Governance of advanced materials: Shaping a safe and sustainable future.

The past few decades of managing the uncertain risks associated with nanomaterials have provided valuable insights (knowledge gaps, tools, methods, etc.) that are equally important to promote safe and sustainable development and use of advanced materials. Based on these insights, the current paper proposes several actions to optimize the risk and sustainability governance of advanced materials. We emphasise the importance of establishing a European approach for risk and sustainability governance of advanced materials as soon as possible to keep up with the pace of innovation and to manage uncertainty among regulators, industry, SMEs and the public, regarding potential risks and impacts of advanced materials. Coordination of safe and sustainable advanced material research efforts, and data management according to the Findable, Accessible, Interoperable and Reusable (FAIR) principles will enhance the generation of regulatory-relevant knowledge. This knowledge is crucial to identify whether current regulatory standardised and harmonised test methods are adequate to assess advanced materials. At the same time, there is urgent need for responsible innovation beyond regulatory compliance which can be promoted through the Safe and Sustainable Innovation Approach. that combines the Safe and Sustainable by Design concept with Regulatory Preparedness, supported by a trusted environment. We further recommend consolidating all efforts and networks related to the risk and sustainability governance of advanced materials in a single, easy-to-use digital portal. Given the anticipated complexity and tremendous efforts required, we identified the need of establishing an organisational structure dedicated to aligning the fast technological developments in advanced materials with proper risk and sustainability governance. Involvement of multiple stakeholders in a trusted environment ensures a coordinated effort towards the safe and sustainable development, production, and use of advanced materials. The existing infrastructures and network of experts involved in the governance of nanomaterials would form a solid foundation for such an organisational structure.

A roadmap to strengthen standardisation efforts in risk governance of nanotechnology.

A roadmap was developed to strengthen standardisation activities for risk governance of nanotechnology. Its baseline is the available standardised and harmonised methods for nanotechnology developed by the International Organization for Standardization (ISO), the European Committee for Standardization (CEN), and the Organisation for Economic Co-operation and Development (OECD). In order to identify improvements and needs for new themes in standardisation work, an analysis of the state-of-the-art concepts and interpretations of risk governance of nanotechnology was performed. Eleven overall areas of action were identified, each including a subset of specific topics. Themes addressed include physical chemical characterisation, assessment of hazard, exposure, risk and socio-economic factors, as well as education & training and social dialogue. This has been visualised in a standardisation roadmap spanning a timeframe of ten years and including key outcomes and highlights of the analysis. Furthermore, the roadmap indicates potential areas of action for harmonisation and standardisation (H&S) for nanomaterials and nanotechnology. It also includes an evaluation of the current level (limited, moderate, intense) of ongoing H&S activities and indicates the time horizon for the different areas of action. As the identified areas differ in their state of development, the number and type of actions varied widely amongst the different actions towards achieving standardisation. Thus, priority areas were also identified. The overall objective of these actions is to strengthen risk governance towards a safe use of nanomaterials and nano-related products. Though not explicitly addressed, risk-based legislation and policies are supported via the proposed H&S actions.

The nanoGRAVUR framework to group (nano)materials for their occupational, consumer, environmental risks based on a harmonized set of material properties, applied to 34 case studies.

The project nanoGRAVUR (BMBF, 2015-2018) developed a framework for grouping of nanomaterials. Different groups may result for each of the three distinct perspectives of occupational, consumer and environmental safety. The properties, methods and descriptors are harmonised between the three perspectives and are based on: Tier 1 intrinsic physico-chemical properties (what they are) or GHS classification of the non-nano-form (human tox, ecotox, physical hazards); Tier 2 extrinsic physico-chemical properties, release from nano-enabled products, in vitro assays with cells (where they go; what they do); Tier 3 case-specific tests, potentially in vivo studies to substantiate the similarity within groups or application-specific exposure testing. Amongst all properties, dissolution and transformation are least modulated by different nanoforms within one substance, whereas dustiness, dispersion stability, abiotic and especially in vitro surface reactivity vary more often between different nanoforms. The methods developed or selected by nanoGRAVUR fill several gaps highlighted in the ProSafe reviews, and are useful to implement (i) the concept of nanoforms of the European Chemicals Agency (ECHA) and (ii) the concept of discrete forms of the United States Environmental Protection Agency (EPA). One cannot assess the significance of a dissimilarity, if the dynamic range of that property is unknown. Benchmark materials span dynamic ranges that enable us to establish bands, often with order-of-magnitude ranges. In 34 case studies we observed high biological similarity within each substance when we compared different (nano)forms of SiO2, BaSO4, kaolin, CeO2, ZnO, organic pigments, especially when we compared forms that are all untreated on the surface. In contrast, different Fe2O3 or TiO2 (nano)forms differ more significantly. The same nanoforms were also integrated in nano-enabled products (NEPs) for automotive coatings, clinker-reduced cements, cosmetic sunscreen, and lightweight polymers.

