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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
data is from study report

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Principles of method if other than guideline:
Acute Oral toxicity test was carried out to study the effects of test chemical on rats
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
SOURCE OF TEST MATERIAL- Source of test material: Sustainability Support Services (Europe) AB, Sweden - Lot/batch No.of test material: 0015- Expiration date of the lot/batch: 13 Feb.; 2021- Purity test date: No dataRADIOLABELLING INFORMATION (if applicable)- Radiochemical purity: No data- Specific activity: No data- Locations of the label: No data- Expiration date of radiochemical substance: No dataSTABILITY AND STORAGE CONDITIONS OF TEST MATERIAL- Storage condition of test material: Ambient Temperature- Stability under test conditions: No data- Solubility and stability of the test substance in the solvent/vehicle: No data- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No dataTREATMENT OF TEST MATERIAL PRIOR TO TESTING- Treatment of test material prior to testing: Test item was moistened with distilled water before application.- Preliminary purification step (if any):No data- Final dilution of a dissolved solid, stock liquid or gel: No data- Final preparation of a solid: No dataFORM AS APPLIED IN THE TEST (if different from that of starting material) No dataOTHER SPECIFICS:Safety Precautions: Safety precautions included use of protective clothing, gloves, masks and eye protection (glasses).

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: National Institute of Biosciences, Pune.- Females (if applicable) nulliparous and non-pregnant: Yes- Age at study initiation: Female rats of the age of approximately 8 to 12 weeks old were used.- Weight at study initiation: The weights were within ± 20% of the mean weight of any animal used for dosing. Body weight range was 190.1 to 199.9 grams.Body weights at the start :FemaleMean : 193.71 g (= 100 %)Minimum : 190.1 g (- 1.86 %)Maximum : 199.9 g (+ 3.20 %)Total No. of animals : 12- 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): Room temperature was maintained at 20.1 to 22.7 degree centigrade.- Humidity (%): Room humidity was maintained at 55.1% to 61.2%.- Air changes (per hr): The animal room was independently provided with at least ten to fifteen air changes per hour of 100% fresh air that had been passed through the HEPA filters. - Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.IN-LIFE DATES: No data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Distilled water
Details on oral exposure:
VEHICLE- Concentration in vehicle: No data- Amount of vehicle (if gavage): No data- Justification for choice of vehicle: No data- Lot/batch no. (if required): No data- Purity: No dataMAXIMUM DOSE VOLUME APPLIED: 10 ml per kg of body weight was considered the maximum volume which could be administered to a rat.DOSAGE PREPARATION (if unusual): No dataCLASS METHOD (if applicable) No data- Rationale for the selection of the starting dose: No data
Doses:
Dose Group I : 300 mg/kgDose Group II : 2000 mg/kg
No. of animals per sex per dose:
Three females were used at each step.
Control animals:
yes
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.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.
Statistics:
No data

Results and discussion

Preliminary study:
no data
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality was observed
Mortality:
Group I Step I:Animals treated at the dose level of 300 mg/kg body weight: All animals survived through the study period of 14 days.Group I Step II:Animals treated at the dose level of 300 mg/kg body weight: All animals survived through the study period of 14 days.Group II Step I:Animals treated at the dose level of 2000 mg/kg body weight: All animals survived through the study period of 14 days.Group II Step II:Animals treated at the dose level of 2000 mg/kg body weight: All animals 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 resulted in diarrhoea (reddish colour stools) in all animals with onset at 2 hours after the dosing. All animals were free of signs of toxicity on day 1 after the dosing.Group II Step II :Animals treated at the dose level of 2000 mg/kg body weight resulted in diarrhoea (reddish colour stools) in all animals with onset at 2 hours after the dosing. All animals were free of signs of toxicity on day 1 after the dosing.Staining of the stool is attributed to the reddish colour of the test item.
Body weight:
Group I Step I (300 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 3.65% and 12.94% respectively. Group I Step II (300 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 4.44% and 13.52% respectively. Group II Step I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 3.92% and 13.72% respectively. Group II Step II (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 5.06% and 14.58% 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:
No data

Any other information on results incl. tables

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

Diarrhoea

(Reddish colour stools)

3

7,8

9

2 hrs. - 6 hrs.

4 hrs. - 6 hrs.

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

Diarrhoea

(Reddish colour stools)

3

10

11,12

4 hrs. - 6 hrs.

2 hrs. - 6 hrs.

0/3

 

Staining of the stool is attributed to the reddish colour of the test item.

 

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

198.20

205.43

3.65

223.83

8.96

12.94

± SD

1.70

0.91

0.93

1.62

0.45

1.49

 

 

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

193.07

201.63

4.44

219.17

8.70

13.52

± SD

0.74

1.50

0.38

1.25

1.42

1.07

 

 

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

192.03

199.57

3.92

218.37

9.42

13.72

± SD

1.86

1.68

0.28

1.80

1.08

0.98

 

 

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

191.53

201.20

5.06

219.43

9.07

14.58

± SD

1.63

3.04

2.17

1.60

0.88

1.65

 

 

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

Applicant's summary and conclusion

Interpretation of results:
other: not classified
Conclusions:
The lethal concentration (LD50) value for acute oral toxicity test was considered to be >2000 mg/kg bw,when female Sprague Dawley rats were treated with test chemical orally via gavage according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).
Executive summary:

The acute oral toxicity profile of test chemical in Sprague Dawley rats according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).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 resulted in diarrhoea (reddish colour stools) in all animals with onset at 2 hours and no mortality after the dosing. As no mortality were observed at 24 hours after the dosing, hence 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 resulted in diarrhoea (reddish colour stools) in all animals with onset at 2 hours and no mortality after the dosing. All animals from 300 mg/kg and 2000 mg/kg dose groups survived through the study period of 14 days. Staining of the stool is attributed to the reddish colour of the test item. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups.hence, Thelethal concentration (LD50) valuefor acute oral toxicity testwas considered to be >2000mg/kg bw,when female Sprague Dawley rats were treated with test chemical orally via gavage according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).