in vitro exposure of human intestinal cells to iron phosphate nanoparticles indicate no direct...

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S242 Abstracts / Toxicology Letters 221S (2013) S59–S256 P24-10 In vitro exposure of human intestinal cells to iron phosphate nanoparticles indicate no direct cytotoxicity Lea von Moos , Ioannis Trantakis, Peter Rast, Florentine Hilty-Vancura, Michael Zimmermann, Sotiris Pratsinis, Shana Sturla ETH, Zurich, Switzerland The use of nanotechnology in the food and nutrition indus- try offers new opportunities to enhance product performance and provide health benefits to consumers. One promising application is food fortification with highly bioavailable nanostructured iron compounds to combat iron deficiency, which is still a major global public health issue. However, the use of engineered nanoparti- cles (ENP) in foods is raising concerns since the fate and safety of ENP upon ingestion is largely unknown. In the present study, the potential cytotoxicity of amorphous iron phosphate nanoparti- cles (FePO 4 -NP) produced by flame spray pyrolysis (FSP) to human intestinal epithelial cells was studied in vitro. Cytotoxicity was evaluated with the MTS assay. Food-grade SiO 2 -NP and FSP made SiO 2 /Ag-NP served as negative and positive controls, respectively. The effect of acute NP exposure was studied by incubating cells with different concentrations (0.1–500 g/mL) of FePO 4 -NP, SiO 2 - NP and SiO 2 /Ag-NP for 24 or 48 h. No cytotoxicity was observed, neither after 24 nor 48 h exposure. These results give a first indi- cation that the tested NPs are not directly toxic to the intestinal epithelial cells. http://dx.doi.org/10.1016/j.toxlet.2013.05.595 P24-11 Influence of nano-polystyrene particles in inducing cytotoxicity in mice co-injected with carbon tetrachloride, cisplatin, or paraquat Katsuhiro Isoda , Shimizu Yoshimi, Tetsuji Nishimura, Masakatsu Tezuka, Isao Ishida Teikyo Heisei University, Chiba, Japan Nanomaterials are used frequently in microelectronics, cos- metics and sunscreens, and research into the development of nanomaterial-based drug delivery systems is providing promising results. However, the toxicity of nanomaterials has yet to be fully investigated. In particular, the interactions between nanomateri- als and therapeutic drugs require further study. We investigated whether nano-sized polystyrene particles affect drug-induced toxicity. The particles, which are widely used industrially, had diameters of 50 (NPP50), 200 (NPP200) or 1000 (NPP1000) nm. The toxic chemicals tested were carbon tetrachloride, cisplatin (a pop- ular anti-tumor agent), and a widely used herbicide, paraquat. Mice were treated intraperitoneally with either carbon tetrachloride (0.01 ml/kg), cisplatin (100 mol/kg) or paraquat (50 mg/kg), with or without intravenous administration of polystyrene particles. All treatments in the absence of the nanoparticles were non-lethal and did not result in severe toxicity. However, when mice were injected with paraquat or cisplatin together with polystyrene par- ticles, synergistic, enhanced toxicity was observed in mice injected with NPP50. These synergic effects were not observed in mice co-injected with NPP200 or NPP1000. These findings suggest that further evaluation of the interactions between polystyrene nano- particles and drugs is a critical prerequisite to the pharmaceutical application of nanotechnology. http://dx.doi.org/10.1016/j.toxlet.2013.05.596 P24-12 Long-term biodistribution, metabolism and toxicity of carbon nanotubes in vivo Xiaoyong Deng 1,, Man Luo 2 , Erlei Shao 1 , Hui Zhao 1 , Xing Yang 1 , Qingshun Ni 1 , Zheng Jiao 1 1 Shanghai University, Shanghai, China, 2 Fudan University, Shanghai, China Due to their unique physical and chemical properties, carbon nanotubes (CNTs) have broad potential application in the fields of electronic technology, novel materials and biomedicine. With the widely using of CNTs, the risk of being exposed to the environment with CNTs becomes higher. Further researches are needed eagerly to find out how these novel materials affect the human health and environment. Here, the long-term distribution, metabolism and toxicity of water soluble CNTs in mice were intensively inves- tigated, which can offer reliable toxicology results for the safety assessment of CNTs. Firstly, the water soluble polyethylene-glycol-functionalized multi-walled CNTs (PEG-MWCNTs) were synthesized and char- acterized by TEM, FTIR and TGA. Based on TGA data, the grafted rate of PEG on MWCNTs is estimated to be 23%. Then, the method of microwave digestion was studied and optimized in tracing the location of CNTs in vivo. Using the developed method, the distri- bution and excretion of CNTs in mice after intravenous exposure for 14 months were investigated, which showed that even after 14 months post exposure, CNTs could not be excreted thoroughly, with 40% of injected dose trapped in liver. Besides, the ultrastructural pathology and the length results indicated that the CNTs activated the self-metabolism mechanism, and the evidences of liver-bile and renal excretion routes were found. Finally, the toxicity of CNTs after intravenous exposure in 14 months was investigated. The results showed that the blood biochemistry results were normal, and the experiments on histological morphology of main organs did not show damage, except for some granulomas were induced in lung. We investigated the long-term toxicity of CNTs, which lasted for 14 months exposure, for the first time. All these results indicate PEG-MWCNTs exhibit good biocompatibility, which provides ref- erence for other researches in the fields of CNTs safety assessment and biomedicine application. http://dx.doi.org/10.1016/j.toxlet.2013.05.597 P24-13 Metabolic response of human keratinocytes to silver nanoparticles: A metabolomics study Joana Carrola 1 , Ana M. Gil 1 , Ana L.D. Silva 1 , Verónica Bastos 2 , Helena Oliveira 2 , José M.P.F. Oliveira 2 , Conceic ¸ ão Santos 2 , Iola F. Duarte 1,1 CICECO, Department of Chemistry, University of Aveiro, Aveiro, Portugal, 2 CESAM & Laboratory of Biotechnology and Cytomics, Department of Biology, University of Aveiro, 3810-193 Aveiro, Portugal Silver nanoparticles (Ag-NPs) have been increasingly incorpo- rated into biomedical and household products mainly due to their remarkable antimicrobial properties. However, there is a narrow window between the bactericidal activity of Ag-NPs and their tox- icity to human cells, thus calling for an improved understanding of Ag-NPs toxicological and biological effects. By offering a detailed, non-selective screening of intra- and/or extracellular metabolites, the metabolomics approach is exquisitely valuable for unveiling

