Registration Dossier

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
Justification for type of information:
Data is from 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:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
Acute Dermal Toxicity Study of test chemical in Wistar albino rats
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Source :Institute for Industrial Research and Toxicology Ghaziabad,
Age: 8 to 10 weeks
Sex: Male and female
Body weight range : 200±20g
Identification : By cage tag and corresponding colour body marking
No. of animals per dose group : 10 (5male & 5 female)
No. of dose groups : Group-I: 2000 mg/kg b.wt (limit test), Group-II: 2000 mg/kg b.wt (confirmatory test)
Acclimatization : 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.
Nutritional conditions : Animals were fasted overnight prior to test and food was offered three hours after dosing.
Environmental conditions : Air conditioned rooms with 10-15 air changes per hour, temperature between 22-250C, relative humidity 40-60% and illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark.
Accommodation : 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 : Pelleted feed supplied by Pranav agro Industries Ltd., B7/6 Ramesh Nagar, Delhi, India
Water : Fresh and clean water filtered through ‘Aqua Guard on line water filter’, was kept in glass bottles Ad libitum


Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
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: Impervious dressing were used.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, cleaned with lukewarm water wiping
- Time after start of exposure:24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg b.wt
- Concentration (if solution):
- Constant volume or concentration used: yes
- For solids, paste formed: no
Duration of exposure:
:24 hours
Doses:
2000 mg/kg b.wt
No. of animals per sex per dose:
Total: 20
2000 mg/kg b.wt (limit test): 5 male & 5 female
2000 mg/kg b.wt (confirmatory test): 5 male & 5 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:Animals were observed for first 4 hours and thereafter for every 1 hrs interval for 24 hrs after dosing and twice a day for 14 days
- Necropsy of survivors performed: yes
- Other examinations performed:Mortality, clinical signs, body weight and gross pathology were examined.

Results and discussion

Effect levels
Key result
Sex:
male/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 at 2000 mg/kg b.wt in wistar albino rats were observed throughout the period of observation14 days.
Clinical signs:
No clinical signs of toxicity were observed in entire the observation period of 14 days.
Body weight:
Normal gain in body weight was observed on day 7th and 14th (post treatment) as compared to day 0th (pre treatment).
Gross pathology:
No significant gross pathological changes related to compound toxicity were observed.

Any other information on results incl. tables

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

 

 

 

20172-1

201.3

207.1

2.88

213.4

6.01

20172-2

200.2

205.3

2.54

210.3

5.04

20172-3

200.5

206.4

2.94

213.2

6.33

20172-4

203.4

210.3

3.39

212.4

4.42

20172-5

199.6

206.7

3.56

210.5

5.46

20172-6

206.4

210.4

1.93

215.3

4.31

20172-7

202.7

207.4

2.31

212.1

4.63

20172-8

207.5

212.4

2.36

217.3

4.72

20172-9

203.4

209.3

2.90

212.4

4.42

20172-10

202.1

205.5

1.68

212.4

5.09

Group-II

2000 mg/kg b. wt

20172-11

198.4

209.2

5.44

208.1

4.88

20172-12

205.5

211.3

2.82

216.6

5.40

20172-13

206.4

212.2

2.81

217.4

5.32

20172-14

202.4

207.4

2.47

213.4

5.43

20172-15

203.5

207.1

1.76

213.1

4.71

20172-16

207.7

214.3

3.17

217.4

4.67

20172-17

200.4

207.3

3.44

209.2

4.39

20172-18

197.4

202.7

2.68

210.2

6.48

20172-19

205.3

210.4

2.48

216.1

5.26

20172-20

206.6

211.4

2.32

218.4

5.71

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

CLINICAL SIGNS AND MORTALITY

Group: II Confirmatory test                                               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

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

INDIVIDUAL ANIMAL FATE & NECROPSY FINDINGS

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

Animal ID

Fate

Time

Gross Findings

20172-1

TS

Day 14

NAD

20172-2

TS

Day 14

NAD

20172-3

TS

Day 14

NAD

20172-4

TS

Day 14

NAD

20172-5

TS

Day 14

NAD

20172-6

TS

Day 14

NAD

20172-7

TS

Day 14

NAD

20172-8

TS

Day 14

NAD

20172-9

TS

Day 14

NAD

20172-10

TS

Day 14

NAD

Day 0 is the day of dose administration.

TS- Terminal Sacrifice

NAD- No abnormality Detected

INDIVIDUAL ANIMAL FATE & NECROPSY FINDING

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

Animal ID

Fate

Time

Gross Findings

20172-11

TS

Day 14

NAD

20172-12

TS

Day 14

NAD

20172-13

TS

Day 14

NAD

20172-14

TS

Day 14

NAD

20172-15

TS

Day 14

NAD

20172-16

TS

Day 14

NAD

20172-17

TS

Day 14

NAD

20172-18

TS

Day 14

NAD

20172-19

TS

Day 14

NAD

20172-20

TS

Day 14

NAD

 Day 0 is the day of dose administration.

TS- Terminal Sacrifice

NAD- No abnormality Detected

FD-Found dead

FD-Found dead

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Conclusions:
LD50 of test compound was found to be more than 2000 mg/kg b.wt. (>2000 mg/kg b.wt.) when Wistar albino male and female rats.treated dermally.
Executive summary:

In a acute dermal toxicity study, Wistar albino male and female rats treated with test chemical dermally at 2000 mg/kg b.wt applied uniformly over approximate 10 percent back skin of total body surface area for 24 hrs 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. After 24 hours, the dressing was removed and the site of application was cleaned with lukewarm water wiping. No mortality at 2000 mg/kg b.wt in wistar albino rats were observed throughout the period of observation14 days. No clinical signs of toxicity were observed in entire the observation period of 14 days. Normal gain in body weight was observed on day 7th and 14th (post treatment) as compared to day 0th (pre treatment). No significant gross pathological changes related to compound toxicity were observed. Therefore, LD50 of test compound was found to be more than 2000 mg/kg b.wt. (>2000 mg/kg b.wt.) when Wistar albino male and female rats treated dermally.