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Administrative data

Link to relevant study record(s)

Description of key information

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 its constituents dierbium trioxide and zirconium dioxide (or, where relevant, other zirconium substances of relevance). For further information, it was checked on the ECHA dissemination site whether or not the additional available toxicological data on erbium oxide (which are not included in this dossier) support the outcome of the assessment, which is the case.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
Absorption rate - dermal (%):
Absorption rate - inhalation (%):

Additional information

A qualitative judgement on the toxicokinetic behaviour of the substance erbium zirconium oxide (EC 939-967-7) was performed based on the physicochemical characteristics of the substance as well as on available reliable toxicological data for zirconium dioxide and other zirconium substances. Toxicological data (An VII endpoints only) on dierbium trioxide have been added to the substance dataset for comparison. Based on the comparison of the available toxicological data for dierbium trioxide with those available for zirconium dioxide, it was concluded that the addition of erbium to the crystal lattice of zirconium dioxide does not alter the unhazardous character of zirconium dioxide.


Erbium zirconium oxide is a pink odourless powder and consists of a stabilised zirconia crystal lattice including the elements erbium, zirconium and oxygen. The substance is characterised by a molecular weight range between 128.6 and 150.7 g/mol, a very low water solubility (< 0.01 mg Zr-Er/L at 20°C) (Manabe, 2013) and a (bulk) density of 6.05 at room temperature (Murakami, 2013). The melting temperature of zirconium dioxide (Lide, 2001 and O’Neil, 2006) and dierbium trioxide (Lide, 2009) was reported in handbooks to be 2680-2710 and 2344°C, respectively, resulting in the conclusion that erbium zirconium oxide also has a high melting point (> 2344°C). For more details see the respective IUCLID Sections or the read across justification document attached to IUCLID Section 13.




Oral absorption


The relevant pH range for the uptake in the gut after oral ingestion is 6 (at the entrance of the duodenum) to 7.4 (at the terminal ileum). Because erbium zirconium oxide is poorly soluble in water (see above), absorption after oral exposure is expected to be very limited. During passage through the stomach, the acidic pH of the gastric environment may cause some dissolution of zirconium and/or erbium from the substance. Any dissolved zirconium however is expected to be rapidly precipitated in the gut due to the presence of ligands such as phosphate and carbonate and formation of strong, insoluble complexes with these ligands. A similar behaviour is expected for erbium.


Studies investigating systemic toxicity of erbium zirconium oxide have not been conducted. However, the absence of systemic toxicity in the experiments carried out with the substance’s constituents dierbium trioxide and zirconium dioxide (or – for some endpoints – its read across compounds), supports the assumption of limited oral absorption:


  • Following a single administration by oral route at a dose of 2000 mg/kg bw (dierbium trioxide) or 5000 mg/kg bw (zirconium dioxide), no mortality and no clinical signs were observed in rats. The body weight gains of the treated rats were normal. No gross abnormalities were observed at necropsy (Clouzeau, 1994; Phycher Bio Developpement, 2008).


  • No adverse effects have been observed in an OECD 422 study performed with the read across substance zirconium acetate in rats (Rossiello, 2013), resulting in NOAEL values ≥ 1000 mg/kg bw/day (i.e. the highest dose tested).


  • No adverse effects were reported after oral administration of the read across substance zirconium basic carbonate (containing 20.9% zirconium dioxide equivalent) to rats during 17 weeks. The equivalent NOAEL for zirconium dioxide was ≥ 3150-7080 mg/kg bw/day (Harrison et al., 1951).


No experimentally obtained data on oral absorption are available for erbium zirconium oxide. 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). 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 (at physiologically relevant pH levels) and therefore higher-than-expected similarities between soluble and insoluble zirconium compounds are expected. 


Based on the reasoning above, the oral absorption of erbium and zirconium from erbium zirconium oxide is expected to be low and a worst case oral absorption factor of 10% is proposed.


Respiratory absorption


Low exposure to the substance is expected based on the inherent properties of the compound. No vapour pressure value has been determined as the product does not melt below 2344°C (see above). Therefore, inhalation of erbium zirconium oxide as a vapour is not likely to occur.


