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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 form study report

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

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:
To assess the toxicity potential of Methyl 2-naphthyl ether (CAS No. – 93-04-9) after single oral administration in rats and observation period of 14 days.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: flakes
Details on test material:
- Name of test material (as cited in study report): Methyl 2-naphthyl ether
- Molecular formula :C11H10O
- Molecular weight :158.19 g/mol
- Substance type: Organic
Specific details on test material used for the study:
- Name of test material (as cited in study report): Methyl 2-naphthyl ether
- Molecular formula :C11H10O
- Molecular weight :158.19 g/mol
- Substance type: Organic

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals 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

Administration / exposure

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:

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

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality 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

Any other information on results incl. tables

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

Applicant's summary and conclusion

Interpretation of results:
not classified
Conclusions:
Under the test conditions, the acute oral LD50 value of Methyl 2-naphthyl ether in female wistar rats was observed at dose concentration of >2000 mg/kg bw
Executive summary:

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 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. From this value it is concluded that the substance Methyl 2-naphthyl etheris not classified as per CLP criteria.