Zirconium

Endpoint summary

Description of key information

As Zr powder is pyrophoric, it is technically not possible to generate an inhalable test atmosphere even for long term studies. The evaluation of repeated dose toxicity inhalation of Zr may not be technically possible.
Based on the same behaviour and toxicological effects, a read across with ZrO2 is performed. No effect was observed following repeated inhalation of ZrO2.

Additional information

• Justification for the read across

The guidance on information requirements and chemical safety assessment deals with the specific category of metals, metal compounds and other inorganic compounds, like zirconium (section R.6.2.5.6). For this category, the hypothesis is that properties are likely to be similar or follow a similar pattern as a result of the presence of a common metal ion (Zr4+ in our case). However, it is the bioavailability of the metal ion at target sites that in most cases determines the occurrence and severity of the effects to be assessed for the read-across of metal substances. Supporting information to assess the bioavailability include information on a number of different factors, like the particle size.

Indeed, particle size influences the deposition behaviour in the respiratory tract and potential toxic effects.

The following distribution was measured for Zr in a granulometry test performed:

D10 = 32.6 µm

D50 = 76.4 µm

D90 = 141.1 µm

Otherwise, this distribution could be different, depending on the manufacturing process employed and the uses envisaged.

In the Spiegl et al. study (1956), the D50 or mass median aerodynamic diameter was set to 1.5 µm for ZrO2. Thus, ZrO2 particles will be able to reach lower parts of the respiratory system. The use of data from ZrO2 particles ("alveolar particles") is toxicologically protective or toxicologically equivalent (for some Zr powder during the manufacturing process) for Zr powder.

According to the REACh recommendations for the DNEL derivation, a read across could be used for substances with similar behaviour and toxic effects in the organism. So, read across with ZrO2 repeated toxicity dose is pertinent.

 

• Available data

One reliable study (Spiegl et al., 1956 - K2) described a 30 day and 60 day repeated dose inhalation test in several animal species. Exposition to 75 mg Zr/m3(100.8 mg/m3 ZrO2) for 30 days or 11 mg Zr/m3 (15.4 mg/m3 ZrO2) for 60 days produced no significant effect on animal mortality, rate, growth, haematology values or histopathology. The NOAEC were deemed to be greater than the concentration tested.

Another study scored K3 (Delongeas et al., 1983) confirmed the absence of effects on mortality, behaviour and growth, following daily instillation of 800 mg/kg zirconium oxychloride (230 mg Zr/ kg/day) via gastric tube, for 16 days.

Human data are also available following several years of exposure (K3 or K: 4 worker cases reported, with very few workers and no information about dose exposures or co-exposition to other chemicals). Despite suspicion that inhalation of zirconium should be capable of causing human pulmonary disease, the reported cases of pulmonary effects, attributed to exposure to zirconium, are rare. These epidemiological data, in addition to the absence of effect observed in the repeated dose toxicity, support a weight of evidence of zirconium harmless.

As 30 day and 60 day studies are available, no longer studies were necessary, taking into account the low toxicity of this substance.

Justification for classification or non-classification

Substances should be classified in category 2 for specific target organ toxicity (repeated exposure) on the basis of observations from appropriate studies in experimental animals in which significant toxic effects, of relevance to human health, were produced at generally moderate exposure concentrations. Based on the available data and the absence of toxicity effects observed, the substance was not classified under the CLP Regulation 1272/2008 and the directive Classification and Labelling 67/548.