Reflections on the scope and the future of Particle and Fibre Toxicology

Within 5 years of its first publication in December 2004, Particle and Fibre Toxicology has become a well recognized open access, peer-reviewed, online journal with an (unofficial) impact factor of 5.5. This major achievement is due to the dedication of former Editors-in-Chief Professors Ken Donaldson and Paul Borm, and, of course also due to the high quality of manuscripts that have been submitted by authors from all over the world. Recent years have shown a significant increase in papers dealing with nanomaterials and nanotoxicology, whilst the small margin between ambient PM exposure and current standards continues to provide a constant flow of manuscripts on this topic. This however, does not imply that we can relax now.</p

Editorial: dose-dependent ZnO particle-induced acute phase response in humans warrants re-evaluation of occupational exposure limits for metal oxides

Epidemiological studies link inhalation of particles to increased risk of cardiovascular disease. Inhaled particles may induce cardiovascular disease by several different mechanisms including translocation of particles to systemic circulation, activation of airway sensory nerves resulting in autonomic imbalance and particle-induced pulmonary inflammation and acute phase response.The acute phase response is the systemic response to acute and chronic inflammatory states caused by for example bacterial infection, virus infection, trauma and infarction. It is characterized by differential expression of ca. 50 different acute phase proteins including C-reactive protein and Serum amyloid A, which are the most differentially up-regulated acute phase response proteins. Blood levels of these two acute phase proteins are closely associated with risk of cardiovascular disease in epidemiological studies and SAA has been causally related to the formation of plaques in the aorta in animal studies.In a recent paper in Particle and Fibre Toxicology, Christian Monsé et al. provide evidence that inhalation of ZnO nanoparticles induces dose-dependent acute phase response in humans at dose levels well below the current mass-based occupational exposure limits in a number of countries including Germany, The Netherlands, UK, Sweden, Denmark and the US.Given the evidence suggesting a causal relationship between increased levels of serum amyloid A and atherosclerosis, the current results call for a re-evaluation of occupational exposure limits for a number of particle exposures including ZnO taking induction of acute phase response into account. Furthermore, it underscores cardiovascular disease as an occupational disease

A new approach to design safe CNTs with an understanding of redox potential

BACKGROUND: Carbon nanotubes (CNTs) are being increasingly industrialized and applied for various products. As of today, although several toxicological evaluations of CNTs have been conducted, designing safer CNTs is not practiced because reaction kinetics of CNTs with bioactive species is not fully understood. RESULTS: The authors propose a kinetic mechanism to establish designing safe CNTs as a new goal. According to a literature search on the behavior of CNTs and the effects of impurities, it is found that chemical reactions on CNT surface are attributed to redox reactions involving metal impurities and carbon structures at the CNT surface. CONCLUSION: A new goal is proposed to design safer CNTs using the redox potential hypothesis. The value of this hypothesis must be practically investigated and proven through the further experiments

Взаємодія архетипних систем в українських, польських, староанглійських і кельтських загадках(на матеріалі праць І.Я.Франка та Ексетерської книги)

Метою дослідження є порівняти архетипні системи українських, польських, кельтських і англосаксонських загадок періоду раннього християнства. Основний акцент робиться на порівнянні українських і староанглійських загадок

Diesel exhaust particles induce CYP1A1 and pro-inflammatory responses via differential pathways in human bronchial epithelial cells

<p>Abstract</p> <p>Background</p> <p>Exposure to diesel engine exhaust particles (DEPs) has been associated with several adverse health outcomes in which inflammation seems to play a key role. DEPs contain a range of different inorganic and organic compounds, including polycyclic aromatic hydrocarbons (PAHs). During the metabolic activation of PAHs, CYP1A1 enzymes are known to play a critical role. In the present study we investigated the potential of a characterised sample of DEPs to induce cytotoxicity, to influence the expression of CYP1A1 and inflammation-related genes, and to activate intracellular signalling pathways, in human bronchial epithelial cells. We specifically investigated to what extent DEP-induced expression of interleukin (IL)-6, IL-8 and cyclooxygenase (COX)-2 was regulated differentially from DEP-induced expression of CYP1A1.</p> <p>Results</p> <p>The cytotoxicity of the DEPs was characterised by a marked time- and concentration-dependent increase in necrotic cells at 4 h and above 200 μg/ml (~ 30 μg/cm²). DEP-induced DNA-damage was only apparent at high concentrations (≥ 200 μg/ml). IL-6, IL-8 and COX-2 were the three most up-regulated genes by the DEPs in a screening of 20 selected inflammation-related genes. DEP-induced expression of CYP1A1 was detected at very low concentrations (0.025 μg/ml), compared to the expression of IL-6, IL-8 and COX-2 (50-100 μg/ml). A CYP1A1 inhibitor (α-naphthoflavone), nearly abolished the DEP-induced expression of IL-8 and COX-2. Of the investigated mitogen-activated protein kinases (MAPKs), the DEPs induced activation of p38. A p38 inhibitor (SB202190) strongly reduced DEP-induced expression of IL-6, IL-8 and COX-2, but only moderately affected the expression of CYP1A1. The DEPs also activated the nuclear factor-κB (NF-κB) pathway, and suppression by siRNA tended to reduce the DEP-induced expression of IL-8 and COX-2, but not CYP1A1.</p> <p>Conclusion</p> <p>The present study indicates that DEPs induce both CYP1A1 and pro-inflammatory responses in vitro, but via differential intracellular pathways. DEP-induced pro-inflammatory responses seem to occur via activation of NF-κB and p38 and are facilitated by CYP1A1. However, the DEP-induced CYP1A1 response does not seem to involve NF-κB and p38 activation. Notably, the present study also indicates that expression of CYP1A1 may represent a particular sensitive biomarker of DEP-exposure.</p