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Page 1: In vitro exposure of human intestinal cells to iron phosphate nanoparticles indicate no direct cytotoxicity

S242 Abstracts / Toxicology Letters 221S (2013) S59–S256

P24-10In vitro exposure of human intestinal cells toiron phosphate nanoparticles indicate no directcytotoxicity

Lea von Moos ∗, Ioannis Trantakis, Peter Rast, FlorentineHilty-Vancura, Michael Zimmermann, Sotiris Pratsinis, ShanaSturla

ETH, Zurich, Switzerland

The use of nanotechnology in the food and nutrition indus-try offers new opportunities to enhance product performance andprovide health benefits to consumers. One promising applicationis food fortification with highly bioavailable nanostructured ironcompounds to combat iron deficiency, which is still a major globalpublic health issue. However, the use of engineered nanoparti-cles (ENP) in foods is raising concerns since the fate and safetyof ENP upon ingestion is largely unknown. In the present study,the potential cytotoxicity of amorphous iron phosphate nanoparti-cles (FePO4-NP) produced by flame spray pyrolysis (FSP) to humanintestinal epithelial cells was studied in vitro. Cytotoxicity wasevaluated with the MTS assay. Food-grade SiO2-NP and FSP madeSiO2/Ag-NP served as negative and positive controls, respectively.The effect of acute NP exposure was studied by incubating cellswith different concentrations (0.1–500 �g/mL) of FePO4-NP, SiO2-NP and SiO2/Ag-NP for 24 or 48 h. No cytotoxicity was observed,neither after 24 nor 48 h exposure. These results give a first indi-cation that the tested NPs are not directly toxic to the intestinalepithelial cells.

http://dx.doi.org/10.1016/j.toxlet.2013.05.595

P24-11Influence of nano-polystyrene particles ininducing cytotoxicity in mice co-injected withcarbon tetrachloride, cisplatin, or paraquat

Katsuhiro Isoda ∗, Shimizu Yoshimi, Tetsuji Nishimura, MasakatsuTezuka, Isao Ishida

