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Description of key information

Acute oral toxicity: 

Acute oral toxicity dose (LD50) was considered based on experimental study conducted on rats for the given test chemical. The LD50 value was considered in between 300-2000 mg/kg bw. Thus, comparing this range with the criteria of CLP regulation, the given test chemical can be classified in “Category 4” for acute oral toxicity.

Acute Inhalation toxicity: 

Acute Inhalation toxicity dose (LC50) was considered based on different studies conducted on mice and rats for the test chemical. The LC50 value was considered to be >1300 mg/L (i.e. >1300000 mg/m3). The study concluded that the LC50 value is >5 mg/L air. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute Inhalation toxicity.

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 >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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Data is from experimental study report.
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Principles of method if other than guideline:
The purpose of this study was to assess the Toxicological profile of test item to a single administration via oral route to Sprague Dawley rats. This study was designed to determine the acute toxicity at fixed dose levels by oral route of the test item.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system 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 197.5 to 205.2 grams.
Body weights at the start : Female Mean: 200.84 g (= 100 %); Minimum : 197.5 g (- 1.67 %); Maximum : 205.2 g (+ 2.17 %)
- 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): 20.0 to 22.0 degree centigrade.
- Humidity (%): 54.4% to 59.3%
- Air changes (per hr): 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: 13-10-2017 to 30-10-2017
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 300 mg/kg, 300 mg/kg and 2000 mg/kg
MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg body weight
Doses:
Dose Group I - 300 mg/kg
Dose Group I - 300 mg/kg
Dose Group I - 300 mg/kg
Dose Group II - 2000 mg/kg
No. of animals per sex per dose:
Three females were used at each step.
Control animals:
not specified
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 all animals, found dead and sacrificed 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 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.
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:
> 300 - <= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Group I Step I : Animals treated at the dose level of 300 mg/kg survived through the study period of 14 days.
Group I Step II : Animals treated at the dose level of 300 mg/kg survived through the study period of 14 days.
Group II Step I : Two animals died at 6 hours and one animal died on day 1 after the dosing at 2000 mg/kg.
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 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 reduced locomotor activity, ataxic gait and loss of righting reflex with onset at 10 minutes to 4 hours after the dosing.
Body weight:
Group I Step I (300 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 6.68% and 14.38% respectively.
Group I Step II (300 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 6.99% and 15.20% respectively.
Group II Step I (2000 mg/kg) - All animals died within 24 hours, hence, body weight gain could not be calculated.
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

 

Laboratory Test Item Code :TAS/122/053

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

Reduced locomotor activity

3

7,8

9

10 min. - 4 hrs.

10 min. - 6 hrs.

3/3

Ataxic gait

3

7,8

9

1 hr. - 4 hrs.

1 hr. - 6 hrs.

Loss of righting reflex

3

7

8

9

4 hrs.

1 hr. - 4 hrs.

2 hrs. - 6 hrs.

 

Table No.II

Mean Body Weight and Percent Body Weight Gain (g)

 

Laboratory Test Item Code :TAS/122/053

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

200.53

213.93

6.68

229.37

7.21

14.38

± SD

4.09

4.31

0.14

4.58

0.45

0.62

 

 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

200.50

214.50

6.99

230.97

7.67

15.20

± SD

2.86

2.49

1.32

3.36

0.33

1.43

  

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

201.50

-

-

-

-

-

± SD

3.45

-

-

-

-

-

 

Table No.III

Summary of Gross Pathological Findings

 

Laboratory Test Item Code :TAS/122/053

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

FD

No abnormality detected

 

                     FD = Found dead

                    TS = Terminal Sacrifice

 

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the condition of the study, the acute oral LD50 value of the given test chemical was considered in between 300-2000 mg/kg body weight. Thus, it was concluded that the acute toxicity study of test chemical, when administered via oral route in Sprague Dawley rats falls into the “Category 4” according to criteria of CLP.
Executive summary:

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

Initially, three female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality after the dosing.

No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg resulted in reduced locomotor activity, ataxic gait and loss of righting reflex with onset at 10 minutes to 4 hours after the dosing. Two animals died at 6 hours and one animal died on day 1 after the dosing.

