Reaction mass of cerium phosphate and lanthanum phosphate and terbium phosphate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 11-JUNE-2007 to 21-NOVEMBER-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:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

cerium(3+) lanthanum(3+) terbium(3+) triphosphate

EC Number:

915-152-1

Molecular formula:

(La,Ce,Tb)PO4

IUPAC Name:

cerium(3+) lanthanum(3+) terbium(3+) triphosphate

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: 211 ± 12 g
- Fasting period before study: for an overnight period of approximately 18 hours before dosing
- Housing: 3 animals (during the treatment period) per polycarbonate cage with stainless steel lid (48 cm x 27 cm x 20 cm)
- Food consumption: free access to SsniffR/M-H pelleted diet (SSNIFF Spezialdiäten GmbH, Soest, Germany)
- Water consumption: 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: 13-JUNE-2007 To: 03-JULY-2007

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 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. : data not available
- Purity: data not available

* Maximum dose volume applied: 10 mL/kg bw
* Dosage preparation: The test item was prepared at the chosen concentration in the vehicle. The test item preparation was made freshly on the morning of administration by the CIT Pharmacy and any unused material was discarded that same day.
* Class method:
- 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:

Under the experimental conditions of this study, the oral LD50 of the test item Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate was higher than 2000 mg/kg in rats. No signs of toxicity were observed at this dose.

Executive summary:

The acute oral toxicity of the test item Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate was evaluated in rats according to OECD (No. 423, 17th December 2001) and EC (2004/73/EC, B.1 tris, 29th April 2004) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

The test item was prepared in purified water and was administered by oral route (gavage), under a volume of 10 mL/kg, to 2 groups of three fasted female Sprague-Dawley rats at a dose level of 2000 mg/kg.

Clinical signs, mortality and body weight gain were checked for a period of up to 14 days following the single administration of the test item. All animals were subjected to necropsy.

No deaths and no clinical signs were noted during the study.

When compared to CIT historical control animals, a slightly lower body weight gain was noted in 2/6 animals between day 8 and day 15. The overall body weight gain of the other animals was not affected by treatment with the test item.

At necropsy, no apparent abnormalities were observed in any animal.

 

Under the experimental conditions of this study, the oral LD50 of the test item Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate was higher than 2000 mg/kg in rats. No signs of toxicity were observed at this dose.

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 rats.