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There are three forms of lanthanides: insoluble (oxides, carbonates), soluble (chlorides, nitrates, acetates) and chelated compounds. Cerium dioxide is an insoluble form or cerium, as illustrated by its very low water solubility (< 0.123 µg/L at 20°C). Most of the available information on lanthanide absorption comes from the soluble lanthanide salts. Different forms of lanthanides have different organ distribution and excretion rates. The lanthanide oxides have been shown in in vitro bioaccessibility studies to have a very low gastrointestinal bioaccessibility of ~6% (Lambert CE, 2005).

The following basic toxicokinetic information can be extrapolated from the experimental toxicology data available on cerium dioxide (under its micrometric (bulk) form), an insoluble inorganic substance:

 

- Regarding its absorption:

Following a single administration either by oral route (at the limit dose of 5000 mg/kg), inhalation (at the concentration of 5.05 mg/L for 4 hours), or dermal route (at the limit dose of 2000 mg/kg), no relevant systemic clinical sign or changes in body weight was observed. Laboured breathing and/or ruffled fur (noted after inhalation exposure) or slightly reduced activity on the day of dermal dosing are poorly specific signs which may be attributed to the technical procedures rather than to the test substance.

No specific study on dermal absorption is available. However, as cerium dioxide is an insoluble inorganic test substance (no logP can be calculated), no significant dermal absorption is expected. As an illustration, following acute exposure of rats to a dermal dose of 2000 mg/kg and observation up to 14 days following application, no noteworthy systemic clinical sign (other than slightly reduced activity on day 1) was observed.

Following repeated dose administration by the oral route at doses up to the limit dose of 1000 mg/kg for up to approximately 42 days in male rats and 54 days in female rats, there was no relevant sign of toxicity in any of the parameters studied, including clinical signs, functional observational battery, body weight, food consumption, hematology or blood biochemistry. The absence of toxic effects indicates that the test substance and/or its degradation products or metabolites are not absorbed or devoid of toxicity following oral dosing with cerium dioxide.

Following inhalation exposure for up to 90 days in rats, the effects observed were consistent with "portal- of-entry" effects and a lung-overload inflammatory response syndrome. No systemic effect resulting from significant absorption was evidenced.

The absorption of cerium dioxide is therefore expected to be extremely low.

 

- Regarding its distribution:

Following repeated dose administration by inhalation (nose only) at concentrations up to 0.5075 mg/L (507.5 mg/m3) for 13 weeks in rats, only loco-regional "portal-of-entry" effects were observed, as changes in segmented neutrophil counts, lung and spleen weights, lung and lymph node gross appearance at necropsy and respiratory tract and lymphoreticular system histopathology. These effects were illustrative of an inflammatory response subsequent to lung overloading with poorly soluble particles, without functional impairment of the immune system. No relevant systemic effects specific to cerium dioxide as such were evidenced.

Therefore, under normal conditions of exposure, no systemic distribution of cerium dioxide is expected.

 

- Regarding its metabolism:

The presence or absence of exogenous metabolic activation system made no difference in the results of in vitro mutagenicity testing. No conclusion can therefore be made regarding the transformation of the test substance and/or its degradation products or metabolites by hepatic microsomal fractions.

No microscopic finding in the major metabolizing tissues (liver, kidneys) 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 42 days in male rats and 54 days in female rats or by inhalation (nose only) at concentrations up to 0.5075 mg/L for 13 weeks in rats.

 

- Regarding its elimination:

Following a single administration by oral route (at the limit dose of 5000 mg/kg), whitish discoloration of the feces was observed, likely indicative of fecal elimination of the test substance as unchanged material.

Based on its insoluble nature, low absorption and distribution potentials, and absence of obvious metabolism, it is probable that cerium dioxide be eliminated under an unmodified form.