Reaction mass of disodium oxide and zirconium dioxide and silicon dioxide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 Apr 2010 - 10 May 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(2010)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of silicon dioxide and zirconium dioxide

EC Number:

910-388-1

Molecular formula:

not applicable (multi-constituent substance)

IUPAC Name:

Reaction mass of silicon dioxide and zirconium dioxide

Details on test material:

- Name of test material (as cited in study report): Silica-Zirkonia Filler
- Physical state: White powder
- Batch: IT-253
- Analytical purity of components: 72.4% silicon dioxide (CAS No. 7631-86-9) and 26.0% zirconium dioxide (CAS No. 1314-23-4) and a not stated percentage of disodium oxide (CAS No. 1313-59-3)
- Storage: at room temperature in the dark
- Stability: stable under storage conditions
- Expiry date: 20 Nov 2010
- not soluble in vehicle propylene glycol

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/J

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France.
- Age at study initiation: 8-14 weeks
- Weight at study initiation: 20-24 g
- Housing: Individual in Macrolon cages on sterilized sawdust bedding
- Diet (ad libitum): pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water (ad libitum): tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/-3
- Humidity (%): 40-84
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (LLNA)

Vehicle:

propylene glycol

Remarks:

(Merck, Germany)

Concentration:

0, 10, 25 and 50% (w/w)

No. of animals per dose:

5

Details on study design:

RANGE FINDING TESTS:
- Compound solubility: The compound was not soluble in the vehicle.
- Irritation: In the preliminary irritation study two substance concentrations were tested (25 and 50% w/w). The highest concentration was the maximum concentration as required in the test guideline (50% for solids). Two young adult animals were treated with one concentration on three consecutive days. Approx. 3-4 hours after the last exposure, the irritation of the ears was assessed. Bodyweights were determined on days 3.
- Lymph node proliferation response: not measured in the pretesting. Ear thickness was not determined.

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Criteria used to consider a positive response: SI ≥3

TREATMENT PREPARATION AND ADMINISTRATION:
On 3 consecutive days, test substances were applied on the ears (25 µL/ear) in a open application manner. Negative control animals were treated similarly, but with the vehicle alone. 3 days after the last exposure, all animals were injected with 3H-methyl thymidine and after 5 hours the draining (auricular) lymph nodes were excised and the relative size of the nodes (as compared to normal) was estimated by visual examination. The lymph nodes were pooled for each animal. After precipitating the DNA of the lymph node cells, radioactivity measurements were performed.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:

The 6-month reliability check with Alpha-hexylcinnamicaldehyde indicated that the LLNA as performed at this laboratory was appropriate for testing contact hypersensitivity.

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: The SI values at 10, 25 and 50% were 1.6, 1.4 and 1.3, respectively.

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: Mean DPM/animal values at 0, 10, 25 and 50% were 285, 466, 391 and 383 DPM.

Any other information on results incl. tables

No irritation of the ears was observed in any of the treated animals. Animals treated at 50% showed white test substance remnants on the ears, but the remnants did not hamper scoring for skin irritation. All auricular lymph nodes of the animals of the experimental and control groups were considered normal in size.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information