Nanoparticles – known and unknown health risks

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

Respiratory function and bronchial responsiveness among industrial workers exposed to different classes of occupational agents: a study from Algeria

Occupational exposures play a role in the onset of several chronic airway diseases. We investigated, in a cross-sectional study, lung function parameters and bronchial hyper-responsiveness to histamine in workers exposed to different airborne compounds

Development of a physiologically based kinetic model for 99m-Technetium-labelled carbon nanoparticles inhaled by humans

International audienceParticulate air pollution is associated with respiratory and cardiovascular morbidity and mortality. Recent studies investigated whether and to which extent inhaled ultrafine particles are able to translocate into the bloodstream in humans. However, their conclusions were conflicting. We developed a physiologically based kinetic model for 99m-technetium-labelled carbon nanoparticles (Technegas). The model was designed to analyse imaging data. It includes different translocation rates and kinetics for free technetium, and small and large technetium-labelled particles. It was calibrated with data from an experiment designed to assess the fate of nanoparticles in humans after inhalation of Technegas. The data provided time courses of radioactivity in the liver, stomach, urine, and blood. Parameter estimation was performed in a Bayesian context with Markov chain Monte Carlo (MCMC) techniques. Our analysis points to a likely translocation of particle-bound technetium from lung to blood, at a rate about twofold lower than the transfer rate of free technetium. Notably, restricting the model so that only free technetium would have been able to reach blood circulation resulted in much poorer fits to the experimental data. The percentage of small particles able to translocate was estimated at 12.7% of total particles. The percentage of unbound technetium was estimated at 6.7% of total technetium. To our knowledge, our model is the first PBPK model able to use imaging data to describe the absorption and distribution of nanoparticles. We believe that our modeling approach using Bayesian and MCMC techniques provides a reasonable description on which to base further model refinement

Comparative toxicity of 24 manufactured nanoparticles in human alveolar epithelial and macrophage cell lines

<p>Abstract</p> <p>Background</p> <p>A critical issue with nanomaterials is the clear understanding of their potential toxicity. We evaluated the toxic effect of 24 nanoparticles of similar equivalent spherical diameter and various elemental compositions on 2 human pulmonary cell lines: A549 and THP-1. A secondary aim was to elaborate a generic experimental set-up that would allow the rapid screening of cytotoxic effect of nanoparticles. We therefore compared 2 cytotoxicity assays (MTT and Neutral Red) and analyzed 2 time points (3 and 24 hours) for each cell type and nanoparticle. When possible, TC50 (Toxic Concentration 50 i.e. nanoparticle concentration inducing 50% cell mortality) was calculated.</p> <p>Results</p> <p>The use of MTT assay on THP-1 cells exposed for 24 hours appears to be the most sensitive experimental design to assess the cytotoxic effect of one nanoparticle. With this experimental set-up, Copper- and Zinc-based nanoparticles appear to be the most toxic. Titania, Alumina, Ceria and Zirconia-based nanoparticles show moderate toxicity, and no toxicity was observed for Tungsten Carbide. No correlation between cytotoxicity and equivalent spherical diameter or specific surface area was found.</p> <p>Conclusion</p> <p>Our study clearly highlights the difference of sensitivity between cell types and cytotoxicity assays that has to be carefully taken into account when assessing nanoparticles toxicity.</p

Agglomeration State of Titanium-Dioxide (TiO2) Nanomaterials Influences the Dose Deposition and Cytotoxic Responses in Human Bronchial Epithelial Cells at the Air-Liquid Interface

Extensive production and use of nanomaterials (NMs), such as titanium dioxide (TiO(2)), raises concern regarding their potential adverse effects to humans. While considerable efforts have been made to assess the safety of TiO(2) NMs using in vitro and in vivo studies, results obtained to date are unreliable, possibly due to the dynamic agglomeration behavior of TiO(2) NMs. Moreover, agglomerates are of prime importance in occupational exposure scenarios, but their toxicological relevance remains poorly understood. Therefore, the aim of this study was to investigate the potential pulmonary effects induced by TiO(2) agglomerates of different sizes at the air–liquid interface (ALI), which is more realistic in terms of inhalation exposure, and compare it to results previously obtained under submerged conditions. A nano-TiO(2) (17 nm) and a non-nano TiO(2) (117 nm) was selected for this study. Stable stock dispersions of small agglomerates and their respective larger counterparts of each TiO(2) particles were prepared, and human bronchial epithelial (HBE) cells were exposed to different doses of aerosolized TiO(2) agglomerates at the ALI. At the end of 4h exposure, cytotoxicity, glutathione depletion, and DNA damage were evaluated. Our results indicate that dose deposition and the toxic potential in HBE cells are influenced by agglomeration and exposure via the ALI induces different cellular responses than in submerged systems. We conclude that the agglomeration state is crucial in the assessment of pulmonary effects of NMs

Is aggregated synthetic amorphous silica toxicologically relevant?

