Plenary Workshop of the UK Natural Dust & Health Network Meeting Notes Key to notes Q Question A Answer S Statement Please refer to list of delegates for expertise of discussion participants Setting the scene Talks: 1. Claire Horwell – Mineralogy and Volcanology. Key Points: Objectives of field: i. To use mineralogy and geochemistry to make rapid assessments of the potential health hazard of natural mineral particles (NMPs) ii. To understand why a mineral or dust may trigger a pathogenic respiratory response. Questions that mineralogy can answer: i. Is the dust small enough to enter the lung? ii. What is the composition of the dust? iii. Is shape relevant (e.g. fibrous)? iv. Is the surface of the dust reactive? v. Are individual particles ‘pure’? vi. Is the crystalline structure relevant? Answers: i. Grain size: for volcanoes, quantity of respirable (<4 um) fraction varies from 0-17%. ii. Composition: Techniques such as SEM-EDS allow characterisation of composition of individual particles. iii. Shape: Also done by techniques such as SEM but can automate process with image analysis. iv. Reactivity: Volcanic silica appears not to generate silica surface radicals but does generate hydroxyl radicals through the Fenton Reaction – ash is rich in reduced iron – unusual for crustal dusts. Ash types containing more iron generate more radicals. v. Purity: Crystalline silica in ash may be modified by more inert minerals by: 1. surface occlusion by glass 2. intergrowth of silica with other minerals 3. substitution of Si from atomic structure by Al & Na. We have confirmed 2 & 3. Work commencing on 1. in 2008. vi. Structure: we have found both alpha and beta cristobalite – may have toxicological relevance. 2. Ken Donaldson – The Toxicology of NMP Key Points: What diseases do particles cause or worsen? Table of different parts of lung with lung site, disease, setting (Occ/Env) and exemplar particles such as coalmine dusts. Exposure effects based on the occupational paradigm: o People exposed to high doses (mg/m3) in peaks followed by zero exposure in the workplace. o Particles: silica, asbestos, welding fume, nuisance dusts o Healthy worker effect – ill people leave. Predominantly healthy males < 65 years old. o Responses: Pneumoconiosis, COPD, cancer, asthma. Exposure effects based on environmental paradigm (PM10) o Exposure very low (tens of ug/m3) – constant with peaks. o Exposure to urban PM10, containing combustion–derived particles. o Everyone exposed but only susceptible, e.g. aged and ill, affected. o Responses: COPD and asthma and exacerbation of cardiovascular disease and cancer. NMPs don’t necessarily fit in with either of the environmental or occupational paradigms. Factors contributing to toxic response: concentration and length of exposure contribute to dose. Intrinsic toxicity important too. General scheme of what happens in the lung with harmful particles: if clearance of particles doesn’t occur, may result in inflammation, oxidative damage, tissue injury and then disease. Biologically effective dose (BED) important. We are poor at measuring BED metrics – different metrics used for different particles. Table showing particle, BED and current metric. Move to have BED as metric rather than mass. Inflammation plays a central role for occupational particles, leading to different disease outcomes depending on the part of the lung which is affected. Inflammation also important for environmental particles too. Oxidative stress – particles intrinsically have the ability to cause oxidative stress which then causes inflammation. Testing approaches: depends on aim (screening, mechanisms, regulatory) o Characterising the physico/chemistry - structure:activity paradigm (mineralogy integration – see Horwell’s presentation). o In vitro (cell-free) e.g. surface reactivity (see Horwell’s presentation) o In vitro (cells) – endpoints must be pathophysiologically relevant. o In vivo assessment. Example of inhalation study with NMP: IOM/Edinburgh Soufrière Hills in vivo study. Importance of using controls to contextualise response e.g. TiO2. Need to compare it with coal mine dust and quartz. Summing up. o Some natural dusts are also occupational dusts e.g. coalmine, asbestos. Do we need to treat them separately? o Do environmental exposures cause disease? o How may people at risk? If not substantial then unlikely to get funding. Need to know documented burden of ill health. Q: