Physiological effects on humans when exposed to nanometer sized airborne particles in well controlled chamber studies Mats Bohgard1*, Jörn Nielsen2, Inger Hagerman3, Katrin Dierschke2, Christina Isaxon1, Ulla B.K. Andersson2, Eva Assarsson2, Margareta Berglund3, Anders Gudmundsson1, Bo A. Jönsson2, Joakim Pagels1, Aneta Wierzbicka1 1 Ergonomics and Aerosol Technology, Lund University, Sweden Occupational and Environmental Medicine, Lund University, Sweden 3 Department of Cardiology, Karolinska University Hospital, Huddinge, Sweden 2 * Corresponding email: Mats.Bohgard@design.lth.se Keywords: nano particles, aerosols, physiological effects, heart rate variability 1 Introduction There is an increasing concern about airborne nano sized particles (ultra fine particles) in indoor environments. Epidemiological studies show relations between exposure to airborne particles and morbidity/mortality in respiratory and cardiovascular diseases (Brook et al., 2004; Brown et al., 2000; Donaldson et al., 1998; Ibfelt et al., 2010) There is a need for experimental studies to get a better understanding of which particle characteristics are important for health effects and of the mechanisms behind these effects. The objective of this study was to develop a method for human exposure studies and apply the method to studies on how nanometer sized particles affect physiological parameters. We have performed studies on human exposure to nanometer sized particles. Prior to the exposure study, particles from burning candles, welding and particles produced by terpene ozone reactions were characterized (Pagels et al. 2008; Isaxon et al., 2009; Wierzbicka et al. 2008). 2 Materials/Methods Test subjects (3 at the time) were exposed in a 20 m3 chamber. In a series of experiments, 22 healthy females were exposed to candle smoke, terpene-ozone generated particles and clean air according to a double blind protocol. In another series of experiments 32 males (21 welders and 11 reference persons) were exposed to welding fume and clean air. Mean concentrations were 907 000 particles/cm3 (200 μg/m3) for candle smoke, 30 000 particles/cm3 (70 μg/m3) for ozone-terpene generated particles and 67 000 particles/cm3 (1000 μg/m3) for welding fume. Exposure times were 3 hours for candle and ozone-terpene particles and 6 hours for welding smoke. Prior to the provocations, test subjects undergo a physical examination including heart and lung status and atopy prick-test. Medical and work history is registered. Before and after exposure, samples of venous blood, urine, breath condensate and nasal lavage are taken for analysis of biochemical markers (oxidative stress and inflammation). The lung function and nasal patency are measured by spirometry and acoustic rhinometry. A venous blood sample is obtained before, after, and 24 hours after the provocation for analysis of biochemical markers of inflammation and oxidative stress. Symptoms from airways are registered according to a symptom score model. Heart Rate Variability (HRV) was registered in periods of ten minutes before and during the provocation (HRV, 1996). Changes in HRV have shown to be related to risk of cardiovascular disease. 3 Results Changes in perceived symptoms were reported depending on the different exposures. However significant relations between exposure and symptoms and results from rhinometry and spirometry could not be observed. The biochemical markers analysed so far, do not show any significant differences for healthy subjects between exposure to clean air and the high concentrations of nano–sized particles. Heart rate was unchanged in all groups during all exposures. There were no impacts on HRV of repeated visits in the chamber. However, exposure to nano sized particles of burning candles and welding influenced HRV. Significant changes for some, but not all, spectral bands were observed. Exposure to ozone-terpene particles had no significant effect neither on HRV, nor on inflammatory markers analysed so far. 4 Conclusions The developed methodology enables quantitative determination of physiological responses in terms of effects on HRV which can be related to exposures. The method may be used to get early risk warnings on physiological effects. This study was financed by The Swedish Research Council FORMAS and performed within the framework of Metalund, the Centre for Medicine and Technology for Working Life and Society, a competence centre at Lund University, Sweden, supported by FAS, the Swedish Council for Working Life and Social Research. 5 References Brook R.D., Franklin B., Cascio W., Hong Y.L., Howard G., Lipsett M., Luepker R., Mittleman M., Samet J., Smith S.C. & Tager I. 2004. Air pollution and cardiovascular disease - A statement for healthcare professionals from the expert panel on population and prevention science of the American Heart Association. Circulation 109, 2655-2671. Brown D.M., Stone V., Findlay P., MacNee W. & Donaldson K. 2000 Increased inflammation and intracellular calcium caused by ultrafine carbon black is independent of transition metals or other soluble components. Occupational and Environmental Medicine 57, 685-691. Donaldson K., Li X.Y. & MacNee W. 1998. Ultrafine (nanometre) particle mediated lung injury. Journal of Aerosol Science 29, 553-56. Heart Rate Variability. Standards of Measurement, Physiological Interpretation and Clinical Use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. 1996. Circulation 93:1043-1065. Ibfelt, E., Bonde, J.P., Hansen, J. 2010. Exposure to metal welding fume particles and risk for cardiovascular disease in Denmark: a prospective cohort study. Occup Environ Med 67,772-777 Isaxon, C. ; Pagels, J. Gudmundsson, A. Asbach, C. and Bohgard, M. 2009. Characteristics of Welding Fume Aerosol Investigated in Three Swedish Workshops, Proc. of 10th International Symposium on Inhaled Particles, Sheffield, England. Pagels J., Wierzbicka A., Nilsson E., Isaxon C., Dahl A., Gudmundsson A., Swietlicki E., Bohgard M., 2008. Chemical Composition and Mass Emission Factors of different Particle types present in Candle Smoke, Journal of Aerosol Science, 40,193-208.. Wierzbicka A., 2008. What are the characteristics of airborne particles that we are exposed to? – Focus on Indoor Environments and Emissions from Biomass Fires District Heating, Doctoral thesis Lund University, Sweden.