Effects of short-term exposure to fine and ultrafine particles from indoor sources on arterial stiffness - A randomized sham-controlled exposure study.

OBJECTIVES: Particulate air pollution is linked to adverse cardiovascular effects, including arterial stiffness. The aim of the study was to investigate the effect of short-term exposure to indoor fine and ultrafine particles on augmentation index (AIx), augmentation pressure (AP), and pulse wave velocity (PWV), early signs of vascular damage. METHODS: We analyzed the association of particle emissions from typical indoor sources (candle burning - CB, toasting bread - TB, and frying sausages - FS) with changes in pulse wave analysis indices in 55 healthy adults 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. AIx and AP were measured before, directly, 2, 4 and 24 h after exposure. PWV was measured directly and 24 h after exposure. We performed multiple mixed linear regression analyses of different particle metrics and AIx, AP and PWV. RESULTS: The highest mean PMC was observed during FS reaching a maximum of 210 µg/m3 PM10. The maximal PNC for UFP <100 nm was reached during CB with 2.3 million particles/cm3. PSC was similar across all three exposures (about 3000 µm2/cm³). Strongest associations between different particles metrics and arterial stiffness indices could be observed for UFP from CB and FS and for PMC from TB. The highest mean increase could be observed for the UFP fraction <10 nm, measured during CB, and AIx with an increase of 9.5%-points (95%-CI: 3.1; 15.9). PSC seemed to follow the pattern of PNC. PM10 and PM2.5 from TB led to clear changes in AIx with biggest increases for PM10 of 5.8%-points (95%-CI: 3.2; 8.4) 2 h after exposure and for PM2.5 of 8.1%-points (95%-CI: 2.5; 13.7) directly after exposure. CONCLUSIONS: Our study indicates effects of indoor exposure to fine and ultrafine particles on systemic arterial stiffness indices that depend on the indoor source as well as on particle metric. Differences in size-specific physical characteristics of source-specific particles might account for these differential effects. We did not observe clear and stable associations of indoor particle exposure and PWV.

Ultrafine and Fine Particle Number and Surface Area Concentrations and Daily Cause-Specific Mortality in the Ruhr Area, Germany, 2009-2014.

BACKGROUND: Although epidemiologic studies have shown associations between particle mass and daily mortality, evidence on other particle metrics is weak. OBJECTIVES: We investigated associations of size-specific particle number concentration (PNC) and lung-deposited particle surface area concentration (PSC) with cause-specific daily mortality in contrast to PM10. METHODS: We used time-series data (March 2009-December 2014) on daily natural, cardiovascular, and respiratory mortality (NM, CVM, RM) of three adjacent cities in the Ruhr Area, Germany. Size-specific PNC (electric mobility diameter of 13.3-750 nm), PSC, and PM10 were measured at an urban background monitoring site. In single- and multipollutant Poisson regression models, we estimated percentage change (95% confidence interval) [% (95% CI)] in mortality per interquartile range (IQR) in exposure at single-day (0-7) and aggregated lags (0-1, 2-3, 4-7), accounting for time trend, temperature, humidity, day of week, holidays, period of seasonal population decrease, and influenza. RESULTS: PNC100-750 and PSC were highly correlated and had similar immediate (lag0-1) and delayed (lag4-7) associations with NM and CVM, for example, 1.12% (95% CI: 0.09, 2.33) and 1.56% (95% CI: 0.22, 2.92) higher NM with IQR increases in PNC100-750 at lag0-1 and lag4-7, respectfully, which were slightly stronger then associations with IQR increases in PM10. Positive associations between PNC and NM were strongest for accumulation mode particles (PNC 100-500 nm), and for larger UFPs (PNC 50-100 nm). Associations between NM and PNC<100 changed little after adjustment for O3 or PM10, but were more sensitive to adjustment for NO2. CONCLUSION: Size-specific PNC (50-500 nm) and lung-deposited PSC were associated with natural and cardiovascular mortality in the Ruhr Area. Although associations were similar to those estimated for an IQR increase in PM10, particle number size distributions can be linked to emission sources, and thus may be more informative for potential public health interventions. Moreover, PSC could be used as an alternative metric that integrates particle size distribution as well as deposition efficiency. https://doi.org/10.1289/EHP2054.

