Due to cardiovascular and respiratory diseases, air pollution remains a global issue for the 21st century. There is an urgent need to establish the real impact of Particulate Matter (PM) on human health by including the analysis of sources, size distribution, physico-chemical (P-chem) composition, and toxicological mechanisms. Increasing in vitro data for establishing pathways of toxicity in human cell lines exposed to specific air pollutants from rigorously characterized emission sources, could help to improve scientifically sound approaches in health risk characterizations, which finally may result in regulatory actions potentially more effective to protect public health. The aim of this thesis was to study the in vitro effects of particles emitted from different combustion sources using human lung cells, focusing on the relationship between the PM P-chem attributes and the cellular and molecular pathways that drive the toxicity. In vitro models, representative of the human respiratory system, were used to study the bio-interaction and toxicological effects of particles. Different exhaust particles were compared, with special emphasis on fine and ultrafine Particles (UFPs), namely Diesel exhaust particles (DEPs) from old and new generation vehicles and on particles emitted from the combustion of solid biomass fuels for residential heating. The emissions from vehicles and biomass-propelled stoves, as well as the PM collection, were performed in collaboration with INNOVHUB SSI (Fuels Department), while the P-chem characterization and toxicological studies were carried out in the Department of Earth and Environmental Sciences (DISAT)- POLARIS research centre (Polveri in Ambiente e Rischio per la Salute) and at the Consumer Products Safety Unit of the European Commission's Joint Research Centre. The results of this work show that testing different material sampled in realistic conditions allows evaluating how the toxicity of particles may vary in relation to the source. These data suggest that oxidative stress and inflammatory cytokines releases are crucial events after DEP exposure, which can also lead to vascular endothelial activation. Comparing an old generation diesel vehicle without DPF (Diesel Particulate Filter) and last generation (or “Euro 6”) one during regeneration of DPF, we proved that Euro 6 is less powerful in activating the biological response, and it is characterized by different metal composition and less concentration of Polycyclic Aromatic Hydrocarbons (PAHs) than the old generation engine, although the exhaust emission from Euro 6 during DPF regeneration is characterized by a higher number of nucleation-mode particles. DEP emitted from an old generation diesel vehicle was confirmed as a very hazardous component of the urban PM, even when compared to Combustion derived particles (CDPs) from wood burning. However, the possible consequences on human health from chronic exposure to the wood CDPs should not be excluded. Moreover, the co-exposure effects of Metal Oxide Nanoparticles (NPs), representative of non-exhaust sources, and DEP were also evaluated. The co-exposure with DEP can either reduce the toxicity of NPs or enhance it. This finding indicates that the possible interaction of different hazardous airborne particles and the toxicity deriving from the mixture effects should be evaluated.

L'inquinamento atmosferico rimane un problema globale per il 21 °secolo, in quanto causa di malattie cardiovascolari e respiratorie. È urgente stabilire il reale impatto del particolato (PM) sulla salute umana includendo l'analisi delle fonti, la distribuzione delle dimensioni, la composizione fisico-chimica (P-chem) e i meccanismi tossicologici. L'aumento dei dati in vitro per stabilire i meccanismi di tossicità utilizzando linee cellulari umane esposte a specifici inquinanti atmosferici da fonti di emissione rigorosamente caratterizzate, potrebbe aiutare a validare approcci scientifici nella caratterizzazione dei rischi per la salute, che alla fine possono determinare azioni normative potenzialmente più efficaci per proteggere la salute pubblica. Lo scopo di questa tesi è stato quello di studiare gli effetti in vitro delle particelle emesse da diverse fonti di combustione utilizzando cellule polmonari umane, concentrandosi sulla relazione tra le caratteristiche P-chem del PM e i processi cellulari e molecolari che inducono la tossicità. Sono stati utilizzati modelli in vitro rappresentativi del sistema respiratorio umano per studiare la bio-interazione e gli effetti tossicologici delle particelle. Sono state confrontate diverse particelle derivate da combustione, con particolare attenzione alle particelle fini e ultrafini (UFPs), ovvero le particelle emesse allo scarico di veicoli di vecchia e nuova generazione diesel (DEP) e alle particelle emesse dalla combustione di biomassa solida per il riscaldamento residenziale. Le emissioni dei veicoli e delle stufe a biomasse, così come la raccolta del PM, sono state eseguite in collaborazione con INNOVHUB SSI (Area Combustibili), mentre la caratterizzazione P-chem e gli studi tossicologici sono stati effettuati presso il Dipartimento di Scienze della Terra e dell'Ambiente (DISAT) - Centro di ricerca POLARIS (Polveri in Ambiente e Rischio per la Salute) e presso l'Unità Consumer Products Safety del Centro Comune di Ricerca della Commissione Europea. I risultati di questo lavoro mostrano che testare diversi materiali campionati in condizioni realistiche consente di valutare come la tossicità delle particelle possa variare in relazione alla fonte. Questi dati suggeriscono che lo stress ossidativo e il rilascio di citochine infiammatorie sono eventi cruciali dopo l'esposizione a DEP, che possono anche portare all'attivazione dell’endotelio vascolare. Confrontando un veicolo diesel di vecchia generazione senza DPF (Diesel Particulate Filter) e uno di ultima generazione (o “Euro 6”) durante la rigenerazione del DPF abbiamo dimostrato che il DEP Euro 6 determina una minore risposta biologica, ed è caratterizzato da diversa composizione metallica e minore concentrazione di Idrocarburi Policiclici Aromatici (IPA) rispetto a quello emesso allo scarico del veicolo di vecchia generazione, sebbene le emissioni da Euro 6 durante la rigenerazione del DPF siano caratterizzate da un maggior numero di particelle in modalità nucleazione. Il DEP emesso da un veicolo diesel di vecchia generazione si è confermato essere un componente molto pericoloso del PM urbano, anche rispetto alle particelle derivate dalla combustione (CDPs) di legna. Tuttavia, non si devono escludere possibili conseguenze sulla salute umana derivanti dall'esposizione cronica alle CDPs da biomassa. Inoltre, sono stati valutati anche gli effetti della co-esposizione di nanoparticelle di ossido di metallo (NPs), rappresentative dell’inquinamento non combustivo in miscela con DEP. La co-esposizione con DEP può ridurre la tossicità delle NPs o aumentarla. Questo risultato indica che è necessario valutare la possibile interazione di diverse particelle pericolose presenti in atmosfera e la tossicità derivante dagli effetti della loro miscela.

