BACKGROUND: Secondary organic aerosols (SOAs) formed from anthropogenic or biogenic gaseous precursors in the atmosphere substantially contribute to the ambient fine particulate matter [PM ≤2.5μm in aerodynamic diameter (PM2.5)] burden, which has been associated with adverse human health effects. However, there is only limited evidence on their differential toxicological impact. OBJECTIVES: We aimed to discriminate toxicological effects of aerosols generated by atmospheric aging on combustion soot particles (SPs) of gaseous biogenic (β-pinene) or anthropogenic (naphthalene) precursors in two different lung cell models exposed at the air-liquid interface (ALI). METHODS: Mono- or cocultures of lung epithelial cells (A549) and endothelial cells (EA.hy926) were exposed at the ALI for 4 h to different aerosol concentrations of a photochemically aged mixture of primary combustion SP and β-pinene (SOAβPIN-SP) or naphthalene (SOANAP-SP). The internally mixed soot/SOA particles were comprehensively characterized in terms of their physical and chemical properties. We conducted toxicity tests to determine cytotoxicity, intracellular oxidative stress, primary and secondary genotoxicity, as well as inflammatory and angiogenic effects. RESULTS: We observed considerable toxicity-related outcomes in cells treated with either SOA type. Greater adverse effects were measured for SOANAP-SP compared with SOAβPIN-SP in both cell models, whereas the nano-sized soot cores alone showed only minor effects. At the functional level, we found that SOANAP-SP augmented the secretion of malondialdehyde and interleukin-8 and may have induced the activation of endothelial cells in the coculture system. This activation was confirmed by comet assay, suggesting secondary genotoxicity and greater angiogenic potential. Chemical characterization of PM revealed distinct qualitative differences in the composition of the two secondary aerosol types. DISCUSSION: In this study using A549 and EA.hy926 cells exposed at ALI, SOA compounds had greater toxicity than primary SPs. Photochemical aging of naphthalene was associated with the formation of more oxidized, more aromatic SOAs with a higher oxidative potential and toxicity compared with β-pinene. Thus, we conclude that the influence of atmospheric chemistry on the chemical PM composition plays a crucial role for the adverse health outcome of emissions. https://doi.org/10.1289/EHP9413.

Department of Applied Physics University of Eastern Finland Kuopio Finland

Department of Earth and Planetary Sciences Faculty of Chemistry Weizmann Institute of Science Rehovot Israel

Department of Environmental and Biological Sciences University of Eastern Finland Kuopio Finland

Department of Environmental Sciences University of Basel Basel Switzerland

Institute for Chemistry and Environmental Engineering University of the Bundeswehr Munich Neubiberg Germany

Institute for Environmental Studies Faculty of Science Charles University Prague Czech Republic

Institute of Computational Biology Helmholtz Zentrum München Neuherberg Germany

Institute of Energy and Climate Research Troposphere Forschungszentrum Jülich GmbH Jülich Germany

JMSC at Analytical Chemistry Institute of Chemistry University of Rostock Rostock Germany

Joint Mass Spectrometry Center at Comprehensive Molecular Analytics Helmholtz Zentrum München Neuherberg Germany

Max Delbrück Centrum für Molekulare Medizin Berlin Germany

Zobrazit více v PubMed

Ackermann M, Stark H, Neubert L, Schubert S, Borchert P, Linz F, et al. . 2020. Morphomolecular motifs of pulmonary neoangiogenesis in interstitial lung diseases. Eur Respir J 55(3):1900933, PMID: , 10.1183/13993003.00933-2019. PubMed DOI

Aivaliotis IL, Pateras IS, Papaioannou M, Glytsou C, Kontzoglou K, Johnson EO, et al. . 2012. How do cytokines trigger genomic instability? J Biomed Biotechnol 2012:536761, PMID: , 10.1155/2012/536761. PubMed DOI PMC