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. https://doi.org/10.1289/EHP424.

Standardisation of a European measurement method for organic carbon and elemental carbon in ambient air: results of the field trial campaign and the determination of a measurement uncertainty and working range.

The European Committee for Standardisation (CEN) Technical Committee 264 'Air Quality' has recently produced a standard method for the measurements of organic carbon and elemental carbon in PM2.5 within its working group 35 in response to the requirements of European Directive 2008/50/EC. It is expected that this method will be used in future by all Member States making measurements of the carbonaceous content of PM2.5. This paper details the results of a laboratory and field measurement campaign and the statistical analysis performed to validate the standard method, assess its uncertainty and define its working range to provide clarity and confidence in the underpinning science for future users of the method. The statistical analysis showed that the expanded combined uncertainty for transmittance protocol measurements of OC, EC and TC is expected to be below 25%, at the 95% level of confidence, above filter loadings of 2 µg cm-2. An estimation of the detection limit of the method for total carbon was 2 µg cm-2. As a result of the laboratory and field measurement campaign the EUSAAR2 transmittance measurement protocol was chosen as the basis of the standard method EN 16909:2017.

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 2h exposure. Systolic and diastolic blood pressure were measured before, during, directly, 2, 4 and 24h 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 10µg/m3 PM10 and PM2.5, systolic BP increased at all time points with largest changes 1h after exposure initiation of 1.5mmHg (95%-CI: 1.1; 1.9) and of 2.2mmHg (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.

Airborne engineered nanomaterials in the workplace-a review of release and worker exposure during nanomaterial production and handling processes.

For exposure and risk assessment in occupational settings involving engineered nanomaterials (ENMs), it is important to understand the mechanisms of release and how they are influenced by the ENM, the matrix material, and process characteristics. This review summarizes studies providing ENM release information in occupational settings, during different industrial activities and using various nanomaterials. It also assesses the contextual information - such as the amounts of materials handled, protective measures, and measurement strategies - to understand which release scenarios can result in exposure. High-energy processes such as synthesis, spraying, and machining were associated with the release of large numbers of predominantly small-sized particles. Low-energy processes, including laboratory handling, cleaning, and industrial bagging activities, usually resulted in slight or moderate releases of relatively large agglomerates. The present analysis suggests that process-based release potential can be ranked, thus helping to prioritize release assessments, which is useful for tiered exposure assessment approaches and for guiding the implementation of workplace safety strategies. The contextual information provided in the literature was often insufficient to directly link release to exposure. The studies that did allow an analysis suggested that significant worker exposure might mainly occur when engineering safeguards and personal protection strategies were not carried out as recommended.

Exposure to ultrafine particles and respiratory hospitalisations in five European cities.

