Zirconium, acetate lactate oxo ammonium complexes

Endpoint summary

Additional information

A qualitative judgement on the toxicokinetic behaviour was performed based on physico-chemical characteristics. Zirconium Dioxide is an inorganic substance and thus some physico-chemical characteristics (like the octanol/water partition coefficient) are not defined, limiting the possibilities of a qualitative assessment.

Absorption

Absorption factors of 10% are proposed for oral, inhalation and dermal absorption, representing default values of what is considered still defendable based on the limited physical/chemical data that can be applied for inorganic substances and 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). It is recognised that the actual absorption factors for Zirconium Dioxide will be much lower. 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 JL et al., Toxicité et pharmacocinétique de l'oxychlorure de zirconium chez la souris et chez le rat; J. Pharmacol (Paris) 1983, 14, 4, 437-447). This well water soluble compound could be regarded as a reference for Zirconium dioxide as it will instantaneously be converted to Zirconium dioxide in aqueous solution.

The available toxicological data provide no reason to deviate from the above absorption factors, but might also indicate significantly lower absorption factors than proposed as the substance has no eye and skin irritating potential, is not a skin sensitizer and is of low acute toxicity. In addition the available repeated dose studies show no systemic effects at the highest dose tested.

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. 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 (Olmedo, D., M.B. Guglielmotti and R.L. Cabrini. An experimental study of the dissemination of Titanium and Zirconium in the body; Journal of Materials Science: Materials in Medicine, Volume 13, Number 8, 2002).

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 (Hamilton, J.G. The Metabolic Properties of the Fission Products and Actinide Elements, University of California, Radioation Laboratory, W-7405-eng-48A-I, 1948) and Dobson et al., 1948 (Dobson, E.L. et al., Studies with Colloids Containing Radioisotopes of Yttrium, Zirconium, Columbium and Lanthaum: 2. The Controlled Selective Localization of Radioisotopes of Yttrium, Zirconium, Columbium in the Bone Marrow, Liver and Spleen,

University of California, Radioation Laboratory, W-7405-eng-48A, 1948)). 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 soluble form, suggest that absorbed Zirconium will be excreted via the kidneys (Delongeas et al., 1983).