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
models.
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.
A workshop of experts systematically analyzed the available information and identified 19 key lessons that can facilitate knowledge exchange between these discipline areas.
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.
There is now an opportunity to apply knowledge from NM toxicology and use it to better inform PM health risk research and vice versa. https://doi.org/10.1289/EHP424.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
IntroductionThe oxidative potential (OP) of particulate matter (PM) has been proposed as a health-relevant metric, but currently few epidemiological studies investigated associations of OP with ...health. Our main aim was to assess associations of long-term exposure to OP with respiratory health in children. Our second aim was to evaluate whether OP is more consistently associated with respiratory health than PM mass, PM composition or nitrogen dioxide (NO2).MethodsFor 3701 participants of a prospective birth cohort, annual average concentrations of OP (assessed by spin resonance (OPESR) and dithiothreitol assay (OPDTT)), PM with an aerodynamic diameter of less than 2.5 µm (PM2.5) mass, NO2, and PM2.5 constituents at the home addresses at birth and at all follow-up addresses were estimated by land-use regression. Repeated questionnaire reports of asthma and hay fever until age 14 years, and measurements of allergic sensitisation, lung function and fractional exhaled nitric oxide at age 12 years were linked with air pollution concentrations.ResultsAsthma incidence, prevalence of asthma symptoms and rhinitis were positively associated with OPDTT (adjusted OR (95% CI) per IQR increase in exposure 1.10 (1.01 to 1.20), 1.08 (1.02 to 1.16), 1.15 (1.05 to 1.26), respectively). These associations persisted after adjustment for most co-pollutants. Forced expiratory volume in 1s and forced vital capacity were negatively associated with OPDTT. These associations were sensitive to adjustment for NO2. Respiratory health was not significantly associated with PM2.5 mass and OPESR.ConclusionsRespiratory health was more strongly associated with OPDTT than with PM2.5 mass; OPDTT associations with lung function, but not symptoms, were sensitive to adjustment for NO2.
Abstract
Particulate matter (PM) is regulated in various parts of the world based on specific size cut offs, often expressed as 10 or 2.5 µm mass median aerodynamic diameter. This pollutant is deemed ...one of the most dangerous to health and moreover, problems persist with high ambient concentrations. Continuing pressure to re-evaluate ambient air quality standards stems from research that not only has identified effects at low levels of PM but which also has revealed that reductions in certain components, sources and size fractions may best protect public health. Considerable amount of published information have emerged from toxicological research in recent years. Accumulating evidence has identified additional air quality metrics (e.g. black carbon, secondary organic and inorganic aerosols) that may be valuable in evaluating the health risks of, for example, primary combustion particles from traffic emissions, which are not fully taken into account with PM2.5 mass. Most of the evidence accumulated so far is for an adverse effect on health of carbonaceous material from traffic. Traffic-generated dust, including road, brake and tire wear, also contribute to the adverse effects on health. Exposure durations from a few minutes up to a year have been linked with adverse effects. The new evidence collected supports the scientific conclusions of the World Health Organization Air Quality Guidelines and also provides scientific arguments for taking decisive actions to improve air quality and reduce the global burden of disease associated with air pollution.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The increasing manufacture and use of products based on nanotechnology raises concerns for both workers and consumers. Various studies report induction of pulmonary inflammation after inhalation ...exposure to nanoparticles, which can vary in aspects such as size, shape, charge, crystallinity, chemical composition, and dissolution rate. Each of these aspects can affect their toxicity, although it is largely unknown to what extent. The aim of the current review is to analyse published data on inhalation of nanoparticles to identify and evaluate the contribution of their physicochemical characteristics to the onset and development of pulmonary inflammation. Many physicochemical characteristics of nanoparticles affect their lung deposition, clearance, and pulmonary response that, in combination, ultimately determine whether pulmonary inflammation will occur and to what extent. Lung deposition is mainly determined by the physical properties of the aerosol (size, density, shape, hygroscopicity) in relation to airflow and the anatomy of the respiratory system, whereas clearance and translocation of nanoparticles are mainly determined by their geometry and surface characteristics. Besides size and chemical composition, other physicochemical characteristics influence the induction of pulmonary inflammation after inhalation. As some nanoparticles dissolve, they can release toxic ions that can damage the lung tissue, making dissolution rate an important characteristic that affects lung inflammation. Fibre-shaped materials are more toxic to the lungs compared to spherical shaped nanoparticles of the same chemical composition. In general, cationic nanoparticles are more cytotoxic than neutral or anionic nanoparticles. Finally, surface reactivity correlates well with observed pulmonary inflammation. With all these characteristics affecting different stages of the events leading to pulmonary inflammation, no unifying dose metric could be identified to describe pulmonary inflammation for all nanomaterials, although surface reactivity might be a useful measure. To determine the extent to which the various characteristics influence the induction of pulmonary inflammation, the effect of these characteristics on lung deposition, clearance, and pulmonary response should be systematically evaluated. The results can then be used to facilitate risk assessment by categorizing nanoparticles according to their characteristics.
