Registration Dossier

Administrative data

Description of key information

Acute oral toxicity

The LD50 value was considered to be >2000 mg/kg bw. When female Wistar rats were treated with test chemical orally.

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 the low vapour  pressure of the test substance, which is reported as 0.0082281755  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  LD50 value was considered to be >2000 mg/kg bw. When male and female wistar rats were treated with test chemical by dermal application .

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:
comparable to guideline study
Justification for type of information:
Data 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:
Acute toxicity study of test chemical was performed on rats.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: In-House Bred
- Age at study initiation: 9- 10 weeks at the time of dosing
- Weight at study initiation: Minimum: 118 g Maximum: 148 g (Individual body weights were within ± 8% prior to treatment after overnight fasting)
- Fasting period before study: 16 to 18 hours, prior to dosing
- Housing:
Bedding : All cages were provided with corn cobs
Husbandry : The animals were housed individually in polycarbonate cages.
Room Sanitation : The experimental room floor and work tops were swept and mopped with disinfectant solution every day.
Cages and water bottle : All the cages and water bottles were changed at least twice every week
- Diet (e.g. ad libitum): animals were provided conventional laboratory rodent diet ad libitum
- Water (e.g. ad libitum): Aqua guard filtered tap water was provided ad libitum via drinking bottles
- Acclimation period: Animal nos. 1-3 were acclimatized for 6 days and 4-6 for 10 days prior to administration of the test item

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Minimum: 19.80°C;Maximum: 23.20°C
- Humidity (%): Minimum: 48.70 %;Maximum: 69.20 %
- Air changes (per hr): More than 12 changes per hour
- Photoperiod (hrs dark / hrs light): 12:12

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2000 mg/kg body weight
- Amount of vehicle (if gavage): 10 ml
- Justification for choice of vehicle: Corn oil was selected as a vehicle because test item was not soluble in the distilled water during solubility testing
- Lot/batch no. (if required): MKBD4650
- Purity:No data available

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

DOSAGE PREPARATION (if unusual):
Transferred the desired quantity of test item to the mortar and triturated using pestle. Added slowly vehicle in to mortar and mixed well. Transferred the formulation to the measuring cylinder and made the volume up to desired quantity (10 ml). The dosing suspension was prepared freshly, shortly prior to dose administration.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no data
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
Six female Wistar rat
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: individual animals were frequently observed at 30 minutes, 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing). Subsequently, all the six animals were observed once a day during the 14 day observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Statistics:
No data available
Preliminary study:
No data available
Key result
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:
No mortality was observed througout the experimentation period.
Clinical signs:
At 2000mg/kg, all the animals were observed with normal clinical signs throughout the experimental period
Body weight:
Mean body weight of animals treated with 2000 mg/kg body weight was observed with gain on day 7 and 14, as compared to day 0
Gross pathology:
No external and internal gross pathological examination were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice
Other findings:
No data available

Table 1: Individual Animal Body Weight (g) andBody Weight Changes(%)

 

Sex:Female

Animal No.

Group/ Dose (mg/kg)

Body Weight (gram)

Body Weight Change (%)

Day 0

Day 7

Day 14

Day

0-7

Day

0-14

1

G1/ 2000

131

165

196

25.95

49.62

2

118

147

165

24.58

39.83

3

129

159

174

23.26

34.88

4

148

170

181

14.86

22.30

5

143

169

185

18.18

29.37

6

136

154

164

13.24

20.59

Table 2: Summary of Animal Body Weight (g) and Body Weight Changes (%)

 

Sex:Female

Group/ Dose (mg/kg)

Rats Body Weight (g)

Body Weight Changes (%)

Day 0

Day 7

Day 14

0-7

0-14

 

G1/ 2000

Mean

134.17

160.67

177.50

20.01

32.76

SD

10.68

9.05

12.34

5.34

11.03

n

6

6

6

6

6

Keys:SD = Standard Deviation, n = Number of Animals.

Table 3: Individual Animal Clinical Signs and Symptoms

 

Sex:Female

Animal No.

Group/ Dose (mg/kg)

Hours (Day 0)

1/2

1

2

3

4

1

G1/ 2000

1

1

1

1

1

2

1

1

1

1

1

3

1

1

1

1

1

4

1

1

1

1

1

5

1

1

1

1

1

6

1

1

1

1

1

 

Animal No.

