Cerium tetranitrate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 6 November 2012 and 6 December 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented GLP study performed according to OECD Guideline 420 and EU Method B.1 bis.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Cerium tetranitrate

EC Number:

236-007-2

EC Name:

Cerium tetranitrate

Cas Number:

13093-17-9

Molecular formula:

Ce.4HNO3

IUPAC Name:

cerium tetranitrate

Test material form:

other: liquid substance in its solvent (i.e. water), as it cannot be obtained without it

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation: eight to twelve weeks of age
- Weight at study initiation: range: 149 - 159 grams
- Fasting period before study: overnight fast immediately before dosing and for approximately three to four hours after dosing
- Housing: The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70% respectively
- Air changes (per hr): at least fifteen air changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: distilled water

Details on oral exposure:

VEHICLE
The test item was formulated within two hours of being applied to the test system. It is assumed that the formulation was stable for this duration.

Doses:

Following a sighting test at dose levels of 338 mg/kg and 2248 mg/kg (equivalent to 300 and 2000 mg/kg active ingredient/kg bodyweight, respectively), a further group of four fasted females was given a single oral dose of test item, as a solution in distilled water, at a dose level of 2248 mg/kg bodyweight (equivalent to 2000 mg active ingredient/kg bodyweight).

No. of animals per sex per dose:

Fixed dose method:
In the absence of data regarding the toxicity of the test item, 338 mg/kg (equivalent to 300 mg active ingredient/kg bodyweight) was chosen as the starting dose using one animal.
In the absence of toxicity at a dose level of 338 mg/kg, an additional animal was treated at a dose level of 2248 mg/kg (equivalent to 2000 mg active ingredient/kg bodyweight).
In the absence of toxicity at a dose level of 2248 mg/kg, an additional group of four animals was treated at a dose level of 2248 mg/kg (equivalent to 2000 mg active ingredient/kg bodyweight).

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical observations were made 1/2, 1, 2, and 4 hours after dosing and then daily for fourteen days.
Morbidity and mortality checks were made twice daily.
Individual bodyweights were recorded on day 0 (the day of dosing) and on days 7 and 14.
- Necropsy of survivors performed: yes: at the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: LD50 > 2248 mg/kg bodyweight

Mortality:

At 338 mg/kg (equivalent to 300 mg active ingredient/kg bodyweight) and 2248 mg/kg (equivalent to 2000 mg active ingredient/kg bodyweight) there was no mortality.

Clinical signs:

other: At 338 mg/kg (equivalent to 300 mg active ingredient/kg bodyweight) no signs of systemic toxicity were noted during the observation period (1 animal). At 2248 mg/kg (equivalent to 2000 mg active ingredient/kg bodyweight) no signs of systemic toxicity were

Gross pathology:

At 338 mg/kg (equivalent to 300 mg active ingredient/kg bodyweight) and 2248 mg/kg (equivalent to 2000 mg active ingredient/kg bodyweight) no abnormalities were noted 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 median lethal dose (LD50) of the test item in female Wistar strain rat was estimated to be greater than 2248 mg/kg bodyweight (equivalent to 2000 mg active ingredient/kg bodyweight).

The test item does not meet the criteria for classification according to Regulation (EC) No 1272/20008, relating to the Classification, Labeling and Packacing of Dangerous Substances.