Cerium trinitrate

Skin sensitisation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Test guideline 2

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)

Test material

Test material information

Constituent 1

Reference substance name:

Cerium trinitrate

EC Number:

233-297-2

EC Name:

Cerium trinitrate

Cas Number:

10108-73-3

Molecular formula:

Ce.3HNO3

IUPAC Name:

cerium trinitrate

Test material form:

solid: crystalline

In vivo test system

Test animals

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

Study design: in vivo (LLNA)

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)

Results and discussion

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

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

1.62

Test group / Remarks:

5%

Results 2

Parameter:

SI

Value:

1.95

Test group / Remarks:

10%

Results 3

Parameter:

SI

Value:

2.12

Test group / Remarks:

25%

Results 4

Parameter:

other: disintegrations per minute (DPM)

Value:

15 251.31

Test group / Remarks:

Vehicle

Results 5

Parameter:

other: disintegrations per minute (DPM)

Value:

24 488.43

Test group / Remarks:

5%

Results 6

Parameter:

other: disintegrations per minute (DPM)

Value:

29 705.23

Test group / Remarks:

10%

Results 7

Parameter:

other: disintegrations per minute (DPM)

Value:

32 368.22

Test group / Remarks:

25%

Any other information on results incl. tables

- 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.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Cerium trinitrate was considered to be a non-sensitiser under the conditions of the test.