Tellurium

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

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

Qualifier:

according to guideline

Guideline:

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

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)

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
Hygienic level at arrival: SPF
Hygienic level during the study: Standard housing conditions
Age of animals at starting: 8 weeks old
Body weight range at starting: 19.1 – 20.9 grams (The weight variation in animals involved in the study did not exceed ± 20 % of the mean weight)
Acclimatization time: 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

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:
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.

Positive control substance(s):

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

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.

Key result

Parameter:

SI

Value:

3.2

Test group / Remarks:

100% Tellurium powder in PG

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: DPM values are presentet in the table below.

Key result

Parameter:

SI

Value:

3.2

Test group / Remarks:

Tellurium powder 50% in PG

Key result

Parameter:

SI

Value:

3.8

Test group / Remarks:

Tellurium powder 25% (w/v) in PG

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.

Larger than normal lymph nodes was observed in the positive 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 (backgroudcorrected)	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	4025	3990.5	8	498.8	3.2
Tellurium dioxide 50% (w/v) in PG	4001	3966.5	8	495.8	3.2
Tellurium dioxide 25% (w/v) in PG	4769	4734.5	8	591.8	3.8
Positive control 25 % HCA in PG	16318	16283.5	8	2035.4	13.0

DPN = DPM divided by the number of lymph nodes

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 powder 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 powder 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. On Day 3, test item precipitate was observed in 100, 50 and 25% (w/v) groups.

Stimulation index values of the test item were 3.2, 3.2 and 3.8 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 powder 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.

Reference 2

Endpoint:

skin sensitisation: in vitro

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

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 powder. Under the conditions of the present assay Tellurium powder 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.

Justification for selection of skin sensitisation endpoint:
Data from the key study are GLP-compliant and of high quality (Klimisch 1).

Justification for classification or non-classification

Skin sensitisation:

In an OECD Guideline 429 study (Skin Sensitisation: Local Lymph Node Assay), stimulation index values of the test item were 3.2, 3.2 and 3.8 at treatment concentrations of 100, 50 and 25% (w/v), respectively.

According to the CLP Regulation (EU GHS Regulation (EC) No 1272/2008) classification and labelling is required for skin sensitisation of tellurium, with category 1B and H317