There are no data available on the aerodynamic diameter but based on the small median particle sizes measured by the registrants, typical grades for erbium zirconium oxide can be considered to contain both inhalable and respirable particles (cut-off level for the latter is ca. 4 µm). When inhaled, the substance, which has a very low water solubility (Manabe, 2013), may reach the alveolar region. In the alveolar region, the particles may be engulfed by alveolar macrophages. These macrophages will then either translocate the particles to the ciliated airways or carry particles into the pulmonary interstitium and lymphoid tissues. For this reason, the respiratory absorption is expected to be very low.


Currently there are no inhalation toxicity studies available performed on the substance itself to support the reasoning above. However, the absence of systemic toxicity in the experiments carried out with the substance’s constituent zirconium dioxide supports this assumption:


  • Following a single inhalation (nose only) exposure assessment during 4 h and at the limit doses of 4.3 mg/L ZrO2 as aerosol (Smith, 2010), no mortalities and no specific test item related adverse effects in body weight, clinical signs and gross pathology were observed.

  • A sub-chronic inhalation study (60 days) applying ZrO2 at a dose of 15.4 mg/m3 air to rats, rabbits, guinea pigs, dogs and cats and a short-term repeated dose inhalation study (30 days) applying ZrO2 at a dose of 100.8 mg/m3 air to rats, rabbits and dogs showed no significant changes in mortality rate, growth, biochemistry, hematology values or histopathology in any of the species tested (Spiegl et al., 1956). Findings on accumulation supporting the macrophage-mediated clean-up mechanism are further discussed in the section on distribution.


The absence of systemic effects in the available inhalation toxicity studies is supportive of the assumption of very low respiratory absorption.


Based on the reasoning above, a worst case inhalation absorption factor of 10% is proposed.


Dermal absorption


Prior to penetrating the skin by diffusive mechanisms, the test substance would have to dissolve in the moisture of the skin. However, as the solubility of erbium zirconium oxide is very low at physiologically relevant pH levels (relevant to skin), no significant dermal uptake is expected because the substance must be sufficiently soluble in water to partition from the lipid rich stratum corneum into the epidermis.



Even though toxicity studies with dermal application are not currently available for erbium zirconium oxide, studies on its constituents dierbium trioxide (Shapiro, 1990; Henzell, 2012) and zirconium dioxide (BIBRA, 1986), as well as zirconium dioxide stabilised with yttrium (Chemicals Inspection and Testing Institute, 1999) demonstrated these substances to be not irritating to skin nor skin sensitising. Therefore, the expected low dermal absorption is not anticipated to be enhanced by any irritating/sensitising effects.


In the absence of measured data on dermal absorption, the ECHA guidance (2017) suggests the assignment of either 10% or 100% default dermal absorption rates. However, the currently available scientific evidence on dermal absorption of some metals (e.g. Zn sulphate, Ni acetate; based on the experience from previous EU risk assessments) indicates that lower figures than the lowest proposed default value of 10% could be expected (HERAG, 2007).


Based on the inherent properties of erbium zirconium oxide, the toxicological data available on its constituents or their read across compounds, demonstrating the absence of systemic toxicity, and the experience from HERAG, no significant dermal absorption is expected for erbium zirconium oxide.


Based on the reasoning above, a worst case dermal absorption factor of 1% is proposed.


Distribution and accumulation


From the above discussion, absorption of the elements zirconium and erbium following exposure to the substance erbium zirconium oxide via the oral, respiratory or dermal pathway is expected to be (very) limited. Nevertheless, the available information on distribution and accumulation of zirconium and erbium is discussed below in order to describe the elements’ most likely behaviour once ending up in the circulatory system.


Oral administration

In the 17-week oral toxicity study performed with the insoluble zirconium basic carbonate (containing 20.9% ZrO2 equivalent) in rats (Harrison et al., 1951), no abnormalities were observed in heart, lungs, thyroids, thymus, liver, spleen, kidneys, adrenals, stomach, intestines, bladder and genital organs.


In the OECD 422 study performed with the water soluble zirconium acetate in rats (Rossiello, 2013), no abnormal findings that could indicate accumulation of the substance in organs were made during histopathological investigation either.


