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EC number: 264-885-7
CAS number: 64417-98-7
No experimental data are available on toxicokinetics for this substance. Therefore, a qualitative assessment of the toxicokinetic behaviour is performed on the basis of its physicochemical and toxicological properties, supported by information on the physicochemical and toxicological properties of zirconium dioxide and other zirconium substances of relevance. For further support, it was checked on the ECHA dissemination site whether or not the available toxicological data on yttrium oxide support the outcome of the assessment, which is the case.
A qualitative judgement on the toxicokinetic behaviour is based on
the physicochemical characteristics of the substance as well as on
available reliable toxicological data for zirconium dioxide and yttrium
zirconium oxide. Data on other zirconium substances (see read across
justification document) are also used. Since yttrium zirconium oxide is
an inorganic substance some physicochemical characteristics
(e.g., the octanol/water partition coefficient) are not defined,
limiting the possibilities of a qualitative assessment.
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.188.8.131.52, Dermal absorption). It is anticipated that the actual
absorption factors for yttrium zirconium oxide 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 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
The results of the available toxicological data for zirconium
dioxide and yttrium zirconium oxide are supportive of the low absorption
factors and even suggest 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. For
endpoints for which no reliable data are available on yttrium zirconium
oxide, data on zirconium dioxide are included in the dossier. No data
were included on yttrium oxide, but as is clear from the information on
the ECHA dissemination website, no adverse effects have been observed in
any of the available reliable toxicity studies either. Further, the
limited water solubility of both zirconium dioxide and yttrium oxide as
well as the similar known complexation behaviour of zirconium and rare
earths such as yttrium (i.e., strong complexation with phosphate,
pH-dependent hydroxide formation and carbonate complexation) strongly
suggest a very similar behaviour of both elements in living organisms,
with an extremely limited bioavailability for uptake to be expected at
physiologically relevant pH levels. However, in the absence of results
from reliable toxicokinetics experiments, the worst case absorption
factors of 10% are not lowered.
Based on available data relevant parameters such as 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 (Olmedo et al. (2002), An
experimental study of the dissemination of titanium and zirconium in the
body, Journal of Materials Science: Materials in Medicine 13, 793-796).
Additional data show distribution of several different zirconium
coumpounds 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
Based on the information on the ECHA dissemination website as well
as the similarities between zirconium and rare earths such as yttrium
concerning behaviour in physiologically relevant media (strong phosphate
complexation, pH-dependent formation of hydroxides and carbonate
complexation, strongly reducing bioavailability of the substance for
uptake and distribution), and the fact that both zirconium dioxide and
yttrium oxide have a very limited water solubility, it is anticipated
that under normal conditions of exposure, no systemic distribution of
yttrium oxide is expected.
Only very limited amounts of yttrium zirconium oxide will be
absorbed. Based on available data it is difficult to predict whether the
main route of excretion (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 can be expected to be eliminated via the
faeces as zirconium dioxide or other insoluble zirconium complexes. A
similar excretion pattern is expected for yttrium.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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