Teikyo Heisei University, Chiba, Japan

Nanomaterials are used frequently in microelectronics, cos-metics and sunscreens, and research into the development ofnanomaterial-based drug delivery systems is providing promisingresults. However, the toxicity of nanomaterials has yet to be fullyinvestigated. In particular, the interactions between nanomateri-als and therapeutic drugs require further study. We investigatedwhether nano-sized polystyrene particles affect drug-inducedtoxicity. The particles, which are widely used industrially, haddiameters of 50 (NPP50), 200 (NPP200) or 1000 (NPP1000) nm. Thetoxic chemicals tested were carbon tetrachloride, cisplatin (a pop-ular anti-tumor agent), and a widely used herbicide, paraquat. Micewere treated intraperitoneally with either carbon tetrachloride(0.01 ml/kg), cisplatin (100 �mol/kg) or paraquat (50 mg/kg), withor without intravenous administration of polystyrene particles. Alltreatments in the absence of the nanoparticles were non-lethaland did not result in severe toxicity. However, when mice wereinjected with paraquat or cisplatin together with polystyrene par-ticles, synergistic, enhanced toxicity was observed in mice injectedwith NPP50. These synergic effects were not observed in miceco-injected with NPP200 or NPP1000. These findings suggest thatfurther evaluation of the interactions between polystyrene nano-particles and drugs is a critical prerequisite to the pharmaceuticalapplication of nanotechnology.

http://dx.doi.org/10.1016/j.toxlet.2013.05.596

P24-12Long-term biodistribution, metabolism andtoxicity of carbon nanotubes in vivo

Xiaoyong Deng 1,∗, Man Luo 2, Erlei Shao 1, Hui Zhao 1, XingYang 1, Qingshun Ni 1, Zheng Jiao 1

1 Shanghai University, Shanghai, China, 2 Fudan University, Shanghai,China

Due to their unique physical and chemical properties, carbonnanotubes (CNTs) have broad potential application in the fields ofelectronic technology, novel materials and biomedicine. With thewidely using of CNTs, the risk of being exposed to the environmentwith CNTs becomes higher. Further researches are needed eagerlyto find out how these novel materials affect the human healthand environment. Here, the long-term distribution, metabolismand toxicity of water soluble CNTs in mice were intensively inves-tigated, which can offer reliable toxicology results for the safetyassessment of CNTs.

Firstly, the water soluble polyethylene-glycol-functionalizedmulti-walled CNTs (PEG-MWCNTs) were synthesized and char-acterized by TEM, FTIR and TGA. Based on TGA data, the graftedrate of PEG on MWCNTs is estimated to be 23%. Then, the methodof microwave digestion was studied and optimized in tracing thelocation of CNTs in vivo. Using the developed method, the distri-bution and excretion of CNTs in mice after intravenous exposurefor 14 months were investigated, which showed that even after 14months post exposure, CNTs could not be excreted thoroughly, with40% of injected dose trapped in liver. Besides, the ultrastructuralpathology and the length results indicated that the CNTs activatedthe self-metabolism mechanism, and the evidences of liver-bile andrenal excretion routes were found. Finally, the toxicity of CNTs afterintravenous exposure in 14 months was investigated. The resultsshowed that the blood biochemistry results were normal, and theexperiments on histological morphology of main organs did notshow damage, except for some granulomas were induced in lung.

We investigated the long-term toxicity of CNTs, which lastedfor 14 months exposure, for the first time. All these results indicatePEG-MWCNTs exhibit good biocompatibility, which provides ref-erence for other researches in the fields of CNTs safety assessmentand biomedicine application.

http://dx.doi.org/10.1016/j.toxlet.2013.05.597

P24-13Metabolic response of human keratinocytes tosilver nanoparticles: A metabolomics study

Joana Carrola 1, Ana M. Gil 1, Ana L.D. Silva 1, Verónica Bastos 2,Helena Oliveira 2, José M.P.F. Oliveira 2, Conceicão Santos 2, Iola F.Duarte 1,∗

1 CICECO, Department of Chemistry, University of Aveiro, Aveiro,Portugal, 2 CESAM & Laboratory of Biotechnology and Cytomics,Department of Biology, University of Aveiro, 3810-193 Aveiro,Portugal

Silver nanoparticles (Ag-NPs) have been increasingly incorpo-rated into biomedical and household products mainly due to theirremarkable antimicrobial properties. However, there is a narrowwindow between the bactericidal activity of Ag-NPs and their tox-icity to human cells, thus calling for an improved understanding ofAg-NPs toxicological and biological effects. By offering a detailed,non-selective screening of intra- and/or extracellular metabolites,the metabolomics approach is exquisitely valuable for unveiling