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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 experimental study report.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015

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 the given test chemical after single oral administration in rats and an observation period of 14 days.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
4-(5,5,6-trimethylbicyclo[2.2.1]hept-2-yl)cyclohexan-1-ol
EC Number:
266-100-3
EC Name:
4-(5,5,6-trimethylbicyclo[2.2.1]hept-2-yl)cyclohexan-1-ol
Cas Number:
66068-84-6
Molecular formula:
C16-H28-O
IUPAC Name:
4-{5,5,6-trimethylbicyclo[2.2.1]heptan-2-yl}cyclohexan-1-ol
Test material form:
liquid: viscous
Details on test material:
- IUPAC Name of the test chemical: 3-(2,3,3-trimethyl-6-bicyclo[2.2.1]heptanyl)cyclohexan-1-ol
- Common Name: Iso camphyl cyclohexanol
- Molecular Formula: C16H28O
- Molecular Weight: 236.396 g/mol
- SMILES Notation: OC1CCC([C@@H]2[C@@H]3C[C@@H](C(C)(C)[C@@H]3C)C2)CC1
- InChI: 1S/C16H28O/c1-10-14-8-12(16(10,2)3)9-15(14)11-4-6-13(17)7-5-11/h10-15,17H,4-9H2,1-3H3
- Substance Type: Organic
- Physical State: Colourless Viscous 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: Healthy young adult animals were used for the study. 8- 11 weeks at the time of dosing.
- Females (if applicable) nulliparous and non-pregnant: yes
- Weight at study initiation:Minimum: 137 g Maximum: 179 g (Individual body weights were within ± 20% 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.
- Bedding: All cages were provided with corn cobs.
- 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):All 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 five days and 4-6 for seven days prior to administration of the test item.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):Minimum: 19.50°C; Maximum: 22.90°C
- Humidity (%):Minimum: Minimum: 42.90 %; Maximum: 69.10 %
- Air changes (per hr):More than 12 changes per hour
- Photoperiod (hrs dark / hrs light):12 hours light and 12 hours dark

IN-LIFE DATES: From: March 16, 2015 To: April 29, 2015

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 300 mg/kg and 2000 mg/kg
- Amount of vehicle (if gavage):10 ml
Doses:
G1/ Step I / 300 mg/kg
G1/ Step II / 300 mg/kg
G2/ Step III / 2000 mg/kg
G2/ Step IV / 2000 mg/kg
No. of animals per sex per dose:
G1/ Step I / 300 mg/kg - 3
G1/ Step II / 300 mg/kg - 3
G2/ Step III / 2000 mg/kg - 3
G2/ Step IV / 2000 mg/kg - 3
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical Observation - After test item administration, 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 animals were observed once a day during the 14 day observation period.
Body weight - All rats were weighed on days 0 (prior to dosing), 7 and 14.
Mortality - All animals were observed twice daily (morning and evening) for morbidity and mortality, throughout the acclimatization and study period.
- Necropsy of survivors performed: yes, at the end of 14 day observation period, all the rats were euthanised by overdose of CO2 for external and internal observations.
Statistics:
not specified

Results and discussion

Preliminary study:
not specified
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed in the animals treated with 300 and 2000 mg/kg body weight dose throughout the 14 days observation period.
Clinical signs:
At 300 and 2000 mg/kg body weight, animals of G1 (Step I and II) and G2 (Step III and IV) were normal throughout the experimental period.
Body weight:
Mean body weight of all the animals of G1 (Step I and II) and G2 (Step III and IV) treated with 300 and 2000 mg/kg body weight respectively, was observed with gain on day 7 and 14, as compared to day 0.
Gross pathology:
No external and internal gross pathological changes were seen in all the animals of G1 (Step I and II) and G2 (Step III and IV) treated with 300 and 2000 mg/kg body weight respectively, during terminal sacrifice.
Other findings:
not specified

Any other information on results incl. tables

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

Sex: Female

Animal No.

Group/Step/ Dose (mg/kg body weight)

Dose Volume

(ml)

Body Weight (gram)

Body Weight Change (%)

Day 0

Day 7

Day 14

Day

0-7

Day

0-14

1

G1/

Step I/ 300

1.7

169

193

212

14.20

25.44

2

1.6

160

179

197

11.88

23.13

3

1.6

162

194

216

19.75

33.33

4

G1/

Step II/

 300

1.8

179

213

230

18.99

28.49

5

1.7

170

203

214

19.41

25.88

6

1.6

160

187

199

16.88

24.38

7

G2/

Step III/

 2000

1.6

164

182

192

10.98

17.07

8

1.6

157

186

198

18.47

26.11

9

1.8

175

200

218

14.29

24.57

10

G2/

Step IV/

 2000

1.4

140

164

177

17.14

26.43

11

1.4

141

165

177

17.02

25.53

12

1.4

137

156

167

13.87

21.90

*= Dose volume calculated based on day 0 body weight,

 

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

Sex: Female

Group/Step/Dose (mg/kg body weight)

Rats Body Weight (g)

Body Weight Changes (%)

Day 0

Day 7

Day 14

0-7

0-14

G1/

Step I/ 300

Mean

163.67

188.67

208.33

15.28

27.30

SD

4.73

8.39

10.02

4.05

5.35

N

3

3

3

3

3

G1/

Step II/

 300

Mean

169.67

201.00

214.33

18.43

26.25

SD

9.50

13.11

15.50

1.36

2.08

N

3

3

3

3

3

G2/

Step III/

 2000

Mean

165.33

189.33

202.67

14.58

22.59

SD

9.07

9.45

13.61

3.76

4.84

N

3

3

3

3

3

G2/

Step IV/

 2000

Mean

139.33

161.67

173.67

16.01

24.62

SD

2.08

4.93

5.77

1.86

2.40

N

3

3

3

3

3

Key: SD = Standard Deviation, n = Number of Animals


Table 3: Individual Animal Clinical Signs and Symptoms

 

Sex: Female

Animal No.

