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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
8 November 1985 to 22 November 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study considered adequately conducted but not to be specified guideline.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report date:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Only two animals per sex per dose level were used. Due to the physical nature of the test substance a dose volume of 20 ml/kg was used, rather than 5 ml/kg as specified in the protocol.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Diammonium bis[carbonato-O]dihydroxyzirconate
EC Number:
269-682-7
EC Name:
Diammonium bis[carbonato-O]dihydroxyzirconate
Cas Number:
68309-95-5
Molecular formula:
C2H2O8Zr.2H4N
IUPAC Name:
diammonium bis[carbonato-O]dihydroxyzirconate
Details on test material:
Aqueous solution of ammonium zirconium carbonate containing 20% ZrO2.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Both sexes of rats of a Sprague-Dawley strain and mice of the MF1 strain, both aged 7-8 weeks were obtained from specified pathogen-free breeding colonies (Olac 1976 Ltd, Bicester, Oxon). They were kept in the study room for 10 days prior to the start of the study

The animals were housed in groups of two according to species and sex in plastic and stainless steel cages with free access to a nutritionally adequate diet (Rat and Mouse No.1, Special Diet Services, Witham, Essex) and tap water. Each cage carried a label identified with the following:
-project number (3.0605)
-project manager (T.I. Mallet)
-treatment (compound and dose level)
-sex and numbers of animals contained
-date of treatment
The cages were kept in a room used solely for the study, with rats and mice clearly separated. It was controlled to the following conditions:
-Temperature: 21-25°C
-Light : artificial 12 hr light (06.00 - 18.00 GMT)
-Air changes : At least 15/hr with no recirculation - filtered air (0.5 pm)
-Relative humidity : 40-65%


Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Groups of two animals of each sex, previously fasted overnight were given a single oral dose by intubation through a rubber cathater for the rats and a plastic tipped metal canula for the mice. The control groups were given the vehicle alone, at the same dose volume as that used for the test material.
Doses:
500, 1650, 5000 and 16500 mg/kg.
The doses mentioned in the study report are based on the 20% solution of ZrO2 and have been re-calculated so the figures above to represent the substance to be registered.
No. of animals per sex per dose:
2 per sex per dose
Control animals:
yes
Details on study design:
Water and food was available ad lib after treatment. The animals were weighed at the time of dosing and after 3, 7 and 14 days. They were observed during the first 6 hours after dosing and then daily for 14 days for signs of reaction to treatment. At day 14 all the surviving animals were killed by a lethal dose of barbiturate anaesthestic and subjected to a post-mortem examination. Any abnormalities were noted but no tissue samples were retained. Any animals that died before the end of the experiment were similarly examined.
Statistics:
LD50 value calculated based on a a method described by Weil, C.S. 1952, Biometrics 8, 249.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 900 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Estimated from study data based on a a method described by Weil, C.S. 1952, Biometrics 8, 2.
Mortality:
Rates dosed at 5000 mg/kg and 16500 mg/kg were all found dead within a few hours of dosing, except for 1 male dosed at 5000 mg/kg which survived until day 1. There were no mortalities in animals dosed at 500 and 1650 mg/kg.
Clinical signs:
No abnormalities were observed in animals of either sex dosed at 500 mg/kg.
Animals of either sex dosed at 1650 mg/kg showed signs of piloerection and reduced activity.
Animals of either sex dosed at 5000 mg/kg showed signs of cold to touch, piloerection, reduced activity, prone posture and slow respiration prior to death.
Animals of either sex dosed at 16500 mg/kg were found dead after 1 hour with no time for clinical observation prior to this.
Body weight:
Weight gain in the surviving animals was little different from the controls. Body weight gain was slightly lower than controls for males treated at 500 mg/kg but sl;ightly higher for those treated at 1650 mg/kg. For female rats, body weight gains in animals treated at either 500 or 1650 mg/kg were slightly higher than controls.
Gross pathology:
Rats found dead after ammonium zirconium carbonate administration showed reddenng of the gut and gut distended with fluid (not seen in those given the highest dose).
Red areas in the.ileum were reported in two rats given 1650 mg/kg and a male rat given ammonium zirconium carbonate at 500 mg/kg was seen to have a distended alimentary canal. Other reported findings were not considered to be related to treatment.

Any other information on results incl. tables

It was considered possible that local irritation, rather than systemic effects, was at the basis of the toxicity observed during the study.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 of the substance was determined to be between 1650 and 5000 mg/kg and has been calculated to be approximately 2900 mg/kg based on a a method described by Weil, C.S. 1952, Biometrics 8, 2.
Executive summary:

A GLP-compliant study study has been conducted to a method similar to OECD Guideline 401.The acute oral LD50 of the substance has been determined to be approximately 2900 mg/kg. This value was calculated based on a a method described by Weil, C.S. 1952, Biometrics 8, 2.