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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:
2014-10-29 to 2014-11-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
2015

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Zirconium dinitrate oxide
EC Number:
237-529-3
EC Name:
Zirconium dinitrate oxide
Cas Number:
13826-66-9
Molecular formula:
N2O7Zr
IUPAC Name:
zirconium dinitrate oxide
Test material form:
solid
Details on test material:
Name of test material (as cited in study report): zirconium dinitrate oxide

Test animals

Species:
rat
Strain:
other: CRL:(WI) SPF
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
- Age at dosing: young, healthy adult rats, 9-10 weeks old
- Weight at treatment: 208-233 g
- Fasting period before study: yes, the night before treatment, food but not water was withheld during an overnight period. Food was returned 3 hours after treatment.
- Housing: 3 animals per cage, in Type II polypropylene/polycarbonate cages with Lignocel Bedding for laboratory animals
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.9-25.0°C
- Humidity (%): 30-70%
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2014-10-29 To: 2014-11-20

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: PBS (phosphate buffered saline)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 or 200 mg/mL (referring to anhydrous zirconium dinitrate oxide)
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: The selection of the vehicle was made during trial formulation with the test item in distilled water and PBS at 3 concentrations that could be used for dosing 2000, 300 and 50 mg/kg as active ingredient (anhydrous zirconium dinitrate oxide). PBS was used further in the study, since the test item has an extremely low pH in distilled water.
- Lot/batch no. (if required): BCBJ5262V
- Purity: no data
- Expiry date: 2017-02-28

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION (if unusual):
The test item was freshly formulated at a concentration of 200 or 30 mg/mL (as active ingredient, anhydrous zirconium dinitrate oxide) in the vehicle, in the Central Dispensary Unit of CiToxLAB Hungary Ltd. on the day of administration. The formulation container was stirred continuously up to finishing the treatment.
CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The initial dose level was most likely to produce mortality in some of the dosed animals. In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.
Doses:
2000 mg/kg bw in one group (as active ingredient) (anhydrous zirconium dinitrate oxide)
300 mg/kg bw in two groups (as active ingredient) (anhydrous zirconium dinitrate oxide)
No. of animals per sex per dose:
3 females per group
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. Individual observations were performed on skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor acitvity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly thereafter. Body weight of the animals found dead was recorded at necropsy
- Necropsy of survivors performed: yes. Macroscopic examination was performed on all animals. The animals were sacrificed by exsanguination under pentobarbital anaesthesia. After examination of external appearance, the cranial, thoracic and the abdominal cavities were opened and organs and tisses were observed. Macroscopic abnormalities were recorded.



Statistics:
no data

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
act. ingr.
Remarks:
anhydrous zirconium dinitrate oxide
Mortality:
Mortality was observed in all animals receiving a single dose of 2000 mg/kg bw (3/3) on Day 1 or 2 or 4. No mortality was observed at the dose level of 300 mg/kg bw.
Clinical signs:
At 2000 mg/kg bw (expressed as anhydrous zirconium dinitrate oxide), the test item caused decreased activity (3/3), hunched back (3/3), incoordination (2/3), piloerection (2/3), dyspnoea (1/3), red discharge from the eye and around the nose (1/3).
At 300 mg/kg bw, hunched back was observed in 5/6 animals. All animals were symptom-free 6 hours after the treatment until the end of the observation period.
Body weight:
Body weight gains of test item treated animals during the study showed no indication of a test item-related effect at the dose level of 300 mg/kg bw.
Gross pathology:
- In animals found dead (from 2000 mg/kg bw group): Diffuse red coloration of the glandular stomach mucosa found in 2/3 found dead females, was considered to be potentially test item-related. However, definitive attribution of this change to the test item cannot be made in absence of histopathological examination. The changes in the lungs were typical for found dead animals.
- In surviving animals: No macroscopic observations were seen at a dose level of 300 mg/kg bw.
Other findings:
- Deviation from the study plan: Due to a typographical error, the pH value of the test item was reported to be 1.73 for the 7.35 mg/mL concentration in distilled water and 1.21 for the 294 mg/mL concentration in PBS in the Study plan. The correct values are 1.79 and 0.68, respectively. This deviation is considered to have no impact on the outcome of the study and interpretation of the results.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the conditions of this study, the acute oral LD50 value of zirconium dinitrate oxide was found to be between 300 and 2000 mg/kg bw in female CRL:(WI) rats. According to the GHS and CLP criteria, zirconium dinitrate oxide can be ranked as Category 4 for acute oral exposure.