.

Dose mg/kg

                            Observed Signs

Total Number of

Animals

 

Animal Nos.

Period of signs in days

 From - to

 

Mortality

II

2000

No clinical signs observed

2

4, 5

Day 0 - Day 14

0/2

Table No. II 

Summary of Evaluation of Dermal Reaction

 

Laboratory Test Item Code :TAS/122/065

Test System : Sprague Dawley Rat

Sex : Female

Dose Finding Study:

Group

 No.

Dose mg/kg

                          

Dermal Reaction

Total Number of

Animals

Animal Nos.

Period of signs

in days

 From - to

I

200

No dermal reaction observed

1

1

Day 0 - Day 14

 

Group

 No.

Dose mg/kg

                          

Dermal Reaction

Total Number of

Animals

Animal Nos.

Period of signs

in days

 From - to

I

1000

No dermal reaction observed

1

2

Day 0 - Day 14

 

Group

 No.

Dose mg/kg

                          

Dermal Reaction

Total Number of

Animals

Animal Nos.

Period of signs

in days

 From - to

I

2000

No dermal reaction observed

1

3

Day 0 - Day 14

 

Main Study:

Group

 No.

Dose mg/kg

                          

Dermal Reaction

Total Number of

Animals

Animal Nos.

Period of signs

in days

 From - to

II

2000

No dermal reaction observed

2

4, 5

Day 0 - Day 14

 

Table No.III

Mean Body Weight and Percent Body Weight Gain (g)

 

Laboratory Test Item Code :TAS/122/065

Test System : Sprague Dawley Rat

Sex : Female

Dose Finding Study:

Group No.

Dose

(mg/kg body weight)

 

Body weight Day 0

Body weight Day 7

% body weight gain

day 0-7

Body weight Day 14

% body weight gain

day 7- 14

% body weight gain

day 0- 14

I

200

Mean

222.8

237.3

6.51

247.7

4.38

11.18

± SD

-

-

-

-

-

-

 

Group No.

Dose

(mg/kg body weight)

 

Body weight Day 0

Body weight Day 7

% body weight gain

day 0-7

Body weight Day 14

% body weight gain

day 7- 14

% body weight gain

day 0- 14

I

1000

Mean

232.7

245.4

5.46

250.0

1.87

7.43

± SD

-

-

-

-

-

-

 

Group No.

Dose

(mg/kg body weight)

 

Body weight Day 0

Body weight Day 7

% body weight gain

day 0-7

Body weight Day 14

% body weight gain

day 7- 14

% body weight gain

day 0- 14

I

2000

Mean

224.1

235.8

5.22

244.7

3.77

9.19

± SD

-

-

-

-

-

-

Main Study:

Group No.

Dose

(mg/kg body weight)

 

Body weight Day 0

Body weight Day 7

% body weight gain

day 0-7

Body weight Day 14

% body weight gain

day 7- 14

% body weight gain

day 0- 14

II

2000

Mean

241.90

253.45

4.77

262.00

3.37

8.31

± SD

0.28

0.21

0.03

0.28

0.20

0.24

Table No.IV

Summary of Gross Pathological Findings

 

Laboratory Test Item Code :TAS/122/065

Test System : Sprague Dawley Rat

Sex : Female

Dose Finding Study:

Group No.

Dose

mg/kg

Animal Numbers

Animal Fate

Gross Pathological Findings

I

200

1

TS

No abnormality detected

 

Group No.

Dose

mg/kg

Animal Numbers

Animal Fate

Gross Pathological Findings

I

1000

2

TS

No abnormality detected

 

Group No.

Dose

mg/kg

Animal Numbers

Animal Fate

Gross Pathological Findings

I

2000

3

TS

No abnormality detected

 

                    Main Study:

Group No.

Dose

mg/kg

Animal Numbers

Animal Fate

Gross Pathological Findings

II

2000

4, 5

TS

No abnormality detected

 

                     TS = Terminal Sacrifice

Interpretation of results:
other: Not classified
Conclusions:
It was concluded that the acute dermal median lethal dose (LD50) of the given test chemical, when administered to 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”.
Executive summary:

The reported study was designed and conducted to determine the acute dermal toxicity profile as per OECD Guideline 402 (Acute Dermal Toxicity) by using the given test chemical in 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.

It was concluded that the acute dermal median lethal dose (LD50) of the given test chemical, when administered to 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”.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Data is Klimisch 1 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 the given test chemical. The studies are summarized as below –

 

The reported study was mentioned in study report and conducted to determine the acute oral toxicity profile as per OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method) by using the given test chemical in Sprague Dawley rats.

Initially, three female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality after the dosing. No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. As no mortality were observed at 24 hours after the dosing, additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - II). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups.

Under the condition of the study, the acute oral LD50 value was considered to be >2000 mg/kg body weight, when Sprague Dawley rats were treated with the given test chemical via oral route. Thus, it falls into the “Category Not classified” as per the criteria of CLP.

 

The above study is supported with another study mentioned in different publications and research article for the given test chemical. The acute oral toxicity study was conducted in rats at the dose concentration of 5000 mg/kg bw. Animals were observed for mortality. No mortality was observed at 5000 mg/kg bw. Hence, the acute oral toxicity dose (LD50) value was considered to be >5000 mg/kg bw, when rats were treated with the given test chemical via oral route.

 

These studies are further supported with the data available in authoritative database and secondary report for the given test chemical. The acute oral toxicity study was conducted in male rats at the dose concentration of 4300 mg/kg bw. The test chemical was dissolved in corn oil and administered via oral route. Animals were observed for mortality. No mortality was observed at 4300 mg/kg bw. Hence, the acute oral toxicity dose determined by APPROXIMATE LETHAL DOSE (ALD) was considered to be >4300 mg/kg bw, when male rats were 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 >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 0.00479 mmHg. 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 the acute dermal toxicity profile as per OECD Guideline 402 (Acute Dermal Toxicity) by using the given test chemical in 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.

It was concluded that the acute dermal median lethal dose (LD50) of the given test chemical, when administered to 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”.

 

This study is supported with the data mentioned in research article and peer-reviewed journal and the study was conducted by using the given test chemical in rabbits at the dose concentration of 5000 mg/kg bw. Animals were observed for mortality. No mortality was observed at 5000 mg/kg bw. Hence, the acute dermal toxicity dose (LD50) value was considered to be >5000 mg/kg bw, when rabbits were treated with the given test chemical by dermal route.

 

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 for the test chemical, it can be concluded that LD50 value is >2000 mg/kg bw, for acute oral toxicity and acute dermal toxicity. Thus, comparing these values 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.