Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23 October 2012 - 22 November 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Lanthanum trihydroxide
EC Number:
238-510-2
EC Name:
Lanthanum trihydroxide
Cas Number:
14507-19-8
Molecular formula:
H3LaO3
IUPAC Name:
lanthanum(3+) trihydroxide
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Description: Yellow powder
Storage Conditions: Room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Strain: RccHan:WIST
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: The bodyweight variation did not exceed ± 20 % of the bodyweight of the initially dosed animal.
- Fasting period before study: The animals were fasted overnight 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 access to mains drinking water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): lighting was controlled by a time switch to give twelve hours continuous light (0600 to 1800) and twelve hours darkness.

IN-LIFE DATES: From: 23 October 2012 To: 22 November 2012

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: distilled water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
1 female animal was dosed at 300 mg/kg
5 female animals were dosed at 2000 mg/kg
Control animals:
no
Details on study design:
SIGHTING STUDY
In the absence of data regarding the toxicity of the test material, 300 mg/kg was chosen as the starting dose.
A single female animal was treated at a dose level of 300 mg/kg (concentration 30 mg/mL, dose volume 10 mL/kg). No toxicity was observed.
In the absence of toxicity at a dose level of 300 mg/kg, an additional female animal was treated at 2000 mg/kg.

MAIN STUDY
No toxicity was observed in the animal treated at 2000 mg/kg, therefore a further four animals were treated, bringing the number treated at this dose level to 5.
All animals were dosed once by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose level to confirm the survival of the previously dosed animals.

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Clinical observations were made 0.5, 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. No tissues were retained.

Results and discussion

Preliminary study:
In the single animal dosed at 300 mg/kg, no mortality was observed and no signs of systemic toxicity were present. The animal showed expected bodyweight gain throughout the observation period. No abnormalities were detected at necropsy.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
At 2000 mg/kg, hunched posture was noted during the day of dosing in the animal that was treated initially. No signs of systemic toxicity were noted in the four additionally treated animals.
No effects observed at 300 mg/kg.
Body weight:
All animals showed the expected gains in bodyweight over the observation period.
Gross pathology:
At 2000 mg/kg, dark kidneys were noted at necropsy of the animal treated initially; no abnormalities were noted at necropsy of the remaining four animals.
No effects observed in the necropsy of the rat dosed at 300 mg/kg

Applicant's summary and conclusion

Interpretation of results:
other: not classified according to EU criteria
Conclusions:
The LD50 of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight and as such requires no classification in accordance with EU criteria.
Executive summary:

The acute oral toxicity of the test material was assessed in the Wistar strain rat in accordance with the standardised guidelines OECD 420 and EU Method B.1 bis.

In the absence of toxicological information, a single fasted female was dosed at 300 mg/kg bw. In the absence of toxicity, a further sighting test was conducted by administering a dose of 2000 mg/kg to one fasted female. Following this, a further group of four fasted females was given a single oral dose of the test material as a suspension in distilled water at a dose level of 2000 mg/kg bodyweight.

No mortality was seen. The animal initially dosed with 2000 mg/kg bw showed hunched posture on the day of dosing; no other signs of systemic toxicity were seen throughout the study. All animals showed expected gains in bodyweight and no abnormalities were noted at necropsy with the exception of dark kidneys noted in the initially dosed animal.

The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight and as such requires no classification in accordance with EU criteria.