The antioxidative response of MRC-5 cell line to Fe2O3 nanoparticles exposure is not efficient

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Abstracts / Toxicology Letters 196S (2010) S37–S351

lung, liver, spleen and kidney. However, the fullerene was also very low in kidney and could not be detected in placenta and fetus. These results indicate that the fullerene absorbed in the body via any route of exposure may distribute to lung, liver, spleen and kidney as the primary exposure target organs, and the fullerene existed in the blood was possibly excreted rapidly into the urine through kidney. doi:10.1016/j.toxlet.2010.03.1145

P303-025 Nanomaterial toxicology—Importance of chronic toxicity assessment J. Kanno, A. Takagi, T. Nishimura, A. Hirose National Institute of Health Sciences, Japan Nanomaterials of carbon origin tend to form various shapes of particles and aggregates in micrometer dimensions. Among them, certain make of multi-wall carbon nanotubes (MWCNT) forms fibrous or rod-shaped particles of length around 10–20 ␮m with an aspect ratio of more than three. Fibrous particles of this dimension including asbestos and some man-made fibers are reported to be carcinogenic, typically inducing mesothelioma. Our first study indicated that such micrometer-sized MWCNT at a fixed high dosage of 3 mg/kg induces mesothelioma when administered intraperitoneally to p53 heterozygous mice that have been reported to be sensitive to asbestos. As a follow up, we further performed a doseresponse study down to 1/1000 of the dosage of the first study, and observed dose-dependent induction of mesotheliomas. It was noted that the latent period was almost identical among the studies and the groups with different dosages. Additionally, in the first study, fullerene administered intraperitoneally as negative control, and it was histologically suggested that the surface of fullerene aggregates were “digested” by phagocytic activities, possibly down to sub-micro to nanometer dimensions and brought out of the peritoneal cavity. Our results indicate that a newly made particulate matter of various sizes might have a potential to exhibit either well known particulate matter toxicity or unknown nature, with a common feature of chronic progression. To maintain sound activity of industrialization of nanomaterials, a system that enables timely transfer of information on the chronic toxicity of the new materials and their products to the manufacturers would be of great importance. In order to facilitate such process, cultivation of proper toxicology scientists who are able to predict such “new” chronic toxicity by making full use of traditional as well as recent methodologies should be promoted. (Supported by Health Sciences Research Grants, the Ministry of Health, Labour and Welfare, Japan.) doi:10.1016/j.toxlet.2010.03.1146 P303-026 The antioxidative response of MRC-5 cell line to Fe2 O3 nanoparticles exposure is not efficient M. Radu 1 , M.C. Munteanu 1 , C. Sima 2 , A.I. Serban 3 , C. Grigoriu 2 , M. Costache 1 , A. Dinischiotu 1 University of Bucharest, Romania, 2 National Institute of Laser, Plasma and Radiation Physics, Romania, 3 University of Agricultural Studies and Veterinary Medicine, Romania

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Ambient particular matter (including nanoparticles) is an environmental factor that has been associated with respiratory morbidity

and mortality. It is well known that the generation of oxidative stress by nanoparticles induces proinflamatory effects in the pulmonary system. The aim of our study was to investigate the way the antioxidative system of MRC-5 lung fibroblast cell line operates after exposure to Fe2 O3 nanoparticles for up to 72 h. The MTT test revealed that a concentration of 30.6 × 109 nanoparticles/ml had produced a decrease in the viability of MRC-5 cells with about 30% and 40% after 48 h, respectively, 72 h. The malondialdehyde concentration increased by 78%, 189%, 169% after 24 h, 48 h, respectively, 72 h and the reduced glutathione one increased with 13% after 24 h and decreased later on under the control level. The total SOD activity slightly increased after 72 h due to the contribution of MnSOD whereas CAT activity was up-regulated by about 40% after 48 h and 72 h of exposure. The GPx and GST specific activities increased after 48 h and 72 h, whereas the GR activity was down-regulated after 24 h and almost unchanged compared to control at longer exposure periods. The expression of Hsp 27, Hsp 70 and Hsp 90 proteins was not changed for up to 72 h, but that of Hsp 60 increased with about 20% compared to control after 72 h of treatment. Taking into account the increase of malondialdehyde level, the decrease of the reduced glutathione one and the up-regulation of Hsp60 protein expression, it can be concluded that the MRC-5 cells cannot counteract the Fe2 O3 nanoparticles induced oxidative stress and pathological events with oxidative background could occur. doi:10.1016/j.toxlet.2010.03.1147

P303-027 Absorption, biodistribution and acute toxicity of cobalt ferrite NP, gold NP hyaluronic acid-coated gold nanoparticles in rats C. Porredon, D. Ramos, J. De Lapuente, L. Camps, M. Borràs Parc Científic de Barcelona, Spain Within the frame of a larger project, we have tested the acute toxicity in rats by intraperitoneal (IP) administration of three kinds of nanoparticles (NPs): gold (AuNP), gold coated by hyaluronic acid (AuNP coated by HA) and cobalt ferrite (CoFe2 O4 NP). The specific aim of the study was to determine an IC50 by and Up&Down protocol and compare these results with the values obtained in parallel for gold (III) chloride (HAuCl4) (IC50 = 106,563 mg/kg) and CoFe2 O4 (IC50 = 116,942 mg/kg) in solution. Toxicity was studied by clinical signs, necropsy, hematological parameters and histopathological exam of kidney, liver, spleen and lung. At the same time, biodistribution by TEM (liver, spleen, kidney and lung) and ICP-MS of different tissues (liver, spleen, pancreas, lymph node, kidney, lung and brain) at 14 days from the administration was assessed. We obtained blood samples at different times ranging from the moment of administration to 3 days later. Determining the concentration of product in each sample allowed to calculate their absorption from intraperitoneal cavity to blood stream. We observed that, for a same dose, the distribution of NPs is quite different; the blood concentrations showed that AuNP with HA was absorbed in a greater amount than CoFe2 O4 NP. Moreover, they were absorbed in a different pattern: CoFe2 O4 NP concentration was constant in time, while AuNP HA showed a peak of absorption at 3 h. Differences where also shown when we observed the distribution in tissues: although NPs were mainly localized in liver and spleen, in the case of CoFe2 O4 NP 50% where in kidney. It was not possible to determine an exact IC50 for NPs, since the maximum concentration tested (limited by the