Fine and ultrafine particles from indoor sources – Effects on healthy humans in a controlled exposure study and on lung epithelial cells in vitro

In recent years increasing concern has been expressed about the potential adverse health effects of particles from indoor sources. The aims of the EPIA project were: (1) to characterize potentially relevant indoor sources of (ultra)fine particles with respect to their emission levels and composition and (2) to investigate their adverse health effects. We investigated the effects of emissions from candle burning (CB), toasting of bread (TB) and sausage frying (FS) in a randomized, cross-over sham-controlled exposure study in healthy adults as well as in vitro in A549 human lung epithelial cells. Participants were exposed for 2 h to each of these sources at two different exposure levels, and examined before, during and after the exposures at defined time-intervals. We found transient associations between exposures and several respiratory and cardiovascular effects as well as inflammatory changes (e.g. lung function, blood pressure, arterial stiffness, interleukin-8 in nasal lavage/blood). Specific effects were found to depend strongly on the emission source and the selected exposure metric (e.g. size-specific particle mass concentration, size-specific particle number concentration, lung deposited surface area concentration). Evaluation of PM2.5 samples in the A549 cells, revealed an increased interleukin-8 release and DNA strand breakage induction for toasting, whereas candle burning only resulted in DNA damage. The results from our project demonstrate that elevated concentrations from certain indoor emission sources may lead to changes in the lung and cardiovascular systems as well as possibly induce inflammation

Lung-depositing surface area (LDSA) of particles in office spaces around Europe : Size distributions, I/O-ratios and infiltration

Air pollution, and specifically particulate matter pollution, is one of the greatest dangers to human health. Outdoor air pollution ranks third in causes for premature death. Improving indoor air quality is of immense importance, as the time spent indoors is often much greater than the time spent outdoors. In this experimental study, we evaluate the levels of particle pollution in indoor air in four offices across Europe, compare the indoor particles to outdoor particles and assess where the particles originate from. The measurements were conducted with an Electrical Low-Pressure Impactor (ELPI+) for particles between 6 nm and 1 μm. The chosen metric, lung-deposited particle surface area (LDSA), targets the health impacts of particle pollution. Based on the measurements, we determined that most of the indoor air particles infiltrated from outdoor air, although two of the offices had very limited indoor activity during the measurement campaigns and may not represent typical use. The highest median indoor LDSA concentration during daytime hours was 27.2 μm2/cm3, whereas the lowest was 2.8 μm2/cm3. Indoor air in general had lower LDSA concentrations than outdoor air, the corresponding outdoor LDSA concentrations being 35.8 μm2/cm3 and 9.8 μm2/cm3. The particle size ranges which contributed to the highest concentrations were 50–100 nm and 300–500 nm. These size ranges correspond to soot mode and accumulation mode particles, which represent local and regional sources, respectively. Based on this study, limiting particle infiltration is the key factor in keeping indoor air in offices free of lung-depositing particles.Peer reviewe

Nanomaterials Versus Ambient Ultrafine Particles: An Opportunity to Exchange Toxicology Knowledge

BACKGROUND: A rich body of literature exists that has demonstrated adverse human health effects following exposure to ambient air particulate matter (PM), and there is strong support for an important role of ultrafine (nanosized) particles. At present, relatively few human health or epidemiology data exist for engineered nanomaterials (NMs) despite clear parallels in their physicochemical properties and biological actions in in vitro models. OBJECTIVES: NMs are available with a range of physicochemical characteristics, which allows a more systematic toxicological analysis. Therefore, the study of ultrafine particles (UFP, <100 nm in diameter) provides an opportunity to identify plausible health effects for NMs, and the study of NMs provides an opportunity to facilitate the understanding of the mechanism of toxicity of UFP. METHODS: A workshop of experts systematically analyzed the available information and identified 19 key lessons that can facilitate knowledge exchange between these discipline areas. DISCUSSION: Key lessons range from the availability of specific techniques and standard protocols for physicochemical characterization and toxicology assessment to understanding and defining dose and the molecular mechanisms of toxicity. This review identifies a number of key areas in which additional research prioritization would facilitate both research fields simultaneously. CONCLUSION: There is now an opportunity to apply knowledge from NM toxicology and use it to better inform PM health risk research and vice versa.info:eu-repo/semantics/publishedVersio

Nitrite enhances neutrophil-induced DNA strand breakage in pulmonary epithelial cells by inhibition of myeloperoxidase

Chronic inhalation of environmental particles is associated with pulmonary carcinogenesis. Although the mechanism has not yet been fully elucidated, influx of inflammatory cells, including neutrophils, is suggested to play a major role in this process. Typically, in the particle-exposed lung, influx of neutrophils is accompanied by an accumulation of nitrite. Previous studies indicated that nitrite may affect the toxicity of neutrophils, involving an interaction with neutrophil-derived myeloperoxidase (MPO). To evaluate the possible consequences of this interaction for inflammation-mediated genotoxicity, we investigated the effect of nitrite on neutrophil-induced DNA damage in pulmonary target cells. Therefore, activated neutrophils were co-cultured with alveolar type II epithelial cells (RLE), and DNA strand breakage was evaluated using single-cell gel electrophoresis (comet assay). In this system, addition of nitrite caused an increase in neutrophil-induced DNA strand breakage in RLE cells, which was associated with an inhibition of MPO activity. Similar results were obtained by co-culturing RLE cells with neutrophils in the presence of the specific MPO inhibitor 4-aminobenzoic acid hydrazide (4-ABAH). To further investigate the mechanism underlying these observations, in vitro experiments were performed using mixtures of nitrite, MPO and its substrate H2O2. DNA strand breakage by reagent H2O2 was inhibited when it was allowed to react with MPO before addition to the RLE cells. However, when MPO and H2O2 were pre-mixed in the presence of nitrite or 4-ABAH, the inhibitory effect of MPO on resultant DNA damage was reversed. Further studies using catalase indicated that DNA strand breakage by the pre-mixtures of MPO, H2O2 and nitrite was H2O2-specific, suggesting that nitrite prevents consumption of H2O2 by MPO. Collectively, our results show that nitrite enhances neutrophil-induced DNA strand breakage in pulmonary epithelial cells. This effect is probably due to an inhibition of MPO activity, which increases the availability of its DNA strand breaking substrate H2O2

