Effect on Mouse Liver Morphology of CeO2, TiO2 and Carbon Black Nanoparticles Translocated from Lungs or Deposited Intravenously

Justyna Modrzynska,Ulla Vogel,Józef Szarek,Alicja Mortensen,Gitte Ravn-Haren,Anne Thoustrup Saber,Trine Berthing

doi:10.3390/applnano2030016

Abstract

Exposure to nanoparticles by various routes results in size-dependent translocation of nanoparticles to the systemic circulation and subsequent accumulation in the liver. The purpose of this study was to determine possible adverse effects in the liver of long-lasting nanoparticle presence in the organ. Mice exposed to a single dose (162 µg/animal equivalent to 9 mg/kg body weight) of TiO2, CeO2 or carbon black nanoparticles by intratracheal instillation or intravenous injection, resulting in relatively low or high liver burdens, were followed for 1, 28 or 180 days. Clinical appearance, feed intake, body and liver weights, hematological indices, and transaminases and alkaline phosphatase activities were unaffected by exposure. Exposure-related foreign material persisted in the liver up to 180 days after intratracheal and intravenous exposure, mainly in sinusoids, near Kupffer cells, or around blood vessels. Increased incidences of histological findings after intratracheal or intravenous exposure included: initially, prominent nuclei of Kupffer cells, the apparent increase in binucleate hepatocytes (TiO2 and carbon black) and inflammatory infiltrations (CeO2); later, cytoplasmic vacuolation, pyknosis and necrosis, especially for CeO2. Thus, neither low nor high nanoparticle burden in the liver affected enzymatic markers of liver injury, but indications of exposure-related necrotic changes, particularly for CeO2 nanoparticles, were noted.

Highlights

Unique properties of nanoparticles, such as small size, large surface area and high surface reactivity in comparison to bulk material, have led to a wide range of nanoparticle applications
The clinical appearance of mice remained unaffected up to 180 days post-exposure, but three spontaneous deaths occurred before the scheduled termination: one in the intravenous 28-day control group, one in the intravenous 180-day TiO2 group, and one in the intratracheal 180-day carbon black group
We found indications of reduced inflammation in the liver following carbon black exposure, as the incidence and/or number of inflammatory cell infiltrations on day 1 and day 28 after intratracheal and intravenous exposure were lower compared to vehicle controls

Summary

Introduction

Unique properties of nanoparticles, such as small size, large surface area and high surface reactivity in comparison to bulk material, have led to a wide range of nanoparticle applications. This increases the risk of adverse health effects following consumer and occupational exposures. The clearance of insoluble nanoparticles from the liver is slow [10], and little is known about the adverse effects of the long-lasting presence of nanoparticles in the organ [11,12]. There are examples of severe adverse effects following liver accumulation of particles. The radioactive thorium dioxide particles were shown to accumulate in the liver and spleen and caused primary liver cancer in exposed patients [14]

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