Cerium dioxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November 1982

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November - December 1982

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Remarks:

study performed before the application of the OECD TG 402 but consistent with technical standards (number of animals used, duration of observation period, observations and measurements...)

GLP compliance:

no

Remarks:

The study was performed before the implementation of GLP

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffa Credo
- Age at study initiation: 6 to 7 weeks old
- Weight at study initiation: 180 - 190 g (males) / 150 - 160 g (females)
- Fasting period before study: no
- Housing: individually in 37.5 x 17 x 15 cm cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 5°C
- Humidity: 55 ± 15%
- Air changes: 10 per hr
- Photoperiod (hrs dark / hrs light): not specified

IN-LIFE DATES: From 25 November 1982 To 2 December 1982

Type of coverage:

occlusive

Vehicle:

other: 10% aqueous gum arabic

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal skin
- % coverage: not specified
- Type of wrap if used: aluminium foil and tape

REMOVAL OF TEST SUBSTANCE
- Washing: no
- Time after start of exposure (removal of dressing): 24 hours

TEST MATERIAL
- Suspension in vehicle applied
- No other details provided

VEHICLE
No details provided

Duration of exposure:

24 hours of occlusive dressing

Doses:

- Preliminary assay: 1000 and 2000 mg/kg
- Main assay: 0 (vehicle) and 2000 mg/kg

No. of animals per sex per dose:

- Preliminary assay: 2/sex
- Main assay: 5/sex

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality, clinical signs and local tolerance: just after dosing, 1, 2, 6 hours after dosing and daily for 14 days
Body weight: days 0, 1, 2, 4, 7 and 14
- Necropsy of survivors performed: yes

Statistics:

Not included

Preliminary study:

Two groups of 2 rats per sex, clipped on the back 24 hours before, were applied a single cutaneous dose of 1000 or 2000 mg/kg kept under an occlusive dressing (adhesive tape and aluminium foil) for 24 hours, and observed for 14 days. No mortality was observed at either dose level.

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the observation period

Clinical signs:

other: Slightly reduced activity was observed on day 1 in rats exposed to the test substance. No signs of cutaneous irritation were seen.

Gross pathology:

No relevant findings were seen at necropsy on day 14

Interpretation of results:

GHS criteria not met

Conclusions:

Dermal LD50 higher than 2000 mg/kg for males and females

Executive summary:

In an acute dermal toxicity study (Institut Français de Toxicologie report No. 301229), groups of 6 to 7-week old Sprague-Dawley rats (5/sex) were applied a single dermal dose of Cerium Oxide, as a suspension in 10% gum arabic, at doses of 0 (vehicle only) or 2000 mg/kg bw (limit test) under an occlusive dressing applied for 24 hours, and observed for 14 days. Mortality, clinical signs and local tolerance were checked just after application, at 1, 2, 6 hours after dosing, and daily for 14 days. Body weight was recorded on days 0, 1, 2, 4, 7 and 14.

 

No mortality occurred during the observation period. Slightly reduced activity was observed on day1 in rats exposed to the test substance. No signs of cutaneous irritation were seen. No significant changes in body weight were seen when compared to controls. No relevant findings were seen at necropsy on day 14.

 

Therefore, the dermal LD50 was higher than 2000 mg/kg for males and females. No classification for acute dermal toxicity is warranted based on the absence of mortality up to a limit dose level, according to UN/EU GHS regulations.

 

This study is classified as acceptable. Its design is compatible with the OECD 402 guideline requirements for acute dermal toxicity.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Remarks:

study performed before the application of the OECD TG 401 but consistent with technical standards (number of animals used, duration of observation period, observations and measurements...)

GLP compliance:

no

Remarks:

The study was performed before the implementation of GLP.

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Cerium dioxide

EC Number:

215-150-4

EC Name:

Cerium dioxide

Cas Number:

1306-38-3

Molecular formula:

CeO2

IUPAC Name:

cerium dioxide

Test material form:

solid: bulk

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffa Credo
- Age at study initiation: 6 to 7 weeks old
- Weight at study initiation: 180 - 190 g (males) / 150 - 160 g (females)
- Fasting period before study: approximately 18 hours
- Housing: by groups of 5 in 37.5 x 23.5 x 16 cm cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 5°C
- Humidity: 55 ± 15%
- Air changes: 10 per hr
- Photoperiod (hrs dark / hrs light): not specified

IN-LIFE DATES: From 23 November 1982 To 30 November 1982

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 10% aqueous gum arabic

Details on oral exposure:

No details provided

Doses:

- Preliminary assay: 1000, 2500 and 5000 mg/kg
- Main assay: 0 (vehicle) and 5000 mg/kg

No. of animals per sex per dose:

- Preliminary assay: 2/sex
- Main assay: 5/sex

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality and clinical signs: just after dosing, 1, 2, 6 hours after dosing and daily for 14 days
Body weight: days 0, 1, 2, 4, 7 and 14
- Necropsy of survivors performed: yes

Statistics:

Not included

Results and discussion

Preliminary study:

Three groups of 2 rats per sex, fasted for 18 hours, were given a single oral dose of 1000, 2500 or 5000 mg/kg. During a subsequent 14-day observation period, no mortality was observed at any dose level.

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD0

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the dosing and observation periods

Clinical signs:

other: Whitish discoloration of the feces was observed on day 1

Gross pathology:

No relevant findings were seen at necropsy on day 14

Other findings:

No other finding

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Oral LD50 higher than 5000 mg/kg for males and females

Executive summary:

In an acute oral toxicity study (Institut Français de Toxicologie report No. 301229), groups of fasted 6 to 7-week old Sprague-Dawley rats (5/sex) were given a single oral dose of Cerium Oxide, as a suspension in 10% aqueous gum arabic, at doses of 0 (vehicle only) or 5000 mg/kg bw (limit test) and observed for 14 days. Mortality and clinical signs were checked just after administration, at 1, 2, 6 hours after dosing, and daily for 14 days. Body weight was recorded on days 0, 1, 2, 4, 7 and 14.

 

No mortality occurred during the dosing and observation periods. Whitish discoloration of the feces was observed on day 1. No significant changes in body weight were seen when compared to controls. No relevant findings were seen at necropsy on day 14.

 

Therefore, the oral LD50 was higher than 5000 mg/kg for males and females. No classification for acute oral toxicity is warranted based on the absence of mortality up to a limit dose level, according to UN/EU GHS criteria.

 

This study is classified as acceptable. Its design is compatible with the OECD 401 guideline requirements for acute oral toxicity.