Registration Dossier

Administrative data

Description of key information

Cerium trinitrate was tested using the LLNA method (OECD 429). The substance was tested at 25%, 10% and 5% (w/w) concentrations. Based on the results of this K1 study, the test item was considered not to be skin sensitiser.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012-11-06 to 2012-11-28
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
GLP compliance:
yes (incl. QA statement)
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
other: CBA/CaOlaHsd
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: harlan laboratories UK Ltd., oxon, UK
- Age at study initiation: eight to twelve weeks old
- Weight at study initiation: 15 to 23 grams
- Housing: animals were housed individually in suspended solid-floor polypropylene cages furnished with softwood wood flakes
- 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 to 25 degrees Celsius
- Humidity (%): 30 to 70 percent
- Air changes (per hr): fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours light and twelve hours darkness
Vehicle:
dimethylformamide
Concentration:
Preliminary Screening: 50% 25%. These concentrations were selected as maximum concentration suitable for dosing in solubility trials.
Main Test: 25%, 10%, 5%, 0% . These concentrations were selected as, at 50%, no excessive irritation was noted.
No. of animals per dose:
Preliminary Screening: Two animals; one per dose level
Main Test: Four animals per tested concentration and in control group
Details on study design:
RANGE FINDING TESTS:
- Compound solubility: the solubility of the test item in different vehicles was determined on the basis of maximising the concentration and solubility whilst producing a solution/suspension suitable for application. The vehicles tested were: acetone/olive oil (4:1) and dimethyl formamide. The concentration tested was 50% (0.5 g test iem + 0.5 g vehicle).
- Irritation: visually
- Lymph node proliferation response: expressed as the number of radioactive disintegrations per minute per lymph node (disintegrations per minute/node) and as the ratio of 3HTdR incorporation into lymph node cells of test nodes relative to that recorded for the control nodes (Stimulation Index).

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: randomisation
- Criteria used to consider a positive response: if at least one concentration results in a 3-fold or greater in 3HTdR incorporation compared to control values.

TREATMENT PREPARATION AND ADMINISTRATION:
- Formulation: the test item was formulated within two hours of being applied. It was assumed that was stable for that duration. No analysis was performed to determine homogeneity, concentration or stability.
- Test item administration: daily application of 25 µL of the appropriate concentration to the dorsal surface of each ear for three consecutive days.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Positive control results:
The positive control resulted in a greater than threefold increase in 3HTdR incorporation (SI = 4.43).
Positive control DPM: 67578.50
Result: positive
Parameter:
SI
Value:
1.62
Test group / Remarks:
5%
Parameter:
SI
Value:
1.95
Test group / Remarks:
10%
Parameter:
SI
Value:
2.12
Test group / Remarks:
25%
Parameter:
other: disintegrations per minute (DPM)
Value:
15 251.31
Test group / Remarks:
Vehicle
Parameter:
other: disintegrations per minute (DPM)
Value:
24 488.43
Test group / Remarks:
5%
Parameter:
other: disintegrations per minute (DPM)
Value:
29 705.23
Test group / Remarks:
10%
Parameter:
other: disintegrations per minute (DPM)
Value:
32 368.22
Test group / Remarks:
25%

- Solubility: the vehicle suitable for dosing was dimethyl formamide.

- Clinical observations and mortality data: there were no deaths. No signs of systemic toxicity were noted in the test or control animals during the test.

- Bodyweight: bodyweight changes of the test animals between day 1 and day 6 were comparable to those observed in the corresponding control group animals over the same period.

- Ear thickness: there were no increase in the ear thickness > 25% in any of the test or control animals on days 3 and 6.

- Skin irritation: no signs of irritation were seen in any of the animals throughout the test.

Interpretation of results:
GHS criteria not met
Conclusions:
Cerium trinitrate was considered to be a non-sensitiser under the conditions of the test.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Henzell (2013) evaluated the skin sensitisation potential of cerium trinitrate in a GLP-study using the LLNA method according to OECD 429. Four CBA mice per dose were treated by topical application on one ear of each animal with 5, 10 and 25% (w/w) of cerium trinitrate for three consecutive days. These doses were selected based on the results of a preliminary screening where, at the dose of 50% (highest dose), increased ear thickness (> 25%) was noted. The control group was identically treated but with dimethylformamide only (vehicle). Hexyl ciannamic aldehyde (prepared as a 15% v/v solution in dimethylformamide) was used as positive control. Animals were observed for three days after the last day of exposure. Clinical signs, bodyweight, skin irritation and ear thickness were recorded.

There was no mortality or signs of systemic toxicity in test animals or controls during the test. Bodyweights changes of the test animals between day 1 and day 6 were comparable to those observed in the corresponding control group animals over the same period. There were no ear thickness > 25% in any of the test or control animals on days 3 and 6. There were no visual signs of skin irritation. The Stimulation Indices were 1.62, 1.95, and 2.12 at 5%, 10% and 25%, respectively.

Based on these results, the test item was considered to be a non-sensitiser under the conditions of the test.


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available data and according to CLP regulation, cerium trinitrate does not to be classified as skin sensitiser.