Toxicity and bio-accumulation of inhaled cerium oxide nanoparticles in CD1 mice

Aalapati, Srinivas; Ganapathy, Selvam; Manapuram, Saikumar; Goparaju, A; Prakya, Balakrishna Murthy

doi:10.3109/17435390.2013.829877

Cited by 98 publications

(123 citation statements)

References 62 publications

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“…The data from the study demonstrated that repeated inhalation exposure to these CeO 2 NMs resulted in significant translocation and accumulation of materials in the extra-pulmonary organs with degenerative changes in the liver and the kidneys. Additionally it was shown that the NMs are relatively difficult to clear and have the potential for some long-term toxicological effects (Aalapati et al 2014).…”

Section: Inhalation Exposurementioning

confidence: 99%

Nanomaterial translocation–the biokinetics, tissue accumulation, toxicity and fate of materials in secondary organs–a review

Kermanizadeh

Balharry

Wallin

et al. 2015

Critical Reviews in Toxicology

141

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Engineered nanomaterials (NMs) offer great technological advantages but their risks to human health are still not fully understood. An increasing body of evidence suggests that some NMs are capable of distributing from the site of exposure to a number of secondary organs. The research into the toxicity posed by the NMs in these secondary organs is expanding due to the realisation that some materials may reach and accumulate in these target sites. The translocation to secondary organs includes, but is not limited to, the hepatic, central nervous, cardiovascular and renal systems. Current data indicates that pulmonary exposure is associated with low (inhalation route-0.00001-1% of total applied dose-24 h) translocation of virtually insoluble NMs such as iridium, carbon black, gold and polystyrene, while slightly higher translocation has been observed for NMs with either slow (e.g., silver, cerium dioxide and quantum dots) or fast (e.g., zinc oxide) solubility. The translocation of NMs following intratracheal, intranasal and pharyngeal aspiration is higher (up to 10% of administered dose), however the relevance of these routes for risk assessment is questionable. Uptake of the materials from the gastrointestinal tract seems to follow the same pattern as inhalation translocation, whereas the dermal uptake of NMs is generally reported to be low. The toxicological effects in secondary organs include oxidative stress, inflammation, cytotoxicity and dysfunction of cellular and physiological processes. For toxicological and risk evaluation, further information on the toxicokinetics and persistence of NMs is crucial. The overall aim of this review is to outline the data currently available in the literature on the biokinetics, accumulation, toxicity and eventual fate of NMs in order to assess the potential risks posed by NMs to secondary organs.

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Section: Inhalation Exposurementioning

confidence: 99%

Nanomaterial translocation–the biokinetics, tissue accumulation, toxicity and fate of materials in secondary organs–a review

Kermanizadeh

Balharry

Wallin

et al. 2015

Critical Reviews in Toxicology

141

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“…In an inhalation study in mice, exposure of nanoceria (15 to 30 nm primary diameter and 30 to 50 m 2 /g specific surface area [SSA]) for 0, 7, 14, or 28 days at an aerosol concentration of 2 mg/m 3 resulted in significant bioaccumulation in pulmonary and extrapulmonary tissues, even 30 days after inhalation exposure 59 . Despite the small primary diameter, the test aerosol was characterized by a MMAD of 1.4 µm and a wide distribution, as indicated by a geometric standard deviation of 2.4.…”

Section: Pulmonary Deposition and Responsementioning

confidence: 99%

The yin: an adverse health perspective of nanoceria: uptake, distribution, accumulation, and mechanisms of its toxicity

