Tris[oxalate(2-)]dicerium

Endpoint summary

Description of key information

For the purposes of human risk assessment, oral absorption of the substance is estimated at 50%, inhalation absorption is estimated at 100% and dermal absorption is estimated at 25%.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

25

Additional information

Introduction

The substance is a white crystalline solid.

No experimental studies of cerium oxalate with animals or humans on absorption, metabolism, distribution, or elimination in mammals are available. However, information is available from existing toxicology studies from which limited inferal of potential toxicokinetic properties might be made.

Systemic availability of cerium oxalate depends on its ability to be absorbed across body surfaces. Factors that affect this process include water solubility, lipophilicity (measured by the partition coefficient, Kow), degree of ionization (the dissociation constant, pKa), and molecular size. The substance has a molecular weight of 544.3 g/mol and is sparingly soluble in water (2.3 mg/L in purified water, rising to 2.6 mg/L at pH 4). No dissociation constant is available for this substance. Kow are not required for inorganic substances.

Absorption

Oral absorption

The acute oral LD50 of the substance was estimated to be greater than 2000 mg/kg bw in an OECD 420 acute oral study, with no clinical signs and no effect on body weight observed. In addition, no gross abnormalities were observed at necropsy. Nothing can be inferred about the nature of oral absorption from this study.

In an OECD 422 repeat-dose/reproductive study treatment with the read-across substance cerium carbonate there is evidence of absorption. Effects observed in this study were in animals treated at 450 and 1000 mg/kg/day. The NOEL for this study was 150 mg/kg/bw. Animals treated at 1000 mg/kg/day had lower white blood cell counts. Females in this group also had lower chloride concentration and higher glucose, potassium, inorganic phosphorus and urea levels. In rats from both sexes treated at 450 and 1000 mg/kg/day, there were microscopic treatment related findings in the stomach that consisted of increased incidence and/or severity of submucosal eosinophil infiltration and pyloric gland hyperplasia. No test material-related microscopic findings were observed at 150 mg/kg/day.

Because of the insolubility of the material in water absorption via the oral route is unlikely, although in the absence of other information, the unquantified effect on solubility of stomach acid, and for the purposes of human DNEL setting, 50% bioavailability is assumed.

Dermal absorption

The acute dermal LD50 of the substance was estimated to be greater than 2000 mg/kg bw in a GLP-compliant OECD 402 study, with no clinical signs and no effect on body weight observed. Furthermore, no gross abnormalities were observed at necropsy.

In addition, some toxicokinetic information can be inferred from the skin sensitisation study. In a GLP-compliant OECD 429 in vivo local lymph node assay in mice, dermal administration of up to 25% w/w (the highest technically achievable concentration) was used to assess sensitisation; no effects were identified supporting the lack of absorption through the skin. The test substance is inorganic in nature and is not expected to be lipophilic. It can be concluded from the study data that significant absorption via the dermal route is unlikely.

For the purposes of DNEL setting however, estimation of mammalian dermal absorption is made in accordance with principles adopted EFSA guidance on estimating dermal absorption of pesticide active substances (EFSA, 2012). On this basis, dermal absorption is estimated at 25% for undiluted material.

Inhalation absorption

The substance is a hygroscopic, lumpy solid and as such it was not possible to conduct an acute inhalation study. Given the physical properties of the substance inhalation exposure is unlikely.

In the absence of any quantitative data, absorption of material that makes it into the alveoli is considered to be 100%.

Distribution, metabolism and excretion

No information is available to describe the distribution, metabolism of the material. Given there is unlikely to be any oral absorption, ingested material is likely to pass through the GIT and merger in the faeces.

Conclusion

For the purposes of human risk assessment, oral absorption of the substance is estimated at 50%, inhalation absorption is estimated at 100% and dermal absorption is estimated at 25%.