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Acute Toxicity: dermal

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

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 in Wistar rats
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
SOURCE OF TEST MATERIAL
- Name of test material (as cited in study report): benzimidazole-2-thiol (2-MBI, 1,3-dihydrobenzimidazole-2-thione)
- Source and lot/batch No.of test material: Ouchi Shinko Chemical Ind., Ltd.(Osaka, Japan)
- Molecular formula (if other than submission substance): C7H6N2S
- Molecular weight (if other than submission substance):150.204 g/mole
- Substance type:organic

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Institute for Industrial Research and Toxicology
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: 200±20g
- Fasting period before study: Animals were fasted overnight prior to test and food was offered three hours after dosing.
- 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 (ad libitum)
- 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.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22-25 degC
- Humidity (%): 40-60%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light):12 hours artificial fluorescent light and 12 hours dark.

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 back skin of total body surface area.
- Type of wrap if used: Adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The site of application was cleaned with lukewarm water

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight.
Duration of exposure:
not specified
Doses:
Two 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: Daily
- Necropsy of survivors performed: yes
- Other examinations performed:
Body weight:
The body weight of all the animals was observed weekly on day 0 (pre treatment), 7th and 14th (post treatment).

Clinical signs
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 autonomic systems, somatomotor activity and behavioral changes. The following clinical signs were observed in female rats to characterize with erythema, hypersensitivity, edema etc. The clinical sign will be graded as 0 = Normal, + = Mild, ++= Moderate, +++ =High & ++++ = Severe.

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.
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 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 showed normal gain in body weight as compared to control group on day 0th (pre treatment).
Gross pathology:
NECROPSY FINDING
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.

1.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
I.Brain- Normal in shape and size.
Other findings:
not specified

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

 

 

 

201310-1

187

193

3.20

206

10.1

201310-2

201

210

4.47

223

10.9

201310-3

206

214

3.88

226

9.70

201310-4

214

224

4.67

228

6.54

201310-5

195

203

4.10

213

9.23

201310-6

183

192

4.91

201

9.83

201310-7

203

211

3.94

223

9.85

201310-8

199

208

4.52

224

12.5

201310-9

215

222

3.25

235

9.30

201310-10

209

216

3.34

229

9.56

Group-II

2000 mg/kg b. wt

201310-11

211

219

3.79

225

6.63

201310-12

185

195

5.40

212

14.5

201310-13

203

209

2.95

219

7./88

201310-14

221

234

5.88

242

9.50

201310-15

183

190

3.82

211

15.3

201310-16

202

211

4.95

217

7.42

201310-17

200

213

6.5

218

9.0

201310-18

193

204

5.69

215

11.3

201310-19

184

193

4.89

205

11.4

201310-20

216

227

5.09

233

7.87

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                                                        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

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Conclusions:
Based on the results obtained from present investigation, it can be concluded that the test compound is non toxic to Wistar albino rats at the dose level of 2000 mg/kg body weight. The acute dermal LD50 of test compound was considered to be >2000 mg/kg b.wt. Thus, according to CLP criteria the test compound can be classify under non toxic category at the tested dose level of 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), 7thand 14th(post treatment). The necropsy was performed on all animals at the termination of the study.

The test compound 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). The necropsy was performed on all animals at the termination of the study did not show any 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.

The test compound did not produce any mortality at the tested dose level of 2000 mg/kg b.wt in wistar albino rats throughout the period of observation. Furthermore, the test compound did not elicit any clinical signs of toxicity during the entire the observation period.

The body weight of each animal treated with test compound observed on day 0th (pre treatment) and then 7th and 14th (post treatment) showed normal gain as compared to day 0. Necropsy was conducted on day 15th(end of study) did not reveal any significant gross pathological changes related to compound toxicity.

Based on the results obtained from present investigation, it can be concluded that the test compound is non toxic to Wistar albino rats at the dose level of 2000 mg/kg body weight. The acute dermal LD50 of test compound was considered to be >2000 mg/kg b.wt. Thus, according to CLP criteria the test compound can be classify under non toxic category at the tested dose level of 2000 mg/kg body weight.