Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From July 2001 to 21 Dec 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
room temperature sometimes out of the target (minor deviation)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
753480-32-9
Cas Number:
753480-32-9
IUPAC Name:
753480-32-9

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, L'Arbresle, France.
- Age at study initiation: on the day of treatment, the animals were approximately 6 weeks old.
- Weight at study initiation: 178 ± 6 g for the males and 132 ± 12 g for the females (on the day of treatment)
- Fasting period before study: approximately 18 hours
- Housing: in polycarbonate cages with stainless steel lid (48 cm x 27 cm x 20 cm), 1 to 7 animals/sex during the acclimation period and 3 rats/sex/group during the treatment period
- Diet: free access to A04 C pelleted diet
- Water: drinking water filtered by a FG Millipore membrane (0.22 micron), 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
- Photoperiod: 12 h light/12 h dark

IN-LIFE DATES: From 18 July 2001 (first treatment) to 8 August 2001 (necropsy of the last animal)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
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.: 70K0127
- Purity: data not available

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION: The test substance was mixed with the required quantity of vehicle, using an ultra-turrax (freshly on the morning of administration).

CLASS METHOD
- Rationale for the selection of the starting dose: the information on the toxic potential of the test substance suggested that mortality was unlikely at the highest dose-level (2000 mg/kg bw).
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 males and 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 substance, and at least once a day thereafter.
> Body weight: just before administration of the test substance on day 1 and then on days 8 and 15.
- Necropsy of survivors performed: yes
Statistics:
not applicable

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No signs of toxicity were observed at this dose-level
Mortality:
No deaths were observed at 2000 mg/kg bw during the study.
Clinical signs:
No clinical signs were observed at 2000 mg/kg bw during the study.
Body weight:
The body weight gain of the treated animals was similar to that of the historical control animals.
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 of the test substance is > 2000 mg/kg bw (with no signs of toxicity at the dose level).
Executive summary:

In an acute oral toxicity study according to OECD TG 423 and GLP (CIT report 22316 TAR), scored as validity 1 according to Klimisch criteria, groups of fasted 6-week old Sprague-Dawley rats (3/sex) were given a single oral dose of cerium and iron oxide isostearate in corn oil at the dose of 2000 mg/kg bw (limit test) and observed for 14 days. Clinical signs and mortality were checked frequently during the hours following administration of the test substance, and at least once a day thereafter. Body weight was measured just before administration of the test substance on day 1 and then on days 8 and 15.

 

Under the experimental conditions, the oral LD50 of the test substance cerium and iron oxide isostearate is higher than 2000 mg/kg in rats.

No effects were observed during the observation period (no clinical signs no mortality and no effect on body weight) and at necropsy.

 

No classification for acute oral toxicity is warranted based on the absence of mortality up to a limit dose level, according to the criteria of EU GHS.

This study is classified as acceptable, as it is performed according to OECD guideline and GLP.