Diammonium hexanitratocerate

Endpoint summary

Description of key information

Acute toxicity: oral: A K1 acute oral toxicity test - fixed dose method was performed in female Wistar rats according to a guideline similar to OECD Guideline 420 and EU Method B.1 bis (Bradshaw, 2013). Following a sighting test at dose levels of 2000 mg/kg and 300 mg/kg, a further group of four fasted females was given a single oral dose of test item, as a solution in distilled water, at a dose level of 300 mg/kg bodyweight. It was concluded that the oral LD50 was between 300-2000 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.  
Acute toxicity: dermal: An acute dermal study does not need to be conducted as the substance is classified as corrosive to the skin. In addition, a reliable study with the source substance cerium trinitrate is available. Based on this study, the LD50 of cerium ammonium nitrate is considered at least 2000 mg/kg body weight.

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:

Between 6 November 2012 and 6 December 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation: 12 weeks
- Weight at study initiation: female at 2000 mg/kg: 153 g at day 0; range for females at 300 mg/kg: 152 to 160 g
- Fasting period before study: Animals had free access to food and drinking water except for overnight immediately prior to dosing
- Housing: Animals were housed in suspended solid-floor polypropylene cages furnished with wood flakes in groups of up to four animals.
- 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): at least 15 changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours darkness

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

distilled water

Details on oral exposure:

The test item formulations were not adjusted for the purity of the test item. For the purpose of the study the test item was freshly prepared, as required, as a solution in distilled water.
The test item was formulated within two hours of being applied to the test system. It is assumed that the formulation was stable for this duration.

Doses:

Sighting test: 2000 mg/kg and 300 mg/kg
Main test: 300 mg/kg

No. of animals per sex per dose:

one female at 2000 mg/kg
five females at 300 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made 30min, 1, 2, and 4 hours after dosing and then daily for up to 14 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 or at death.
- Necropsy of survivors performed: yes: at the end of the observation period the surviving 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.

Statistics:

No data

Preliminary study:

The animal treated at a dose level of 2000 mg/kg was found dead one day after dosing. Signs of systemic toxicity noted in the animal treated at a dose level of 2000 mg/kg on the day of dosing were hunched posture, pilo-erection and ptosis. Haemorrhage and epithelial sloughing of the gastric mucosa was noted at necropsy. No deaths or signs of systemic toxicity were observed at a dose level of 300 mg/kg.

Sex:

female

Dose descriptor:

LD50

Effect level:

300 - 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths at a dose level of 300 mg/kg.

Clinical signs:

other: There were no signs of systemic toxicity at a dose level of 300 mg/kg.

Gross pathology:

Raised limiting ridge of the stomach was noted at necropsy of one animal treated at a dose level of 300 mg/kg. No abnormalities were noted at necropsy of four animals.

Other findings:

No data

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 was estimated to be in the range of 300 - 2000 mg/kg bw. The test substance is therefore considered classified as category 4 acute oral toxicant according to CLP Regulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

300 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

Reference 1

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as corrosive to the skin

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

No reliable acute dermal toxicity study with cerium ammonium nitrate is available. The results of a key study with the read across source substance cerium trinitrate are used to cover this endpoint. Justification of the read across approach is included in section 13.

Reason / purpose for cross-reference:

read-across source

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Acute toxicity: oral

Bradshaw (2013) performed an acute oral toxicity study - fixed dose method (gavage) in female Wistar rats similar to the OECD 420 and EU Method B.1 bis test guideline. Following a sighting test at dose levels of 2000 and 300 mg/kg bw, a further group of four fasted females was given a single oral dose of test item, as a solution in distilled water, at a dose level of 300 mg/kg bw. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. The animal treated at a dose level of 2000 mg/kg was found dead one day after dosing. There were no deaths at a dose level of 300 mg/kg bw. In addition, no signs of systemic toxicity was observed at 300 mg/kg, nor any abnormalities in bodyweight gain. The LD50 is assumed to be between 300 and 2000 kg/bw. 

Acute toxicity: inhalation

One key study (K1) is available for the oral route of exposure and one key study entry is available for the 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

An acute dermal study does not need to be conducted as the substance is classified as corrosive to the skin (according to REACH Annex VIII section 8.5, column 2). In addition, a key, reliable study with the read across source substance cerium trinitrate is available. 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 intial test, a further goup of 8 animals (4 males and 4 females) was similarly treated. Clinical signs and body weight development were monitored durign 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 body weight over the sutdy 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 body weight.

Justification for classification or non-classification

Based on the results of the acute oral toxicity study and according to the criteria of the CLP Regulation, cerium ammonium nitrate should be classified as acute toxic after oral exposure category 4 (H302).

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

For the dermal route of exposure, read-across was performed to cerium trinitrate. Based on the results of the acute dermal toxicity study with this substance and according to the criteria of the CLP Regulation, cerium ammonium nitrate should not be classified for the dermal route of exposure.