All animals from 300 mg/kg dose group survived and exhibited normal body weight gain through the study period of 14 days. 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 of the given test chemical was considered in between 300-2000 mg/kg body weight. Thus, it was concluded that the acute toxicity study of test chemical, when administered via oral route in Sprague Dawley rats falls into the “Category 4” according to criteria of CLP.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 000 mg/kg bw
Quality of whole database:
Data is Klimisch 1 and study report.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
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 peer reviewed journal
Qualifier:
according to guideline
Guideline:
other: as mentioned below
Principles of method if other than guideline:
An acute inhalation study was carried out on guinea pigs to estimate the inhalation toxicity of ketonic vapors
GLP compliance:
no
Test type:
other: No data
Limit test:
no
Specific details on test material used for the study:
- Name of test material: 2-octanone
- IUPAC name: octan-2-one
- Molecular formula: C8H16O
- Molecular weight: 128.2134 g/mol
- Substance type: Organic
- Physical state: Liquid
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
No data
Route of administration:
inhalation
Type of inhalation exposure:
other: saturated atmosphere
Vehicle:
not specified
Details on inhalation exposure:
Guinea-pig was exposed to an essentially saturated atmosphere (1300 ppm)
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
14 h
Concentrations:
1300 mg/L
No. of animals per sex per dose:
No data available
Control animals:
not specified
Details on study design:
Details on study design
Duration of observation period following administration: 14 days (or other?): clinical signs, behavioral changes were examined.
Statistics:
No data available
Preliminary study:
No data available
Key result
Sex:
not specified
Dose descriptor:
LC50
Effect level:
> 1 300 mg/L air
Based on:
test mat.
Exp. duration:
14 h
Remarks on result:
other: no other details specified
Key result
Sex:
not specified
Dose descriptor:
LC0
Effect level:
1 300 mg/L air
Based on:
test mat.
Exp. duration:
14 h
Remarks on result:
other: No mortality observed
Mortality:
No mortality was observed in treated guinea pig till 1300 mg/L, LC50 was considered as > 1300 mg/L
Clinical signs:
other: Nasal irritation developed immediately after the guinea-pig was exposed to an essentially saturated atmosphere (1300 mg/lt) This was followed by muscular weakness after exposure for approximately 10 hr and by coma after approximately 12 hr
Body weight:
No data available
Gross pathology:
No data available
Other findings:
No data available
Interpretation of results:
other: Not classified
Conclusions:
As no mortality was observed in treated guinea pig till 1300 mg/L of exposed test chemical for 14 hrs, the acute inhalation LC50 was considered as > 1300 mg/L (i.e. 1300000 mg/m3).
Executive summary:

In a acute inhalation toxicity study, guinea pig were exposed with test chemical in the concentration of 1300 mg/L in saturated atmosphere for 14 hours. No mortality was observed in treated guinea pig at 1300 mg/L and Nasal irritation developed immediately after the guinea-pig was exposed to an essentially saturated atmosphere (1300 mg/lt). This was followed by muscular weakness after exposure for approximately 10 hr and by coma after approximately 12 hr. As no mortality was observed in treated guinea pig till 1300 mg/L of exposed test chemical, acute inhalation LC50 was considered as > 1300 mg/L.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
1 300 000 mg/m³
Quality of whole database:
Data is Klimisch 2 and from peer reviewed journal.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Data is from experimental study report.
Qualifier:
according to guideline
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) or to establish a non-lethal dose level of 2000 milligram of test item per kilogram of body weight.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system 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 221.9 to 250.8 grams at initiation of dosing.
Body weights at the start : Female Mean: 234.08 g (= 100 %); Minimum : 221.9 g (- 5.20 %); Maximum : 250.8 g (+ 7.14 %)
- 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): 19.2 to 21.8 degree centigrade.
- Humidity (%): 56.0% to 59.1%.
- 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: 11-09-2017 to 24-11-2017
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal surface and sides from scapular to pelvic area
- % coverage: at least 10% of the 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 for first 24 hours exposure period. 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 mg/kg
Group I : 1000 mg/kg
Group I : 2000 mg/kg
Main Study:
Group II : 2000 mg/kg
No. of animals per sex per dose:
Total No. of animals : 5
Control animals:
not specified
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 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 at 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.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Dose Range Finding Study: The animals survived through the study period of 14 days treated at the dose level of 200 mg/kg, 1000 mg/kg and 2000 mg/kg.
Main Study: All animals survived through the study period of 14 days treated at the dose level of 2000 mg/kg body weight.
Clinical signs:
Dose Range Finding Study: Animal treated at the dose level of 200 mg/kg, 1000 mg/kg and 2000 mg/kg did not result in any signs of toxicity during the study period of 14 days.
Main Study: 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 6.75% and 10.88% respectively.
Group I (1000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 6.35% and 11.81% respectively.
Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 4.75% and 9.72% respectively.
Main Study: Group II (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 3.82% and 8.28% 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: Animal treated at the dose level of 200 mg/kg, 1000 mg/kg and 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.
Main Study: 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/122/053