Epidemiological evidence on the associations between exposure to ultrafine particles (UFP), with aerodynamic electrical mobility diameters <100 nm, and health is limited. We gathered data on UFP from five European cities within 2001-2011 to investigate associations between short-term changes in concentrations and respiratory hospitalisations.We applied city-specific Poisson regression models and combined city-specific estimates to obtain pooled estimates. We evaluated the sensitivity of our findings to co-pollutant adjustment and investigated effect modification patterns by period of the year, age at admission and specific diagnoses.Our results for the whole time period do not support an association between UFP and respiratory hospitalisations, although we found suggestive associations among those 0-14 years old. We nevertheless report consistent adverse effect estimates during the warm period of the year, statistically significant after lag 2 when an increase by 10 000 particles per cm(3) was associated with a 4.27% (95% CI 1.68-6.92%) increase in hospitalisations. These effect estimates were robust to particles' mass or gaseous pollutants adjustment.Considering that our findings during the warm period may reflect better exposure assessment and that the main source of non-soluble UFP in urban areas is traffic, our results call for improved regulation of traffic emissions.

Influence of agglomeration and specific lung lining lipid/protein interaction on short-term inhalation toxicity.

Lung lining fluid is the first biological barrier nanoparticles (NPs) encounter during inhalation. As previous inhalation studies revealed considerable differences between surface functionalized NPs with respect to deposition and toxicity, our aim was to investigate the influence of lipid and/or protein binding on these processes. Thus, we analyzed a set of surface functionalized NPs including different SiO2 and ZrO2 in pure phospholipids, CuroSurf(TM) and purified native porcine pulmonary surfactant (nS). Lipid binding was surprisingly low for pure phospholipids and only few NPs attracted a minimal lipid corona. Additional presence of hydrophobic surfactant protein (SP) B in CuroSurf(TM) promoted lipid binding to NPs functionalized with Amino or PEG residues. The presence of the hydrophilic SP A in nS facilitated lipid binding to all NPs. In line with this the degree of lipid and protein affinities for different surface functionalized SiO2 NPs in nS followed the same order (SiO2 Phosphate ∼ unmodified SiO2 < SiO2 PEG < SiO2 Amino NPs). Agglomeration and biomolecule interaction of NPs in nS was mainly influenced by surface charge and hydrophobicity. Toxicological differences as observed in short-term inhalation studies (STIS) were mainly influenced by the core composition and/or surface reactivity of NPs. However, agglomeration in lipid media and lipid/protein affinity appeared to play a modulatory role on short-term inhalation toxicity. For instance, lipophilic NPs like ZrO2, which are interacting with nS to a higher extent, exhibited a far higher lung burden than their hydrophilic counterparts, which deserves further attention to predict or model effects of respirable NPs.

A redox proteomics approach to investigate the mode of action of nanomaterials.

Numbers of engineered nanomaterials (ENMs) are steadily increasing. Therefore, alternative testing approaches with reduced costs and high predictivity suitable for high throughput screening and prioritization are urgently needed to ensure a fast and effective development of safe products. In parallel, extensive research efforts are targeted to understanding modes of action of ENMs, which may also support the development of new predictive assays. Oxidative stress is a widely accepted paradigm associated with different adverse outcomes of ENMs. It has frequently been identified in in vitro and in vivo studies and different assays have been developed for this purpose. Fluorescent dye based read-outs are most frequently used for cell testing in vitro but may be limited due to possible interference of the ENMs. Recently, other assays have been put forward such as acellular determination of ROS production potential using methods like electron spin resonance, antioxidant quantification or the use of specific sensors. In addition, Omics based approaches have gained increasing attention. In particular, redox proteomics can combine the assessment of oxidative stress with the advantage of getting more detailed mechanistic information. Here we propose a comprehensive testing strategy for assessing the oxidative stress potential of ENMs, which combines acellular methods and fast in vitro screening approaches, as well as a more involved detailed redox proteomics approach. This allows for screening and prioritization in a first tier and, if required, also for unraveling mechanistic details down to compromised signaling pathways.

Size matters--The phototoxicity of TiO2 nanomaterials.