Group/ Dose (mg/kg)

Days post dosing

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1

G1/ 2000

1

1

1

1

1

1

1

1

1

1

1

1

1

1

2

1

1

1

1

1

1

1

1

1

1

1

1

1

1

3

1

1

1

1

1

1

1

1

1

1

1

1

1

1

4

1

1

1

1

1

1

1

1

1

1

1

1

1

1

5

1

1

1

1

1

1

1

1

1

1

1

1

1

1

6

1

1

1

1

1

1

1

1

1

1

1

1

1

1

Keys:  1 = Normal

Table 4: Individual Animal Mortality Record

 

Sex:Female

 

Animal No.

Group/ Dose (mg/kg)

Day of Observation (Day 0 to 14)

Morning Observations

Evening Observations

1

G1/ 2000

No mortality and morbidity

No mortality and morbidity

2

No mortality and morbidity

No mortality and morbidity

3

No mortality and morbidity

No mortality and morbidity

4

No mortality and morbidity

No mortality and morbidity

5

No mortality and morbidity

No mortality and morbidity

6

No mortality and morbidity

No mortality and morbidity

Table 5: Gross Necropsy Observation

 

Sex:Female                                                                                                                                        

Animal No.

Group/ Dose (mg/kg)

 

Mode of Death

Gross Observation

External

Internal

1

G1/ 2000

Terminal sacrifice

No abnormality detected

No abnormality detected

2

Terminal sacrifice

No abnormality detected

No abnormality detected

3

Terminal sacrifice

No abnormality detected

No abnormality detected

4

Terminal sacrifice

No abnormality detected

No abnormality detected

5

Terminal sacrifice

No abnormality detected

No abnormality detected

6

Terminal sacrifice

No abnormality detected

No abnormality detected

Interpretation of results:
other: not classified
Conclusions:
The LD50 value was considered to be >2000 mg/kg bw. When female Wistar rats were treated with test chemical orally.
Executive summary:

Acute Oral Toxicity Study of test chemical in Rats was performed as per OECD No. 423.Six female Wistar rats were selected for acute oral toxicity study.The test material was dissolved in corn oil and given in dose concentration 2000 mg/kg bw by oral gavage route.The animals were fasted for minimum 16-18 hours prior to dosing and for 4 hours post dosing, with food withheld but drinking water providedad libitum. The time intervals between dosing were determined by the onset, duration and severity of toxic signs.

Three rats of group G1 were dosed with starting dose of 2000 mg/kg body weight and the animals showed no mortality post dosing, so another three rats of the same group were dosed with 2000 mg/kg weight and no mortality was observed. Hence, further dosing was stopped. Mean body weight of all six animals was observed with gain on day 7 and 14. Normal clinical signs were observed throughout the experimental period. No external and internal gross pathological examination were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice.Hence the LD50 value was considered to be >2000 mg/kg bw. When female Wistar rats were treated with test chemical orally.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The data is K1 level.The data has been obtained from the experimental study from the OECD GLP lab.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
exposure considerations
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
Endpoint conclusion
Quality of whole database:
waiver

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Justification for type of information:
Data from experimental study report.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
Acute dermal toxicity study of test chemical was performed in rats.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: In-House Bred
- Age at study initiation: no data
- Weight at study initiation: Male: Minimum: 248 g and Maximum: 271 g
(Prior to Treatment) Female: Minimum: 202 g and Maximum: 249 g

- Fasting period before study: no data
- Housing:
Bedding : All cages were provided with corn cobs
Husbandry : The animals were housed individually in polycarbonate cages
Room Sanitation : The experimental room floor and work tops were swept and mopped with disinfectant solution every day.
Cages and water bottle : All the cages and water bottles were changed at least twice every week.
- Diet (e.g. ad libitum): animals were provided conventional laboratory rodent diet ad libitum
- Water (e.g. ad libitum): Aqua guard filtered tap water was provided ad libitum via drinking bottles
- Acclimation period: All animals were acclimatized to the test conditions for 6 days prior to administration of the test item.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Minimum: 19.80 °C Maximum: 23.20 °C
- Humidity (%): Minimum: 50.60% Maximum: 63.20%
- Air changes (per hr): More than 12 changes per hour
- Photoperiod (hrs dark / hrs light): 12:12

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: Approx. 10% of body surface area of rat
- Type of wrap if used: porous gauze dressing and non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test item was removed by using distilled water
- Time after start of exposure: 24-hour exposure period

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- Concentration (if solution): Individual rat was applied with an amount of test item moistened with 0.2 ml distilled water
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.2ml
Duration of exposure:
24 hrs
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
Five male and five female wistar rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: individual animals were frequently observed at 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing). Subsequently, all animals were observed once a day during the 14 day observation period
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology were observed
Statistics:
No data available
Preliminary study:
No data available
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed
Mortality:
No mortality was observed at limit dose of 2000 mg/kg body weight of test item during the 14 day observation period
Clinical signs:
All the animals were observed with normal clinical signs throughout the experimental period
Body weight:
Mean body weight of male and female was observed with increase on day 7 and 14, as compared to day 0
Gross pathology:
The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality
Other findings:
No data available

Table 1: Individual Animal Body Weight (g) andBody Weight Changes(%)

 

Dose:2000 mg/ kg bodyweight                                                                                                         

Animal No.

