Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 11, 2012 - December 12, 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): NOPCOTE 1661
- Physical state: Clear, light yellow solution
- Analytical purity: 46% in water solution.
- Lot/batch No.: 79389
- Expiration date of the lot/batch: 11 January 2013
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld.- Age at study initiation: Young healthy adult rats, approximately 8-9 weeks old.- Weight at study initiation: 171 - 190 g.- Fasting period before study: The night before treatment the animals will be fasted. - Housing: 3 animals/cage.- Diet (e.g. ad libitum): Ad libitum.- Water (e.g. ad libitum): Ad libitum.- Acclimation period: 5-6 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 19.9 – 24.1°C- Humidity (%): 30 - 52 %.- Air changes (per hr): 15-20 air exchanges/hour .- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
(distilled)
Details on oral exposure:
VEHICLE:- Amount of vehicle (if gavage): 200 mg/mL- Lot/batch no. (if required): 3450611MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bwDOSAGE PREPARATION (if unusual): The test item was freshly formulated at a concentration of 200 mg/mL in the vehicle. The formulation container was stirred continuously up to finishing the treatment. The purity factor was 2.18, therefore the dose to be adjusted was 2000 x 2.18 mg/kg bw prepared in distilled water at a dose volume of 10 ml/kg bw. With this the dose level was 2000 mg/kg bw referring to the dry component (46%) of the test item.CLASS METHOD (if applicable)- Rationale for the selection of the starting dose: In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 females rats per group (group 1 and confirmatory group 2).
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.- Frequency of observations and weighing: Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was measured on Days -1, 0 and 7 and Day 14 before necropsy.- Necropsy of survivors performed: Yes, all animals were subjected to a necropsy and a macroscopic examination.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Treatment did not cause mortality.
Clinical signs:
Treatment caused decreased activity, hunched back and piloerection.
Body weight:
Body weight gains did not show any test item related effect during the study.
Gross pathology:
Treatment was not associated with any test item related gross findings.

Any other information on results incl. tables

Table 1. Clinical observations.

 

Dose level: 2000 mg/kg bw, Treatment on day 0.                                     Sex: Female.

Cage No.

Animal number

Observations

Observation days

Frecuency

0

1

2

3

4

5

6-14

30’

1h

2h

3h

4h

6h

1

8156

Symptom Free

-

-

-

-

-

-

-

+

+

+

+

+

13/20

Activity decreased

-

-

-

1

1

-

-

-

-

-

-

-

2/20

Hunched back

+

+

+

+

+

+

-

-

-

-

-

-

6/20

Piloerection

-

-

+

+

+

+

+

-

-

-

-

-

5/20

8157

Symptom Free

-

-

-

-

-

-

+

+

+

+

+

+

14/20

Activity decreased

-

-

-

1

1

-

-

-

-

-

-

-

2/20

Hunched back

+

+

+

+

+

+

-

-

-

-

-

-

6/20

Piloerection

-

-

+

+

+

-

-

-

-

-

-

-

3/20

8158

Symptom Free

-

-

-

-

-

-

+

+

+

+

+

+

14/20

Activity decreased

-

-

-

1

-

-

-

-

-

-

-

-

1/20

Hunched back

+

+

+

+

+

+

-

-

-

-

-

-

6/20

Piloerection

-

-

+

+

+

-

-

-

-

-

-

-

3/20

2

8159

Symptom Free

-

-

-

-

-

-

+

+

+

+

+

+

14/20

Hunched back

+

+

+

+

+

+

-

-

-

-

-

-

6/20

Piloerection

-

-

-

+

+

-

-

-

-

-

-

-

2/20

8160

Symptom Free

-

-

-

-

-

-

+

+

+

+

+

+

14/20

Hunched back

+

+

+

+

+

+

-

-

-

-

-

-

6/20

Piloerection

-

-

-

+

+

-

-

-

-

-

-

-

2/20

8161

Symptom Free

-

-

-

-

-

-

+

+

+

+

+

+

14/20

Hunched back

+

+

+

+

+

+

-

-

-

-

-

-

6/20

Piloerection

-

-

-

+

+

-

-

-

-

-

-

-

2/20

Remarks:

+ = present                          - = absent

h = hour (s)                          ‘ = minute

Frequency of observation = number of occurrence of observation / total number of observations

Severities: 1 = Slight/Small/Few; 2 = Moderate/Medium; 3 = Marked/Large/Many

 

  

Table 2. Body weight data.

 

Dose level: 2000 mg/kg bw, Treatment on day 0.                                     Sex: Female.

Cage No.

Animal number

Body weight (g)

Days

Body Weight Gain (g)

-1

0

7

14

-1 - 0

0 - 7

7 - 14

-1 - 14

1

8156

191

181

203

224

-10

22

21

33

8157

200

184

224

252

-16

40

28

52

8158

198

187

217

229

-11

30

12

31

2

8159

185

171

198

205

-14

27

7

20

8160

195

189

218

226

-6

29

8

31

8161

199

190

221

238

-9

31

17

39

Mean:

194.7

183.7

213.5

229.0

-11.0

29.8

15.5

34.3

Standard deviation:

5.8

7.0

10.5

15.6

3.6

5.9

8.1

10.6

 

  

Table 3. Necropsy findings.

 

Dose level: 2000 mg/kg bw, Treatment on day 0.                                     Sex: Female.

Cage No.

Animal number

Necropsy Day

External Observations

Internal Observations

Organ/Tisuue

1

8156

Day 14

No external observations recorded

No internal observations recorded

Not applicable

8157

Day 14

No external observations recorded

No internal observations recorded

Not applicable

8158

Day 14

No external observations recorded

No internal observations recorded

Not applicable

2

8159

Day 14

No external observations recorded

No internal observations recorded

Not applicable

8160

Day 14

No external observations recorded

No internal observations recorded

Not applicable

8161

Day 14

No external observations recorded

No internal observations recorded

Not applicable

 

 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 value of the test substance was >2000 mg/kg bw in female rats.
Executive summary:

The single-dose oral toxicity was performed according to OECD 423 Guideline and EU B.1tris Method (acute toxic class method) in female CRL: (WI) rats. Two groups (one confirmatory group) of three rats were exposed by single oral treatment to 2000 mg/kg bw. Mortality, clinical observations and body weight were analyzed for 14 days after exposure. In day 14, necropsy was performed and all animals were subjected to a necropsy and a macroscopic examination. No effects on mortality, body weight and macroscopic findings were observed. Treatment caused decreased activity, hunched back and piloerection. Under the conditions of this study, the acute oral LD50 was determined to be greater than 2000 mg/kg bw in female rats.