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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Justification for type of information:
Data is from experimental study report.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
The study was conducted to find out the LD50 value, clinical sign and histopathological effect of the given test chemical at different dose level in wistar albino rats.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

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
Remarks:
albino
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Institute for Industrial Research and Toxicology Ghaziabad,
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: 200±20g
- Housing: Groups of three animals of same sex in polypropylene cages with stainless steel grill top, facilities for food and water bottle, and bedding of clean paddy husk.
- Diet (e.g. ad libitum): Pelleted feed
- Water (e.g. ad libitum): Fresh and clean water filtered through ‘Aqua Guard on line water filter’, was kept in glass bottles Ad libitum
- Acclimation period:The healthy wistar albino rats selected for study acclimatized to standard laboratory condition for period of one week under close Veterinary supervision.
- Randomization:After acclimation and Veterinary examination all the animals randomly divided into two groups and each group having five male and five female rats.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): between 22-25°C
- Humidity (%): 40-60%
- Air changes (per hr): Air conditioned rooms with 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark.

Administration / exposure

Type of coverage:
open
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: back skin of total body surface area
- % coverage: Approximate 10 percent
- Type of wrap if used: The test compound was held in contact with the skin with an impervious dressing secured in place with an adhesive tape.The animals were then housed individually in cages with a collar around the neck in order to avoid the ingestion of the test compound.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dressing was removed and the site of application was cleaned with lukewarm water wiping the test compound.
- Time after start of exposure:24 hours
Duration of exposure:
24 hours
Doses:
No. of dose groups
Group-I: 2000 mg/kg b.wt (limit test)
Group-II: 2000 mg/kg b.wt (confirmatory test)
No. of animals per sex per dose:
10 (5male & 5 female)
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The treated animals were closely observed for clinical signs of intoxication, first 4 hours and thereafter for every 1 hrs interval for 24 hrs after dosing and twice a day for 14 days. All the rats were observed at least twice daily with the purpose of recording any symptoms of ill-health or behavioral changes. These observations included changes in skin and fur in the eyes and mucous membranes, respiratory, circulatory, central nervous and autonomous systems, somatomotor activity and behavior changes. The following clinical signs were observed in female rats to characterize with erythema, hypersensitivity, edema etc.
Mortality - All the animals were observed for mortality at 30 minutes time interval for first six hours on the day of test compound administration and thereafter twice a day for 14 days.
Body weight: The body weight of all the animals was observed weekly on day 0 (pre treatment), 7th and 14th (post treatment).
- Necropsy of survivors performed: yes, necropsy was carried out on all the animals that died during the study or surviving animals were sacrificed at the end of the study to observe any gross pathological changes.
- Other examinations performed: The organ which showed gross pathological change during necropsy subjected for histopathological study.
Statistics:
not specified

Results and discussion

Preliminary study:
not specified
Effect levels
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:
The test compound did not produce any mortality throughout the observation period of 14 days
Clinical signs:
The test compound did not elicit any clinical signs at the dose level of 2000 mg/kg b.wt. in entire observation period.
Body weight:
All the animals treated with the test compound at the dose level of 2000 mg/kg b.wt did not show any significant loss or gain in their weight when observed on day 0th (pre treatment) and then 7th and 14th (post treatment).
Gross pathology:
EXTERNAL
i. Skin- Skin and hair coat was observed wet.
ii. All external orifices- Normal
B. INTERNAL
i. Subcutaneous- No changes was observed.
ii. Superficial and deep lymph nodes- No change in mesenteric lymph node.
ABDOMINAL CAVITY
i. Opening and general examination- In the abdominal cavity all the organs were present in normal position.
ii. Spleen- No changes were recorded.
iii. Digestive system- No gross changes were observed in stomach and intestine.
iv. Liver and biliary ducts- No gross pathological changes were observed
v. Excretory system- No gross pathological changes were observed.
vi. Adrenal- Observed normal.
vii. Male/female genital organs – Showed normal colour, consistency and no inflammatory changes.
2. THORACIC CAVITY
i. Opening and general examination- Thoracic cavity was found to be normal without any fluid, mucous or blood etc.
ii. Lungs- No changes were recorded.
iii. Heart- No changes were observed in color and consistency. Heart found normal.
iv. Thyroid- Normal in shape, size and surface.
3. CRANIAL CAVITY
Brain- Normal in shape and size.
Other findings:
not specified

Any other information on results incl. tables

TABLE – 2

SUMMARY OF BODY WEIGHT (gm)

Group

Animal ID

Day 0

Day 7

% Gain/loss

Day 14

% Gain/loss

Group-I

2000 mg/kg b. wt

 

 

 

20174-1

198.2

203.5

2.67

209.3

5.60

20174-2

201.4

205.6

2.08

211.5

5.01

20174-3

200.6

204.5

1.94

213.2

6.28

20174-4

205.4

211.4

2.92

214.4

4.38

20174-5

204.2

210.3

2.98

215.3

5.43

20174-6

203.1

209.4

3.10

215.2

5.95

20174-7

204.7

211.1

3.12

216.7

5.86

20174-8

200.5

205.5

2.49

214.2

6.83

20174-9

202.6

208.5

2.91

214.1

5.67

20174-10

202.5

207.2

2.32

215.3

6.32

Group-II

2000 mg/kg b. wt

20174-11

197.5

203.1

2.83

208.6

5.62

20174-12

206.2

211.4

2.52

217.3

5.38

20174-13

203.4

208.2

2.35

213.4

4.91

20174-14

202.7

207.4

2.31

215.3

6.21

20174-15

205.3

210.3

2.43

216.7

5.55

20174-16

199.7

204.8

2.55

212.4

6.35

20174-17

204.9

209.6

2.29

217.5

6.14

20174-18

202.2

208.4

3.06

215.6

6.62

20174-19

201.4

206.2

2.38

211.4

4.96

20174-20

200.8

205.2

2.19

213.4

6.27

TABLE – 3

CLINICAL SIGNS AND MORTALITY

Group: I Limit test                                                              Dose: 2000 mg/kg b.wt

 

Parameters

Incidence of Clinical Signs Observed after Dosing on

Mortality

Day 0

DAY

Min

Hour

30

1

2

4

6

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Total

%

Mortality (total)

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0/10

0

Clinical Signs- Local

 

Redness

-

-

-

-

-

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Pain

-

-

-

-

-

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Swelling

-

-

-

-

-

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Systemic signs

Clinical signs

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

-          =Observed after 24 hrs

0        = No clinical signs

+        = Mild

++      = Moderate

+++    = High

++++  = Severe


TABLE – 3 Contd…………….

CLINICAL SIGNS AND MORTALITY

Group: II Confirmatory test                                                        Dose: 2000 mg/kg b.wt.

                                                                                                                                      

 

Parameters

Incidence of Clinical Signs Observed after Dosing on

Mortality

Day 0

DAY

Min

Hour

30

1

2

4

6

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Total

%

Mortality (total)

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0/10

0

Clinical Signs- Local

 

Redness

-

-

-

-

-

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Pain

-

-

-

-

-

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Swelling

-

-

-

-

-

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Systemic signs

Clinical signs

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

-          =Observed after 24 hrs

0        = No clinical signs

+        = Mild

++      = Moderate

+++    = High

++++  = Severe

TABLE – 4

SUMMARY OF NECROPSY FINDINGS

S. No.

 

Fate

 

Wistar albino rats

Dose (mg/kg b. wt)

2000

(limit test)

2000

(confirmatory test)

1

Terminal sacrifice

10/10

10/10

2

Found Dead

0/10

0/10

3

Abnormalities detected

0/10

0/10

TABLE – 5

INDIVIDUAL ANIMAL FATE & NECROPSY FINDINGS

Group-I (limit test)                                                                         2000 mg/kg b.wt.