The regulatory definition(s) of nanomaterials (NMs) frequently uses the term 'agglomerates and aggregates' (AA) despite the paucity of evidence that AA are significantly relevant from a nanotoxicological perspective. This knowledge gap greatly affects the safety assessment and regulation of NMs, such as synthetic amorphous silica (SAS). SAS is used in a large panel of industrial applications. They are primarily produced as nano-sized particles (1-100 nm in diameter) and considered safe as they form large aggregates (> 100 nm) during the production process. So far, it is indeed believed that large aggregates represent a weaker hazard compared to their nano counterpart. Thus, we assessed the impact of SAS aggregation on in vitro cytotoxicity/biological activity to address the toxicological relevance of aggregates of different sizes

Air Pollution–Related Prothrombotic Changes in Persons with Diabetes

Background: Population studies suggest that persons with diabetes are more sensitive to the effects of particulate matter (PM) air pollution. However, the biological mechanisms of a possible prothrombotic effect underlying this enhanced susceptibility remain largely unknown.Objective: We hypothesized that exposure to PM causes prothrombotic changes in persons with diabetes, possibly via systemic inflammation.Methods: Our study included 137 nonsmoking adults with diabetes who were outpatients at the University Hospital Leuven. Recent exposure (2 hr before examination) to ambient PM was measured at the entrance of the hospital. Individual chronic exposure to PM was assessed by measuring the area occupied by carbon in airway macrophages obtained by sputum induction. Platelet function was measured ex vivo with the PFA-100 platelet function analyzer, which simulates a damaged blood vessel; we analyzed the function of platelets in primary hemostasis under high shear conditions. Total and differential blood leukocytes were counted.Results: Independent of antiplatelet medication, an interquartile range (IQR) increase of 39.2 microg/m3 in PM10 (PM with aerodynamic diameter </= 10 microm) concentration measured 2 hr before the clinical examination (recent exposure) was associated with a decrease of 21.1 sec [95% confidence interval (CI), 35.3 to 6.8] in the PFA-100 closure time (i.e., increased platelet activation) and an increase in blood leukocytes of 512 per microliter of blood (95% CI, 45.2979). Each area increase of 0.25 microm2 (IQR) in carbon load of airway macrophages (chronic exposure) was associated with an increase of 687 leukocytes per microliter of blood (95% CI, 2241,150).Conclusions: A relevant increase in recent PM exposure was associated with a change in platelet function toward a greater prothrombotic tendency. The magnitude of the change was about two-thirds (in the opposite direction) of the average effect of antiplatelet medication. Diabetic patients showed evidence of proinflammatory response to both recent and chronic exposure to PM air pollution. Editor's SummaryDiabetics are at increased risk of cardiovascular diseases, and the association between particulate matter (PM) air pollution and cardiovascular outcomes may be stronger among diabetics than among nondiabetics. Jacobs et al. (p. 191) hypothesized that susceptibility to adverse cardiovascular outcomes among diabetics might be related to prothrombotic and inflammatory effects of PM. The authors estimated associations between PM exposures and measures of platelet function (estimated using the PFA-100 platelet function analyzer) and systemic inflammation (total and differential white blood cell counts) among 63 well-controlled diabetics (29 type I, 34 type II). Exposures included modeled estimates of average ambient residential PM10 (PM with aerodynamic diameter </= 10 microm), recent PM10 and PM2.5 (aerodynamic diameter </= 2.5 microm) exposures (at the study hospital), and a proxy measure of chronic carbon load (median area occupied by carbon in 50 airway macrophages from an induced sputum sample.) The authors report that recent PM10 exposure was associated with increased platelet activation, both before and after adjustment for type of diabetes and use of medications that inhibit platelet aggregation, and that carbon load was positively associated with platelet and white blood cell counts. The authors conclude that findings are consistent with proinflammatory responses to PM air pollution among diabetics.status: publishe