Ben Williamson: Should we study dust which is extremely fresh as this is what people are exposed to? A: Ken Donaldson: Quartz ages rapidly over a few hours so most people exposed to aged particles. A: Bice Fubini: Mechanisms of formation of fresh particulates might be similar with different NMPs and combustion particles. Also volcanic particles are similarly formed to rock blasting Q: Mike Moore: Coastal areas have sea water droplets – viral soup – probably in aerosol at nano size. Will they interact with NMPs and coat them which might change reaction? A: Ross Anderson: No epidemiological information to show that seaside areas have higher incidence of disease. A: Ken Donaldson: Concentrated Edinburgh air (high salt) showed no effects. A: Jon Ayres: Coastal asthma known A: Ross Anderson: Hard to study as would need so many data to untangle individual effects of constituents – would run out of statistical power. 3. Peter Baxter – Health effects of coarse airborne particles (2.5-10um) Key Points: Crustal particles – volcanic ash, soil-derived in urban air, dust storms and wind-blown ash (Review Refs: Horwell & Baxter, Bull. Volcanol. 2006; Brunekreef & Forsberg, Eur Respir J, 2005). Review of Mt St Helens eruption, USA, May 1980: loggers had greatest exposure. Confusion over silica content. Acute respiratory effects observed. Review of Soufrière Hills eruption, Montserrat, 1995-present. Unprecedented exposure to volcanic particulate matter. Summary of studies done: Asthma studies in school children, 1998 & 2008 Cristobalite hazard quantified in 1999 & 2003 papers Cumulative exposure assessment 1996-2000 Toxicological studies by different UK labs. Silicosis risk quantified. Chest Xray and lung function studies done in adults and children. Factors affecting lung toxicity of silica particles (covered by Horwell & Donaldson’s presentations) Health hazards of volcanic ash review summary (Horwell & Baxter 2006) Few epidemiological or clinical studies around the world Mostly poor characterisation of ash samples Inadequate exposure information Only MSH & SHV have had detailed studies Variable results but asthma outbreak seen at Cerro Negro, Nicaragua, 1992. Effects of coarse PM on short-term mortality. Cardiovascular disease seen in US (nonvolcanic studies). Effects of coarse PM on long-term mortality. Six studies found effect for fine fraction. Effects of coarse PM on short-term morbidity. In several studies, coarse fraction is a better predictor than fine fraction for daily numbers of respiratory admissions. Effects of dust storms and wind blown dust: no consistent findings. Summary – is volcanic ash a model for crustal particle toxicity? But many different forms of NMPs. COMEAP report was based on PM2.5 and may be influenced by cofactors such as sulphate. 4. Anthony Seaton – NMPs: risks and their controls Key Points: General rules for reduction of risk from inhaled substances: Good information for exposed public, Total avoidance of exposure (substitution of materials or evacuation), Exposure reduction – limiting duration, reduce activities, personal protection. Then audit for effectiveness of measures. What are the health effects of oil shale exploration? Seaton did study. Am J Indust Med, 1986, 9, 409. In order to prevent disease you don’t need to know the cause of disease. Coal diseases affected by several factors such as smoking and the coal rank. Air quality standards and guidelines: Problems with: Different dust compositions, some of which are mixed dust. Difficulty of regulation, monitoring and compliance Lack of epidemiology. Would be possible to publish a management strategy based on analogous mineralogical, epidemiological and toxicological evidence – done on Montserrat. Main Group Discussion Output – a document highlighting main areas for future research in the area. Q: Peter Baxter Can we use volcanological particles as a model transferable to other NMPs and maybe urban air pollution? A: Bill Rose Volcanological particles are affected by distance from volcano and size. He is looking at ‘total size distribution’ – linked to mechanism of formation e.g. milling in pyroclastic flows. Mature particles (that don’t fall out from an ash cloud immediately) fall into different classes: Particles with fresh, new surfaces > 5um. Sulphates < 0.5 um diameter, liquid droplets formed during eruption. ~ 1um class – elemental particles (some soluble, e.g. halides, sulphates, metals (akin to fumarole environment)). Diverse with each volcano having a different signature e.g. vanadium, thallium, rhenium, copper, molibdinum, lead, tungsten. Can be modelled thermodynamically. Source is subducted oceanic slab and subsequent interaction of wet slab with mantle as slab melts. Metals and acids may coat larger particles. Hydroxyl radicals seen in plume from Hekla volcano (Iceland) – may be formed in eruption and then frozen or form in stratosphere with iron interaction and H2O2 found in atmosphere. Plume transforms with time. (Rose et al, 20061) Q: Ben Williamson Could charging affect radical formation and aggregation from electrical storms in plume? S: John Ayres Charging also affects deposition in the lung. A: question not answered but general agreement that mechanism potentially possible. S: Steve Smith In relation to Bill Rose’s statement re. different fractions: There are parallels with urban size distributions and reactions e.g. aqueous environments. Fractions known as: Nucleation mode, accumulation mode and coarse (>2.5 um) mode. S: Bill Rose By the time one samples in an aircraft, often several hours after eruption so distribution skewed to fine mode. Also, silicate mode is dominant early on in the clouds, then other modes stand out later on. Q: Bice Fubini Temperature formation may be important - ash generated is hot – is there a parallel to incinerators? A: Bill Rose There may be a parallel with forest fires - also creates stratospheric cloud with ice nuclei. S: Bice Fubini Surface of the particle would be different because silica crushed is very fresh. Q: Bill Rose Could we do lab work which shows newly created ash surfaces and simulate reactions between particles e.g. explosive vesiculation (experiments could be done on dome rock at Prof. Don Dingwell’s labs in Munich). Might produce different results from grinding (e.g. work published in Horwell et al. 20032). Q: Anthony Seaton How are stratospheric interactions (e.g. those observed in Rose et al. (20061) appropriate to human health exposure? A: Bill Rose We may not have many other choices but to look at stratospheric interactions. It is hard to collect particles, especially as volcanologists usually collect samples close to volcanoes, and distally may be low concentration. The idea of using aircraft is also hard as can damage engines so hard to set up experiments. Observations of Hekla plume happened by mistake. Heavy exposure does occur distally at ground level, e.g. E. Washington following Mt St Helens eruption, 1980. Q: Peter Baxter Montserrat and Mt St Helens ash not as toxic expected. Were the right samples used? S: Claire Horwell Variety of samples, standards and techniques used. Montserrat results much more constrained. Toxicology results for Mt St Helens varied from very toxic to non-toxic so results not clear. S: Jon Ayres Aged dust vs fresh dust - hard to compare in toxicology studies as using stored dusts, which have aged, are not reproducible. S: John Cherrie Difficulty with samples – airborne collected vs. bulk samples. S: Pierre Delmelle There are high temperature experiments of ash generation and surface reactivity. Even exposing ash to water affects results. Surface area is fairly low compared with other crustal dusts containing clay minerals. Also, processes in a volcanic plume are extremely different to wind blown crustal dust, particularly due to temperatures of eruption. S: Augusto Neri We should distinguish between the source of the ash (plume) from the ash cloud. Plume is complex – multi-phase mixture – v. hard to model. Ash cloud is less complex – gravity and interaction of particles. Q: Anna Hansell As an epidemiologist, how can we simplify all the characteristics of particles for use by medics? Can we use remote sensing to sample instead of trying to collect particles? A: Rod Jones May need a new level of instrumentation to address the impurity levels in ash. S: Bill Rose We already use quartz crystal micro cascade impactors – used in a plume or cloud if you can get instrument into the cloud. Measures particles by size, measures them in situ. S: Anthony Seaton Epidemiologists use simple instruments (elutriator which mimics collection ability of human lung and measures mass). Reminding us that we need to relate this to health. What is needed is an instrument that samples biological relevant fraction with free radical generation, for example. Sample