Acute Toxicity of Intravenously Administered Titanium Dioxide Nanoparticles in Mice

Jiaying Xu,Hongsheng Yu,Baobo Zou,Lissy Lazar,Cui Yang,Jinshun Zhao,Magaye Ruth,Aiguo Wu,Hongbo Shi,David L Mccormick

doi:10.1371/journal.pone.0070618

Abstract

BackgroundWith a wide range of applications, titanium dioxide (TiO2) nanoparticles (NPs) are manufactured worldwide in large quantities. Recently, in the field of nanomedicine, intravenous injection of TiO2 nanoparticulate carriers directly into the bloodstream has raised public concerns on their toxicity to humans.MethodsIn this study, mice were injected intravenously with a single dose of TiO2 NPs at varying dose levels (0, 140, 300, 645, or 1387 mg/kg). Animal mortality, blood biochemistry, hematology, genotoxicity and histopathology were investigated 14 days after treatment.ResultsDeath of mice in the highest dose (1387 mg/kg) group was observed at day two after TiO2 NPs injection. At day 7, acute toxicity symptoms, such as decreased physical activity and decreased intake of food and water, were observed in the highest dose group. Hematological analysis and the micronucleus test showed no significant acute hematological or genetic toxicity except an increase in the white blood cell (WBC) count among mice 645 mg/kg dose group. However, the spleen of the mice showed significantly higher tissue weight/body weight (BW) coefficients, and lower liver and kidney coefficients in the TiO2 NPs treated mice compared to control. The biochemical parameters and histological tissue sections indicated that TiO2 NPs treatment could induce different degrees of damage in the brain, lung, spleen, liver and kidneys. However, no pathological effects were observed in the heart in TiO2 NPs treated mice.ConclusionsIntravenous injection of TiO2 NPs at high doses in mice could cause acute toxicity effects in the brain, lung, spleen, liver, and kidney. No significant hematological or genetic toxicity was observed.

Highlights

Due to smaller size, larger surface area per unit mass and stronger catalytic activity, TiO2 NPs, have been widely used in many applications such as drug delivery, antibacterial materials, cosmetics and electronics [1,2]
The average size distribution of TiO2 NPs The average size distribution of TiO2 NPs was 42.3064.60 nm as detected by optimas 6.5 image analysis software
Image of TiO2 NPs was captured by scanning electron microscopy (SEM) (Figure 1)

Summary

Introduction

Larger surface area per unit mass and stronger catalytic activity, TiO2 NPs, have been widely used in many applications such as drug delivery, antibacterial materials, cosmetics and electronics [1,2]. Ferin et al [11] studied the pulmonary retention of TiO2 NPs and fine particles in rats after a single intratracheal instillation and a 12 week inhalation of different sizes of TiO2 particles (12, 21, 230, and 250 nm). Both acute and sub-chronic inhalation studies showed that TiO2 NPs at equivalent masses access the pulmonary interstitium to a larger extend than fine particles They found that the translocation process appeared to be related to the particle size, the delivered dose, and the delivered dose rate. Fabian et al [12] investigated the tissue distribution after intravenous administration of TiO2 NPs. The levels were highest in the liver, followed by the spleen, lung, and in decreasing order, respectively. In the field of nanomedicine, intravenous injection of TiO2 nanoparticulate carriers directly into the bloodstream has raised public concerns on their toxicity to humans

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