Toxicologic evaluation of tungsten: 28-day inhalation study of tungsten blue oxide in rats

Abstract

The toxicity and toxicokinetics of tungsten blue oxide (TBO) were examined. TBO is an intermediate in the production of tungsten powder, and has shown the potential to cause cellular damage in in vitro studies. However, in vivo evidence seems to indicate a lack of adverse effects. The present study was undertaken to address the dearth of longer-term inhalation toxicity studies of tungsten oxides by investigating the biological responses induced by TBO when administered via nose-only inhalation to rats at levels of 0.08, 0.325, and 0.65 mg TBO/L of air for 6 h/day for 28 consecutive days, followed by a 14-day recovery period. Inhaled TBO was absorbed systemically and blood levels of tungsten increased as inhaled concentration increased. Among the tissues analyzed for tungsten levels, lung, femur and kidney showed increased levels, with lung at least an order of magnitude greater than kidney or femur. By exposure day 14, tungsten concentration in tissues had reached steady-state. Increased lung weight was noted for both terminal and recovery animals and was attributed to deposition of TBO in the lungs, inducing a macrophage influx. Microscopic evaluation of tissues revealed a dose-related increase in alveolar pigmented macrophages, alveolar foreign material and individual alveolar foamy macrophages in lung. After a recovery period there was a slight reduction in the incidence and severity of histopathological findings. Based on the absence of other adverse effects, the increased lung weights and the microscopic findings were interpreted as nonadverse response to exposure and were not considered a specific reaction to TBO.

An update to the toxicological profile for water-soluble and sparingly soluble tungsten substances

“…The ATSDR's toxicological profile ( Keith et al 2005 , 2007 ) did not identify data on the quantitative absorption or distribution of tungsten by the inhalation, oral, or dermal routes in humans, and our search did not identify any recent studies that could fill this gap. Instead, our search found seven new toxicokinetic studies conducted after 2005, using rats and mice ( McDonald et al 2007 , Weber et al 2008 , Radcliffe et al 2009 , 2010 , Guandalini et al 2011 , Rajendran et al 2012 , Kelly et al 2013 ). One study was on WO 3-x (a sparingly water-soluble tungsten substance), and six studies were on ST (a water-soluble substance).…”

“…Inhalation exposure. Three rat inhalation toxicokinetic studies were published after 2005: two on ST ( Radcliffe et al 2009 , 2010 ), and one on WO 3-x ( Rajendran et al 2012 ). The study designs and results are briefly described below.…”

“… Rajendran et al (2012) exposed rats to WO 2.91 at 0.08, 0.325, and 0.65 mg/L of air, with MMAD ranging from 2.63 to 2.87 μm (estimated to be 15, 62, and 124 mg/kg/d, respectively) for 6 h/d for 28 consecutive days, followed by a 14-day recovery period. Inhaled WO 2.91 was absorbed systemically, and blood levels of tungsten increased as inhaled concentration increased.…”

“…The most recent inhalation studies on water-soluble and sparingly soluble tungsten forms confirm that both forms are readily absorbed and rapidly distributed to various organs (e.g. thyroid, spleen, lung, femur, liver), and the primary route of elimination is via urinary excretion ( Radcliffe et al 2010 , Rajendran et al 2012 ). An important new finding from the ST studies is that olfactory transport plays a minimal role in delivering tungsten to the brain in rats ( Radcliffe et al 2009 ).…”

Modeling of inertial deposition in scaled models of rat and human nasal airways: Towards in vitro regional dosimetry in small animals

“…Kelly, Bobbitt, and Asgharian (2001a) measured particle deposition in the nasal airways of twenty-two female Long-Evans rats and reported significantly higher deposition fractions for pulsatile flows than steady-state flows. Recent in vivo toxicity studies of inhaled particles in rats include cigarette smoke (Dorman et al, 2012), tungsten (Rajendran et al, 2012), and uranium (Petitot et al, 2013). Recent in vivo intranasal delivery to rats include Abdel-Bar, Abdel-Reheem, Awad, and Mortada (2013), Abdelbary and Tadros (2013), among others.…”