Hydroxido potassium zirconium carbonate, where there are 0, 1 or 2 hydroxide groups and 2, 3 or 4 potassium atoms and 2, 3 or 4 carbonate groups.

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

6 February 1992 - 8 April 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: A GLP study performed to standardised guidelines with a sufficient level of detail to assess the quality of the submitted data.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Potassium Zirconium Carbonate

IUPAC Name:

Potassium Zirconium Carbonate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test 1: 6 February-20 February 1992

Five male and 5 female nulliparous and non-pregnant young adult rats of the Sprague-Dawley strain were used. They were 6-8 weeks old and weighed 154-194 g at dosing. They were supplied by Charles River (UK) Limited, Manston Road, Margate, Kent, and arrived at Elphinstone Research Centre on 28 January 1992.
The rats were housed by sex in polypropylene cages with mesh floors suspended over absorbent paper lined trays, with a maximum of 5 animals per cage.
The rats were fed Rat and Mouse No. 1 Maintenance Diet, supplied by Special Diets Services, 1 Stepfield, Witham, Essex, CM8 3AD, but were deprived of food overnight prior to dosing and 4 h post dosing. Tap water was available ad libitum throughout the study. The diet and water are analysed on a regular basis and meet the criteria laid down by IRI.
Mean environmental maximum and minimum temperatures were 21°C and 20°C and mean relative humidity was 37%. A 12 h light/dark cycle was in operation (light hours 0700-1900 h). Mean relative humidity was outwith protocol requirements, however, this is not considered to have affected the integrity of the study.

Test 2: 25 March-8 April 1992

Five male and 5 female nulliparous and non-pregnant young adult rats of the Sprague-Dawley strain were used. They were 6-8 weeks old and weighed 133-178 g at dosing. They were supplied by Harlan Olac Limited, Shaw's Farm, Blackthorn, Bicester, and arrived at IRI on 18 March 1992.
The rats were housed by sex in polypropylene cages with mesh floors suspended over absorbent paper lined trays, with a maximum of
5 animals per cage.
The rats were fed Rat and Mouse No. 1 Maintenance Diet, supplied by Special Diets Services, 1 Stepfield, Witham, Essex, CM8 3AD, but were deprived of food overnight prior to dosing and 4 h post dosing. Tap water was available ad libitum throughout the study. The diet and water are analysed on a regular basis and meet the criteria laid down by IRI.
Mean environmental maximum and minimum temperatures were 21°C and 19°C and mean relative humidity was 39%. At 12 h light/dark cycle was in operation (light hours 0700-1900 h). Mean relative humidity was outwith protocol requirements, however, this is not considered to have affected the integrity of the study.

The rats were allowed an acclimatisation period of 9 days before commencement of the first test and 7 days before commencement of the second test.
The rats were uniquely identified within the study using an ear punch system routinely used at IRI.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

On each day of dosing the test material was freshly prepared in distilled water. The test material was administered orally to 2 groups of 5 male and 5 female rats in a single dose by means of a gavage at dose levels of 5000 mg/kg and 2000 mg/kg. A constant dose volume of 10 ml/kg was employed.

Doses:

5000 mg/kg and 2000 mg/kg

No. of animals per sex per dose:

5 per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: The rats were observed frequently on the day of dosing and once daily for 14 days following dosing.
- Frequency of weighing: They were weighed immediately prior to dosing, 7 days after dosing and at sacrifice at the end of the 14 day observation period.
- Necropsy of survivors performed: Yes, each animal was sacrifice by carbon dioxide asphyxiation and subjected to necropsy.
- Other examinations performed: clinical signs.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

5000 mg/kg: There were 5 deaths (2 males and 3 females) following a single oral dose of the test material at a dose level of 5000 mg/kg.
2000 mg/kg: There was no mortality following a single oral dose of the test material at a dose level of 2000 mg/kg.

Clinical signs:

other: 5000 mg/kg: Clinical signs, noted 10 minutes - 7 hours after dosing, included ataxia, subdued behaviour, increased salivation, hunched appearance, laboured breathing, hyperventilation, red ocular discharge and prostration. 2000 mg/kg: Clinial signs, note

Gross pathology:

5000 mg/kg: Necropsy findings, noted in 2 males and 2 females, were limited to a distended stomach filled with clear fluid.
2000 mg/kg: No abnormalities were detected at necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral toxicity of the test material was determined to be LD₅₀ > 2000 mg/kg in rats. The test material was administered via oral gavage at 2000 and 5000 mg/kg bw to both male and female test animals.

Executive summary:

The acute oral toxicity potential of the test material was investigated in rats. The vehicle for the dosing solution was distilled water. Two dose levels were investigated, 5000 and 2000 mg/kg.

At a dose level of 5000 mg/kg there were 5 deaths, 2 males and 3 females. Clinical signs, noted 10 minutes - 7 hours after dosing, included ataxia, subdued behaviour, increased salivation, hunched appearance, laboured breathing, hyperventilation, red ocular discharge and prostration. Necropsy findings, noted in premature decedents only, were limited to a distended stomach filled with clear fluid.

At a dose level of 2000 mg/kg there were no deaths. Clinical signs, noted at 0.5 h after dosing, were limited to one male animal which showed increased salivation. No abnormalities were detected at necropsy.

The Median Oral Lethal Dose (LD₅₀) of the test material in rats is greater than 2000 mg/kg.