Quantitative biokinetics of titanium dioxide nanoparticles after intravenous injection in rats (Part 1)

Submicrometer TiO2 particles, including nanoparticulate fractions, are used in an increasing variety of consumer products, as food additives and also applications in drug delivery are envisaged. Beyond exposure of occupational groups this entails an exposure risk to the public. However, nanoparticle translocation from the organ of intake and potential accumulation in secondary organs is poorly understood and in many investigations excessive doses are applied. The present study investigates the biokinetics and clearance of a low single dose (typically 40-400 μg/kg BW) of 48V-radiolabeled, pure TiO2 anatase nanoparticles ([48V]TiO2NP) with a median aggregate/agglomerate size of 70 nm in aqueous suspension after intravenous injection into healthy adult female Wistar rats. Biokinetics and clearance were followed from one hour to four weeks. The use of radiolabeled nanoparticles allowed a quantitative [48V]TiO2NP balancing of all organs, tissues, carcass and excretions of each rat without having to account for chemical background levels possibly caused by dietary or environmental titanium exposure. Highest [48V]TiO2NP accumulations were found in liver (95.5% ID in the first day), followed by spleen (2.5%), carcass (1%), skeleton (0.7%) and blood (0.4%). Detectable nanoparticle levels were found in all other organs. The [48V]TiO2NP content in blood decreased rapidly after 24h while the distribution in other organs and tissues remained rather constant until 28 days. The present biokinetics study is part 1 of a series of studies comparing biokinetics after three classical routes of intake (intravenous (IV) injection (part 1), ingestion (part 2), intratracheal instillation (part 3)) under identical laboratory conditions, in order to study whether IV injection is a suitable predictor for the biokinetics fate of nanoparticles administered by different routes.

KREYLING Wolfgang;  HOLZWARTH Uwe;  HABERL Nadine;  KOZEMPEL J.;  HIRN Stephanie;  WENK A.;  SCHLEH Carsten;  SCHAEFFLER Martin;  LIPKA Jens;  SEMMLER-BEHNKE Manuela;  GIBSON Peter; 

2017-04-27

TAYLOR & FRANCIS LTD

JRC105650

1743-5390,   

http://dx.doi.org/10.1080/17435390.2017.1306892,    https://publications.jrc.ec.europa.eu/repository/handle/JRC105650,   

10.1080/17435390.2017.1306892,