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/122/053

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/122/053

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

225.1

240.3

6.75

249.6

3.87

10.88

± 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

221.9

236.0

6.35

248.1

5.13

11.81

± 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

225.4

236.1

4.75

247.3

4.74

9.72

± 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

249.00

258.50

3.82

269.60

4.29

8.28

± SD

2.55

1.13

0.61

1.27

0.04

0.60

 

Table No.IV

Summary of Gross Pathological Findings

 

Laboratory Test Item Code :TAS/122/053

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 of the given test chemical as per OECD Guideline 402 (Acute Dermal Toxicity) 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
Value:
2 000 mg/kg bw
Quality of whole database:
Data is Klimisch 1 and study report.

Additional information

Acute oral toxicity:

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

Initially, three female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality after the dosing.

No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg resulted in reduced locomotor activity, ataxic gait and loss of righting reflex with onset at 10 minutes to 4 hours after the dosing. Two animals died at 6 hours and one animal died on day 1 after the dosing.

All animals from 300 mg/kg dose group survived and exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups.

Thus, based on the above summarised study on test chemical, all rats were died at 2000 mg/kg bw, hence the LD100 was considered to be 2000 mg/kg bw. Considering this value, the LD50 value can be assumed to be 1000 mg/kg bw. Therefore, comparing this value with the criteria of CLP regulation, the given test chemical can be classified in “Category 4 (300 – ≤ 2000)” for acute oral toxicity.

Acute Inhalation Toxicity:

In different studies, the given test chemical has been investigated for acute inhalation 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 -

 

In an acute inhalation toxicity study, guinea pigs were exposed with the given test chemical in the concentration of 1300 mg/L in saturated atmosphere for 14 hours. No mortality was observed in treated guinea pig at 1300 mg/L and Nasal irritation developed immediately after the guinea-pig was exposed to an essentially saturated atmosphere (1300 mg/lt). This was followed by muscular weakness after exposure for approximately 10 hr and by coma after approximately 12 hr. As no mortality was observed in treated guinea pig till 1300 mg/L of exposed test chemical, acute inhalation LC50 was considered as > 1300 mg/L.

 

The above study is further supported with the study mentioned in databases for the test chemical. In an acute inhalation test, rats were inhaled with the given test chemical in the concentration of 2132 mg/L for 6 hours. No mortality was observed in treated rats at 2132 mg/L. Therefore, LC50 was considered to be > 2132 mg/ when rats were inhaled by test chemical for 6 hours.

 

Both the above studies are further supported with the study mentioned in database for the test chemical. An acute inhalation study was carried out on mouse at the dose concentration of 102000 mg/m3. 50 % mortality was observed at 102000 mg/m3 when mice were treated with test chemical. Therefore, the LC50 was considered to be 102000 mg/m3 when mice were inhaled by test chemical.

 

Thus, based on the above summarised studies on the test chemical, it can be concluded that LC50 value is >5 mg/L air. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute inhalation toxicity.

 

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.

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”.

 

The above study is supported with the study mentioned in publication for the test chemical. In an acute dermal toxicity study, rabbits were treated with test chemical in the concentration of 5000 mg/kg bw by dermal application. No mortality was observed in treated rabbits at 5000 mg/kg bw. Therefore, LD50 was considered to be >5000 mg/kg bw when rabbits were treated with test chemical by dermal application.

 

Thus, based on the above summarised studies on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw. 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; LC50 value is >5 mg/L air, for acute inhalation toxicity; and LD50 value is >2000 mg/kg bw, for acute dermal toxicity. Thus, comparing these values and range with the criteria of CLP regulation, the given test chemical can be classified in “Category 4 (300 – ≤ 2000)” for acute oral toxicity and cannot be classified for acute inhalation and acute dermal toxicity.