Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
27 September 2011 to 12 October 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

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 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
other: JMAFF 12 Nousan 8147 (2000)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Physical state: White to pale yellow powder with a slightly characteristic odour.
- Storage condition of test material: Room temperature (15-25 ºC) in the dark.

Test animals

Species:
rat
Strain:
other: CRL:(WI)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 9 weeks old.
- Weight at study initiation: 238 – 265 g.
- Fasting period before study: Yes, animals were fasted the day before dosing, food being returned 3 hours after treatment.
- Housing: Animals were housed in groups of 3 in Type II polypropylene/polycarbonate cages.
- Diet: Complete feed for rats and mice, ad libitum.
- Water: Municipal tap water, ad libitum.
- Acclimation period: At least 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 15-20 air exchanges/hour.
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 06:00 to 18:00 hours.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
DOSAGE PREPARATION: Test material was freshly formulated at a concentration of 200 mg/mL in the vehicle on the day of administration. The formulation container was stirred continuously up to finishing the treatment.

CLASS METHOD
- Rationale for the selection of the starting dose: The initial dose level was selected by the study director to be that which was most likely to produce mortality in some of the dosed animals.

ADMINISTRATION: Group 1 was dosed first at 2000 mg/kg bw . The results were then confirmed by dosing Group 2 in the same manner.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Six females per dose, tested in two groups of 3 animals.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing:
> Clinical observations were performed at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and then daily until day 14. Observations included assessment of the skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
> Bodyweights were measured on Days -1, 0, 7 and 14 prior to necropsy.
- Necropsy of survivors performed: yes
- Other examinations performed: After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed in either Group 1 or 2.
Clinical signs:
Liquid faeces was observed in all animals, treated at a dose level of 2000 mg/kg bw, on the day of dosing. All animals fully recovered and were symptom free from 6 hours after the treatment until the end of the observation period.
Body weight:
No treatment related effects were observed.
Gross pathology:
There was no evidence of treatment related findings at necropsy. Pelvic dilatation of the right kidney was incidentally observed in one animal.

Any other information on results incl. tables

Table1: Clinical Observations

Group

Animal No.

Observations

Observation Days

Frequency

0

1 - 14

30 min

1 h

2 hrs

3 hrs

4 hrs

6 hrs

1

8861

Symptom Free

+

+

+

-

+

+

+

19/20

Faeces liquid

-

-

-

1

-

-

-

1/20

8862

Symptom Free

+

+

+

-

+

+

+

19/20

Faeces liquid

-

-

-

1

-

-

-

1/20

8863

Symptom Free

+

+

+

-

-

+

+

18/20

Faeces liquid

-

-

-

1

1

-

-

2/20

2

8864

Symptom Free

+

+

+

-

+

+

+

19/20

Faeces liquid

-

-

-

1

-

-

-

1/20

8865

Symptom Free

+

+

+

-

+

+

+

19/20

Faeces liquid

-

-

-

1

-

-

-

1/20

8866

Symptom Free

+

+

+

-

+

+

+

19/20

Faeces liquid

-

-

-

1

-

-

-

1/20

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

 

Table 2: Bodyweights (g)

Group No.

Animal No.

Body weight (g) on Days

Weight Gain (g)

-1

0

7

14

-1 - 0

0 - 7

7 -14

-1 - 14

1

8861

281

265

296

301

-16

31

5

20

8862

273

256

288

296

-17

32

8

23

8863

269

251

290

304

-18

39

14

35

2

8864

266

249

281

290

-17

32

9

24

8865

257

239

267

277

-18

28

10

20

8866

255

238

257

274

-17

19

17

19

Mean:

266.8

249.7

279.8

290.3

-17.2

30.2

10.5

23.5

Standard Deviation:

9.8

10.3

15.0

12.5

0.8

6.6

4.3

6.0

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, no signs of acute toxicity were observed, and it can be concluded that the acute oral LD50 is greater than 2000 mg/kg bw.
Executive summary:

The acute oral toxicity of the test material was assessed in study performed under GLP conditions and in line with OECD 423 and EU Method B.1 tris according to the acute toxic class method. Female CRL:(WI) rats were treated with the test material at a dose level of 2000 mg/kg bw in two groups. Initially, three females (Group 1) were treated at a dose level of 2000 mg/kg bw. As no mortality was observed, a confirmatory group (Group 2) was treated at the same dose level.

Under the conditions of the study no mortality was observed in either group. Animals showed normal weight gain. Liquid faeces were observed in all animals on the day of dosing; all animals had fully recovered, and were symptom free, from 6 hours after the treatment until the end of the observation period. There was no evidence of treatment related findings at necropsy. Pelvic dilatation of the right kidney was incidentally observed in one animal. It can therefore be concluded that the acute oral LD50 of the test material is in excess of 2000 mg/kg bw.