Sex

Body Weight (gram)

Body Weight Change (%)

Day 0

Day 7

Day 14

Day 0-7

Day 0-14

1

Male

248

262

282

5.65

13.71

2

270

283

323

4.81

19.63

3

254

277

300

9.06

18.11

4

271

278

304

2.58

12.18

5

263

276

300

4.94

14.07

6

Female

249

239

255

-4.02

2.41

7

214

217

225

1.40

5.14

8

219

228

234

4.11

6.85

9

202

204

204

0.99

0.99

10

203

212

223

4.43

9.85

Table 2: Individual Animal Clinical Signs and Symptoms

 

Dose:2000 mg/kg body weight

Animal

No.

Sex

Hour(s) - Day 0

Day

1

2

3

4

1

2

3

4

5

6

7

1

Male

1

1

1

1

1

1

1

1

1

1

1

2

1

1

1

1

1

1

1

1

1

1

1

3

1

1

1

1

1

1

1

1

1

1

1

4

1

1

1

1

1

1

1

1

1

1

1

5

1

1

1

1

1

1

1

1

1

1

1

6

Female

1

1

1

1

1

1

1

1

1

1

1

7

1

1

1

1

1

1

1

1

1

1

1

8

1

1

1

1

1

1

1

1

1

1

1

9

1

1

1

1

1

1

1

1

1

1

1

10

1

1

1

1

1

1

1

1

1

1

1

 

Animal

No.

Sex

Day

8

9

10

11

12

13

14

1

Male

1

1

1

1

1

1

1

2

1

1

1

1

1

1

1

3

1

1

1

1

1

1

1

4

1

1

1

1

1

1

1

5

1

1

1

1

1

1

1

6

Female

1

1

1

1

1

1

1

7

1

1

1

1

1

1

1

8

1

1

1

1

1

1

1

9

1

1

1

1

1

1

1

10

1

1

1

1

1

1

1

Key: 1 = Normal

Table 3: Individual Animal Mortality Record

 

Dose:2000 mg/kg body weight

       Animal No.

Sex

Days of Observation (0 to 14)

Morning Observations

Evening Observations

1

Male

No mortality and morbidity

No mortality and morbidity

2

No mortality and morbidity

No mortality and morbidity

3

No mortality and morbidity

No mortality and morbidity

4

No mortality and morbidity

No mortality and morbidity

5

No mortality and morbidity

No mortality and morbidity

6

Female

No mortality and morbidity

No mortality and morbidity

7

No mortality and morbidity

No mortality and morbidity

8

No mortality and morbidity

No mortality and morbidity

9

No mortality and morbidity

No mortality and morbidity

10

No mortality and morbidity

No mortality and morbidity

Table 4:Summaryof Animal Body Weight (g) and Body Weight Changes (%)

 

Dose:2000 mg/kg body weight

Sex

Body Weight (gram)

Body Weight Changes (%)

Day 0

Day 7

Day 14

Day 0-7

Day 0-14

Male

Mean

261.20

275.20

301.80

5.41

15.54

SD

10.03

7.85

14.60

2.34

3.17

n

5

5

5

5

5

Female

Mean

217.40

220.00

228.20

1.38

5.05

SD

19.09

13.73

18.54

3.39

3.53

n

5

5

5

5

5

Keys:SD= Standard deviation, n = Number of animals

Table 5: GrossNecropsyObservation

 

 Dose:2000 mg/kg body weight                                               Mode of Death:Terminal Sacrifice

Animal No.

Sex

Gross Observation

External

Internal

1

Male

No abnormalities detected

No abnormalities detected

2

No abnormalities detected

No abnormalities detected

3

No abnormalities detected

No abnormalities detected

4

No abnormalities detected

No abnormalities detected

5

No abnormalities detected

No abnormalities detected

6

Female

No abnormalities detected

No abnormalities detected

7

No abnormalities detected

No abnormalities detected

8

No abnormalities detected

No abnormalities detected

9

No abnormalities detected

No abnormalities detected

10

No abnormalities detected

No abnormalities detected

Interpretation of results:
other: not classified
Conclusions:
The LD50 value was considered to be >2000 mg/kg bw. When male and female wistar rats were treated with test chemical by dermal application .
Executive summary:

Acute dermal toxicity study of test chemical in Rats was performed as per OECD No. 402. Five male and five female healthy young adult rats were randomly selected and used for conducting acute dermal toxicity study. Rats free from injury and irritation of skin were selected for the study. Twenty four hours prior to dermal application of test item, approximately 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight of test item moistened with 0.2 ml distilled water was applied by single dermal application and observed for 14 days after treatment.

On test day 0, an amount of test item moistened with 0.2 ml distilled water was applied directly on the intact skin of clipped area of rats; the porous gauze dressing was put on to the intact skin of clipped area.This porous gauze dressing was covered with a non-irritating tape.After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water.The skin reactions were assessed. All the animals were observed for mortality, clinical signs, body weight and gross pathology. No mortality were observed in any animal, normal clinical signs were observed. Mean body weight of male and female was observed with increase on day 7 and 14, as compared to day 0. No pathological abnormality were observed. Thus the LD50 value was considered to be >2000 mg/kg bw. When male and female wistar rats were treated with test chemical by dermal application .

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The data is K1 level.The data has been obtained from the experimental study from the OECD GLP lab.

Additional information

Acute oral toxicity

In different studies,test chemical has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats.

The experimental study conducted in a OECD GLP laboratory (Sustainability Support Services (Europe) AB has the letter of access).Acute Oral Toxicity Study of Methyl 2-naphthyl ether in Rats was performed as per OECD No. 423.Six female Wistar rats were selected for acute oral toxicity study. The test material was dissolved in corn oil and given in dose concentration 2000 mg/kg bw by oral gavage route. The animals were fasted for minimum 16-18 hours prior to dosing and for 4 hours post dosing, with food withheld but drinking water provided ad libitum. The time intervals between dosing were determined by the onset, duration and severity of toxic signs. Three rats of group G1 were dosed with starting dose of 2000 mg/kg body weight and the animals showed no mortality post dosing, so another three rats of the same group were dosed with 2000 mg/kg weight and no mortality was observed. Hence, further dosing was stopped. Mean body weight of all six animals was observed with gain on day 7 and 14. Normal clinical signs were observed throughout the experimental period. No external and internal gross pathological examination was seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice. Hence the LD50 value was considered to be >2000 mg/kg bw. When female Wistar rats were treated with test chemical orally.

It is supported by experimental study given by Opdyke, D. L. J (Food and Cosmetics Toxicology. Vol. 13, Pg. 885, 1975.)The acute toxicity study was conducted to evaluate the toxic effects of administration of methyl 2-naphthyl ether in male and female rat by the oral route. No mortality was observed at dose concentration 5000mg/kg bw. Hence LD50 value was considered to be >5000 mg/kg of body weight. When rats were treated with test chemical orally.

Thus, based on the above 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 test chemical can be “Not 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 the low vapour  pressure of the test substance, which is reported as 0.0082281755  mm Hg. Thus, exposure to inhalable dust,  mist and vapour of the chemical is highly unlikely. Therefore this study is considered for waiver

Acute dermal toxicity

In different studies,test chemical has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats.

The experimental study conducted in a OECD GLP laboratory (Sustainability Support Services (Europe) AB has the letter of access). Acute dermal toxicity study of test chemical in Rats was performed as per OECD No. 402. Five male and five female healthy young adult rats were randomly selected and used for conducting acute dermal toxicity study. Rats free from injury and irritation of skin were selected for the study. Twenty four hours prior to dermal application of test item, approximately 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight of test item moistened with 0.2 ml distilled water was applied by single dermal application and observed for 14 days after treatment.

On test day 0, an amount of test item moistened with 0.2 ml distilled water was applied directly on the intact skin of clipped area of rats; the porous gauze dressing was put on to the intact skin of clipped area. This porous gauze dressing was covered with a non-irritating tape. After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water. The skin reactions were assessed. All the animals were observed for mortality, clinical signs, body weight and gross pathology. No mortality was observed in any animal, normal clinical signs were observed. Mean body weight of male and female was observed with increase on day 7 and 14, as compared to day 0. No pathological abnormality was observed. Thus the LD50 value was considered to be >2000 mg/kg bw. When male and female wistar rats were treated with test chemical by dermal application.

It is supported by experimental study The acute dermal toxicity study of test chemical was performed in rabbit by the dermal route. No mortality was observed at dose concentration 5000 mg/kg bw. Hence the lethal dose (LD50) value was considered to be >5000 mg/kg of body weight. When rabbits were treated with test chemical by dermal application.

Thus, based on the above 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 test chemical can be “Not classified” for acute dermal toxicity.

 

Justification for classification or non-classification

Thus, comparing this value with the criteria of CLP test chemical can be “Not classified” for acute oral, dermal and inhalation toxicity.