Cerium(3+) acetate

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

100

Additional information

No experimental studies on the absorption, distribution, metabolism or elimination of cerium acetate (EC 208-654-0, CAS 537-00-8) in mammals are available. However, the physical chemical properties and the existing in vitro and in vivo toxicology studies on the substance (and results for the read across substance cerium trinitrate: EC 10294-41-1, CAS 600-370-9), have been used to infer as far as possible, its potential toxicokinetic profile.

Based on in vitro and in vivo data from studies performed with cerium acetate or the read across substance cerium trinitrate, oral absorption is estimated at 50%, inhalation absorption is estimated at 100% and dermal absorption is estimated at 10%.  The potential for bioaccumulation is considered to be low.

 

Introduction

Physico-chemical properties of cerium acetate (EC 208-654-0, CAS 537-00-8) and the results of in vitro and in vivo studies conducted with cerium acetate, or the read across substance cerium trinitrate (EC 10294-41-1, CAS 600-370-9), have been used to determine, as far as possible, a toxicokinetic profile.

Physicochemical properties

The substance cerium acetate is a white, granular solid (Tremain 2017) and has the molecular formula Ce(C2H3O2)3 with a molecular weight of 317.25 g/mol (Lide 1995).  It is soluble in water at approximately 20 g/100 mL at room temperature (Flatschacher 2017) and it has a vapour pressure of <10-3 Pa at 20°C (Demangel 2017) and a pH of 6.25 (Flatschacher 2017). As cerium acetate is an inorganic substance, no partition coefficient has been determined.

The read across substance cerium trinitrate is a white crystalline solid with the molecular formula Ce(NO3)3 and molecular weight of 326.13 g/mol (Perry 2011).  

Absorption

Oral absorption

In an acute oral toxicity study, the acute median lethal dose (LD50) of cerium acetate was estimated to be >2000 mg/kg body weight. There were no signs of systemic toxicity (observations were limited to noisy respiration noted in two animals treated at a dose level of 2000 mg/kg) or abnormalities at necropsy and animals gained weight as expected (Pooles 2017). There was therefore little evidence that cerium acetate was absorbed from the gut.

The read across substance, cerium trinitrate, was tested in a combined repeated dose toxicity study with reproduction/developmental toxicity screening test performed according to the OECD TG 422 (1996) (Braun 2013).  Treatment-related morphological changes in the stomach were observed at 330 mg/kg/day and 1000 mg/kg/day, which were attributed to local irritation effects rather than systemic toxicity.  The majority of the other treatment-related findings, which included reductions in body weight and food consumption, changes in clinical chemistry parameters and changes in organ weights, also occurred at 330 and/or 1000 mg/kg/day and were considered to be secondary to the changes observed in the stomach. With respect to reproductive toxicity, effects included increased post-implantation loss, decreased mean litter size, increased postnatal loss and decreased group mean pup weights (day 1 post partum) at 1000 mg/kg/day only. These changes are considered to be secondary effects resulting from chemical stress observed in pregnant females (i.e. local irritation in the stomach after repeated oral gavage of the compound).

Data on the in vitro eye irritation effects of cerium acetate provides further evidence that the substance causes local irritation effects. In a bovine corneal opacity and permeability test (performed according to OECD TG 437) treatment with cerium acetate as a 20% w/v solution resulted in an in vitro irritation score (IVIS) of 13.8, although due to the limitations of this ex vivo test no prediction can be made for IVIS values of >3 but ≤55.

Overall, the available in vivo data, suggests that oral absorption of cerium acetate is unlikely, however, due to the local irritation effects in the stomach and reproductive toxicity findings, and in the absence of any other information, for the purposes of human DNEL setting, 50% oral absorption is assumed for risk assessment purpose.

Dermal absorption

No dermal toxicity data are available for cerium acetate or the read across substance. Some toxicokinetic information can be inferred from the in vitro skin sensitisation, irritation and corrosion studies. In a GLP-compliant OECD 406 guinea pig maximisation test, dermal administration of up to 40% w/w did not cause skin sensitisation; furthermore cerium acetate did not cause any skin corrosion or skin irritation in vitro (GLP studies performed according to OECD TG 431 and 439).  These data support a lack of absorption through the skin.

The test substance is inorganic in nature and is not expected to be lipophilic. In addition, as it is highly water soluble, it maybe too hydrophilic to cross the lipid rich environment of the stratum corneum. Therefore, it can be concluded that significant absorption via the dermal route is unlikely.

For the purposes of DNEL setting however, estimation of human dermal absorption is made in accordance with principles adopted in the EFSA guidance on estimating dermal absorption of pesticide active substances (Buist H 2017).  Consequently, based on the physical form (granular solid), dermal absorption is estimated at 10% for risk assessment purposes.

Inhalation absorption

No data on acute toxicity by inhalation are available for cerium acetate or the read across substance. This was scientifically unjustified on the grounds that inhalation exposure to the substance is unlikely under normal conditions of use.

In the absence of any quantitative data, absorption by inhalation is assumed to be 100%.

Distribution, Metabolism and Elimination

No information is available to describe the distribution, metabolism or elimination of the material.

In the in vitro genotoxicity tests on either cerium acetate or the read across substance cerium trinitrate (Thompson 2017), (Bowles 2013), (Morris 2013) there are qualitative differences in toxicity and solubility between treatments conducted in the presence of an exogenous rat metabolising system (induced liver S9), which may be suggestive of metabolism by liver enzymes.  However, there is insufficient data available to indicate whether this could happen in vivo.

The moderate molecular weight and high water solubility of the substance would suggest that diffusion across lipid membranes would be slow and therefore wide distribution is unlikely.

Given there is unlikely to be any oral absorption, and the relatively high molecular weight, ingested material is likely to pass through the gastrointestinal tract and be eliminated in the faeces and possibly also via the bile.

Conclusion

Based on in vitro and in vivo data from studies performed with cerium acetate or the read across substance cerium trinitrate, oral absorption is estimated at 50%, inhalation absorption is estimated at 100% and dermal absorption is estimated at 10%.  The potential for bioaccumulation is considered low. 

References

Bowles, A. 2013. “Cerium trinitrate: chromosome aberration test in human lymphocytes In vitro.”

Braun, WH. 2013. “Cerium trinitrate: combined repeated dose toxicity study with reproduction/developmental toxicity screening test in the Han Wistar Rat.”

Buist H, Craig P, Dewhurst I, Hougaard Bennekou S, Kneuer C, Machera K, Pieper C, Court Marques D, Guillot G, Ruffo F, Chiusolo C. 2017. “Guidance on dermal absorption.” EFSA Journal 15 (6).

Demangel, B. 2017. “Vapour pressure test on Cerium triacetate CAS No. 537-00-8.”

Flatschacher. 2017. “Cerium acetate analytical report.”