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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
20 July 2009 - 16 September 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report date:
2009

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
Concerning: Housing and Feeding Conditions, study plan, p. 11 Before: Semi-barrier in an air-conditioned room New: Full-barrier in an air-conditioned room Reason: Typing error. This deviation did not influence the quality or integrity of the present study
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Test System
Species/strain: Healthy rats, WISTAR rats Crl: WI(Han) (Full-Barrier)
Source: Charles River, 97633 Sulzfeld, Germany
Sex: female, non-pregnant, nulliparous
Number of animals: 3 per step
Age at the beginning of the study: 8 - 10 weeks old
Body weight at the beginning of the study:
Animals no. 1 – 3, step 1: 162 – 181 g;
Animals no. 4 – 6, step 2: 165 – 170 g;
The animals were derived from a controlled full barrier maintained breeding system (SPF). According to Art. 9.2, No.7 of the German Act on Animal Welfare the animals were bred for experimental purposes.

Housing and Feeding Conditions
- Full barrier in an air-conditioned room
- Temperature: 22  3 °C
- Relative humidity: 55  10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x / hour
- Free access to Altromin 1324 maintenance diet for rats and mice (lot no. 1131)
- Free access to tap water, sulphur acidified to a pH value of approx. 2.8 (drinking water, municipal residue control, microbiologically controlled at
frequent intervals)
- The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 050109)
- Certificates of food, water and bedding are filed at BSL BIOSERVICE
- Adequate acclimatisation period

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Doses:
The starting dose was selected to be 2000 mg/kg body weight. No compound related mortality was recorded for any animal of step 1 or 2. Based on these results and according to the acute toxic class method regime no further testing was required.
No. of animals per sex per dose:
6 female WISTAR Crl: WI (Han) rats
Control animals:
no
Details on study design:
Preparation of the Animals
The animals were marked for individual identification by tail painting.
Prior to the administration a detailed clinical observation was made of all animals.
Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted). Following the period of fasting the animals were weighed and the test item was administered. Food was provided again approximately 4 hours post dosing.

Administration
The test item was administered at a single dose by gavage using a feeding tube. For all animals, the test item was administered at a dose volume of 10 mL/kg body weight.

Dose Level
The starting dose was selected to be 2000 mg/kg body weight. No compound related mortality was recorded for any animal of step 1 or 2. Based on these results and according to the acute toxic class method regime no further testing was required.

Observation Period
All animals were observed for 14 days after dosing for general clinical signs, morbidity and mortality.

Weight Assessment
The animals were weighed on day 1 (prior to the administration) and on day 8 and on day 15.

Clinical Examination
A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). As soon as symptoms were noticed they were recorded. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities were recorded. Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Pathology
At the end of the observation period, the animals were sacrificed by an overdosage of pentobarbital injected intraperitoneally (Narcoren®, Merial; lot no.: 189039; expiry date: March 2012) at a dosage of approx. 8 mL/kg bw. All animals were subjected to gross necropsy. All gross pathological changes were
recorded.

Evaluation of Results
Results were interpreted according to OECD Guideline 423, Annex 2 (see also flow charts in the appendix of the study plan).
Individual reactions of each animal were recorded at each time of observation.
Toxic response data were recorded by dose level.
Nature, severity and duration of clinical observations were described.
Body weight changes were summarised in tabular form.
Necropsy findings were described.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
5 000 mg/kg bw
Mortality:
Under the conditions of the present study, single oral application of the test item Diniobium Pentaoxide (Nb2O5) to rats at a dose of 2000 mg/kg body weight was neither associated with signs of toxicity nor mortality.
Clinical signs:
no signs of toxicity during the whole observation period
Body weight:
None of the animals showed weight loss during the observation period
Gross pathology:
With the exception of acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no special gross pathological changes were recorded for any animal of the two steps.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information