its effect rather than what it’s made of. S: Bice Fubini You do need to know what it’s made of otherwise you can’t compare different samples. Need controls too. This could build up to producing a predictive model for the toxicity of ash. Q: Peter Baxter How does this relate to desert dust? A: Ed Derbyshire Glacial system grinds rock. Other processes, frost shatter and salt crystal growth (paleolakes) – extend over a wide range of environments. Finer than sand, the population is carried in suspension. Silt and clay grade particles are angular (except biogenic silica, diatoms). Glacier outwash dries out and particles are then lofted in winds and travel 1000s km. Exposure to desert dust is a frequent chronic event, affecting high density rural populations. Deposits show low density packing on settlement (high void ratio) especially after landslide. Dust storms can be triggered by ploughing (machine). We also compact surfaces and reduce vulnerability of resuspension by wind action. Clay grade quartz frequently found. Q: Ben Williamson What epidemiological data are there for desert regions? Have people built up genetic resistance which wouldn’t exist with climate change (dryland advance posing new threat)? A: Ed Derbyshire Limited literature. Most in N. China. A: Jon Ayres There are several studies done on villagers in Ladakh (Northern India) where there are no sources of industrial pollution but frequent desert dust storms. Need for systematic review of the literature. A: Claire Horwell In Ladakh, there is pneumoconiosis which must be due to the dust storms. S: Ed Derbyshire Acute effects are important too: dust storms from Sahara for 9-10 days – needs formal quantification of acute effects. Derbyshire is getting together a team for a pilot study on Canary Islands. Evidence that hospital admissions for respiratory disorders coincide with dust storms. Mineralogy varies enormously with different sources too. Q: Pierre Delmelle Spain Saharan impact – has anyone compared urban vs. desert dust impact? A: Ed Derbyshire There are single studies along Mediterranean. (CHECK) We are still observing now but there are no good datasets. In W Med, 83 % by wet sedimentation and lower elsewhere. S/Q: Peter Baxter Move discussion on to coarse fraction in urban air pollution – what is it composed of? A: Ross Anderson Methodological issue. Time series studies based on exposure assessment over 24 hrs by urban monitor – taken as exposure for a city on a certain day. PM2.5 is homogeneously distributed in a city but there is greater variation in spatial distribution of coarse fraction. In Birmingham, on windy days, PM2.5 levels decrease but coarse fraction goes up. Very different behaviour of two components presents epidemiological challenge as never focused just on coarse fraction. A meta-analysis of relationship between coarse fraction and mortality does show significant associations. Problems because of low signal to noise ratio. Also, very dependent on decent exposure estimates as we currently have little idea of what the population exposure actually is. Q: Ross Anderson Is there a role for analysing autopsy lungs rather than trying to collect particles from atmosphere to see what people have been exposed to? A: Peter Baxter Autopsies can also be done on grazing animals. A: Anthony Seaton Hard to do autopsy studies as not many post mortems done on normal people. A: Ben Williamson Autopsies only tells us part of the story as particles may be cleared after inducing acute disease. S: Ross Anderson A large amount of coarse fraction is now brake or tyre wear so not crustal. Complicates the issue. S: Johan Ovrevik Most reports show that coarse fraction more potent (cell cultures) which goes against epidemiology. S: Johan Ovrevik Endotoxin may also have an effect – seen on road dusts. Well documented heterogeneity in personal response which may be linked to susceptibility. S: Ken Donaldson We don’t know whether endotoxin on particles in air or grew during storage of particles in lab. S: Johan Ovrevik Very few studies measuring endotoxin in outdoor air. S: Jon Ayres Animal dung stuffed with endotoxin and also found in cigarette smoke. May well have differential toxicity as many different forms of endotoxin. S: Anthony Seaton Farmer’s lung from bacteria in fields. Also, greatest exposure is indoor at home. S: Ken Donaldson Effects of pollen and spores are substantial. (paper mentioned – CHECK) S: Ross Anderson Mould spores more important as smaller. S: Peter Baxter Wind storms also full of biological material S: Ed Derbyshire Desert dusts transport: virus, funghi and bacteria – travelling intercontinentally – Dale Griffin review (CHECK). Q: Rod Jones Why is animal response different from human response? A: Jon Ayres Animals breath through nose whereas we breath through mouth. A: Mike Moore Paper in Science showing that many bacteria spend part of their life cycle in atmosphere (CHECK paper) - so bacteria will be mixed up with dusts S: Ross Anderson There was a workshop last year in Bonn convened by WHO which addressed differential toxicity of particles by source, size and chemistry. Concluded that for all particles in PM10 fraction there is evidence for health effects regardless of size, composition and source but not enough evidence to quantify differential toxicity.(CHECK report – on web). Has recommendations. S: John Cherrie Sources – environmental exposure to quarries or open cast mining. S/Q: Peter Baxter Move on to discussing how well we can screen particles for toxicity for biological activity, asthma response linked to surface properties, oxidative potential or cell tests. How close are we to being able to take a sample, and get useful information leading to further studies? S: Jon Ayres EPSRC nanogroup – proceedings address this topic for ultrafines in Inhalation Toxicology. CHECK A: Frank Kelly Coarse particles from urban environments contain same or more oxidative potential than fine particles on a mass basis. Shown in Dutch studies and London studies (CHECK). There is little difference between oxidative capacity of coarse and fine particles with lung lining cells. Thereafter, with interaction with lung cells – lots of inflammation. So toxicologists sitting on the fence as to whether coarse or fine fractions most important. Believes it is transition metals that are causing particles to oxidise. Biological endpoints are starting to fit with health responses that are seen. Urban research could be very informative for NMPs A: Jon Ayres There is not one screening test A: Frank Kelly Need to compare methods directly and then choose cheapest if they show the same thing. A: John Cherrie We need a good formal systematic review of published literature in order to move the field forward. We should recommend that approach. Then can identify messages. Underwhelmed by health impact from what he’s heard. Biological/toxicology evidence is good but epidemiology evidence is thin. S/Q: Peter Baxter Moving discussion on, are there developments with exposure assessment? A: Ross Anderson Has to go hand in hand with exposure investigations. From a health impact point of view, he thinks necessary – World Bank done modelling exercise to model global exposure to PM10 and PM2.5 (CHECK). May be possible to do that for coarse fraction. Once you have a handle on trends in population exposure then you can integrate better with toxicology results which become more meaningful. NERC Strategy Talk by Mike Moore for Roy Harrison Presentations of Breakout Groups giving research priorities following group discussions Presentation Group 1 We should be looking at “Health Impact of Environmental Exposure to Crustal Particles” (instead of ‘NMP’) We recommend systematically assessing the hazard of representative crustal minerals by mineralogical and toxicological assessment of structure/activity relationships Exposure – we need to know more about airborne levels, satellite imaging and modelling Response – we need to know more about health impacts Output – systematic review as first output – driver for direction of strategy for research. First need to define our protocol – what dusts are included? Other group 1 ideas (not in presentation) o Ross Anderson is involved in a group carrying out a review of air pollution studies in Asia – translations being carried out. We may be able to use some of this information. o Claire Horwell’s definition of NMP is where the source of the particle is natural (so includes coal, quarry dust etc). Presentation Group 2 What is the health burden from natural mineral dusts? On basis of what we know – systematic review What is/are the best metrics of exposure? Mass, number, SA Other physical characteristics How best to measure these with ref to epidemiological study What are the mechanisms? Inflammation Oxidative stress Genotoxicity Protein