Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study without any deviations

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

Test material

Constituent 1
Chemical structure
Reference substance name:
Zirconium
EC Number:
231-176-9
EC Name:
Zirconium
Cas Number:
7440-67-7
Molecular formula:
Zr
IUPAC Name:
zirconium
Details on test material:
Purity: > 99.4%
Density: 6.5 g/cm³
Colour: grey
Physical State at RT: solid, powder (< 0.1 mm)
Storage: at room temperature, in a tightly closed package
Stability in Container after Opening: stable

Safety Precautions: Beside routine hygienic procedures additional actions will be taken to assure personnel health and safety, such as
- Powder was stored and handled under Argon gas
- No water was used for any of the dose preparations
- Personal protective equipment was used while handling the substance

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Females were non-pregnant and nulliparous.
Age at the beginning of the study: approximately 8 - 9 weeks old
Body weight at the beginning of the study: animals no. 1 – 3, step 1: 159 – 177 g; animals no. 4 – 6, step 2: 161 – 168 g;
The animals were derived from a controlled full-barrier maintained breeding system (SPF).

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 diet and tap water
- The animals were kept in groups in IVC cages
- Certificates of food, water and bedding are filed at BSL BIOSERVICE
- Adequate acclimatisation period (at least five days)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The test item was administered at a single dose by gavage using a feeding tube.
The test item was administered at a dose volume of 5 mL/kg body weight.

Details on test item preparation
A solubility test was performed with the vehicle corn oil. No solubility was achieved, but a suspension applicable to the animals. Homogeneity of the test item in the vehicle was maintained by shaking the prepared suspension thoroughly before every dose administration.
For all animals of the first and second step, 2 g of the test item were suspended in the vehicle to gain a final volume of 5 mL and to achieve a dose of 2000 mg/kg body weight at a dose volume of 5 mL/kg body weight.
The dose formulations were made shortly before each dosing occasion.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 per step
Control animals:
no
Details on study design:
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.
Statistics:
no

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 cut off
Mortality:
no mortality
Clinical signs:
no signs of toxicity observed
Body weight:
Throughout the 14-day observation period, the body weight gain of the animals was within the normal range of variation for this strain.
Gross pathology:
With the exception of acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no specific gross pathological changes were recorded for any animal

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the condition of this test, a single oral application of Zirconium Powder to rats at a dose of 2000 mg/kg body weight was associated with no signs of toxicity or mortality. The median lethal dose of Zirconium Powder after a single oral administration to female rats, observed over a period of 14 days, is 5000 mg/kg body weight.
Executive summary:

Two groups, each of three female WISTAR Crl: WI(Han) rats, were treated with Zirconium by oral gavage administration at a dosage of 2000 mg/kg body weight.The animals were observed on delivery, on inclusion in the study and before administration for mortality/morbidity and other clinical signs. All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the observation period. Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15.

All animals were necropsied and examined macroscopically. Throughout the 14-day observation period, all animals survived until the end of the study without showing any signs of toxicity.In conclusion, the median lethal dose of Zirconium after a single oral administration to female rats, observed over a period of 14 days is 5000 mg/kg body weight (LD50 cut off).

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