Organ burden of inhaled nanoceria in a 2-year low-dose exposure study: dump or depot?

Tentschert, Jutta; Laux, Peter; Jungnickel, Harald; Brunner, Josephine; Estrela‐Lopis, Irina; Merker, Carolin; Meijer, Jan; Ernst, Heinrich; Ma‐Hock, Lan; Keller, Jana; Landsiedel, Robert; Luch, Andreas

doi:10.1080/17435390.2020.1736355

Cited by 17 publications

(24 citation statements)

References 52 publications

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“…Precipitation and formation of cerium phosphate particles might contribute to the slow clearance of nanoceria from the lung reported in [4,9,51,61]. Cerium ions, introduced as such or released during nanoceria dissolution, in the presence of phosphate form cerium phosphate [48,52,[62][63][64] as was reported after introduction of cerium ions into the lung [65].…”

Section: Role Of Phosphate In the Fate Of Cerium/ Nanoceriamentioning

confidence: 85%

“…After systemic administration of solvothermally synthesized nanoceria, cerium phosphate particles were seen in rat liver and spleen [48,63]. After inhaling 3 mg/m 3 NM-212 for two years, CeO + and CePO 4 + were seen in rat femur [9]. These studies demonstrate a certain extent of dissolution of both nanoceria [66,69]).…”

Section: Role Of Phosphate In the Fate Of Cerium/ Nanoceriamentioning

confidence: 94%

“…The European Union funded a comprehensive two-year whole-body combined chronic toxicity/carcinogenicity inhalation study in female rats exposed to 0, 0.1, 0.3, 1, or 3 mg/m 3 NM-212, six hours daily on five consecutive working days per week (EU FP7 project 'NANoREG', Grant Agreement number 310584). Lung cerium burden after three, twelve, and 24 months of exposure positively correlated with exposure time and nanoceria concentration, with deposition fractions of 12%, 15%, 14%, and 8%, and predicted clearance half-lives of 86, 114, 164, and 200 days [9]. These studies showed that pulmonary exposure to NM-212 could lead to longterm biological persistence and have adverse consequences and raised the question whether its method of preparation and solubility are contributing factors.…”

Section: Introductionmentioning

confidence: 95%

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The preparation temperature influences the physicochemical nature and activity of nanoceria

Yokel

Wohlleben

Keller

et al. 2021

Beilstein J. Nanotechnol.

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Cerium oxide nanoparticles, so-called nanoceria, are engineered nanomaterials prepared by many methods that result in products with varying physicochemical properties and applications. Those used industrially are often calcined, an example is NM-212. Other nanoceria have beneficial pharmaceutical properties and are often prepared by solvothermal synthesis. Solvothermally synthesized nanoceria dissolve in acidic environments, accelerated by carboxylic acids. NM-212 dissolution has been reported to be minimal. To gain insight into the role of high-temperature exposure on nanoceria dissolution, product susceptibility to carboxylic acid-accelerated dissolution, and its effect on biological and catalytic properties of nanoceria, the dissolution of NM-212, a solvothermally synthesized nanoceria material, and a calcined form of the solvothermally synthesized nanoceria material (ca. 40, 4, and 40 nm diameter, respectively) was investigated. Two dissolution methods were employed. Dissolution of NM-212 and the calcined nanoceria was much slower than that of the non-calcined form. The decreased solubility was attributed to an increased amount of surface Ce4+ species induced by the high temperature. Carboxylic acids doubled the very low dissolution rate of NM-212. Nanoceria dissolution releases Ce3+ ions, which, with phosphate, form insoluble cerium phosphate in vivo. The addition of immobilized phosphates did not accelerate nanoceria dissolution, suggesting that the Ce3+ ion release during nanoceria dissolution was phosphate-independent. Smaller particles resulting from partial nanoceria dissolution led to less cellular protein carbonyl formation, attributed to an increased amount of surface Ce3+ species. Surface reactivity was greater for the solvothermally synthesized nanoceria, which had more Ce3+ species at the surface. The results show that temperature treatment of nanoceria can produce significant differences in solubility and surface cerium valence, which affect the biological and catalytic properties of nanoceria.

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Section: Role Of Phosphate In the Fate Of Cerium/ Nanoceriamentioning

confidence: 85%

Section: Role Of Phosphate In the Fate Of Cerium/ Nanoceriamentioning

confidence: 94%

Section: Introductionmentioning

confidence: 95%

See 1 more Smart Citation

The preparation temperature influences the physicochemical nature and activity of nanoceria

Yokel

Wohlleben

Keller

et al. 2021

Beilstein J. Nanotechnol.

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“…The ICP-MS organ burden data also exhibited high interlaboratory reproducibility: Upon 28-day exposure to 50 mg m −3 BaSO 4 NM-220 in female Wistar rats, a lung burden of ≈840 ± 180 µg was recorded (Table 1 and ref. [17]). Schwotzer et al [46] reported a rat lung burden of 1078 ± 197 µg after 28-day exposure to 50 mg m −3 of the same batch of BaSO 4 NM-220, that is, only 28% higher.…”

Section: Technical and Biological Variability Of The Lung Burden Datamentioning

confidence: 99%

The Use of Nanomaterial In Vivo Organ Burden Data for In Vitro Dose Setting

Ma‐Hock

Sauer²,

Ruggiero

et al. 2021

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Effects of nanomaterials are usually observed at higher concentrations in vitro compared to animal studies. This is pointing to differences between in vivo situations and generally less complex in vitro models. These differences concern toxicodynamics and the internal exposure (at the target cells of the in vitro and in vivo test system). The latter can be minimized by appropriate in vivo to in vitro dose extrapolations (IVIVE). An IVIVE six‐step procedure is proposed here: 1) determine in vivo exposure; 2) identify in vivo organ burden at lowest observed adverse effect concentration; 3) extrapolate in vivo organ burden to in vitro effective dose; 4) extrapolate in vitro effective dose to nominal concentration; 5) set dose ranges to establish dose–response relationships; and 6) consider uncertainties and specificities of in vitro test system. Assessing the results of in vitro studies needs careful consideration of discrepancies between in vitro and in vivo models: apart from different endpoints (usually cellular responses in vitro and adverse effects on organs or organisms in vivo), nanomaterials can also have a different potency in relatively simple in vitro models and the more complex corresponding organ in vivo. IVIVE can, nonetheless, reduce the differences in exposures.

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“…Note that this comparison should be done at lung burdens that do not induce lung toxicity, as this usually reduces lung clearance. A factor of 2-fold reflects the limited precision of half-time measurements (few time points, individual, intra-experimental and interexperimental variability, limited analytical precision) (Tentschert et al 2020).…”

Section: Thresholds For In Vivo Testingmentioning

confidence: 99%

Rationale and decision rules behind the ECETOC NanoApp to support registration of sets of similar nanoforms within REACH

2020

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Organ burden of inhaled nanoceria in a 2-year low-dose exposure study: dump or depot?

Cited by 17 publications

References 52 publications

The preparation temperature influences the physicochemical nature and activity of nanoceria

The preparation temperature influences the physicochemical nature and activity of nanoceria

The Use of Nanomaterial In Vivo Organ Burden Data for In Vitro Dose Setting

Rationale and decision rules behind the ECETOC NanoApp to support registration of sets of similar nanoforms within REACH

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