Finally, macroscopic investigation of rats that received a single dose of 2000 mg/kg bw dierbium trioxide (Clouzeau, 1994) or 5000 mg/kg bw zirconium dioxide (Phycher Bio Developpement, 2008) did not show any visible accumulation of the test material in the body.



The findings of the studies mentioned above support the assumption that no distribution to and no accumulation of (erbium and zirconium from) erbium zirconium oxide in the organs will take place after oral ingestion.


Administration via inhalation

In the short-term (30-day) repeated dose inhalation study in dog, rabbit and rat applying ZrO2 (Spiegl et al., 1956), an apparently granular material, brownish-black and doubly refracting, was found in the alveolar walls and in phagocytes during the histopathological examination. Occasionally, this dust was also seen in bronchi and lymph nodes. Similar findings were made in the sub-chronic (60-day) study in dogs, rabbits, rats, guinea pigs and cats.


This finding suggests that accumulation of poorly soluble zirconium dioxide in the lungs may occur under certain conditions, but also that the substance may at least partly be removed by a mechanism involving macrophages and consequent transport to/accumulation in the lymph nodes associated with the lungs. There is no evidence though of true absorption in the circulatory system and consequent distribution to and accumulation in organs.


Dermal administration

There are no dermal toxicity studies available on erbium zirconium oxide and zirconium dioxide, but based on the predicted very low dermal absorption of the substance, no accumulation or distribution is expected either.


Intraperitoneal administration

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.


Other information

Additional data show distribution of several other 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; Dobson et al., 1948). Data from the latter two studies should be treated with care as substances were 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. In the study from Spiegl et al. (1956) described above for zirconium dioxide, a repeated dose inhalation study was also performed with zirconium dichloride oxide (i.e. a water soluble zirconium compound). In this study, similar observations were made as in the experiments with zirconium dioxide, but very small amounts of zirconium were also found in femur, liver and kidney. These findings can most likely be explained by further distribution throughout the body of accumulated insoluble material in the lymph nodes via fagocytic cells of the reticuloendothelial system, followed by (slow) elimination.


Finally, based on the information on the ECHA dissemination website as well as the similarities between zirconium and rare earths such as erbium 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 erbium oxide have a very limited water solubility, it is anticipated that under normal conditions of exposure, no systemic distribution of erbium is expected from erbium oxide or a solid solution such as erbium zirconium oxide.


In conclusion, under normal conditions of exposure relevant under REACH, no or only limited systemic distribution of erbium zirconium oxide is expected, depending on the route of exposure.



The elements zirconium and erbium can be neither created nor destroyed within the body. In addition, there are no indications of transformation to more hazardous forms in the liver or kidney, which is also supported by the fact that erbium zirconium oxide as well as zirconium dioxide were demonstrated not to be mutagenic in vitro, both in the absence and presence of metabolic activation (Thompson, 2013; LAUS, 2008; NOTOX, 2010a,b).



Based on the substance’s insoluble nature, low absorption and distribution potential, and absence of obvious metabolism, it is probable that after oral intake, non-absorbed erbium zirconium oxide will be eliminated via the faeces, either as erbium zirconium oxide or other insoluble zirconium and erbium species. After inhalation exposure, as mentioned above, distribution of particulate material may occur to the lung-associated lymph nodes, from which further distribution may occur as well as (consequent) slow excretion/elimination. No experimental data is available specifically investigating the excretion/elimination pathways and kinetics, apart from a study by Delongeas et al. (1983). In this study, 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, was administered to rats using a single oral dose of 450 mg/kg bw (i.e., 128 mg Zr/kg bw). In this study, 90-99% of the administered zirconium was eliminated via the faeces within 24 h. The limited absorbed fraction was (at least partly) excreted via the kidneys, with 0.0011 to 0.0015% of the total administered dose being excreted within 72 h.





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Clouzeau, 1994. Acute Oral Toxicity in Rats. CIT, Evreux, France.


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.


Dobson 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, Radiation Laboratory, W-7405-eng-48A, 1948.

ECHA Guidance on Information Requirements and Chemical Safety Assessment Chapter R.7c: Endpoint specific guidance, Version 3.0, November 2017.


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