Zirconium dioxide

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Documentation insufficient for assessment.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

The acute, chronic and topical toxicity of zirconium carbonate.

Author:

Harrison, J.W.E., Trabin, B., Martin, E.W.

Year:

1951

Bibliographic source:

Journal of Pharmacology and Experimental Therapeutics 102, 179-184

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

9-week exposure of kittens via the diet

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

[μ-[carbonato(2-)-O:O']]dihydroxydioxodizirconium

EC Number:

260-633-5

EC Name:

[μ-[carbonato(2-)-O:O']]dihydroxydioxodizirconium

Cas Number:

57219-64-4

IUPAC Name:

57219-64-4

Test material form:

semi-solid (amorphous): gel

Remarks:

migrated information: paste

Details on test material:

- Name of test material (as cited in study report): hydrated zirconium carbonate
- Molecular formula (if other than submission substance): 3ZrO2.CO2.H2O
- Physical state: water insoluble moist paste
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: containing 20.9 % ZrO2

Test animals

Species:

cat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: kittens
- Weight at study initiation: 600 g
- Fasting period before study: no data
- Housing: kittens at the same dosage level were housed together
- Diet (e.g. ad libitum): normal diet
- Water (e.g. ad libitum): normal diet
- Acclimation period: acclimitazed

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

2 groups of 3 kittens each were fed during 9 weeks with a mixture of kitten diet and hydrated zirconium carbonate (HZC) at 1 and 5% (w/w).

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

9 weeks

Frequency of treatment:

continuously in the diet

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
1% (w/w)
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
5% (w/w)
Basis:
nominal in diet

No. of animals per sex per dose:

1 male and 2 females

Control animals:

yes, plain diet

Details on study design:

Kittens were distributed as litter mates throughout the dosage levels.

Positive control:

No positive control

Examinations

Observations and examinations performed and frequency:

Kittens were weighed weekly, observed daily and autopsied at the end of the 9 weeks

Sacrifice and pathology:

Gross pathology

Statistics:

No data

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Details on results:

Each kitten consumed ca. 7250 g of food during the 9-week period. This corresponds to an intake of 72 g and 372 g of HZC per kitten in the respective dosage groups. The weight gain was normal. All animals were healthy and at autopsy nothing abnormal was encountered.

Effect levels

Dose descriptor:

NOAEL

Effect level:

>= 78 other: g/animal

Based on:

other: 20.9% of ZrO2 in test material

Sex:

male/female

Basis for effect level:

other: Equivalent NOAEL for ZrO2 based on the total compound intake during the 9 week period.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Ingestion of equivalent cumulative doses of 72 and 372 g of hydrated zirconium carbonate (equivalent to 15 and 78 g of ZrO2) for a period of 9 weeks does not cause any deaths in the 6 kittens exposed during the test. This indicates the absence of toxic effects of HZC and thus ZrO2 when ingested over a prolonged period of time and confirms the results obtained in rats.