Zirconium dioxide

Endpoint summary

Description of key information

No 'key' information was identified, however, an assessment was made based on physical/chemical characteristics of the substance as well as on available reliable toxicological data for both zirconium dioxide and other zirconium substances (see read across justification document). Preliminary (worst-case) absorption factors of 10% for the oral, dermal and inhalation pathway were put forward in the absence of key information from toxicokinetics experiments.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

10

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

10

Additional information

A qualitative judgement on the toxicokinetic behaviour was performed based on the physicochemical characteristics of the substance as well as on available reliable toxicological data for both zirconium dioxide and other zirconium substances (see read across justification document). However, because there are no experimental toxicokinetics data available that are reliable enough for endpoint coverage (only supporting information available), this qualitative judgement is to be considered as reliable with restrictions.

Absorption

Although the available data suggest extremely limited absorption of zirconium via all exposure routes, worst case absorption factors of 10% are proposed for oral, inhalation and dermal absorption, following the lowest proposed default dermal absorption factor of 10% based on physical/chemical properties (ECHA Endpoint specific guidance, Chapter R.7c; section R.7.12.2.1, Dermal absorption). The reason for setting these worst case absorption factors is the absence of experimental toxicokinetics data that are sufficiently reliable to allow lowering these values.

Supporting information on toxicokinetics however suggests much more limited absorption. Data on zirconium dichloride oxide in mouse and rat show oral absorption to be at levels of 0.01 to 0.05% of the administered dose (Delongeas et al. (1983), Toxicité et pharmacocinétique de l'oxychlorure de zirconium chez la souris et chez le rat, Journal de Pharmacologie (Paris) 14, 437-447). This 'water soluble' zirconium compound could be regarded as a reference for zirconium dioxide as it will instantaneously be converted to zirconium dioxide in aqueous solutions at physiologically relevant pH levels.

The results of the available toxicological data (both on zirconium dioxide and other zirconium compounds, see read across justification document) are supportive of the low absorption factors and even suggest much more limited absorption, as none of the available studies revealed any adverse effects up to and including the highest test doses or at least the agreed limit test doses via the different exposure routes, both after single and repeated exposure. However, in the absence of results from reliable toxicokinetics experiments, the worst case absorption factors of 10% are not lowered.

Distribution

Based on available physico-chemical data, relevant parameters like tissue affinity, ability to cross cell membranes and protein binding are difficult to predict. No further assessment is thus done for the distribution of the substance through the body.

Olmedo et al. (2002) studied the dissemination of zirconium dioxide after intraperitoneal administration of this substance in rats. The histological analysis revealed the presence of abundant intracellular aggregates of metallic particles of zirconium in peritoneum, liver, lung and spleen.

Additional data show distribution of several different zirconium compounds through the body with main presence in bone and liver, but also in spleen, kidney and lungs (Spiegl et al., 1956; Hamilton, 1948 (The Metabolic Properties of the Fission Products and Actinide Elements, University of California, Radiation Laboratory, W-7405-eng-48A-I); Dobson et al., 1948 (Studies with Colloids Containing Radioisotopes of Yttrium, Zirconium, Columbium and Lanthanum: 2. The Controlled Selective Localization of Radioisotopes of Yttrium, Zirconium, Columbium in the Bone Marrow, Liver and Spleen,

University of California, Radiation Laboratory, W-7405-eng-48A)). These data should be treated with care as substances were mainly administered via injection and thus not only the chemical but also the physical form which becomes systemically available might be different compared to administration via the oral, dermal or inhalation route.

Excretion

Based on available physico-chemical data it is difficult to predict whether the main route of elimination (after absorption) will be via the kidneys or bile. Data on zirconium dichloride oxide (a 'water soluble' zirconium compound which is instantaneously converted to zirconium dioxide or other insoluble zirconium species in aqueous solutions at physiologically relevant pH levels) suggest that absorbed zirconium will be excreted via the kidneys (Delongeas et al., 1983). Following oral intake, non-absorbed zirconium (which can be assumed to be the largest fraction) can be expected to be excreted via the faeces, either as zirconium dioxide or other insoluble zirconium complexes.