Group/Step/ Dose (mg/kg body weight)

Hours (Day 0)

1/2

1

2

3

4

1

G1/

Step I/ 300

1

1

1

1

1

2

1

1

1

1

1

3

1

1

1

1

1

4

G1/

Step II/

 300

1

1

1

1

1

5

1

1

1

1

1

6

1

1

1

1

1

7

G2/

Step III/

 2000

1

1

1

1

1

8

1

1

1

1

1

9

1

1

1

1

1

10

G2/

Step IV/

 2000

1

1

1

1

1

11

1

1

1

1

1

12

1

1

1

1

1

 

Animal No.

Group/Step/ Dose (mg/kg body weight)

Days post dosing

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1

G1/

Step I/ 300

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

G1/

Step II/

 300

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

7

G2/

Step III/

 2000

1

1

1

1

1

1

1

1

1

1

1

1

1

1

8

1

1

1

1

1

1

1

1

1

1

1

1

1

1

9

1

1

1

1

1

1

1

1

1

1

1

1

1

1

10

G2/

Step IV/

 2000

1

1

1

1

1

1

1

1

1

1

1

1

1

1

11

1

1

1

1

1

1

1

1

1

1

1

1

1

1

12

1

1

1

1

1

1

1

1

1

1

1

1

1

1

Key:1 = Normal


Table 4: Individual Animal Mortality Record

 

Sex: Female

Animal No.

Group/Step/ Dose (mg/kg body weight)

Day of Observation (Day 0 to 14)

Morning Observations

Evening Observations

1

G1/

Step I/ 300

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

G1/

Step II/

 300

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

7

G2/

Step III/

 2000

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

G2/

Step IV/

 2000

No mortality and morbidity

No mortality and morbidity

11

No mortality and morbidity

No mortality and morbidity

12

No mortality and morbidity

No mortality and morbidity

 


Table 5: Gross Necropsy Observation

 

Sex: Female                                                                             Mode of Death: Terminal Sacrifice

Animal No.

Group/Step/ Dose (mg/kg body weight)

Gross Observation

External

Internal

1

G1/

Step I/ 300

No abnormality detected

No abnormality detected

2

No abnormality detected

No abnormality detected

3

No abnormality detected

No abnormality detected

4

G1/

Step II/

 300

No abnormality detected

No abnormality detected

5

No abnormality detected

No abnormality detected

6

No abnormality detected

No abnormality detected

7

G2/

Step III/

 2000

No abnormality detected

No abnormality detected

8

No abnormality detected

No abnormality detected

9

No abnormality detected

No abnormality detected

10

G2/

Step IV/

 2000

No abnormality detected

No abnormality detected

11

No abnormality detected

No abnormality detected

12

No abnormality detected

No abnormality detected

 

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Conclusions:
Under these study conditions, the acute oral toxicity dose (LD50) was considered to be >2000 mg/kg bw, when female Wistar rats were treated with the given test chemical via oral route. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical does not exhibit acute oral toxicity. CLP Classification "Not classified"

Executive summary:

Acute oral toxicity study of the given test chemical was conducted as per OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method) in Wistar female rats.

Twelve 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 feed 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 (Step I) were dosed with starting dose of 300 mg/kg body weight and no mortality was observed.

Based on the results from G1 (Step I), additional three animals of group G1 (Step II) were dosed with 300 mg/kg body weight. As there was no mortality at group G1 (Step I and II) dose levels, three rats of group G2 (Step III) was dosed with 2000 mg/kg body weight and no mortality was observed so another three rats of group G2 (Step IV) were dosed with 2000 mg/kg body weight. Since there was no mortality in both the groups G1 (Step I and II) and G2 (Step III and IV), further dosing was not required.

Body weights were re­corded on day 0 (prior to dosing) 7 and 14. Mean body weight of all the animals (Step I, Step II, Step III and Step IV) treated with 300 and 2000 mg/kg body weight and was observed with gain on day 7 and 14, as compared to day 0.

At 300 and 2000 mg/kg body weight, animals of G1 (Step I and II) and G2 (Step III and IV) were normal throughout the experimental period.

No external and internal gross pathological changes were seen in all the animals of G1 (Step I and II) and G2 (Step III and IV) treated with 300 and 2000 mg/kg body weight respectively, during terminal sacrifice.

Under these study conditions, the acute oral toxicity dose (LD50) was considered to be >2000 mg/kg bw, when female Wistar rats were treated with the given test chemical via oral route. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical does not exhibit acute oral toxicity. CLP Classification "Not classified"