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Description of key information

Acute toxicity: oral:A K2 acute oral toxicity test was performed in female Sprague-Dawley rats according to a guideline similar to OECD Guideline 401 (Bruce DW, 1963) with cerium nitrate. This study was selected as key study. The LD50 was considered to be 4200 mg/kg bw 
Acute toxicity: inhalation: A key study is available for the oral and dermal route of exposure. According to the REACH Regulation, only one additional route of exposure should be tested other than the oral route of exposure for acute toxicity (column 2, annex VIII, section 8.5). Therefore, it is not necessary to perform an acute toxicity study via the inhalation route of exposure. In addition the substance appears as a clump and formation of respirable suspended particulate matter is unlikely.
Acute toxicity: dermal:A K1 acute dermal toxicity test was performed in male and female Wistar rats according to OECD Guideline 402 and EC method B3 (Bradshaw, 2013). In this study, the LD50 was found to be > 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
data not available
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Scientifically sound study with methods similar to OECD 401 with the following deviations: The number of deaths at each dose were not reported; the specific doses (mg/kg) were not provided; individual clinical observations, body weights, pathology were not reported; sex of the animals was not provided
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
not specified
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: no data available
- Age at study initiation: no data available
- Weight at study initiation: 190 g to 250 g
- Fasting period before study: no data available
- Housing: the animals were housed in air-conditioned quarters
- Diet (e.g. ad libitum): yes, ad libitum (food: Rockland rat diet or Rockland mouse pellets)
- Water (e.g. ad libitum): yes, ad libitum
- Acclimation period: no data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data available
- Humidity (%): no data available
- Air changes (per hr): no data available
- Photoperiod (hrs dark / hrs light):no data available
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The solution was given in single dose orally by stomach tube to female rats as 50% aqueous solution.
No. of animals per sex per dose:
5 or 10 animals by groups
Details on study design:
- Duration of observation period following administration: 30 days
Sex:
female
Dose descriptor:
LD50
Effect level:
4 200 mg/kg bw
95% CL:
3 684 - 4 788
Remarks on result:
other: LD50 calculated according to Litchfied and Wilcoxon.
Mortality:
The animals were observed for 30 days although no deaths occurred later than 4 days after administration of the nitrate salts by the oral route.
Clinical signs:
Within 1 to 2 hours after oral administration of the rare earth nitrates most of the rats were depressed, and animals that received a lethal dose showed little activity during the survival period.
Body weight:
no data
Gross pathology:
Throughout the observation period no gross pathologic changes were noted.
Interpretation of results:
GHS criteria not met
Conclusions:
Oral LD50 (female rat) was 4200 mg/kg on the basis of 50% aqueous solution. Based on the criteria in the CLP Regulation, the test substance is not to be classified as acute oral toxicant.
Executive summary:

In an acute oral toxicity study (Bruce, 1963), groups of female rats (5 to 10 females/group) were given a single oral dose of cerium nitrate (purity > 98 %) at 50% aqueous solution and observed for 30 days. Animals were then observed for 30 days.

No deaths occurred later than 4 days after administration of the nitrate salts by the oral route.

Oral LD50 Females was 4200 mg/kg bw with 95% confidence limits of 3684 -4788 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
4 200 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 31 October 2012 to 21 November 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation: eight to twelve weeks of age
- Weight at study initiation: All animals weighed at least 200 gram
- Fasting period before study:
- Housing: The animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of up to four, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 °C
- Humidity (%): between 30 and 70 %
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): twelve hours light and twelve hours darkness

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: the back and flanks of each animal
- % coverage: 10% of the total body surface area
- Type of wrap if used: The test material was applied as evenly as possible and a piece of surgical gauze was placed over the treatment area and semi-occluded with self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the 24-hour contact period the bandages were carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test item.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg

Duration of exposure:
24 hours
Doses:
Single 2000 mg/kg
No. of animals per sex per dose:
Initially, two animals (one male and one female) were given a single, 24 hour, semi-occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg bodyweight. Based on the results of the initial test, a further group of eight animals (four males and four females) was similarly treated.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: individual body weights were recorded prior to application of the test item on day 0 and on days 7 and 14.
- Necropsy of survivors performed: yes. At the end of the study 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.
- Other examinations performed: Any other skin reactions, if present were also recorded.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality
Clinical signs:
No signs of systemic toxicity were observed
Body weight:
Except one female, which showed a loss in bodyweight during the first week but expected weight gain the second week, all animals showed expected bodyweight gain.
Gross pathology:
No abnormalities were observed
Other findings:
Signs of dermal irritation noted at the test site of one female were very slight erythema (days 1 to 14 post dose), slight desquamation (days 4 to 13 post dose) and small superficial scattered scabs days 9 to 14 post dose). There were no signs of dermal irritation noted in the remaining animals.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal median lethal dose of cerium trinitrate in the Wistar rat is greater than 2000 mg/kg bodyweight. Based on the criteria of the CLP Regulation, the substance is not to be classified as acute dermal toxicant.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Acute toxicity: oral

Bruce DW (1963) investigated the acute oral toxicity via gavage of a single oral dose of cerium nitrate (50% aqueous solution) in 5 to 10 female Sprague-Dawley rats. The animals were observed for 30 days although no deaths occurred later than 4 days after administration. Within 1 to 2 hours after oral administration of the rare earth nitrate, most of the rats were depressed, and animals that received lethal doses showed little activity during the survival period. In this study the LD50 was found to be equal to 4200 mg/kg bw. This study is designated as key study.

In addition, one K2 study (Shapiro, 1990, also published by Lambert et al in 1993) was disregarded as the dose level used (5000 mg/kg bw) was inappropriate (too high dose, killing all the animals; LD100 = 5000 mg/kg bw) and the study did not permit to conclude about the toxicity of cerium nitrate.

Acute toxicity: inhalation

No reliable studies were available for the inhalation route. However, a key study is available for the oral and dermal route of exposure. According to the REACH Regulation, only one additional route of exposure should be tested other than the oral route of exposure for acute toxicity (column 2, annex VIII, section 8.5). Therefore, it is not necessary to perform an acute toxicity study via the inhalation route of exposure. In addition the substance appears as a clump and formation of respirable suspended particulate matter is unlikely.

Acute toxicity: dermal

Bradshaw (2013) investigated the acute dermal toxicity of the cerium trinitrate in Wistar rats. Initially, two animals (one male and one female) were given a single, 24 hour, semi-occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg body weight (expressed as cerium trinitrate). Based on the results of the initial test, a further group of eight animals (four males and four females) was similarly treated. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy. There were neither deaths nor signs of systemic toxicity. Signs of dermal irritation noted at the test site of one female were very slight erythema, slight desquamation and small superficial scattered scabs. There were no signs of dermal irritation noted in the remaining animals. Animals showed expected gains in bodyweight over the study period except for one female which showed body weight loss during the first week but expected gain in body weight during the second week. No abnormalities were noted at necropsy. The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

Acute toxicity: other routes

Bruce (1963) studied the acute toxic effects of cerium trinitrate (purity 98%) after intraperitoneal exposure in rats and in mouse. The LD50 values were respectively 290 and 470 mg/kg. After intravenous exposure in rats, females seemed more sensitive than males to the substance (LD50 values of 4 mg/kg (F) and 49.6 mg/kg (M)). No explanation could be found for this difference.

Justification for classification or non-classification

Based on the results of the acute oral and dermal toxicity study and according to the criteria of the CLP Regulation, cerium trinitrate should not be classified as an acute oral or dermal toxicant.

No data were available to decide on the classification for the inhalation route.