Toxicological effects of nanoparticles following oral administration in rat
Francesca Maranghi, Laura Narciso, Roberta Tassinari
(Istituto Superiore di Sanità – Dpt. Veterinary Public Health and Food Safety, Rome Italy)
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A repeated-dose 90-day oral toxicity study in rat with synthetic amorphous silica (SiO2) nanoparticle (NM203 from JRC Repository) has been carried out (OECD guideline 408) in the frame of the NANoREG project (http://nanoreg.eu/), with specific focus on reproductive-endocrine-immune/inflammatory related parameters and genotoxicity. The aim was the identification of hazards and to obtain dose-response data to characterize the risk of nanomaterials highly relevant for food safety. Six groups of Sprague-Dawley rats were treated by gavage with 0 (control, vehicle only - ultrapure water), 2, 5, 10, 20 and 50 mg/kg body weight per day. Dispersion protocol from the Nanogenotox project has been used and specific characterization of dispersions has been performed before the study. General toxicity data showed no differences between treated and control rats. Death incidence was not increased by the treatments. Preliminary immunotoxicity data showed alterations in blood count, PHA-induced lymphocyte proliferation (spleen, MLN) and LPS-induced NO and cytokine production (peritoneal resident macrophages). Preliminary genotoxicity (micronucleus in target organs and pig-a tests in blood cells) and reproductive toxicity data didn’t show any significant effect. Clinical biochemistry showed no alteration in both sexes concerning liver biomarkers. Kidney biomarkers showed significant alteration in creatinine in males at 10, 20 and 50 mg/kg and in females in all treated groups. Comet assay in male bone marrow showed significant increased DNA damage at 2, 10 and 50 mg/kg, in ovaries at 5 and 50 mg/kg and in male spleen at 5, 10 and 50 mg/kg. No genotoxic effects at the gastrointestinal level have been recorded. Liver and spleen showed tissue alterations in both sexes at different dose levels. Histopathological analyses, biodistribution/bioaccumulation and electron microscopy observations in target tissues are in progress. Preliminary data showed in general the presence of gender differences and the difficulty in individuating a critical dose (effective in different parameters) and a dose-response relationship.
The study is supported by the EU Framework 7 Programme, contract no 310584, NANoREG Project.