Under solar radiation several titanium dioxide nanoparticles (nano-TiO2) are known to be phototoxic for daphnids. We investigated the influence of primary particle size (10, 25, and 220 nm) and ionic strength (IS) of the test medium on the acute phototoxicity of anatase TiO2 particles to Daphnia magna. The intermediate sized particles (25 nm) showed the highest phototoxicity followed by the 10 nm and 220 nm sized particles (median effective concentrations (EC50): 0.53, 1.28, 3.88 mg/L). Photoactivity was specified by differentiating free OH radicals (therephthalic acid method) and on the other hand surface adsorbed, as well as free OH, electron holes, and O2(-) (electron paramagnetic resonance spectroscopy, EPR). We show that the formation of free OH radicals increased with a decrease in primary particle size (terephthalic acid method), whereas the total measured ROS content was highest at an intermediate particle size of 25 nm, which consequently revealed the highest photoxicity. The photoactivities of the 10 and 220 nm particles as measured by EPR were comparable. We suggest that phototoxicity depends additionally on the particle-daphnia interaction area, which explains the higher photoxicity of the 10 nm particles compared to the 220 nm particles. Thus, phototoxicity is a function of the generation of different ROS and the particle-daphnia interaction area, both depending on particle size. Phototoxicity of the 10 nm and 25 nm sized nanoparticles decreased as IS of the test medium increased (EC50: 2.9 and 1.1 mg/L). In conformity with the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory we suggest that the precipitation of nano-TiO2 was more pronounced in high than in low IS medium, causing a lower phototoxicity. In summary, primary particle size and IS of the medium were identified as factors influencing phototoxicity of anatase nano-TiO2 to D. magna.

Proteomic analysis of protein carbonylation: a useful tool to unravel nanoparticle toxicity mechanisms.

BACKGROUND: Oxidative stress, a commonly used paradigm to explain nanoparticle (NP)-induced toxicity, results from an imbalance between reactive oxygen species (ROS) generation and detoxification. As one consequence, protein carbonyl levels may become enhanced. Thus, the qualitative and quantitative description of protein carbonylation may be used to characterize how biological systems respond to oxidative stress induced by NPs. METHODS: We investigated a representative panel of 24 NPs including functionalized amorphous silica (6), zirconium dioxide (4), silver (4), titanium dioxide (3), zinc oxide (2), multiwalled carbon nanotubes (3), barium sulfate and boehmite. Surface reactivities of all NPs were studied in a cell-free system by electron spin resonance (ESR). NRK-52E cells were treated with all NPs, analyzed for viability (WST-1 assay) and intracellular ROS production (DCFDA assay). Carbonylated proteins were assessed by 1D and/or 2D immunoblotting and identified by matrix assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF/TOF). In parallel, tissue homogenates from rat lungs intratracheally instilled with silver NPs were studied. RESULTS: Eleven NPs induced elevated levels of carbonylated proteins. This was in good agreement with the surface reactivity of the NPs as obtained by ESR and the reduction in cell viability as assessed by WST-1 assay. By contrast, results obtained by DCFDA assay were deviating. Each NP induced an individual pattern of protein carbonyls on 2D immunoblots. Affected proteins comprised cytoskeletal components, proteins being involved in stress response, or cytoplasmic enzymes of central metabolic pathways such as glycolysis and gluconeogenesis. Furthermore, induction of carbonyls upon silver NP treatment was also verified in rat lung tissue homogenates. CONCLUSIONS: Analysis of protein carbonylation is a versatile and sensitive method to describe NP-induced oxidative stress and, therefore, can be used to identify NPs of concern. Furthermore, detailed information about compromised proteins may aid in classifying NPs according to their mode of action.

Agreement of central site measurements and land use regression modeled oxidative potential of PM2.5 with personal exposure.

Oxidative potential (OP) of ambient particulate matter (PM) has been suggested as a health-relevant exposure metric. In order to use OP for exposure assessment, information is needed about how well central site OP measurements and modeled average OP at the home address reflect temporal and spatial variation of personal OP. We collected 96-hour personal, home outdoor and indoor PM2.5 samples from 15 volunteers living either at traffic, urban or regional background locations in Utrecht, the Netherlands. OP was also measured at one central reference site to account for temporal variations. OP was assessed using electron spin resonance (OP(ESR)) and dithiothreitol (OP(DTT)). Spatial variation of average OP at the home address was modeled using land use regression (LUR) models. For both OP(ESR) and OP(DTT), temporal correlations of central site measurements with home outdoor measurements were high (R>0.75), and moderate to high (R=0.49-0.70) with personal measurements. The LUR model predictions for OP correlated significantly with the home outdoor concentrations for OP(DTT) and OP(ESR) (R=0.65 and 0.62, respectively). LUR model predictions were moderately correlated with personal OP(DTT) measurements (R=0.50). Adjustment for indoor sources, such as vacuum cleaning and absence of fume-hood, improved the temporal and spatial agreement with measured personal exposure for OP(ESR). OP(DTT) was not associated with any indoor sources. Our study results support the use of central site OP for exposure assessment of epidemiological studies focusing on short-term health effects.