interactions Who is susceptible? Standard suite of particles needed Presentation Group 3 We need to find natural situations where we can explore the 1 um fraction – samples can be collected from Masaya – test samples for oxidative potential. Independent assessment of toxicology literature needed and what papers tell us about crustal particles. Compare with dusts that we know have strong toxic properties. Capacity to respond to environmental episodes. If eruption in Iceland we are only just 1 day downwind. Surface reactivity and properties, relating to toxicological endpoints. Very important unifying theme across whole field of crustal particles. Existing documentation on episodes. Children – NMPs might have very important role and biomass burning too – particles from biomass burning could be tested for oxidative potential. Presentation Group 4 Go get data – lack of information Sampling – what is relevant? Toxicity – what makes a particle toxic? Importance to human health? How big is the problem? Review available literature. Presentation Group 5 4 types of NMP that we should consider: (volcanic, crustal, biogenic and fire) With volcanic – epidemiology, toxicology and characterisation done for MSH & Montserrat Epidemiology may be a priority Characterisation – standard materials and effects of ageing Crustal – need for epidemiological studies and characterisation studies and what about genetics and resistivity? Fire – minerals generated by burning. Group discussion Do we include biomass burning within this group? Group decides it is a big separate issue. Related to combustion. Do we include biogenic dust? Yes. What makes particles toxic? … we need a better understanding of why quartz is toxic. Idea of comparing mixed dusts with standard mixed dusts rather than using single mineral controls. Problem is – maybe mixed dusts just aren’t very toxic because of other minerals. Silica (quartz) is unusual because causes its own disease. ASK BICE FOR CLARIFICATION What about other minerals? Are silicates a vector for transporting iron into the lung? What about transition metals and redox active metals? Iron, zinc, copper, arsenic. Exposure – what should we try to measure? Probably PM10 as we are interested in the coarse (2.5-10 um) fractions. Surface area – perhaps have a standardised methodology but not sure what is best way. Differences between BET and other techniques – we need to know why numbers don’t agree. Mass and number are easiest to measure in the field. Epidemiology – what studies should we do to look at burden of ill health related to crustal particles? Need better exposure measurements Saharan dust would be a good study as know that it happens frequently and if have conviction that acute health effects might occur. School children good to study as can get school set up for study. Canaries well positioned (Las Palmas 7th biggest city in Spain). EU Funding? John Cherrie said new dust monitors which are low cost (in development CHECK). May get money under climate change – desertification. Possibilities in NW China – harder environment but attractive because millions of people and potential population affected is much higher than Saharan exposure. Systematic review – divvy up between the group - decide at 3rd meeting A panel of particles which are well characterised mineralogically and toxicologically. What would it comprise? Samples would need to be respirable – crushed then aerosolised and collected in a high volume aerosol sampler. Come up with an average crust composition for comparison. Iron oxides, iron rich minerals, volcanic glass (dominant phase), plagioclase, hornblende, quartz, cristobalite, clays. French group which has mapped this (Durant CHECK). Upper Pleistocene loess of China is very similar in composition to the average crustal composition (Ed CHECK). Do nanoparticles exist in crustal emissions? The Future Listserv In toxicology, nano is the way forward. Lots of funding available. o Naonrisk (South Ken) natural particles may be included in that study (CHECK) o Rob Martin study used TEM on plume silicates References W. I. Rose, G. A. Millard, T. A. Mather, D. E. Hunton, B. Anderson, C. Oppenheimer, B. F. Thornton, T. M. Gerlach, A. A. Viggiano, Y. Kondo, T. M. Miller and J. O. Ballenthin, J. Geophys. Res., 2006, 111, D20206. C. J. Horwell, I. Fenoglio, K. V. Ragnarsdottir, R. S. J. Sparks and B. Fubini, Environmental Research, 2003, 93, 202-215.