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Effects on fertility

Description of key information
Not required
Additional information

As Zr and ZrO2 are expected to give similar toxicological effects (owing to their behaviour), a read across with ZrO2 is performed. Zirconium dioxide shows limited toxicological effects as highlighted by the acute toxicity studies via oral and inhalation route, as well as by the repeated dose toxicity studies via inhalation.

The available information indicates no adverse effects on reproductive organs or tissues. Two reliable studies on ZrO2 were available for this endpoint (Klimisch 2): a 30 day repeated dose inhalation test in dog, rabbit and rat and a 60 day repeated dose toxicity test in cat, dog, guinea pig, rabbit and rat. No effects were reported in any of the species studied after inhalation of ZrO2 dust (NOAEC > 75 mg Zr/m3 air in the 30 day study and NOAEC >11 mg Zr/m3 air in the 60 day study), with no abnormal findings noted for the reproductive organs. 

In another study, realised with a poorly soluble zirconium substance, zirconium basic carbonate (ZBC) (Harrisson et al., 1951), rats were exposed to a diet containing ZBC for 17 weeks and did not find any effects on the genital organs.

It is interesting to mention that in the study by Spiegl et al. (1956), exposure to zirconium tetrachloride dissolved into water, so in the form of zirconium dichloride oxide was as well realized. Sixty animals were exposed during 60 days at 6 mg Zr/m3. In this study, testicular atrophy in 2 cats was observed. An additional study on zirconium dichloride oxide (ZOC) was done by oral route by Delongeas et al. (1983). This study showed that a weak fraction of Zr was absorbed after oral exposure of rats to ZOC (3000 and 5300 mg/kg). However a small portion of this absorbed fraction could reach the ovaries and induce hypervascularization.

 

Based on these results we can suppose that there may be a difference between soluble and poorly soluble Zr compounds and conclude that for an insoluble compound of zirconium such as zirconium dioxide the effects on reproductive organs and the toxicity to reproduction are limited. However, this does not provide sufficient data to justify a lower priority for testing for effects on development. Therefore, a teratology study (OECD 414) is proposed in the frame of ZrO2 dossier. The results of this test will provide data on the effects of the substance on implantation, resorptions, foetal growth, morphological variations and malformations.

 

Consequently, in case of clear negative results, any additional testing is deemed not relevant and it can then be concluded that zirconium dioxide will not be toxic to reproduction. In case of any positive results in the teratogenicity study, more information on toxicity to reproduction would be necessary as well and would subsequently be investigated in an OECD 416 study.

Once the results of the ZrO2 test is available, an update of the Zr dossier will be made.


Short description of key information:
Based on the same behaviour and toxicological effects, and their very low systemic absorption, a read across with ZrO2 is performed.
A testing proposal according to OECD 414 is relevant. Nevertheless, as this testing proposal is already made in the frame of ZrO2 dossier, a supplementary teratogenicity testing does not need to be proposed for Zr metal but read-across to the study on ZrO2 will be made. Once the results of the ZrO2 test is available, an update of the Zr dossier will be made. If no effect is observed on the teratogenicity study, the two-generation reproductive study will not be initiated.

Effects on developmental toxicity

Description of key information
Based on the same behaviour and toxicological effects, a read across with ZrO2 was relevant. As this testing proposal is already made in the frame of ZrO2 dossier, a supplementary teratogenicity testing does not need to be proposed for Zr metal but read-across to the study on ZrO2 will be made.
Additional information

As Zr and ZrO2 are expected to give similar toxicological effects (owing to their behaviour), a read across with ZrO2 was relevant. As a testing proposal for the evaluation of the teragenicity (OECD 414) is already made in the frame of ZrO2 dossier, a supplementary teratogenicity testing does not need to be proposed for Zr metal but read-across to the study on ZrO2 will be made.

Once the results of the ZrO2 test is available, an update of the Zr dossier will be made.

Toxicity to reproduction: other studies

Additional information

Not required

Justification for classification or non-classification

Based on the available data, the substance was not classified under the CLP Regulation 1272/2008 and the directive Classification and Labeling 67/548.

Additional information

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