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Administrative data

Description of key information

Acute oral toxicity: 

The acute oral toxicity dose (LD50) was considered based on experimental study conducted on rats for the test chemical. 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 the low vapour pressure of the test chemical, which is reported to be 0.02055169 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 experimental study conducted on rats 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 (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 at the commencement of its dosing.
- Weight at study initiation: Body weight range was 195.3 to 207.0 grams.
Body weights at the start : Female Mean: 199.64 g (= 100 %); Minimum : 195.3 g (- 2.17 %); Maximum : 207.0 g (+ 3.69 %)
- 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): 20.1 to 22.2 degree centigrade.
- Humidity (%): 56.1% to 61.1%.
- 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: 10-07-2017 to 29-07-2017
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
(Distilled water)
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.
Doses:
Dose Group I : 300 mg/kg
Dose Group I : 300 mg/kg
Dose Group II : 2000 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
- 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 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 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 9.14% and 19.17% respectively.
Group I Step II (300 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 4.89% and 15.45% respectively.
Group II Step I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 8.18% and 16.68% respectively.
Group II Step II (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 6.93% and 15.12% 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

199.13

217.37

9.14

237.33

9.20

19.17

± SD

4.07

6.86

1.29

6.09

0.85

0.63

 

 

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

196.87

206.50

4.89

227.30

10.06

15.45

± SD

1.56

5.00

1.95

7.23

1.02

3.14

 

 

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

198.47

214.73

8.18

231.60

7.86

16.68

± SD

1.80

6.03

2.06

6.09

0.83

2.05

 

 

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

204.10

218.27

6.93

235.00

7.66

15.12

± SD

3.31

6.17

1.31

7.35

0.73

1.89

 

 

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 of the given test chemical was considered to be >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 Not classified” 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 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 of the given test chemical was considered to be >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 Not classified” criteria of CLP.

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 from study report.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Quality of whole database:
Waiver

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
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:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Age at study initiation: Young adult male and female rats aged between 8 – 12 weeks were used.
- Weight at study initiation: The weight range of approximately 217.8 to 251.8 grams at initiation of dosing.
Body weights at the start : Male Mean : 246.46 g (= 100 %); Minimum : 238.5 g (- 3.23 %); Maximum : 251.8 g (+ 2.17 %)
Female Mean: 221.36 g (= 100 %); Minimum : 217.8 g (- 1.61 %); Maximum : 224.3 g (+ 1.33 %)
- 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): 20.1 to 22.3 degree centigrade.
- Humidity (%): 54.8% to 58.8%.
- 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: 18-07-2017 to 02-08-2017
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Trunk (dorsal surface and sides from scapular to pelvic area)
- % coverage: Approximately 10% of the body surface area.
- Type of wrap if used: Porous gauze dressing and non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Distilled water was used to remove residual test item.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
Duration of exposure:
24 hours
Doses:
A single dose of 2000 mg of the test item per kilogram of body weight was administered to ten rats (five males and five females).
No. of animals per sex per dose:
10 (5/sex).
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
- Other examinations performed: Clinical Observations and General Appearance: Animals were observed for clinical signs, mortality, until sacrifice.
Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily thereafter for 14 day. Daily observation was done as far as possible at the same time.
The observations were included general clinical signs, observations of eyes, mucous membranes, respiratory, circulatory system and behavior pattern.

Evaluation of Dermal Reaction: Dermal reaction was observed daily for study period of 14 days.

Body weights: Individual animal body weights were recorded pre-test (prior to administration of the test item), day 7 and at termination on day 14.

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

Histopathology: No gross abnormalities were observed in animals sacrificed terminally hence, no histopathology was performed.
Statistics:
not specified
Preliminary study:
not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Sex : Male Group I - Animal treated at the dose level of 2000 mg/kg body weight: All animals survived through the study period of 14 days.
Sex : Female Group I - Animal treated at the dose level of 2000 mg/kg body weight: All animals survived through the study period of 14 days.
Clinical signs:
Sex : Male Group I - Animal treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days.
Sex : Female Group I - Animal treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days.
Body weight:
Sex : Male Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 8.14% and 16.70% respectively.
Sex : Female Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 4.74% and 9.61% respectively.
Gross pathology:
Gross pathological examination did not reveal any abnormalities in animals from 2000 mg/kg dose group.
Other findings:
- Other observations: Evaluation of Dermal Reaction
Sex : Male Group I - Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.
Sex : Female Group I - Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.

Table No. I

Summary of Clinical Signs of Toxicity and Mortality

Test System : Sprague Dawley Rat

Sex : Male

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

5

1 - 5

Day 0 - Day 14

0/5

 

Sex : Female

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

5

6 - 10

Day 0 - Day 14

0/5

 

 

 Table No. II

Summary of Evaluation of Dermal Reaction

Test System : Sprague Dawley Rat

Sex : Male 

Group

 No.

