Reaction mass of disodium oxide and zirconium dioxide and silicon dioxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-04-13 to 2010-04-29

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 guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of silicon dioxide and zirconium dioxide

EC Number:

910-388-1

Molecular formula:

not applicable (multi-constituent substance)

IUPAC Name:

Reaction mass of silicon dioxide and zirconium dioxide

Details on test material:

- Name of test material (as cited in study report): Silica-Zirkonia Filler
- Physical state: White powder
- Batch: IT-253
- Analytical purity of components: 72.4% silicon dioxide (CAS No. 7631-86-9) and 26.0% zirconium dioxide (CAS No. 1314-23-4) and a not stated percentage of disodium oxide (CAS No. 1313-59-3)
- Storage: at room temperature in the dark
- Stability: stable under storage conditions
- Expiry date: 20 Nov 2010
- not soluble in water

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 8 weeks old)
- Weight at study initiation: weight variation did not exceed +/- 20% of the sex mean
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available
- Housing: 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom)
- Diet (e.g. ad libitum): SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0
- Humidity (%): 40-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: According to guideline

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

2 sets of 3 animals were treated with the same dose:
First set of females on 13 April 2010
Second set of females on 15 April 2010

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/Viability: Twice daily; Body weights: Days 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical signs: At periodic intervals on the day of dosing (within 5 minutes after dosing and approximately 2 and 4 hours after dosing on Day 1) and once daily thereafter, until Day 15.

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Mortality:

No mortality occurred.

Clinical signs:

other: Hunched posture and/or piloerection were noted for all animals on Day 1.

Gross pathology:

No abnormalities

Any other information on results incl. tables

The oral LD50 value of Silica-Zirkonia Filler in Wistar rats was established to exceed 2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU