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Description of key information

Repeated dose toxicity - oral: No reliable repeated dose toxicity with the test substance is available. Braun (2013) performed a combined repeated dose toxicity study with reproduction/developmental toxicity screening test in rats according to OECD guideline 422 (GLP) with the read-across substance cerium trinitrate. Based on the results of this study, a NOAEL value for systemic toxicity of 330 mg/kg bw/day was derived.

Repeated dose toxicity - dermal: A key study is available for the oral route of exposure. According to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity via the dermal route of exposure. Furthermore, as the substance is classified as corrosive to the skin, serious local effects may be expected after repeated dermal exposure to the diluted test item and, for reasons of animal welfare, the test should be avoided.

Repeated dose toxicity - inhalation: A key study is available for the oral route of exposure. According to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity via the inhalation route of exposure. Furthermore, due to formation of clumps, the inhalation route is unlikely a possible route of exposure as the formation of respirable suspended particulate matter is unlikely. In addition, the substance is classified as corrosive to the skin and serious local effects might be expected after repeated inhalation exposure to the diluted test item. therefore, for reasons of animal welfare, the test should be avoided.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Referenceopen allclose all

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
No reliable short term repeated dose toxicity data with the target substance is available. This endpoint is covered based on data with the source substance cerium trinitrate. Justification for the read across approach is included in section 13.
Reason / purpose:
read-across source
Key result
Dose descriptor:
NOAEL
Effect level:
330 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: The NOAEL for systemic toxicity of the parent animals was considered to be 330 mg/kg/day as two animals treated with 1000 mg/kg/day dies as a result of the treatment-related effects in the stomach (local irritation)
Dose descriptor:
NOEL
Effect level:
100 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: see 'Remark'
Critical effects observed:
not specified
Endpoint:
sub-chronic toxicity: oral
Data waiving:
other justification
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
330 mg/kg bw/day
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: dermal
Data waiving:
other justification
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: dermal
Data waiving:
other justification
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Repeated dose toxicity: oral

No reliable repeated dose toxicity study is available with the test substance cerium ammonium nitrate. Braun (2013) performed a combined repeated dose toxicity study with reproduction/developmental toxicity screening test in RccHan: WIST (SPF) rats with the read-across substance cerium trinitrate. Cerium trinitrate was administered to male rats for 47 days and to female rats for at least 6 weeks. The study was performed according to OECD guideline 422 and in compliance with good Laboratory Practice (GLP).

The following dose levels (expressed as anhydrous active ingredient) were applied:

Group 1: 0 mg/kg bw/day (control group)

Group 2: 110 mg/kg bw/day

Group 3: 330 mg/kg bw/day

Group 4: 1000 mg/kg bw/day

Control animals were dosed with the vehicle (bidistilled water) alone.

The NOEL for systemic toxicity of the parent animals was considered to be 110 mg/kg/day, based upon the changes in the stomachs of rats treated with 330 mg/kg bw/day and 1000 mg/kg bw/day as well as differences in the mean daily food consumption/body weight development at 1000 mg/kg bw/day. In addition, two animals treated with 1000 mg/kg bw/day died as a result of the stomach findings. Therefore, a NOAEL for systemic toxicity of the parent animals was defined to be 330 mg/kg bw/day.

Although an NOAEL (parents) for systemic toxicity was estimated in this study, it can not be considered relevant for systemic toxicity after repeated oral exposure as this value is based on local effects rather than systemic effects: the morphological changes in the stomachs were reported to be local effects (irritation after repeated oral gavage) rather than systemic toxicity and the differences in the food consumption/body weight were considered secondary to the changes in the stomach.

Repeated dose toxicity: inhalation

A key study is available for the oral route of exposure. According to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2, annex VIII, section 8.6.1). Therefore, it is not necessary to perform a repeated dose toxicity study via the inhalation route of exposure. Furthermore, due to formation of clumps, the inhalation route is unlikely a possible route of exposure as the formation of reqpirable suspended particulate matter is unlikely. In addition, the substance is classified as corrosive to the skin and serious local effects might be expected after repeated inhalation exposure to the diluted test item. Therefore, for reasons of animal welfare, the test should be avoided.

Repeated dose toxicity: dermal

A key study is available for the oral route of exposure. According to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2, annex VIII, section 8.6.1). Therefore, it is not necessary to perform a repeated dose toxicity study via the dermal route of exposure. Furthermore, as the substance is classified as corrosive to the skin, serious local effects may be expected after repeated dermal exposure to the diluted test item and, for reasons of animal welfare, the test should be avoided.

Annex IX further testing:

The read-across substance cerium trinitrate has been tested in an OECD 422 study. In the high (1000 mg/kg bw/d) and the mid (330 mg/kg bw/d) dose groups, morphological changes in the stomach were observed. However, these effects are considered as local (irritation after repeated oral gavage of the compound) rather than systemic effects. In the high dose group, differences in the mean daily food consumption/body weight development at 1000 mg/kg bw/day were observed and considered secondary to the changes in the stomach. In addition, in the highest dose group, two animals died as a result of the stomach findings (local effects).

Although the NOAEL for systemic toxicity in the study was derived to be 330 mg/kg bw/day, there is suffiecient evidence that this value is not relevant for systemic toxicity but for the local effects in the stomach. On the basis of these results it can be concluded that no systemic adverse effects need to be addressed by a subchronic test (according to OECD guideline 408). The read-across justification is added in Section 13 of IUCLID. Therefore, and considering the animal welfare, no further testing is advised.

Justification for classification or non-classification

Based on the available data of the read-across substance cerium trinitrate and according to the criteria of the CLP Regulation, cerium ammonium nitrate should not be classified for STOT repeated exposure via the oral route.