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Administrative data

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 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
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Principles of method if other than guideline:
The aim of this study was to assess the toxicity potential of test chemical after single oral administration in rats.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
3-(5,5,6-trimethylbicyclo[2.2.1]hept-2-yl)cyclohexan-1-ol
EC Number:
222-294-1
EC Name:
3-(5,5,6-trimethylbicyclo[2.2.1]hept-2-yl)cyclohexan-1-ol
Cas Number:
3407-42-9
Molecular formula:
C16H28O
IUPAC Name:
3-(5,5,6-trimethylbicyclo[2.2.1]hept-2-yl)cyclohexanol
Test material form:
liquid: viscous
Details on test material:
- Name of test material (as cited in study report):3-(5, 5, 6-trimethylbicyclo [2.2.1] hept-2-yl) cyclohexan-1-ol
- Molecular formula :C16H28O
- Molecular weight :236.39 g/mol
- Substance type:Organic
- Physical state:Colourless Liquid

Test animals

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:8- 11 weeks at the time of dosing
- Weight at study initiation: 168-192 g (Individual body weights were within ± 5% prior to treatment after overnight fasting)
- Fasting period:The animals were fasted for minimum 16-18 hours prior to dosing and for 3-4 hours post dosing.
- Housing: The animals were housed individually in polycarbonate cages with corn cobs as bedding in a controlled environment.
- Diet (e.g. ad libitum): Conventional laboratory rodent diet (Nutrivet Life Sciences, Pune), ad libitum
- Water (e.g. ad libitum): Aqua guard filtered tap water, ad libitum
- Acclimation period: Animal numbers 1-3 were acclimatized for five days, and 4-6 for seven days prior to administration of the test item.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):20.40 - 23.10°C
.- Humidity (%):Minimum: 37.40 - 56.00%
- Air changes (per hr): More than 12 changes per hour
- Photoperiod (hrs dark / hrs light): 12-hrs light/12-hrs dark

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage):10 ml
- Justification for choice of vehicle: Corn oil was selected because test item was not miscible in distilled water.
- Lot/batch no. (if required): MKBD4650- Purity: No data av available

MAXIMUM DOSE VOLUME APPLIED:10 ml/kg body weight
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 female rats
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical Observation, body weight and mortality.
Statistics:
No data available

Results and discussion

Preliminary study:
No data available
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other:
Remarks:
No mortality observed
Mortality:
No mortality was observed in the animals treated with 2000 mg/kg throught out the 14 days observation period post dosing.
Clinical signs:
other: At 2000 mg/kg, animal nos. 1, 2, 3, 4 and 6 were observed normal at 30 minutes, mild to moderate diarrhea at 1, 2, 3 and 4 hours and mild epistaxis at 3 and 4 hours followed by normal clinical sign till day 14. Additionally, animal no. 2 was observed with
Gross pathology:
No external or internal gross pathological changes 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

174

193

216

10.92

24.14

2

171

185

210

8.19

22.81

3

168

192

202

14.29

20.24

4

192

205

218

6.77

13.54

5

178

149

178

-16.29

0.00

6

174

189

198

8.62

13.79

 

 

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

176.17

185.50

203.67

5.42

15.75

SD

8.45

19.10

14.77

10.95

8.91

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

49++

49+

64+

49+

64+

49+

2

1

49++

49+

64+

49+

64+

49+

3

1

49++

49+

64+

49+

64+

49+

4

1

49+

49++

64+

49++

64+

49+

5

1

1

49+

64+

49+

49+

64+

6

1

49++

49++

64+

49+

49+

64+

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

182

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, 49 = Diarrhoea, 64 = Epistaxis, 182 = Soiled anal region with fecal material,+= Mild,++= Moderate

 

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:
other: Not classified
Conclusions:
Body weight gain was observed in all the animals treated with 2000 mg/kg body weight, during the 14-day observation period. At 2000 mg/kg, animal number 1, 2, 3, 4 and 6 were observed normal at 30 minutes, mild to moderate diarrhea at 1, 2, 3 and 4 hours and mild epistaxis at 3 and 4 hours followed by normal clinical sign till day 14. Additionally, animal number 2 was observed with soiled anal region with fecal material on day1. Animal number 5 was observed normal at 30 minutes and 1 hour, mild diarrhea at 2, 3 and 4 hours and mild epistaxis at 3 and 4 hours followed by normal clinical sign till day 14. No external and internal gross pathological changes were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice
The acute oral LD50 value for the test chemical was considered to be greater than 2000 mg/kgbw.
Executive summary:

An acute oral toxicity study of test chemical was conducted in female Wistar rats as per OECD No. 423.Six Wistar female rats were for the acute oral toxicity study. Prior to dosing, the animals were fasted for minimum 16-18 hours and for 3-4 hours post dosing, with food withheld but drinking water provided ad libitum. Corn oil was selected as the vehicle because test item was not miscible in distilled water. Three rats of the first group were dosed with starting dose of 2000mg/kgbw and the animals didnot show any mortality so another three rats of the same group were dosed with 2000 mg/kgbw and no mortality was observed. Hence, further dosing was stopped. Body weight gain was observed in all the animals treated with 2000 mg/kg body weight, during the 14-day observation period. At 2000 mg/kg, animal number 1, 2, 3, 4 and 6 were observed normal at 30 minutes, mild to moderate diarrhea at 1, 2, 3 and 4 hours and mild epistaxis at 3 and 4 hours followed by normal clinical sign till day 14. Additionally, animal number 2 was observed with soiled anal region with fecal material on day1. Animal number 5 was observed normal at 30 minutes and 1 hour, mild diarrhea at 2, 3 and 4 hours and mild epistaxis at 3 and 4 hours followed by normal clinical sign till day 14. No external and internal gross pathological changes were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice. The acute oral LD50 value for the test chemical was considered to be greater than 2000 mg/kgbw.