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Abstracts / Toxicology L

ggregation of NPs at higher concentration) showed no toxic-ty.

oi:10.1016/j.toxlet.2010.03.1148

303-028nhalation toxicity studies with 12 nanomaterials—Comparingffects and distribution in the lung

. Landsiedel, L. Ma-Hock, S. Treumann, V. Strauss, W.ohlleben, K. Wiench, B.V. Ravenzwaay

BASF SE, Germany

everal studies demonstrate that identical mass concentrationsf nanoparticles are more toxic to the lung than larger particlesf similar chemistry. Surface area and particle count concentra-ion have been discussed as critical factor responsible for higherulmonary toxicity of nanoparticles (Oberdoerster et al., 2000,es. Rep. Health Eff. Inst. 96, 5–86, Stoeger et al., 2006, EHP 114,28–333, Wittmaack, 2007, EHP 115, 187–194).

We tested the toxicity of 15 substances (12 nanomaterials: SiO2,urface coated SiO2, TiO2 P25, coated TiO2, CeO2, doted CeO2, ZrO2,aSO4, carbon black, MWCNT1, MWCNT2 and – for comparison3-�m-scaled materials: quartz, TiO2, and ZnO) after inhalation

xposure. All materials were sufficiently characterized and testedy the well-established short-term inhalation toxicity protocol foranomaterials (Ma-Hock et al., 2009, Inhal. Toxicol., 21, 102); totalrotein concentration and polymorphonuclear neutrophils in bron-hoalveolar lavage fluide were used as sensitive indicators of effectsn the lung.

For the tested insoluble nanomaterials we did not see a translo-ation from the lung to other tissues but the draining lymph nodes,ith the exception of coated silica, which was also detected in

he spleen. The lung toxicity varied over two orders of magnitudeusing mass concentration as dosimetry). And no single materialroperty (chemical identity, size, shape, surface area, surface chem-

stry) alone could be correlated to the toxic effect. We thereforeonclude that nanomaterial’s toxicity is spanning a wide rangend is different for different nanomaterials. Hence there is no gen-ral nanotoxicity but the toxicity of individual nanomaterials. Toetermine this toxicity testing is need (until a correlation of mate-ial properties with toxic effects has been established). This posterresents a short-term inhalation test for nanomaterials which waseveloped – and appears to be useful – in efficiently assessing nano-aterials toxicity.

oi:10.1016/j.toxlet.2010.03.1149

303-029etallic nanoparticles and in vitro cytotoxicity assessment

. Parkkola, L. Vivero, M. Vega, M. Ramis, J. Querol, J. Sendra

Endor Nanotechnologies, Spain

anotechnology is a rapidly developing field of biomedicalesearch. Among numerous nanomaterials there are wide differ-nces in properties and a growing need for understanding theirffects on human health and environment. Biological activity of

anoparticles (NPs) depends on physicochemical characteristicsparticle size and distribution, agglomeration state, shape, crystaltructure, chemical composition, surface area, surface chemistrynd surface charge and porosity) that are not routinely consideredn toxicity screening tests.

196S (2010) S37–S351 S281

Our laboratory has used different cell viability assays to evaluatebiocompatibility of different metallic nanoparticles. Mitochon-drial metabolism (MTT & WST-1 assays) and lysosomal membraneintegrity (Neutral red) experiments showed differing results. Wefound that NPs can react with the components of some of these testsand interfere with the colorimetric assays. According to our dataWST-1 was the most efficient assay to assess nanoparticle toxicity.

We want to point out that in vitro techniques for toxicity eval-uation and their suitability for different NPs must be carefullyconsidered to prevent false-positive or false-negative results. Stan-dardizing nanotoxicological assays in regard to the material usedis highly substantial for achieving reproducible results.

doi:10.1016/j.toxlet.2010.03.1150

P303-030Toxicity studies of poly(anhydride) nanoparticles

P. Ojer 1, A. Lopez De Cerain 1, P. Areses 2, I. Penuelas 2, J.M.Irache 1

1 University of Navarra, Spain, 2 Clínica Universidad de Navarra,Spain

In recent years poly(anhydride) nanoparticles have successfullybeen developed as oral drug delivery systems, immunization orallergy treatment. Given that the obtained results have been ratherpromising, it is essential to evaluate their toxicity. In this context,conventional (NP), pegylated (PEG-NP) and cyclodextrin (HPCD-NP) nanoparticles were prepared by desolvation method, preservedby spray drying and characterized by studying size, zeta potentialand morphology. Nanoparticles displayed a size of approximately170 nm with negative surface charge. Cytotoxicity studies weredeveloped by MTS and LDH assays in HepG2 cells; results showedthat after 48 and 72 h incubation, significant cytotoxic effect wasobserved at the highest concentrations tested (1 and 2 mg/mL). Inorder to evaluate in vivo toxicity, single oral dose study was per-formed according to OCDE guideline 425 in female Wistar rats.Taking into account the results obtained, the LD50 for the for-mulations was found to be higher than 2.000 mg/kg bw. Thesefindings coincide with biodistribution studies with nanoparticleslabeled with 99mtechnetium. When nanoparticles were adminis-tered orally, they were located in the animals gut, with no evidenceof distribution in other organs or nanoparticle translocation. Inshort, poly(anhydride) nanoparticles (NP, PEG-NP and HPCD-NP)did not show any toxic effects under the experimental conditionsused in these studies.

doi:10.1016/j.toxlet.2010.03.1151

P303-031Difficulties encountered in the evaluation of the cytotoxicity ofbare and coated gold nanoparticles by WST-1 and LDH

A. Egizabal 1, L. Goikoetxea 1, N. Briz 1, N. Alvarez 1, L. Ballester 1, J.Lorenzo 1, J. Sendra 2

1 INASMET Tecnalia, France, 2 ENDOR Nanotechnologies, Spain

Currently, nanoparticle in vitro cytotoxicity testing is based on

methods established for hazard characterization of chemicals, as nonano-specific European standard exists. Many of these tests eval-uate the viability of the cells by using different indicator dyes toanalyze the absorption/fluorescent emission.