Multi-level approaCh to the study of exposure to nanoparticles.

Background and aims Exposure to nanoaerosols (particles with diameter below 100 nm) is an important topic in epidemiological and toxicological studies and is deemed to be a major risk affecting human health, both for general population (exposed to “ultrafine particles” - UFP) and for workers (involved in the production or application of manufactured nanomaterials -MNM- and nanoparticles - NP). In fact, high concentrations of airborne nano-sized particles are associated with increased pulmonary and cardiovascular mortality. Further, recent studies assesse that UFP and NP can reach the deeper region of the respiratory system and overcome the alveolar barrier and enter the bloodstream, contributing to increased risk of cancer, thrombosis, and cardiovascular diseases. An increasing number of studies are indicating that the health risk deriving from exposure to airborne nanoaerosols is not adequately addressed by conventional exposure evaluation methods and strategies capable of measuring exposure against these attributes. In fact, in recent years, society has become increasingly sensitive to individual risks, and thus data on the exposure needs to be personalized. Therefore, airborne particle studies were performed in the recent years to identify the main UFP and NP sources and to characterize population exposure. In this regard, personal monitoring is considered as the only way to obtain accurate exposure data, which are critical to further reduce exposure misclassification in epidemiological studies. The drawback of such method, however, is the high cost of implementation and the associated small number of observations that tends to produce sample biases. For this reason, personal monitoring is often used as a complement in exposure models to assess air pollution exposures in health studies. These models use personal or household exposure monitoring, and appear well-suited to overcome the problem of achieving population representative samples while understanding the role of exposure variation at the individual level. The monitoring and characterization techniques discussed in this thesis aims to evaluate nanoaerosols exposure in terms of mass, surface-area and/or number concentration. These methods were developed and used to exposure characterization both in environmental and occupational settings. The goal of this PhD project is firstly to perform an exposure assessment of UFP using innovative techniques and strategies. Secondly, it will be shown that microenvironmental models are effective tool, capable to model exposure to UFP in populations and sub populations. Finally, newly developed strategies and techniques are applied in occupational settings, in order to perform an occupational exposure assessment for workers involved in the production or application of MNM and NP. Materials and methods Exposure to airborne pollutants can be determined using indirect exposure models or through a direct approach (i.e. air quality measurements). In this study, UFP concentrations in different urban microenvironments (ME) were firstly measured by personal monitoring in repeated sampling campaigns, along fixed routes in two Italian cities, in order to measure personal exposure in transport MEs. Measurements followed a multi-parametric and multi-metric approach, including on-line monitoring of UFP Particle Number Concentration (PNC), mean diameter (mean d) and lung-deposited surface area (LDSA). Secondly, average daily UFP exposure of adult Milan subpopulations (defined on the basis of gender and then for age, employment or educational status), in different exposure scenarios (typical working day in summer and winter) were simulated using a microenvironmental stochastic simulation model. The basic concept of this kind of model is that time-weighted average exposure is defined as the sum of partial microenvironmental exposures, which are determined by the product of UFP concentration and time spent in each microenvironment. Furthermore, this thesis describes the development of an instrumental approach for measurement of NP exposures in occupational settings, which takes into account the major potential route of exposure and factors that may influence biological activity and potential toxicity of nanomaterials and incorporates a risk management approach: different methods were used to measure and assess occupational exposures to engineered nanoparticles (NP) with a multi-parametric approach: the first method involved off-line gravimetric analysis of filter samples collected with Low Pressure Impactor. The second method used different, hand-held, direct-reading instruments to obtain a time series of particle number concentrations (PNC), mean diameter and surface-area concentration for NP. Results and conclusions This thesis provides important insights into UFP exposure in urban environments, that should be considered in developing additional and larger studies on population’s exposure. First, continuous real-time monitoring provided the information necessary to define the influence of local sources or changes in local circumstances on UFP concentrations. In addition, continuous monitoring allowed for the evaluation of short-term particle concentrations and demonstrated temporal and spatial variability for the studied urban microenvironments. Further, the simulation model, used to estimate the average daily UFP exposure of adult subpopulations in a major Italian urban area and in different exposure scenarios, have defined that demographic and socio-demographic factors (e.g., gender, age, profession, instruction level), as well as environmental patterns, have to be considered as major determinants of pollutant exposure in urban environments. Furthermore, this research detected UFP levels and average particle sizes and their seasonal variability, as well as comprehensive information on average particle number and mass concentrations, sizes and surface area in various microenvironments within urban areas, which is fundamental to evaluate the variability of human exposure in urban environments and to support the relevance of traffic-related exposure for health. Thus, findings derived from this study may represent an important tool in the definition of health and social implication of UFP exposure for general population and to provide complete and accurate exposure assessment data for risk assessors, including exposure metrics, mostly relevant as health effects indicators. Finally, regarding occupational settings, this study defined an experimental protocol, which was intended to be useful in determining potential exposure to engineered nanomaterials and nanoparticles in the workplace with complementary approaches. These information may also be used to determine whether engineering controls are effective in preventing release of the engineered nanomaterials to the workplace atmosphere.