Peter Hoet

BACKGROUND: Pollution by particulates has been consistently associated with increased cardiovascular morbidity and mortality. However, the mechanisms responsible for these effects are not well-elucidated. METHODS AND RESULTS: To assess to what extent and how rapidly inhaled pollutant particles pass into the systemic circulation, we measured, in 5 healthy volunteers, the distribution of radioactivity after the inhalation of "Technegas," an aerosol consisting mainly of ultrafine (99m)Technetium-labeled carbon particles (<100 nm). Radioactivity was detected in blood already at 1 minute, reached a maximum between 10 and 20 minutes, and remained at this level up to 60 minutes. Thin layer chromatography of blood showed that in addition to a species corresponding to oxidized (99m)Tc, ie, pertechnetate, there was also a species corresponding to particle-bound (99m)Tc. Gamma camera images showed substantial radioactivity over the liver and other areas of the body. CONCLUSIONS: We conclude that inhaled (99m)Tc-labeled ultrafine carbon particles pass rapidly into the systemic circulation, and this process could account for the well-established, but poorly understood, extrapulmonary effects of air pollution.

Abstract Manmade nanoparticles range from the well-established multi-ton production of carbon black and fumed silica for applications in plastic fillers and car tyres to microgram quantities of fluorescent quantum dots used as markers in biological imaging. As nano-sciences are experiencing massive investment worldwide, there will be a further rise in consumer products relying on nanotechnology. While benefits of nanotechnology are widely publicised, the discussion of the potential effects of their widespread use in the consumer and industrial products are just beginning to emerge. This review provides comprehensive analysis of data available on health effects of nanomaterials.

Silica nanoparticles (SNPs) are produced on an industrial scale and are an addition to a growing number of commercial products. SNPs also have great potential for a variety of diagnostic and therapeutic applications in medicine. Contrary to the well-studied crystalline micron-sized silica, relatively little information exists on the toxicity of its amorphous and nano-size forms. Because nanoparticles possess novel properties, kinetics and unusual bioactivity, their potential biological effects may differ greatly from those of micron-size bulk materials. In this review, we summarize the physico-chemical properties of the different nano-sized silica materials that can affect their interaction with biological systems, with a specific emphasis on inhalation exposure. We discuss recent in vitro and in vivo investigations into the toxicity of nanosilica, both crystalline and amorphous. Most of the in vitro studies of SNPs report results of cellular uptake, size- and dose-dependent cytotoxicity, increased reactive oxygen species levels and pro-inflammatory stimulation. Evidence from a limited number of in vivo studies demonstrates largely reversible lung inflammation, granuloma formation and focal emphysema, with no progressive lung fibrosis. Clearly, more research with standardized materials is needed to enable comparison of experimental data for the different forms of nanosilicas and to establish which physico-chemical properties are responsible for the observed toxicity of SNPs.

The mechanisms of particulate pollution-related cardiovascular morbidity and mortality are not well understood. We studied the passage of radioactively labeled ultrafine particles after their intratracheal instillation. Hamsters received a single intratracheal instillation of 100 microg albumin nanocolloid particles (nominal diameter < or = 80 nm) labeled with 100 microCi technetium-99m and were killed after 5, 15, 30, and 60 min. In blood, radioactivity, expressed as percentage of total body radioactivity per gram blood, amounted to 2.88 +/- 0.80%, 1.30 +/- 0.17%, 1.52 +/- 0.46%, and 0.21 +/- 0.06% at 5, 15, 30, and 60 min, respectively. Thin-layer chromatography showed only one peak of radioactivity corresponding to unaltered (99m)Tc-albumin nanocolloid. In the liver, radioactivity, expressed as percentage of total radioactivity per organ, amounted to 0.10 +/- 0.07%, 0.23 +/- 0.06%, 1.24 +/- 0.27%, and 0.06 +/- 0.02% at 5, 15, 30, and 60 min, respectively. Lower values were observed in the heart, spleen, kidneys, and brain. Dose dependence was assessed at 30 min following instillation of 10 microg and 1 microg (99m)Tc-albumin per animal (n = 3 at each dose), and values of the same relative magnitudes as after instillation of 100 microg were obtained. We conclude that a significant fraction of (99m)Tc-albumin, taken as a model of ultrafine particles, rapidly diffuses from the lungs into the systemic circulation.