Dicerium tricarbonate

Endpoint summary

Additional information

There are three forms of lanthanides: insoluble (oxides, carbonates), solubles (chlorides, nitrates, acetates) and chelated compounds.
Cerium carbonate is a realtively insoluble form or cerium, as illustrated by its very low water solubility (3.95 + 0.2 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, 2005).
The following basic toxicokinetic information can be extrapolated from the experimental toxicology data available on dicerium tricarbonate, an insoluble inorganic substance:

- Regarding its absorption:

Following a single administration either by oral route (at the limit dose of 5000 mg/kg) or dermal route (at the limit dose of 2000 mg/kg), no relevant systemic clinical sign or changes in body weight were observed. No specific study on dermal absorption is available. However, as cerium carbonate is an insoluble inorganic test substance (no log P 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 was observed.

Following repeated dose administration by the oral route at doses up to the limit dose of 1000 mg/kgbw/day of dicerium tricarbonatefor up to approximately 42 days in male rats and 54 days in female rats,there wasno relevant sign of toxicity in clinical signs, functional observational battery, body weight,andfood consumption. However, there was some evidence of absorption as changes in haematology/clinical chemistry was observed in male and female animals treated atthe highest dose tested1000 mg/kg bw/dayand no effect were observed at the lower doses tested (450 and 150 mg/kg bw/day).Following inhalation exposure for up to 90 days in rats, the effects observedof an analogous (cerium oxide)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 dicerium tricarbonate is therefore expected to be low.

 

- Regarding its distribution:

Following repeated dose administration by inhalation (nose only)of the analogous: cerium dioxide 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 systemhistopathology. 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 dicerium tricarbonate 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)of the analogous substance: cerium oxideat concentrations up to 0.5075 mg/L for 13 weeks in rats.

 

- Regarding its elimination:

Based on their insoluble nature, low absorption and distribution potentials, and absence of obvious metabolism, it is probable that dicerium tricarbonate will be eliminated under an unmodified form.