Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Harrisson et al. (1951) examined the skin sensitisation potential of hydrated zirconium carbonate (indicated as 3ZrO2.CO2.H2O) using white guinea pigs. The animals were exposed epicutaneously to an ointment containing 21% of the test substance, using a rubber (occlusive) sleeve. After 9 days they were again exposed and observed for a total period of 60 days. The result was negative; no vascularization under the treated areas was observed. The test was not conducted according to current standard methods so was given a Klimisch 3 score. Therefore another study is used in a 'weight-of-evidence' approach to cover this endpoint.

Hydrated zirconium carbonate is indicated as a water-insoluble compound. Another water-insoluble compound is yttrium stabilised zirconium dioxide (zirconium oxide containing 5.15 wt% yttrium oxide intercrystallized), which was tested for skin sensitisation in a guinea pig maximisation test (Chemicals Inspection and Testing Institute, 1999). This test was conducted according to OECD guideline 406. Intradermal and occlusive epicutaneous induction (2.5% and 25% test item, respectively), followed by occlusive epicutaneous challenge exposure at 2.5 and 25% test item, induced no positive effects in 10 female Hartley guinea pigs. The positive control (0.1% DNCB) was clearly positive, indicating the validity of the test system.

Based on the abovementioned information, it can be concluded that zirconium basic carbonate is not a skin sensitiser.

The read-across justification with yttrium stabilised zirconium dioxide is included in the Section 13 of IUCLID.

A 'case study' in humans supports also this assumption. This study is summarized in IUCLID section 7.10.4. In the past, especially in the United States, zirconium compounds have been used in deodorants (mainly soluble zirconium compounds) and in ointments for treatment of poison ivy dermatitis (mainly insoluble zirconium compounds). Zirconium carbonate has been used in such ointments. Several studies are available that link the presence of zirconium compounds in ointments or deodorants with granuloma formation. Baler (1956) described a case report of a 15 year old white girl with sarcoid-like reddish-brown papules and nodules which consisted mainly of epithelioid cells (see IUCLID section 7.10.4) and even after 20 months contained small amounts of ZrO2. The girl had used a ZrO2-containing ointment to successfully treat poison ivy dermatitis, but a few months after using the ointment, the granulomas appeared. When applying a cream consisting of 4% pure ZrO2 on intact skin and abraded skin, granulomas appeared only on the abraded sites, indicating that penetration of ZrO2 through the skin is essential for further reactions to occur. Cutaneous reactions are less common for insoluble zirconium compounds compared to soluble zirconium compounds, as insoluble compounds do not easily cross the dermal membranes. Furthermore, as ZrO2 tested negative in the mouse local lymph node assay, it is not likely that insoluble zirconium compounds like ZrO2 or zirconium basic carbonate cause skin sensitisation.

Epstein et al. (1962) investigated the effects of zirconium lactate (insoluble zirconium compound) after intradermal injection (4% in saline) in several hundreds of human subjects. Only 5 persons became sensitized after 6 weeks to 6 months. These persons and a group of non-sensitised persons were repeatedly challenged with various (soluble and insoluble) zirconium compounds. Histologically, the initial reaction was the same for all persons, both sensitised and non-sensitised, namely a non-specific (foreign body) reaction. Insoluble zirconium lactate elicited acute and subacute inflammatory responses in the corium, with macrophages forming granules which contained zirconium and a diffuse accumulation of lymphocytes. In epithelioid cells, originating within focal collections of lymphocytes in sensitive subjects (specific reaction), no zirconium was present. These epithelioid cell granulomas were independent of the location of the zirconium-containing macrophages. A difference was observed between soluble and insoluble zirconium compounds: in sensitive persons, the reactions caused by soluble zirconium compounds were significantly less intense (e.g. immature granulomas) than those produced by insoluble compounds, probably due to prolonged retention in the dermal tissue.

At the time of writing this publication, the science of immunology was not that far as current understandings. Epithelioid cells

are actually activated macrophages resembling epithelial cells and are linked to granulomatous inflammation. Granulomas form in response to antigens that are resistant to 'first-responder' inflammatory cells such as neutrophils and eosinophils.

Skin sensitisation is an allergic disease resulting in contact dermatitis and is caused by cell-mediated hypersensitivity.

Granulomas have principally nothing to do with skin sensitisation as granulomas are caused by macrophages while skin sensitisation is primarily linked to lymphocytes.

Taking all above information together in a weight of evidence approach, it can be argued that zirconium basic carbonate will not cause skin sensitisation, based on the non-sensitising effects in the available studies on (mainly insoluble) zirconium compounds and the lack of a clear linkage between granuloma formation after contact with zirconium compounds and skin sensitisation.

Migrated from Short description of key information:
A weight of evidence approach is presented to cover the skin sensitisation endpoint for zirconium basic carbonate.
Only one study (Harrisson et al., 1951) assesses the skin sensitisation potential of zirconium carbonate (in guinea pigs). The outcome was negative. However this study is scored Klimisch 3 and therefore is not sufficient to cover this endpoint. Thus, other study is used in a 'weight-of-evidence' approach: a Japanese study, scored Klimisch 2, on the read-across susbtance yttrium zirconium dioxide (Chemical Evaluation and Research Institute, 1999) which was negative. This study was performed according to OECD guideline 406.
Overall, zirconium basic carbonate is not a skin sensitiser. The read-across justification is included in the Section 13 of IUCLID.

Justification for selection of skin sensitisation endpoint:
No test is selected as the endpoint is covered by 'Weight-of-evidence' approach.

Justification for classification or non-classification

The above weight of evidence evaluation concluded that zirconium basic carbonate does not need to be classified as a skin sensitiser.