Mobility of coated and uncoated TiO2 nanomaterials in soil columns--Applicability of the tests methods of OECD TG 312 and 106 for nanomaterials.

Nanomaterials are commonly used in everyday life products and during their life cycle they can be released into the environment. Soils and sediments are estimated as significant sinks for those nanomaterials. To investigate and assess the behaviour of nanomaterials in soils and sediments standardized test methods are needed. In this study the applicability of two existing international standardized test guidelines for the testing of nanomaterials, OECD TG 106 "Adsorption/Desorption using a Bath Equilibrium Method" and the OECD TG 312 "Leaching in Soil Columns", were investigated. For the study one coated and two uncoated TiO2 nanomaterials were used, respectively. The results indicate that the OECD TG 106 is not applicable for nanomaterials. However, the test method according to OECD TG 312 was found to be applicable if nano-specific adaptations are applied. The mobility investigations of the OECD TG 312 indicated a material-dependent mobility of the nanomaterials, which in some cases may lead to an accumulation in the upper soil layers. Whereas no significant transport was observed for the uncoated materials for the double-coated material (coating with dimethicone and aluminiumoxide) a significant transport was detected and attributed to the coating.

Oxidative potential of particulate matter at a German motorway.

Ambient particulate matter (PM10) was sampled alongside a motorway in North-Rhine Westphalia, Germany, during a one-year period. In sum, 120 PM10 samples on quartz fibre filters, 60 samples at each side of the motorway, were taken during clear cross-wind direction situations, i.e. upwind (local background situation) and downwind (traffic influenced). To quantify the traffic-related oxidative potential (OP), or more precisely the hydroxyl radical (OH˙) generation potency, these samples were analysed to study their hydrogen peroxide dependent oxidant generation by Electron Paramagnetic Resonance (EPR) spectroscopy using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide. In addition the PM10 mass, the chemical composition and the NOx concentrations were determined. For PM10 mass and traffic tracers like Sb, Ba, elemental and organic carbon as well as for NOx, an additional contribution to the background concentration caused by the traffic was observed (factor: 1.3-6.0). The downwind measurements showed in 72% of cases higher OH˙ generation potencies with an average factor of 1.4. Significant correlations to OH˙ were detected for Fe (r > 0.58) and Cu (r > 0.57) for the upwind and overall (upwind + downwind, r > 0.44) dataset. At the downwind side these correlations were absent and are assumed to be covered by the interferences with additional soot particles leading to a quenching of OH˙. Accordingly, no significant overall correlation of the OH˙ generation potency with the traffic intensity was detected. The suggested quenching effect was confirmed via standard diesel soot (SRM 2975) measurements using the EPR approach. In summary, the traffic related PM causes an intrinsic OH˙ generation via Fenton-like reaction but obviously also leads to interferences and scavenging by traffic related carbonaceous compounds. In consequence, for future studies that would link the intrinsic OP and adverse health effects we suggest to analyse the relationship to EC/OC and to use in parallel also a further OP detection method.

Associations between three specific a-cellular measures of the oxidative potential of particulate matter and markers of acute airway and nasal inflammation in healthy volunteers.