Pro-inflammatory responses to PM0.25_{0.25} from airport and urban traffic emissions

Airport particulate matter (PM) emissions are the known source of air pollution in the proximity of an airport. Often large airports are located near metropolises, and airport emissions may have a potentially considerable impact on public health in the surrounding urban areas. However, little is known about the sources that are relevant to air quality and health in the vicinity of airports. Therefore, the effect of the chemical composition of airport-related PM on adverse health risks was investigated in comparison to urban traffic emissions. PM0.25 were collected at the Los Angeles International Airport (LAX) and at a central Los Angeles site (USC campus), along with PM2.5 collected directly from turbine and diesel engines. The chemical composition, oxidative potential (OP) of particles as well as the reactive oxygen species (ROS) activity, inflammatory potential (IL 6, IL 8 and TNF–α) release and cytotoxicity on human bronchial epithelial (16HBE) cells were assessed. Chemical composition measurements confirmed that aircraft emissions were the major source to LAX PM0.25, while the sources of USC samples were more complex, including traffic emissions, suspended road and soil dust, and secondary sulfate. The traffic-related transition metals (Fe and Cu) in LAX and USC samples mainly affected OP values of particles, while multiple factors such as compositions, size distribution and internalized amount of particles contributed to the promotion of ROS generation in 16HBE cells during 4 h exposure. Internalized particles in cells might also play an important role in activating inflammatory responses during 20 h recovery period, with LAX particles being more potent. Our results demonstrate considerable toxicity of airport-related particles, even at low exposure concentrations, which suggests that airport emission as source of PM0.25 may also contribute to the adverse effects on public health attributable to PM

Physicochemical characterisation of combustion particles from vehicle exhaust and residential wood smoke

BACKGROUND: Exposure to ambient particulate matter has been associated with a number of adverse health effects. Particle characteristics such as size, surface area and chemistry seem to influence the negative effects of particles. In this study, combustion particles from vehicle exhaust and wood smoke, currently used in biological experiments, were analysed with respect to microstructure and chemistry. METHODS: Vehicle exhaust particles were collected in a road tunnel during two seasons, with and without use of studded tires, whereas wood smoke was collected from a stove with single-stage combustion. Additionally, a reference diesel sample (SRM 2975) was analysed. The samples were characterised using transmission electron microscopy techniques (TEM/HRTEM, EELS and SAED). Furthermore, the elemental and organic carbon fractions were quantified using thermal optical transmission analysis and the content of selected PAHs was determined by gas chromatography-mass spectrometry. RESULTS: Carbon aggregates, consisting of tens to thousands of spherical primary particles, were the only combustion particles identified in all samples using TEM. The tunnel samples also contained mineral particles originating from road abrasion. The geometric diameters of primary carbon particles from vehicle exhaust were found to be significantly smaller (24 ± 6 nm) than for wood smoke (31 ± 7 nm). Furthermore, HRTEM showed that primary particles from both sources exhibited a turbostratic microstructure, consisting of concentric carbon layers surrounding several nuclei in vehicle exhaust or a single nucleus in wood smoke. However, no differences were detected in the graphitic character of primary particles from the two sources using SAED and EELS. The total PAH content was higher for combustion particles from wood smoke as compared to vehicle exhaust, whereas no source difference was found for the ratio of organic to total carbon. CONCLUSION: Combustion particles from vehicle exhaust and residential wood smoke differ in primary particle diameter, microstructure, and PAH content. Furthermore, the analysed samples seem suitable for assessing the influence of physicochemical characteristics of particles on biological responses

Cytokine release from alveolar macrophages exposed to ambient particulate matter: Heterogeneity in relation to size, city and season

BACKGROUND: Several studies have demonstrated an association between exposure to ambient particulate matter (PM) and respiratory and cardiovascular diseases. Inflammation seems to play an important role in the observed health effects. However, the predominant particle component(s) that drives the inflammation is still not fully clarified. In this study representative coarse (2.5–10 μm) and fine (0.1–2.5 μm) particulate samples from a western, an eastern, a northern and a southern European city (Amsterdam, Lodz, Oslo and Rome) were collected during three seasons (spring, summer and winter). All fractions were investigated with respect to cytokine-inducing potential in primary macrophages isolated from rat lung. The results were related to the physical and chemical parameters of the samples in order to disclose possible connections between inflammatory potential and specific characteristics of the particles. RESULTS: Compared on a gram-by gram basis, both site-specific and seasonal variations in the PM-induced cytokine responses were demonstrated. The samples collected in the eastern (Lodz) and southern (Rome) cities appeared to be the most potent. Seasonal variation was most obvious with the samples from Lodz, with the highest responses induced by the spring and summer samples. The site-specific or seasonal variation in cytokine release could not be attributed to variations in any of the chemical parameters. Coarse fractions from all cities were more potent to induce the inflammatory cytokines interleukin-6 and tumour necrosis factor-α than the corresponding fine fractions. Higher levels of specific elements such as iron and copper, some polycyclic aromatic hydrocarbons (PAHs) and endotoxin/lipopolysaccaride seemed to be prevalent in the coarse fractions. However, variations in the content of these components did not reflect the variation in cytokine release induced by the different coarse fractions. Addition of polymyxin B did not affect the particle-induced cytokine release, indicating that the variations in potency among the coarse fractions are not explained by endootoxin. CONCLUSION: The inflammatory potential of ambient PM demonstrated heterogeneity in relation to city and season. The coarse particle fractions were consistently more potent than the respective fine fractions. Though a higher level of some elements, PAH and endotoxin was found in the coarse fractions, the presence of specific components was not sufficient to explain all variations in PM-induced cytokine release