Yttrium oxide

Endpoint summary

Description of key information

The lanthanides carbonates and oxides have been shown in in vitro bioaccessibility studies to have a very low gastrointestinal bioaccessibility of ~6% (Lambert CE and Ledrich ML, 2014).
A single absorption either by oral route or inhalation revealed no systemic effect, no dose effect toxicity were observed on the species tested with Yttrium oxide. According to Chapter R.7c: Endpoint specific guidance - november 2014), the substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis. Therefore if the water solubility is below 1 mg/L (0.7 mg/L in case of yttrium oxide), dermal uptake is likely to be low. As nor systemic effect were observed by oral and inhalation route, nor local effects were observed by dermal route (Lambert, 1993 ; RCC studies on dermal sensitisation, 2006), no significant dermal absorption is expected. 
Repeated dose administration by oral route (according to OECD (422 and GLP requirements) and by inhalation (study quoted Klimisch 2, 30 days of exposure on beagle dogs) showed no relevant systemic effect, which probably results from a non-significant absorption of yttrium oxide. The susbtance which is an inorganic salt with a very poor solubility and no calculable log P is as a consequence not expected to be absorbed by dermal system.
The substance is therefore expected to present a low adsorption.
Based on the absence of systemic effects by oral and inhalation routes by acute and repeated toxicity, the absence of local effects by dermal route, the low gastrointestinal bioaccessibility of oxide forms, the insolubility of the substance, it is probable that yttrium oxide be eliminated without modification of its form.

Additional information

There are three forms of lanthanides: insoluble (oxides, carbonates), soluble (chlorides, nitrates, acetates) and chelated compounds.
Yttrium oxide is an insoluble form of yttrium (0.7 mg/L at 20°C). Most of the available information on lanthanides absorption, comes from the soluble lanthanides salts. Different forms of lanthanides have different organ distribution and excretion rates.
The lanthanides carbonates and oxides have been shown in in vitro bioaccessibility studies to have a very low gastrointestinal bioaccessibility of ~6% (Lambert CE and Ledrich ML, 2014).
The following basic toxicokinetic information can be extrapolated from the experimental toxicology data available on yttrium oxide, an insoluble inorganic substance:

- Regarding its absorption:

Following a single administration either by oral route (at the limit dose of 5000 mg/kg) or inhalation route (at the limit dose of 5.09 mg/m3), no relevant systemic clinical sign or changes in body weight were observed. No specific study on dermal absorption is available. However, as yttrium oxide is an insoluble inorganic test substance (no log P can be calculated), no significant dermal absorption is expected.

Following repeated dose administration by the oral route at doses up to the limit dose of 1000 mg/kgbw/day of yttrium oxide for up to approximately 28 days in male rats and 54 days in female rats,there was no relevant sign of toxicity in clinical signs, functional observational battery, body weight, haematology/clinical chemistry, food consumption and macroscopic or microscopic findings..

Following inhalation exposure for 30 days in dogs, the effects observed were consistent with a local inflammatory response syndrome. No systemic effect resulting from significant absorption was evidenced. The absorption of yttrium oxide is therefore expected to be low.

 

- Regarding its distribution:

According to the document "Yttrium and yttrium compounds - Health-based Reassessment of Administrative Occupational Exposure Limits Committee on Updating of Occupational Exposure Limits " published by the Committee of the Health Council of the Netherlands: "after oral uptake yttrium is poorly absorbed from the gastrointestinal tract, more than 90% is excreted via the faeces in rats. The uptake after inhalation exposure varied between 25% in mice and 50% in rats. In humans 11 - 55% is

retained after inhalation. After intravenous injection yttrium accumulated in liver, lung and spleen, with a half-life time for clearance from the liver of 144 days in rats. Accumulation of yttrium in bone is possible, but it is less than in other organs and there seems to be a maximum to the uptake by

bone. Also the excretion of yttrium from the bone is slow. After inhalation exposure the clearance of yttrium has three phases, two rather quick, with a half-life time of approximately 8 and 20 days in humans, the third one very slow, with a half-life time of 420 days or 1 - 3 years."

Following repeated dose administration by inhalation at concentrations up to 20.63 mg Y2O3/m3 during 30 days in dogs, only loco-regional inflammatory effects were observed, as changes in segmented neutrophil counts, lung and lymph node gross appearance at necropsy. These effects were illustrative of an inflammatory response subsequent to lung exposure with poorly soluble particles, without functional impairment of the immune system. No relevant systemic effects specific to yttrium oxide as such were evidenced.

Following a 28 days repeated dose toxicity study performed by gavage at a maximum concentration of 1000 mg/Kg/day in rats (study done according to GLP accreditation and scored as Klimisch 1), no treatment releated changes were noted nor for haematology, nor for histopatological findings in all organs (macroscopic and microscopic observations). These results reveal that there is no significant accumulation of the substance in blood and in organs which indicated no relevant distribution of the substance in the tested animals.

Therefore, under normal conditions of exposure, no systemic distribution of yttrium oxide leading to systemic adverse effect is expected.

 

- Regarding its metabolism:

No macroscopic / microscopic finding in the major metabolizing tissues (liver, kidneys), no effect on haematological parameters, illustrative of metabolic activity were seen following repeated dose administration by the oral route at doses up to the limit dose of 1000 mg/kg for up to approximately 28 days in male rats and 54 days in female rats by gavage or by inhalation route up to 20.63 mg Y2O3/m3 on dogs during 30 days.

 

- Regarding its elimination:

According to the document "Yttrium and yttrium compounds - Health-based Reassessment of Administrative Occupational Exposure Limits Committee on Updating of Occupational Exposure Limits " published by the Committee of the Health Council of the Netherlands: "after oral uptake yttrium is poorly absorbed from the gastrointestinal tract, more than 90% is excreted via the faeces in rats.

Based on their insoluble nature, low absorption and distribution potentials in organs, absence of obvious metabolism, and absence of systemic effects, it is probable that yttrium oxide will be eliminated under an unmodified form.