Dose mg/kg

                          

Dermal Reaction

Total Number of

Animals

 

Animal Nos.

Period of signs

in days

 From - to

 

Mortality

I

2000

No dermal reaction observed

5

1 - 5

Day 0 - Day 14

0/5

 

Sex : Female

 

Group

 No.

Dose mg/kg

                          

Dermal Reaction

Total Number of

Animals

 

Animal Nos.

Period of signs

in days

 From - to

 

Mortality

I

2000

No dermal reaction observed

5

6 - 10

Day 0 - Day 14

0/5

 

 

Table No.III

Mean Body Weight and Percent Body Weight Gain (g)

Test System : Sprague Dawley Rat

Sex : Male

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

246.46

266.50

8.14

287.54

7.91

16.70

± SD

5.29

4.67

1.08

3.15

1.48

1.82

 

Sex : Female

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

221.36

231.84

4.74

242.62

4.65

9.61

± SD

2.63

2.75

0.95

3.32

0.60

1.42

 

Table No.IV

Summary of Gross Pathological Findings

Test System : Sprague Dawley Rat

Sex : Male

Group No.

Dose

mg/kg

Animal Numbers

Animal Fate

Gross Pathological Findings

I

2000

1 - 5

TS

No abnormality detected

 

Sex : Female

Group No.

Dose

mg/kg

Animal Numbers

Animal Fate

Gross Pathological Findings

I

2000

6 - 10

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 male and female Sprague Dawley rats was considered to be >2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical does not classify as an acute dermal toxicant.
CLP Classification: “Not classified”.
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.

The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment.

Under the condition of this, it was concluded that the acute dermal median lethal dose (LD50) of the given test chemical, when administered to male and female Sprague Dawley rats was considered to be >2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical does not classify as an acute dermal toxicant.

CLP Classification: “Not classified”.

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 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 test chemical. The studies are summarized as below - 

 

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 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 of the given test chemical was considered to be >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 Not classified” criteria of CLP.

 

Above study is supported with the data mentioned in different publications, handbook and secondary database for the test chemical. The acute oral toxicity study of the given test chemical was conducted in 4 females/dose CFE strain rats at the dose concentration range of 1100 - 11300 mg/kg bw. The given test chemical (Purity – 98%; undiluted) was administered via oral route. The animals were observed for mortality and clinical signs for 7 days. Autopsies were performed on the animals that died.

There was no mortality at 2250 mg/kg bw or less, but 100% mortality at the next higher dose of 3380 mg/kg bw. Death occurred 18-48 hr after dosage without recovery of consciousness. At the higher doses there was a short period of less than 15 min during which there was an increase in exploratory behaviour. This was followed, between 4 and 24 hr after dosage, by a decrease in motor activity and by a failure to respond to painful stimuli. The only other abnormality seen was piloerection from 4 hr and some red-colored nasal discharge in the last hours before death. No abnormal signs were seen in the surviving animals. At autopsy the only abnormal finding was slight reddening of the lung tissue. There were no abnormalities at autopsy after 7 days.

Under the condition of this, the LD50 value was considered in between >2250 - <3380 mg/kg bw, when 4 females/dose CFE strain rats were treated with test chemical via oral route.

 

Both the above studies are further supported with the study mentioned in publications and secondary database for the test chemical. The acute oral toxicity study of the given test chemical was conducted in 10/dose rats at the dose concentrations of 2500, 3180, and 4000 mg/kg bw. Mortality was 0, 3, and 6 of 10 rats at 2500, 3180, and 4000 mg/kg bw, respectively.

Therefore, the LD50 value was considered to be 3700 mg/kg bw, with 95% confidence limit of 3000 – 4500 mg/kg bw, when 10/dose rats were treated with test chemical via oral route.

 

Thus, based on the above summarised experimental studies on test chemical, 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 the low vapour pressure of the test chemical, which is reported to be 0.02055169 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 reported study was designed and conducted to determine the acute dermal toxicity profile of the given test chemical as per OECD Guideline 402 (Acute Dermal Toxicity) in Sprague Dawley rats.

The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment.

Under the condition of this, it was concluded that the acute dermal median lethal dose (LD50) of the given test chemical, when administered to male and female Sprague Dawley rats was considered to be >2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical does not classify as an acute dermal toxicant. CLP Classification: “Not classified”.

 

The above study is supported with the study mentioned in publications and secondary database for the test chemical. The acute dermal toxicity study of the given test chemical was conducted in 4 rabbits at the dose concentrations of 5000 mg/kg bw.

There was no mortality observed in treated animals. Hence, the LD50 value was considered to be >5000 mg/kg bw, when 4 rabbits were treated with the given test chemical by dermal application.

 

Thus, based on the above summarised experimental studies on 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.

Justification for classification or non-classification

Based on the above studies on test chemical, it can be concluded that the 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. For acute inhalation toxicity wavier was added so, not possible to classify.

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