(2021). STUDY ON THE BIO-INTERACTION AND TOXIC EFFECTS OF PARTICLES EMITTED FROM DIFFERENT SOURCES: CONTRIBUTION TO RISK MANAGEMENT. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2021).

STUDY ON THE BIO-INTERACTION AND TOXIC EFFECTS OF PARTICLES EMITTED FROM DIFFERENT SOURCES: CONTRIBUTION TO RISK MANAGEMENT

ZERBONI, ALESSANDRA
2021

Abstract

Due to cardiovascular and respiratory diseases, air pollution remains a global issue for the 21st century. There is an urgent need to establish the real impact of Particulate Matter (PM) on human health by including the analysis of sources, size distribution, physico-chemical (P-chem) composition, and toxicological mechanisms. Increasing in vitro data for establishing pathways of toxicity in human cell lines exposed to specific air pollutants from rigorously characterized emission sources, could help to improve scientifically sound approaches in health risk characterizations, which finally may result in regulatory actions potentially more effective to protect public health. The aim of this thesis was to study the in vitro effects of particles emitted from different combustion sources using human lung cells, focusing on the relationship between the PM P-chem attributes and the cellular and molecular pathways that drive the toxicity. In vitro models, representative of the human respiratory system, were used to study the bio-interaction and toxicological effects of particles. Different exhaust particles were compared, with special emphasis on fine and ultrafine Particles (UFPs), namely Diesel exhaust particles (DEPs) from old and new generation vehicles and on particles emitted from the combustion of solid biomass fuels for residential heating. The emissions from vehicles and biomass-propelled stoves, as well as the PM collection, were performed in collaboration with INNOVHUB SSI (Fuels Department), while the P-chem characterization and toxicological studies were carried out in the Department of Earth and Environmental Sciences (DISAT)- POLARIS research centre (Polveri in Ambiente e Rischio per la Salute) and at the Consumer Products Safety Unit of the European Commission's Joint Research Centre. The results of this work show that testing different material sampled in realistic conditions allows evaluating how the toxicity of particles may vary in relation to the source. These data suggest that oxidative stress and inflammatory cytokines releases are crucial events after DEP exposure, which can also lead to vascular endothelial activation. Comparing an old generation diesel vehicle without DPF (Diesel Particulate Filter) and last generation (or “Euro 6”) one during regeneration of DPF, we proved that Euro 6 is less powerful in activating the biological response, and it is characterized by different metal composition and less concentration of Polycyclic Aromatic Hydrocarbons (PAHs) than the old generation engine, although the exhaust emission from Euro 6 during DPF regeneration is characterized by a higher number of nucleation-mode particles. DEP emitted from an old generation diesel vehicle was confirmed as a very hazardous component of the urban PM, even when compared to Combustion derived particles (CDPs) from wood burning. However, the possible consequences on human health from chronic exposure to the wood CDPs should not be excluded. Moreover, the co-exposure effects of Metal Oxide Nanoparticles (NPs), representative of non-exhaust sources, and DEP were also evaluated. The co-exposure with DEP can either reduce the toxicity of NPs or enhance it. This finding indicates that the possible interaction of different hazardous airborne particles and the toxicity deriving from the mixture effects should be evaluated.
MANTECCA, PARIDE
CASADEI, SIMONE
scarico diesel; particolato; tossicità; cellule polmonari; in vitro
diesel exhaust; particulate matter; toxicity; lung cells; in vitro
BIO/06 - ANATOMIA COMPARATA E CITOLOGIA
English
23-apr-2021
SCIENZE CHIMICHE, GEOLOGICHE E AMBIENTALI
33
2019/2020
open
(2021). STUDY ON THE BIO-INTERACTION AND TOXIC EFFECTS OF PARTICLES EMITTED FROM DIFFERENT SOURCES: CONTRIBUTION TO RISK MANAGEMENT. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2021).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/314179
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