Abstract
Safe-by-Design (SbD) has been put forward as a concept to assure that only safe nanomaterials will reach the market and that safety aspects have already been considered in a very early stage ...of the innovation process. In practice, several laboratory test have been proposed to screen newly developed nanomaterials and nano-enabled products to assess their hazardous nature. These tests need to have sufficient predictive power for possible adverse effects on human health, not only due to acute (peak) exposures, but also for long-term (low dose) exposures as these materials may accumulate over time in organs and tissues.
•Only few in vivo toxicity and epidemiological studies focused specifically on non-exhaust sources.•Further experiments are needed to better separate individual contributions and health effects.•Need ...of understanding of the interaction between road surface texture, moisture, chemistry, dust load and dust emission.•Poor emission inventorying on resuspension and heavy metals.•The optimal mitigation strategy for each climatic region is still unknown.
About 400,000 premature adult deaths attributable to air pollution occur each year in the European Region. Road transport emissions account for a significant share of this burden. While important technological improvements have been made for reducing particulate matter (PM) emissions from motor exhausts, no actions are currently in place to reduce the non-exhaust part of emissions such as those from brake wear, road wear, tyre wear and road dust resuspension. These “non-exhaust” sources contribute easily as much and often more than the tailpipe exhaust to the ambient air PM concentrations in cities, and their relative contribution to ambient PM is destined to increase in the future, posing obvious research and policy challenges.
This review highlights the major and more recent research findings in four complementary fields of research and seeks to identify the current gaps in research and policy with regard to non-exhaust emissions. The objective of this article is to encourage and direct future research towards an improved understanding on the relationship between emissions, concentrations, exposure and health impact and on the effectiveness of potential remediation measures in the urban environment.
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.
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.
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.
The capacity of Particulate Matter (PM) to oxidise target molecules, defined as its oxidative potential (OP), has been proposed as a biologically more relevant metric than PM mass. Different assays ...exist for measuring OP and their methodologies vary in the choice of extraction solvent and filter type. Little is known about the impact of extraction and filter type on reported OP. Four a-cellular assays; electron spin resonance (ESR), dithiothreitol (DTT), ascorbate acid depletion (AA) and reductive acridinium triggering (CRAT) assay were chosen to evaluate whether these differences affect the OP measurement, the correlation between OP from different assays and the association with PM chemical composition. We analysed 15 urban 48–72 h PM2.5 samples collected on quartz and Teflon filters. The choice of extraction solvent had only a significant effect on OPDTT, while all OP measures for quartz filters were heavily attenuated. OP values derived from quartz were, however, highly correlated with those derived from Teflon. OPDTT correlated highly with OPCRAT, and OPESR correlated highly with OPAA. These correlations were affected by the choice of filter type. Correlations between OP and PM chemical composition were not affected by filter type and extraction solvent. These findings indicate that the measurement of relative OP reactivity is not greatly influenced by filter type and extraction solvent for the investigated assays. This robustness is also promising for exploratory use in monitoring and subsequent epidemiological studies.
•We examined effects of filter type and extraction solvent on oxidative potential (OP).•Extraction solvent had a significant effect on OPDTT, but not on OPESR or OPAA.•OP values measured from quartz filter extracts were heavily attenuated for all assays.•However, OP values from quartz filters were highly correlated with those from Teflon.•OP measured with ESR direct method showed promising results.
The development of engineered nanomaterials is growing exponentially, despite concerns over their potential similarities to environmental nanoparticles that are associated with significant ...cardiorespiratory morbidity and mortality. The mechanisms through which inhalation of nanoparticles could trigger acute cardiovascular events are emerging, but a fundamental unanswered question remains: Do inhaled nanoparticles translocate from the lung in man and directly contribute to the pathogenesis of cardiovascular disease? In complementary clinical and experimental studies, we used gold nanoparticles to evaluate particle translocation, permitting detection by high-resolution inductively coupled mass spectrometry and Raman microscopy. Healthy volunteers were exposed to nanoparticles by acute inhalation, followed by repeated sampling of blood and urine. Gold was detected in the blood and urine within 15 min to 24 h after exposure, and was still present 3 months after exposure. Levels were greater following inhalation of 5 nm (primary diameter) particles compared to 30 nm particles. Studies in mice demonstrated the accumulation in the blood and liver following pulmonary exposure to a broader size range of gold nanoparticles (2–200 nm primary diameter), with translocation markedly greater for particles <10 nm diameter. Gold nanoparticles preferentially accumulated in inflammation-rich vascular lesions of fat-fed apolipoproteinE-deficient mice. Furthermore, following inhalation, gold particles could be detected in surgical specimens of carotid artery disease from patients at risk of stroke. Translocation of inhaled nanoparticles into the systemic circulation and accumulation at sites of vascular inflammation provides a direct mechanism that can explain the link between environmental nanoparticles and cardiovascular disease and has major implications for risk management in the use of engineered nanomaterials.
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