RETRACTED: Genotoxicity assessment of cerium oxide nanoparticles in female Wistar rats after acute oral exposure

Kumari, Monika; Kumari, Sushma; Kamal, S.S. Kalyan; Grover, Paramjit

doi:10.1016/j.mrgentox.2014.09.009

Cited by 61 publications

(42 citation statements)

References 54 publications

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“…Although we did not test systemic genotoxicity in our study, the absent effects reported by Cordelli et al [18] indicate a restriction of effects to pulmonary organs. In contrast, systemic genotoxic effects were reported after single and repeated oral administration of CeO 2 [49, 50]. Considering that respective findings were present only at high concentrations of >300 mg/kg BW, a potential for the induction of DNA damage via secondary rather than primary genotoxic mechanisms could be assumed for CeO 2 nanoparticles.…”

Section: Discussionmentioning

confidence: 99%

Effects from a 90-day inhalation toxicity study with cerium oxide and barium sulfate nanoparticles in rats

et al. 2017

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BackgroundNanomaterials like cerium oxide and barium sulfate are frequently processed in industrial and consumer products and exposure of humans and other organisms is likely. Generally less information is given on health effects and toxicity, especially regarding long-term exposure to low nanoparticle doses. Since inhalation is still the major route of uptake the present study focused on pulmonary effects of CeO2NM-212 (0.1, 0.3, 1.0, 3.0 mg/m3) and BaSO4NM-220 nanoparticles (50.0 mg/m3) in a 90-day exposure setup. To define particle-related effects and potential mechanisms of action, observations in histopathology, bronchoalveolar lavage and immunohistochemistry were linked to pulmonary deposition and clearance rates. This further allows evaluation of potential overload related effects.ResultsLung burden values increased with increasing nanoparticle dose levels and ongoing exposure. At higher doses, cerium clearance was impaired, suggesting lung overload. Barium elimination was extremely rapid and without any signs of overload. Bronchoalveolar lavage fluid analysis and histopathology revealed lung tissue inflammation with increasing severity and post-exposure persistency for CeO2. Also, marker levels for genotoxicity and cell proliferation were significantly increased. BaSO4 showed less inflammation or persistency of effects and particularly affected the nasal cavity.ConclusionCeO2 nanoparticles penetrate the alveolar space and affect the respiratory tract after inhalation mainly in terms of inflammation. Effects at low dose levels and post-exposure persistency suggest potential long-term effects and a notable relevance for human health. The generated data might be useful to improve nanoparticle risk assessment and threshold value generation. Mechanistic investigations at conditions of non-overload and absent inflammation should be further investigated in future studies.

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Section: Discussionmentioning

confidence: 99%

Effects from a 90-day inhalation toxicity study with cerium oxide and barium sulfate nanoparticles in rats

et al. 2017

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“…It is also likely that the DNA damage results from the inflammation and/or oxidative stress which took place in the different organs studied. It has been reported that oral administration of high dose (1000 mg/kg bw) of CeO 2 NPs induces significant DNA damage in peripheral blood leukocytes and liver cells, micronucleus formation in bone marrow and blood cells, and total cytogenetic changes in bone marrow [58]. Moreover, it has been shown that CeO 2 NPs induce oxidative stress and genotoxicity in human skin melanoma cells and human dermal fibroblasts [59, 60].…”

Section: Discussionmentioning

confidence: 99%

Cerium Oxide Nanoparticles in Lung Acutely Induce Oxidative Stress, Inflammation, and DNA Damage in Various Organs of Mice

Nemmar

Yuvaraju

Beegam

et al. 2017

Oxidative Medicine and Cellular Longevity

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CeO2 nanoparticles (CeO2 NPs) which are used as a diesel fuel additive are emitted in the particulate phase in the exhaust, posing a health concern. However, limited information exists regarding the in vivo acute toxicity of CeO2 NPs on multiple organs. Presently, we investigated the acute (24 h) effects of intratracheally instilled CeO2 NPs in mice (0.5 mg/kg) on oxidative stress, inflammation, and DNA damage in major organs including lung, heart, liver, kidneys, spleen, and brain. Lipid peroxidation measured by malondialdehyde production was increased in the lungs only, and reactive oxygen species were increased in the lung, heart, kidney, and brain. Superoxide dismutase activity was decreased in the lung, liver, and kidney, whereas glutathione increased in lung but it decreased in the kidney. Total nitric oxide was increased in the lung and spleen but it decreased in the heart. Tumour necrosis factor-α increased in all organs studied. Interleukin- (IL-) 6 increased in the lung, heart, liver, kidney, and spleen. IL-1β augmented in the lung, heart, kidney, and spleen. Moreover, CeO2 NPs induced DNA damage, assessed by COMET assay, in all organs studied. Collectively, these findings indicate that pulmonary exposure to CeO2 NPs causes oxidative stress, inflammation, and DNA damage in multiple organs.

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“…In contrast, the exposure to the same doses of CeO 2 micro materials resulted in no significant translocation or material accumulation in any tissue. The data above indicated that size and dose are very important contributors to secondary tissue bio-accumulation for the CeO 2 NMs after acute oral exposure (Kumari et al 2014b). …”

Section: Nm-induced Adverse Effects In Secondary Organsmentioning

confidence: 97%

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

138

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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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RETRACTED: Genotoxicity assessment of cerium oxide nanoparticles in female Wistar rats after acute oral exposure

Cited by 61 publications

References 54 publications

Effects from a 90-day inhalation toxicity study with cerium oxide and barium sulfate nanoparticles in rats

Effects from a 90-day inhalation toxicity study with cerium oxide and barium sulfate nanoparticles in rats

Cerium Oxide Nanoparticles in Lung Acutely Induce Oxidative Stress, Inflammation, and DNA Damage in Various Organs of Mice

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

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