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justify the use of these biomarkers in the evaluation of genotoxiceffects in human populations exposed to low levels of styrene.

doi:10.1016/j.toxlet.2011.05.249

64 Abstracts / Toxicology L

1013orphyrins in liver of rabbit as biomarkers of exposure to theesticide diazinon

. Hernández-Moreno ∗, M. Gil, M.P. Míguez, F. Soler,. Pérez-López

Toxicology Group, University of Extremadura, Cáceres, Spain

Changes in hepatic porphyrin patterns have been described inesponse to a broad variety of drugs and chemicals causing dis-urbances in heme synthesis. As porphyrins can be detected inifferent biological materials at low concentrations, they wereroposed as sensitive biomarkers of exposure to environmentalontaminants. In the present study, the effect of a short-termxposure to an organophosphorus pesticide on the hepatic por-hyrin profile in rabbit was evaluated, in order to assess its uses biomarker of environmental contamination in the wild. Thessayed xenobiotic was diazinon. In this experience, 15 female Newealand rabbits were randomly divided in three groups of 5 ani-als each one (included a control group). A single oral dose of the

esticide (1/10 and ½ LD50 of diazinon, corresponding to 25 and25 �g/kg) was administered. Animals were euthanized after 30ays and liver was sampled. After tissue homogenization and acidxtraction, total as well as individual 8-, 7-, 6-, 5-, 4-, and 2-carboxylorphyrin concentrations in liver were readily detectable by HPLC�exc: 400 nm; �em: 622 nm). Liver samples showed decreased 6-arboxyporphyrins in females when compared to controls, whereaso changes were observed to the other porphyrins. The findingsuggest that rabbit may serve as a suitable model species in which toonitor the effects of field contaminant exposure to wildlife based

n changes in tissue porphyrin levels.Authors wish to thank the Ministerio de Educación y Ciencia

rom Spain, which financially supported this work (CTM2007-0041), to Junta de Extremadura and FEDER funds.

oi:10.1016/j.toxlet.2011.05.247

1014evelopment of biomarkers for ensuring safety ofanomaterials

. Higashisaka 1,∗, Y. Yoshioka 2, K. Yamashita 1, Y. Morishita 1,. Nabeshi 1, S. Tsunoda 3, N. Itoh 1, Y. Tsutsumi 1

Department of Toxicology and Safety Science, Graduate School ofharmaceutical Sciences, Osaka University, Suita, Osaka, Japan, 2 MEIenter, Osaka University, Suita, Osaka, Japan, 3 Laboratory ofiopharmaceutical Research (LBR), National Institute of Biomedical

nnovation (NiBio), Suita, Osaka, Japan

Purpose: Recently, nanomaterials have become an integral partf our daily lives. However, there is increasing concern about theotential risks to human health. Here, we attempted to developotential biomarkers of nanomaterials using a proteomics analysisith the aim of developing safe forms of nanomaterials. Methods:e attempted to identify protein biomarkers in mice by analyzing

hanges in the level of each plasma protein following treatmentith silica nanoparticles using SDS–PAGE analysis and LC/TOF/MSethod. Results: Our analyses identified haptoglobin, one of the

cute phase proteins, as a candidate biomarker. The results of ELISA

howed that the level of haptoglobin was significantly elevatedn plasma of mice exposed to silica nanoparticles with a diame-er of 70 nm (nSP70) compared to normal mice. Furthermore, theevel of haptoglobin is elevated as the particle size of silica parti-

205S (2011) S60–S179

cles decreases and that an increase of haptoglobin is dependent onthe concentration of silica nanoparticles. Also the other acute phaseproteins, C-reactive protein (CRP) and serum amyloid A (SAA) wereelevated in plasma of nSP70 treated mice. In addition, the level ofthese acute phase proteins was elevated in the plasma of mice afterintranasal treatment with nSP30. Our results suggest that acutephase proteins such as haptoglobin, CRP, and SAA can act as usefulbiomarkers for analyzing the risk of exposure to nanomaterilas andtheir associated toxicity. We believe this study will contribute tothe development of global risk management techniques for nano-materials.

doi:10.1016/j.toxlet.2011.05.248

P1015Evaluation of cytogenetic damage on workers exposed to lowlevels of styrene

M.J. Prieto-Castelló 1,∗, D. Marhuenda Amorós 2, J.M.García-Sagredo 3, A. Cardona Llorens 2

1 Pathology and Surgery, Miguel Hernández University, San Juan deAlicante, Spain, 2 Pathology and Surgery, Faculty of Medicine, MiguelHernandez University, San Juan de Alicante, Spain, 3 Medical GeneticsService, Ramon y Cajal Universitary Hospital, Madrid, Spain

Styrene is a commercially important chemical widely used inthe manufacture of synthetic rubber, resins, polyesters, plastics,latex paints and reinforced marble products. Styrene is metab-olized by oxidation to its reactive metabolite styrene-7,8-oxide(SO) which is considered responsible for the genotoxic effects ofstyrene. SO is mainly hydrolysed to styrene glycol and subse-quently oxidized to the main urinary metabolites, mandelic acid(MA) and phenylglyoxylic acid (PGA).The objective of this workwas to evaluate cytogenetic damage in styrene-exposed workersfrom marble industry. Urinary concentrations of MA and PGA weredetermined and genetic damage was studied by means of micronu-cleus (MN) test. Forty-three male workers exposed to styrene andforty controls took part in the study. The average concentrationof MA + PGA (mean ± SD) in the urine of the exposed workers was117 ± 96 mg/g creatinine and none of workers exceeded the bio-logical exposure index (400 mg/g creatinine) showing low valuesfor styrene exposure. The exposed workers showed a significantlyhigher frequency of MN 8.42 ± 2.67 compared to control subjects6.48 ± 2.16. Effects of smoking, age and duration of exposure onthe genotoxicity parameters analyzed were also evaluated. A nega-tive correlation was seen between the frequency of MN and urinarylevel of MA + PGA (P = 0.05) in non-smoker subjects. Although ourdata do not demonstrate a clear dose–response relationship, theincrease of MN in the exposed group with regard to control group