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Skin sensitisation

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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 guidelineopen allclose all
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)

Test material

Constituent 1
Chemical structure
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)

Resultsopen allclose all
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%

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.