INTRODUCTION: We evaluated associations between three a-cellular measures of the oxidative potential (OP) of particulate matter (PM) and acute health effects. METHODS: We exposed 31 volunteers for 5 h to ambient air pollution at five locations: an underground train station, two traffic sites, a farm and an urban background site. Each volunteer visited at least three sites. We conducted health measurements before exposure, 2 h after exposure and the next morning. We measured air pollution on site and characterised the OP of PM2.5 and PM10 using three a-cellular assays; dithiotreitol (OP(DTT)), electron spin resonance (OP(ESR)) and ascorbic acid depletion (OP(AA)). RESULTS: In single-pollutant models, all measures of OP were significantly associated with increases in fractional exhaled nitric oxide and increases in interleukin-6 in nasal lavage 2 h after exposure. These OP associations remained significant after adjustment for co-pollutants when only the four outdoor sites were included, but lost significance when measurements at the underground site were included. Other health end points including lung function and vascular inflammatory and coagulation parameters in blood were not consistently associated with OP. CONCLUSIONS: We found significant associations between three a-cellular measures of OP of PM and markers of airway and nasal inflammation. However, consistency of these effects in two-pollutant models depended on how measurements at the underground site were considered. Lung function and vascular inflammatory and coagulation parameters in blood were not consistently associated with OP. Our study, therefore, provides limited support for a role of OP in predicting acute health effects of PM in healthy young adults.

A multicentre study of air pollution exposure and childhood asthma prevalence: the ESCAPE project.

The aim of this study was to determine the effect of six traffic-related air pollution metrics (nitrogen dioxide, nitrogen oxides, particulate matter with an aerodynamic diameter <10 µm (PM10), PM2.5, coarse particulate matter and PM2.5 absorbance) on childhood asthma and wheeze prevalence in five European birth cohorts: MAAS (England, UK), BAMSE (Sweden), PIAMA (the Netherlands), GINI and LISA (both Germany, divided into north and south areas). Land-use regression models were developed for each study area and used to estimate outdoor air pollution exposure at the home address of each child. Information on asthma and current wheeze prevalence at the ages of 4-5 and 8-10 years was collected using validated questionnaires. Multiple logistic regression was used to analyse the association between pollutant exposure and asthma within each cohort. Random-effects meta-analyses were used to combine effect estimates from individual cohorts. The meta-analyses showed no significant association between asthma prevalence and air pollution exposure (e.g. adjusted OR (95%CI) for asthma at age 8-10 years and exposure at the birth address (n=10377): 1.10 (0.81-1.49) per 10 µg · m(-3) nitrogen dioxide; 0.88 (0.63-1.24) per 10 µg · m(-3) PM10; 1.23 (0.78-1.95) per 5 µg · m(-3) PM2.5). This result was consistently found in initial crude models, adjusted models and further sensitivity analyses. This study found no significant association between air pollution exposure and childhood asthma prevalence in five European birth cohorts.

Elemental composition of particulate matter and the association with lung function.

BACKGROUND: Negative effects of long-term exposure to particulate matter (PM) on lung function have been shown repeatedly. Spatial differences in the composition and toxicity of PM may explain differences in observed effect sizes between studies. METHODS: We conducted a multicenter study in 5 European birth cohorts-BAMSE (Sweden), GINIplus and LISAplus (Germany), MAAS (United Kingdom), and PIAMA (The Netherlands)-for which lung function measurements were available for study subjects at the age of 6 or 8 years. Individual annual average residential exposure to copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc within PM smaller than 2.5 µm (PM2.5) and smaller than 10 µm (PM10) was estimated using land-use regression models. Associations between air pollution and lung function were analyzed by linear regression within cohorts, adjusting for potential confounders, and then combined by random effects meta-analysis. RESULTS: We observed small reductions in forced expiratory volume in the first second, forced vital capacity, and peak expiratory flow related to exposure to most elemental pollutants, with the most substantial negative associations found for nickel and sulfur. PM10 nickel and PM10 sulfur were associated with decreases in forced expiratory volume in the first second of 1.6% (95% confidence interval = 0.4% to 2.7%) and 2.3% (-0.1% to 4.6%) per increase in exposure of 2 and 200 ng/m, respectively. Associations remained after adjusting for PM mass. However, associations with these elements were not evident in all cohorts, and heterogeneity of associations with exposure to various components was larger than for exposure to PM mass. CONCLUSIONS: Although we detected small adverse effects on lung function associated with annual average levels of some of the evaluated elements (particularly nickel and sulfur), lower lung function was more consistently associated with increased PM mass.