Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
4 June 2010 - 20 June 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material : J-37
- Substance type: red powder
- Physical state: powder
- Analytical purity: 99.3%
- Lot/batch No.: 91116
- Expiration date of the lot/batch: 16th April 2011
- Storage condition of test material: at room temperature in the dark in desiccators
- Stability under test conditions: stable

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approximately. 8 weeks old
- Weight at study initiation: Body weight variation did not exceed ± 20% of the sex mean.
- Fasting period before study: Overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available.
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm) containing sterlised sawdust as bedding material (Litalabo, S. P. P. S., Argenteuil, France) and paper as cage- enrichment (Enviro-dri, Wm. Lilico & Son (Wonham Mill Ltd), Surrey, UK).
- Diet : free access to pelleted rodent diet (SM R/M-Z from SSNIFF Spezialdiäten GmBH, Soest, Germany)
- Water : free access to tap water
- Acclimation period: 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0 (actual range: 19.7 - 21.5)
- Humidity (%): 40 - 70 (actual range: 38 - 75)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours artifical fluorescent light and 12 hours darkness per day

IN-LIFE DATES: 4 June 2010 - 20 June 2010

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/ kg

Doses:
2000 mg/kg bw and 300 mg/kg bw
No. of animals per sex per dose:
6 animals at 300 mg/kg bw
3 animals at 2000 mg/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Mortality/viability - twice daily. Body weights - Days 1 (pre-administration), 8 and 15 at death (if found deat or sacrificed after Day 1). Clinical signs - At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: yes. The moribund animal and animals surviving to the end of the observation period were sacrificed by oxygen/carbon dioxide procedure.
- Other examinations performed: histopathology.

Clinical signs: The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1)
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
other: LD50 cut-off value according to OECD 423 test guideline
Effect level:
500 mg/kg bw
Based on:
test mat.
Mortality:
All females at 2000 mg/kg were found dead or sacrificed in moribund condition on Day 2. No mortality occurred at 300 mg/kg (Table 1).
Clinical signs:
At the 2000 mg/kg dose level - Lethargy, flat/hunched posture, piloerection,watery discharge from the eye, pale appearance and/or hypothermia on Day 1 and/or 2 (all animals).
At 300 mg/kg dose level- Hunched posture and/or piloerection on Day 1 (all animals).
Body weight:
The body weight gain shown by the survivng animals over the study period was considered to be similar to the expected of normal untreated animals of the same age and strain (Table 2).
Gross pathology:
At the 2000 mg/kg dose level - watery-clear fluid in the abdominal cavity on one animal, a beginning stage of autolysis in two animals and hard contents of the stomach in all animals (Table 3).
At 300 mg/kg dose level- Pelvic dilation of the kidneys (one animal).

Any other information on results incl. tables

Table 1.Mortality data.

Test Day

1

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

Hours after treatment

0

2

4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Female 2000 mg/kg

-

-

-

3

-

-

-

-

-

-

-

-

-

-

-

-

-

Female 300 mg/kg

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Female 300 mg/kg

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Table 2. Body weight.

Sex/ dose level

Animal

Day 1

Day 2

Day 8

Day 15

Female 2000 mg/kg

 

 

 

 

 

1

169

169

-

-

2

169

171

-

-

3

169

172

-

-

Mean

169

171

-

-

St.Dev

0

2

-

-

N

3

3

0

0

Female 300 mg/kg

 

 

 

 

 

4

159

-

194

209

5

153

-

173

185

6

160

-

188

195

Mean

157

-

185

196

St.Dev

4

-

11

12

N

3

0

3

3

Female 300 mg/kg

 

 

 

 

 

7

167

-

193

204

8

150

 

175

186

9

158

-

181

194

Mean

158

 

181

194

St.Dev

9

-

9

9

N

3

0

3

3

 

   Table 3. Macroscopic findings.

Animal

Organ

Finding

Day of Death

Female 2000 mg/kg

 

 

 

1

General observations

Abdominal cavity: contains fluid, watery clear

Killed in extremis Day 2 after treatment.

Stomach

Contents: hard

2

General observations

Beginning autolysis.

Spontaneous death Day 2 after treatment.

Stomach

Contents: hard

3

General observations

Beginning autolysis.

Spontaneous death Day 2 after treatment.

Stomach

Contents: hard

Female 300 mg/kg

 

 

 

4

 

No findings noted

Scheduled necropsy Day 15 after treatment.

5

 

No findings noted

Scheduled necropsy Day 15 after treatment.

6

Kidneys

Both sides; pelvic dilations.

Scheduled necropsy Day 15 after treatment.

Female 300 mg/kg

 

 

 

7

 

No findings noted

Scheduled necropsy Day 15 after treatment.

8

 

No findings noted

Scheduled necropsy Day 15 after treatment.

9

 

No findings noted

Scheduled necropsy Day 15 after treatment.

 


Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU