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Description of key information

No studies are available. Based on molecular structure, molecular weight, water solubility and experimental toxicology data available, it can be expected that absorption rates (oral, dermal or inhalation) are extremely low, distribution in the body is minor and that elimination occurs mainly under an unmodified form (no extensive metabolism proved). The lack of adverse effects in the experimental toxicology data available (acute/repeated exposure, by oral or dermal route or by inhalation) confirm that the substance has a low absorption rate or is devoid of toxicity.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

General information

Name: Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate

Molecular weight: 235 g/mol < M g/mol < 241 g/mol

Molecular formula: (La,Ce,Tb)PO4

Physical state: powder

Stability: substance very stable

Water solubility: 2.06 µg/L

n-octanol/water partition coefficient: not applicable (inorganic substance)

Vapour pressure: not determined

Relative density: 4.798

Toxicological information

Acute toxicity rat, oral > 2000mg/kg (no mortality and no sign of toxicological relevance at this dose)

Acute toxicity rat, dermal > 2000mg/kg (no mortality and no sign of toxicological relevance at this dose)

Acute toxicity, rat, inhalation 4-hr LC50 inhalation > 5.04 mg/L (no mortality and no sign of toxicological relevance at this dose)

Skin irritation: really slightly irritating but not classified

Eye irritation: slightly irritating but not classified

Skin sensitisation: Not sensitising (LLNA test)

In-vitro mutagenicity: no evidence of mutagenicity (Ames test, mammalian chromosome aberration test, and gene mutation assay in mammalian cells)

No Observed Adverse Effect Level (NOAEL) for systemic toxicity is 1000 mg/kg bw/day (highest dose level tested) for both male and female rats (OECD 422, oral gavage, up to 39 days in males and up to 55 days in females)

No Observed Adverse Effect Level (NOAEL) for reproductive performance (mating and fertility) is 1000 mg/kg bw/day (highest dose level tested) for both male and female rats (OECD 422, oral gavage, up to 39 days in males and up to 55 days in females)

 

There is no toxicokinetic data available for the Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate. However, the following basic toxicokinetic information can be extrapolated from the experimental toxicology data available on that substance, an insoluble (water solubility = 2.06 µg/L at 20°C) inorganic substance.

Furthermore, toxicokinetic data via the intravenous route are available for a water-soluble lanthanum compound (as chloride); the lanthanum representing the main component of the reaction mass (57 % as phosphate). Additionally, there are oral pharmacokinetic studies published for lanthanum carbonate and for the drug Fosrenol® (Shire Pharmaceuticals), which contains lanthanum carbonate hydrate. Like lanthanum phosphate, lanthanum carbonate is practically insoluble in water (1.84 mg/l). It was however reported to dissociate in the acid environment of the upper gastrointestinal tract and liberate free lanthanum ions (Curran and Robinson, 2009). Soluble lanthanum ions bind dietary phosphate in the lumen of the gut and form highly insoluble lanthanum phosphate complexes. These complexes can not easily pass through the wall of the gastrointestinal tract and are excreted in the faeces. Therefore, the absorption of lanthanum from the gastrointestinal tract is expected to be very low (< 0.002%). Following oral administration of lanthanum carbonate, the great majority of the dose is excreted unabsorbed in the faeces: 99% and 93% of the dose was recovered in the faeces of rats (Damment and Pennick, 2007) and dogs (FDA (2002, 2004), respectively and in humans (Pennick et al., 2006).. The small absorbed fraction is excreted predominantly via the liver into bile (Pennick et al., 2006; Damment and Pennick, 2007). Biliary elimination (80%) and direct transport across the gut wall into the lumen (13%) represent the main routes of elimination after i. v. administration of lanthanum chloride to rats.

 

- Regarding its absorption:

Following a single administration of Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate, either by oral route (at the limit dose of 2000 mg/kg), dermal route (at the limit dose of 2000 mg/kg) or by inhalation at 5.04 mg/L for 4 hours, no relevant systemic clinical sign or changes in body weight was observed.

No specific study on dermal absorption is available. However, as Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate is an insoluble inorganic substance, 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.

In a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test performed by the oral route with Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate at doses up to the limit dose of 1000 mg/kg bw/d for up to39 days in male rats and up to 55 days in female rats (OECD guideline No. 422), 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, and gross- or histopathology. The absence of toxic effects in this study indicates that the test substance and/or its degradation products or metabolites are not absorbed or devoid of toxicity following oral dosing with Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate.

No toxicologically meaningful sign of toxicity towards reproductive parameters was also observed up to the highest dose of 1000 mg/kg bw/day in the same study (OECD guideline 422).

The absorption of Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate is therefore expected to be extremely low.

 

- Regarding its distribution:

Following repeated dose administration by the oral route at doses up to the limit dose of 1000 mg/kg bw/d in rats (OECD guideline No. 422), Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate showed no relevant sign of toxicity in any of the parameters studied, including clinical signs, functional observation battery, body weight, food consumption, hematology or blood biochemistry, gross- or histopathology, and reproductive parameters.

Therefore, under normal conditions of exposure, no systemic distribution of Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate 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 with Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate. 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 adverse microscopic finding in the major metabolizing tissues (liver, kidneys) illustrative of metabolic activity were seen following repeated dose administration of Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate by the oral route at doses up to the limit dose of 1000 mg/kg bw/d for up to 39 days in male rats and up to 55 days in female rats.

- Regarding its elimination:

No specific study on elimination is available.

Based on its insoluble nature, low absorption and distribution potentials, and absence of obvious metabolism, it is probable that Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate is eliminated under an unmodified form.

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