[No public or meaningful name is available]

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-05-30 to 2012-06-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according 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:

Tellurium dioxide

EC Number:

231-193-1

EC Name:

Tellurium dioxide

Cas Number:

7446-07-3

Molecular formula:

O2Te

IUPAC Name:

oxotellane oxide

Test material form:

solid: particulate/powder

Details on test material:

lot/batch No.of test material: EK1008F023

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: ELEVAGE JANVIER; Route des Chènes Secs B.P. 4105; 53940 LE GENEST-ST-ISLE, France
- Age at study initiation: 8 weeks
- Weight at study initiation: 19.1 - 20.9 g
- Housing: Group caging - mice were provided with glass tunneltubes; Type II. polypropylene/ polycarbonate
- Diet (e.g. ad libitum): ssniff SM R/M-Z+H Autoclavable complete diet for rats and mice - ad libitum
- Water (e.g. ad libitum): tap water from the municipal supply from 500 ml bottle, ad libitum.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 15-20 air exchange/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily light

Study design: in vivo (LLNA)

Vehicle:

propylene glycol

Concentration:

Preliminary experiment: 0, 50 and 100 %
Main experiment: 0, 25, 50, 100 %

No. of animals per dose:

Preliminary experiment: 2 females per dose
Main experiment: 4 females per dose, 8 animals for negative control

Details on study design:

RANGE FINDING TESTS:
- Compound solubility: examined in a short Preliminary Compatibility Test; the 100 % w/v formulation (suspension) using Propylene glycol (PG)
as vehicle was suitable for the test.
- Irritation: no signs of irritation were observed in the preliminary test
- Lymph node proliferation response: not assessed, according to guideline

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: proliferation of lymphocytes in the lymph nodes; incorporation of ³H-methyl thymidine is measured by β-scintillation counting as disintegrations per minute (DPM).
- Criteria used to consider a positive response: A stimulation index of 3 or greater is an indication of a positive result.

TREATMENT PREPARATION AND ADMINISTRATION:
During the assay, each mouse was topically dosed on the dorsal surface of each ear with 25 μl of the appropriate formulation applied using a pipette. Each animal was dosed once a day for three consecutive days (Days 1, 2 and 3). There was no treatment on Days 4, 5 and 6.

Positive control substance(s):

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

Results and discussion

Positive control results:

A significant lymphoproliferative response (stimulation index value of 13.0) was noted for the positive control chemical and this result confirmed the validity of the assay.

In vivo (LLNA)

Results

Results 1

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: DPM values are presentet in the table below.

Results 2

Parameter:

SI

Value:

3.7

Test group / Remarks:

100 % (w/v)

Results 3

Parameter:

SI

Value:

2

Test group / Remarks:

50 % (w/v)

Results 4

Parameter:

SI

Value:

3.9

Test group / Remarks:

25 % (w/v)

Any other information on results incl. tables

No mortality or sign of systemic toxicity or local irritation were observed during the study. Test item precipitate was observed in all test item treated groups.

No treatment related effects were observed on animal body weights.

The appearance of the lymph nodes was normal in the negative control group and in all test item treated groups.

DPM, DPN and Stimulation Index Values for all Groups

Test Group Name	Measured DPM/group	Group DPM (backgroud corrected)	No. of Nodes	DPN	Stimulation Index Values
Background (5 (w/v) % TCA )	34.5		-
Negative control PG	2538	2503.5	16	156.5	1.0
Tellurium dioxide 100% (w/v) in PG	4634	4599.5	8	574.9	3.7
Tellurium dioxide 50% (w/v) in PG	2562	2527.5	8	315.9	2.0
Tellurium dioxide 25% (w/v) in PG	4920	4885.5	8	610.7	3.9
Positive control 25 % HCA in PG	16318	16283.5	8	2035.4	13.0

DPN = DPM divided by the number of lymph nodes

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP; EU GHS (Regulation (EC) No 1272/2008)

Conclusions:

Under the conditions of the present assay Tellurium dioxide tested in Propylene Glycol as vehicle, was shown to have a sensitization potential
(sensitizer) in the Local Lymph Node Assay. However, the dose response was not clear, no high SI values were seen and metals are known to
have a lower predictivity in the LLNA than organic molecules.

Executive summary:

In an OECD Guideline 429 study (Skin Sensitisation: Local Lymph Node Assay), groups of four female CBA/J Rj mice were treated with: 100, 50 and 25% (w/v) Tellurium dioxide in PG. The negative control group received PG and the positive control group received 25 % α-Hexylcinnamaldehyde (HCA) in PG.

The solutions of the test item were applied on the dorsal surface of ears of experimental animals (25 μl/ear) for three consecutive days (Days 1, 2 and 3). There was no treatment on Days 4, 5 and 6. On Day 6, the cell proliferation in the local lymph nodes was measured by incorporation of tritiated methyl thymidine (3HTdR) and the values obtained were used to calculate stimulation indices (SI).

No mortality or sign of systemic toxicity or local irritation were observed during the study. No treatment related effects were observed on animal body weights in any treated groups. Test item precipitate was observed in all test item treated groups.

Stimulation index values of the test item were 3.7, 2.0 and 3.9 at treatment concentrations of 100, 50 and 25% (w/v), respectively.

α-Hexylcinnamaldehyde (25% (w/v) dissolved in PG) was used as a positive control to demonstrate the appropriate performance of the assay. A significant lymphoproliferative response (stimulation index value of 13.0) was noted for the positive control chemical and this result confirmed the validity of the assay.

In conclusion, under the conditions of the present assay Tellurium dioxide tested in Propylene Glycol as vehicle, was shown to have a sensitization potential (sensitizer) in the Local Lymph Node Assay. However, the dose response was not clear, no high SI values were seen and metals are known to have a lower predictivity in the LLNA than organic molecules.