Inhalable Saharan dust induces oxidative stress, NLRP3 inflammasome activation, and inflammatory cytokine release

Desert dust is increasingly recognized as a major air pollutant affecting respiratory health. Since desert dust exposure cannot be regulated, the hazardousness of its components must be understood to enable health risk mitigation strategies. Saharan dust (SD) comprises about half of the global desert dust and contains quartz, a toxic mineral dust that is known to cause severe lung diseases via oxidative stress and activation of the NLRP3 inflammasome-interleukin-1β pathway. We aimed to assess the physicochemical and microbial characteristics of SD responsible for toxic effects. Also, we studied the oxidative and pro-inflammatory potential of SD in alveolar epithelial cells and the activation of the NLRP3 inflammasome in macrophage-like cells in comparison to quartz dusts and synthetic amorphous silica (SAS).Characterization revealed that SD contained Fe, Al, trace metals, sulfate, diatomaceous earth, and endotoxin and had the capacity to generate hydroxyl radicals. We exposed A549 lung epithelial cells and wild-type and NLRP3-/- THP-1 macrophage-like cells to SD, three well-investigated quartz dusts, and SAS. SD induced oxidative stress in A549 cells after 24 h more potently than the quartz dusts. The quartz dusts and SAS upregulated interleukin 8 expression after 4 h and 24 h while SD only caused a transient upregulation. SD, the quartz dusts, and SAS induced interleukin-1β release from wild-type THP-1 cells>20-fold stronger than from NLRP3-/- THP-1 cells. Interleukin-1β release was lower for SD, in which microbial components including endotoxin were heat-destructed.In conclusion, microbial components in SD are pivotal for its toxicity. In the epithelium, the effects of SD contrasted with crystalline and amorphous silica in terms of potency and persistence. In macrophages, the strong involvement of the NLRP3 inflammasome emphasizes the acute and chronic health risks associated with desert dust exposure

Arterial blood pressure responses to short-term exposure to fine and ultrafine particles from indoor sources – a randomized sham-controlled exposure study of healthy volunteers

Objectives Particulate air pollution is linked to adverse cardiovascular effects. The aim of the study was to investigate the effect of short-term exposure to indoor particles on blood pressure (BP). Methods We analyzed the association of particle emissions from indoor sources (candle burning, toasting bread, frying sausages) with BP changes in 54 healthy volunteers in a randomized cross-over controlled exposure study. Particle mass concentration (PMC), size-specific particle number concentration (PNC) and lung-deposited particle surface area concentration (PSC) were measured during the 2 h exposure. Systolic and diastolic blood pressure were measured before, during, directly, 2, 4 and 24 h after exposure. We performed multiple mixed linear regression analyses of different particle metrics and BP. Results BP significantly increased with increasing PMC, PSC and PNC resulting from toasting bread. For example, an increase per 10 µg/m3 PM10 and PM2.5, systolic BP increased at all time points with largest changes 1 h after exposure initiation of 1.5 mmHg (95%-CI: 1.1; 1.9) and of 2.2 mmHg (95%-CI: 1.3; 3.1), respectively. Conclusions Our study suggests an association of short-term exposure to fine and ultrafine particles emitted from toasting bread with increases in BP. Particles emitted from frying sausages and candle burning did not consistently affect BP

How Structured Metadata Acquisition Contributes to the Reproducibility of Nanosafety Studies: Evaluation by a Round-Robin Test

It has been widely recognized that nanosafety studies are limited in reproducibility, caused by missing or inadequate information and data gaps. Reliable and comprehensive studies should be performed supported by standards or guidelines, which need to be harmonized and usable for the multidisciplinary field of nanosafety research. The previously described minimal information table (MIT), based on existing standards or guidelines, represents one approach towards harmonization. Here, we demonstrate the applicability and advantages of the MIT by a round-robin test. Its modular structure enables describing individual studies comprehensively by a combination of various relevant aspects. Three laboratories conducted a WST-1 cell viability assay using A549 cells to analyze the effects of the reference nanomaterials NM101 and NM110 according to predefined (S)OPs. The MIT contains relevant and defined descriptive information and quality criteria and thus supported the implementation of the round-robin test from planning, investigation to analysis and data interpretation. As a result, we could identify sources of variability and justify deviating results attributed to differences in specific procedures. Consequently, the use of the MIT contributes to the acquisition of reliable and comprehensive datasets and therefore improves the significance and reusability of nanosafety studie