Reaction mass of cerium dioxide and lanthanum oxide and lanthanum fluoride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 21-MAY-2007 to 31-OCT-2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was performed according to EU / OECD guidelines and GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

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 (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 001

EC Number:

909-701-4

Molecular formula:

(Ce (1-x)Lax)OyFz

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approximately 8 weeks old
- Weight at study initiation: 206 ± 12 g
- Fasting period before study: for an overnight period of approximately 18 hours before dosing
- Housing: 3 animals per polycarbonate cage with stainless steel lid (48 cm x 27 cm x 20 cm)
- Diet: free access to SsniffR/M-H pelleted diet (SSNIFF Spezialdiäten GmbH, Soest, Germany)
- Water: Drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum
- Acclimation period: at least 5 days before the beginning of the study


ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2°C
- Humidity: 30 to 70%
- Air changes: approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod: 12 h dark/12 h light


IN-LIFE DATES: From: 23-MAY-2007 To: 13-JUN-2007

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5% methylcellulose in purified water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle: 10 mL/kg
- Justification for choice of vehicle: data not available
- Lot/batch no.: 125K0055
- Purity: data not available


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw


DOSAGE PREPARATION: On the day of treatment, the test item was ground to a fine powder using a mortar and pestle, then was prepared at the chosen concentration in the vehicle.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: according to the information provided by the Sponsor

Doses:

2000 mg/kg/bw

No. of animals per sex per dose:

2 x 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
> Clinical signs and mortality: frequently during the hours following administration of the test item. Thereafter, observation of the animals was made at least once a day
> Body weight: just before administration of the test item on day 1 and then on days 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: none

Statistics:

not applicable

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No deaths were observed during the study

Clinical signs:

other: No clinical signs were observed during the study

Gross pathology:

Macroscopic examination of the main organs of the animals revealed no apparent abnormalities

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

As the LD 50 is higher than 2000 mg/kg, reaction mass of Cerium dioxide and Lanthanum oxide and Lanthanum fluoride is not classified according to Annex VI of the Directive 67/548/CEE and according to EU Regulation 1272/2008 (CLP).

Executive summary:

The reaction mass of Cerium dioxide and Lanthanum oxide and Lanthanum fluoride has been tested in an acute oral toxicity study using Sprague Dawley rats, according to OECD guideline n° 423 and EU guideline n° B.1 tris in compliance with Good Laboratory Practice.

The test item was prepared in 0.5% methylcellulose and was administered once by oral route (gavage) to a group of three fasted female rats at a dose level of 2000 mg/kg. As no death occurred in the first groups the results were confirmed in 3 other females treated following the same experimental conditions. Clinical signs, mortality and body weight gain were checked for a period of up to 14 days after the single administration of The reaction mass of Cerium dioxide and Lanthanum oxide and Lanthanum fluoride. All animals were subjected to necropsy.

 

No mortality and no clinical signs were recorded in both groups during the study. Body weight gain of the treated animals was not affected by treatment. At necropsy, no abnormalities were observed in any animal.

 

As the LD 50 is higher than 2000 mg/kg, The reaction mass of Cerium dioxide and Lanthanum oxide and Lanthanum fluoride is not classified according to Annex VI of the Directive 67/548/CEE and according to EU Regulation 1272/2008 (CLP). This acute oral study is classified as acceptable. It does satisfy the guideline requirement for an acute oral study (EU B.1 tris) in the rat.