Animal ID

Fate

Time

Gross Findings

20174-1

TS

Day 14

NAD

20174-2

TS

Day 14

NAD

20174-3

TS

Day 14

NAD

20174-4

TS

Day 14

NAD

20174-5

TS

Day 14

NAD

20174-6

TS

Day 14

NAD

20174-7

TS

Day 14

NAD

20174-8

TS

Day 14

NAD

20174-9

TS

Day 14

NAD

20174-10

TS

Day 14

NAD

Day 0 is the day of dose administration.

TS- Terminal Sacrifice

NAD- No abnormality Detected

FD-Found dead

TABLE-5 Contd………..

INDIVIDUAL ANIMAL FATE & NECROPSY FINDINGS

Group: II(confirmatory test)                                                     Dose: 2000 mg/kg b.wt.                                                                                

Animal ID

Fate

Time

Gross Findings

20174-11

TS

Day 14

NAD

20174-12

TS

Day 14

NAD

20174-13

TS

Day 14

NAD

20174-14

TS

Day 14

NAD

20174-15

TS

Day 14

NAD

20174-16

TS

Day 14

NAD

20174-17

TS

Day 14

NAD

20174-18

TS

Day 14

NAD

20174-19

TS

Day 14

NAD

20174-20

TS

Day 14

NAD

 

Day 0 is the day of dose administration.

TS- Terminal Sacrifice

NAD- No abnormality Detected

FD-Found dead

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Conclusions:
From the results obtained from present investigation, it can be concluded that the test chemical is non toxic to Wistar albino rats at the dose level of 2000 mg/kg body weight and the LD50 of this compound is >2000 mg/kg body weight.
Executive summary:

The acute dermal toxicity study of the given test chemical was conducted on wistar albino rats under OECD guideline-402 Guideline for Testing of Chemicals.

LIMIT TEST (2000 mg/kg b.wt): Ten healthy wistar albino rats of both sex (ranging b.wt 200±20 gm) selected for study after acclimatization. Approximate 10 percent back skin of total body surface area was prepared 24 hrs prior to application of test compound. The test chemical was applied dermally at the dose level of 2000 mg/kg b.wt for each animal. The treated animals were observed for clinical signs of intoxication and mortality at different time interval for a period of 14 days. The body weight of each rat was observed on day 0 (pre treatment), 7th and 14th (post treatment). The necropsy was performed on all animals which was died during the study or were sacrificed at termination of the study.

The test chemical applied at the dose level of 2000 mg/kg b.wt in Wistar albino rats did not show any clinical signs of toxicity throughout the observation period of 14 days.   Furthermore, no mortality was observed throughout the period of observation (14 days). After 14 days necropsy was conducted on all the animals which did not reveal any significant gross pathological changes.

CONFIRMATORY TEST:  After 72 hrs. a confirmatory test was conducted in same species of animals to confirm the limit test of test compound (OECD-402 guidelines).

Ten healthy Wistar albino rats of both sex (ranging b.wt 200±20 gm) selected for study after acclimatization. Approximate 10 percent back skin of total body surface area was prepared 24 hrs prior to application of test compound. The test chemical was applied dermally at the dose level of 2000 mg/kg b.wt for each animal. The treated animals were observed for clinical signs of intoxication and mortality at different time interval for a period of 14 days. The body weight of each rat was observed on day 0 (pre treatment), 7th and 14th (post treatment). The necropsy was performed on all animals at the termination of the study.

There was no mortality recorded throughout the observation period after application of the test compound at the dose level of 2000 mg/kg body weight. The test compound did not elicit any clinical signs of toxicity during the entire observation period. The body weight of each animal treated with test compound observed on day 0th(pre treatment) and then 7thand 14th(post treatment) did not show any significant increase or decrease in their body weight. Necropsy was conducted on day 15th(end of study) on all the animals which did not reveal any significant gross pathological changes related to compound toxicity.

From the results obtained from present investigation, it can be concluded that the test chemical is non toxic to Wistar albino rats at the dose level of 2000 mg/kg body weight and the LD50 of this compound is >2000 mg/kg body weight.

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