Yokel

Hussain

Garantziotis

et al. 2014

Environ. Sci.: Nano

111

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This critical review evolved from a SNO Special Workshop on Nanoceria panel presentation addressing the toxicological risks of nanoceria: accumulation, target organs, and issues of clearance; how exposure dose/concentration, exposure route, and experimental preparation/model influence the different reported effects of nanoceria; and how can safer by design concepts be applied to nanoceria? It focuses on the most relevant routes of human nanoceria exposure and uptake, disposition, persistence, and resultant adverse effects. The pulmonary, oral, dermal, and topical ocular exposure routes are addressed as well as the intravenous route, as the latter provides a reference for the pharmacokinetic fate of nanoceria once introduced into blood. Nanoceria reaching the blood is primarily distributed to mononuclear phagocytic system organs. Available data suggest nanoceria’s distribution is not greatly affected by dose, shape, or dosing schedule. Significant attention has been paid to the inhalation exposure route. Nanoceria distribution from the lung to the rest of the body is less than 1% of the deposited dose, and from the gastrointestinal tract even less. Intracellular nanoceria and organ burdens persist for at least months, suggesting very slow clearance rates. The acute toxicity of nanoceria is very low. However, large/accumulated doses produce granuloma in the lung and liver, and fibrosis in the lung. Toxicity, including genotoxicity, increases with exposure time; the effects disappear slowly, possibly due to nanoceria’s biopersistence. Nanoceria may exert toxicity through oxidative stress. Adverse effects seen at sites distal to exposure may be due to nanoceria translocation or released biomolecules. An example is elevated oxidative stress indicators in the brain, in the absence of appreciable brain nanoceria. Nanoceria may change its nature in biological environments and cause changes in biological molecules. Increased toxicity has been related to greater surface Ce3+, which becomes more relevant as particle size decreases and the ratio of surface area to volume increases. Given its biopersistence and resulting increased toxicity with time, there is a risk that long-term exposure to low nanoceria levels may eventually lead to adverse health effects. This critical review provides recommendations for research to resolve some of the many unknowns of nanoceria’s fate and adverse effects.

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“…If particles were found in extra-pulmonary 1642 tissues at all, they were mainly restricted to the liver (but also 1643 occurred to minimal extents in other organs, including the brain). 1644 For CeO 2 nanoparticles, a 28-day inhalation study using male mice 1645 provided evidence of nephrotoxicity (Aalapati et al, 2014), a 1646 finding that, however, was not observed in any studies using rats 1647 (Moreno-Horn and Gebel, 2014). Also for silver nanoparticles, sys-1648 temic translocation was low, as assessed in a sub-chronic inhala-1649 tion study with rats, in spite of its higher bioavailability than the 1650 poorly soluble TiO 2 or CeO 2 nanoparticles (Moreno-Horn and 1651 Gebel, 2014).…”

mentioning

confidence: 99%

A decision-making framework for the grouping and testing of nanomaterials (DF4nanoGrouping)

Arts

Hadi

Irfan

et al. 2015

Regulatory Toxicology and Pharmacology

230

227

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The European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) 'Nano Task Force' proposes a Decision-making framework for the grouping and testing of nanomaterials (DF4nanoGrouping) that consists of 3 tiers to assign nanomaterials to 4 main groups, to perform sub-grouping within the main groups and to determine and refine specific information needs. The DF4nanoGrouping covers all relevant aspects of a nanomaterial's life cycle and biological pathways, i.e. intrinsic material and system-dependent properties, biopersistence, uptake and biodistribution, cellular and apical toxic effects. Use (including manufacture), release and route of exposure are applied as 'qualifiers' within the DF4nanoGrouping to determine if, e.g. nanomaterials cannot be released from a product matrix, which may justify the waiving of testing. The four main groups encompass (1) soluble nanomaterials, (2) biopersistent high aspect ratio nanomaterials, (3) passive nanomaterials, and (4) active nanomaterials. The DF4nanoGrouping aims to group nanomaterials by their specific mode-of-action that results in an apical toxic effect. This is eventually directed by a nanomaterial's intrinsic properties. However, since the exact correlation of intrinsic material properties and apical toxic effect is not yet established, the DF4nanoGrouping uses the 'functionality' of nanomaterials for grouping rather than relying on intrinsic material properties alone. Such functionalities include system-dependent material properties (such as dissolution rate in biologically relevant media), bio-physical interactions, in vitro effects and release and exposure. The DF4nanoGrouping is a hazard and risk assessment tool that applies modern toxicology and contributes to the sustainable development of nanotechnological products. It ensures that no studies are performed that do not provide crucial data and therefore saves animals and resources.

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Toxicity and bio-accumulation of inhaled cerium oxide nanoparticles in CD1 mice

Cited by 98 publications

References 62 publications

Nanomaterial translocation–the biokinetics, tissue accumulation, toxicity and fate of materials in secondary organs–a review

Nanomaterial translocation–the biokinetics, tissue accumulation, toxicity and fate of materials in secondary organs–a review

The yin: an adverse health perspective of nanoceria: uptake, distribution, accumulation, and mechanisms of its toxicity

A decision-making framework for the grouping and testing of nanomaterials (DF4nanoGrouping)

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