Åkerlund E, Islam MS, McCarrick S, Alfaro-Moreno E, Karlsson HL. 2019. Inflammation and (secondary) genotoxicity of Ni and NiO nanoparticles. Nanotoxicology 13(8):1060–1072, PMID: , 10.1080/17435390.2019.1640908. PubMed DOI

Andreae MO, Gelencsér A. 2006. Black carbon or brown carbon? The nature of light-absorbing carbonaceous aerosols. Atmos Chem Phys 6(10):3131–3148, 10.5194/acp-6-3131-2006. DOI

Aranda E, Owen GI. 2009. A semi-quantitative assay to screen for angiogenic compounds and compounds with angiogenic potential using the EA.hy926 endothelial cell line. Biol Res 42(3):377–389, PMID: , 10.4067/S0716-97602009000300012. PubMed DOI

Arashiro M, Lin YH, Zhang Z, Sexton KG, Gold A, Jaspers I, et al. . 2018. Effect of secondary organic aerosol from isoprene-derived hydroxyhydroperoxides on the expression of oxidative stress response genes in human bronchial epithelial cells. Environ Sci Process Impacts 20(2):332–339, PMID: , 10.1039/c7em00439g. PubMed DOI

Atkinson R, Arey J. 1994. Atmospheric chemistry of gas-phase polycyclic aromatic hydrocarbons: formation of atmospheric mutagens. Environ Health Perspect 102(suppl 4):117–126, PMID: , 10.1289/ehp.94102s4117. PubMed DOI PMC

Atkinson R, Arey J. 2003. Atmospheric degradation of volatile organic compounds. Chem Rev 103(12):4605–4638, PMID: , 10.1021/cr0206420. PubMed DOI

Atkinson RW, Butland BK, Anderson HR, Maynard RL. 2018. Long-term concentrations of nitrogen dioxide and mortality: a meta-analysis of cohort studies. Epidemiology 29(4):460–472, PMID: , 10.1097/EDE.0000000000000847. PubMed DOI PMC

Atkinson R, Carter WPL. 1984. Kinetics and mechanisms of the gas-phase reactions of ozone with organic compounds under atmospheric conditions. Chem Rev 84(5):437–470, 10.1021/cr00063a002. DOI

Ayala A, Muñoz MF, Argüelles S. 2014. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev 2014:360438, PMID: , 10.1155/2014/360438. PubMed DOI PMC

Barmet P, Dommen J, DeCarlo PF, Tritscher T, Praplan AP, Platt SM, et al. . 2012. OH clock determination by proton transfer reaction mass spectrometry at an environmental chamber. Atmos Meas Tech 5(3):647–656, 10.5194/amt-5-647-2012. DOI

Barosova H, Meldrum K, Karakocak BB, Balog S, Doak SH, Petri-Fink A, et al. . 2021. Inter-laboratory variability of A549 epithelial cells grown under submerged and air-liquid interface conditions. Toxicol In Vitro 75:105178, PMID: , 10.1016/j.tiv.2021.105178. PubMed DOI

Bengalli R, Mantecca P, Camatini M, Gualtieri M. 2013. Effect of nanoparticles and environmental particles on a cocultures model of the air-blood barrier. Biomed Res Int 2013:801214, PMID: , 10.1155/2013/801214. PubMed DOI PMC

Bond TC, Doherty SJ, Fahey DW, Forster PM, Berntsen T, DeAngelo BJ, et al. . 2013. Bounding the role of black carbon in the climate system: a scientific assessment. J Geophys Res Atmos 118(11):5380–5552, 10.1002/jgrd.50171. DOI

Brook RD, Rajagopalan S, Pope CA III, Brook JR, Bhatnagar A, Diez-Roux AV, et al. . 2010. Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the American Heart Association. Circulation 121(21):2331–2378, PMID: , 10.1161/CIR.0b013e3181dbece1. PubMed DOI

Bruns EA, El Haddad I, Keller A, Klein F, Kumar NK, Pieber SM, et al. . 2015. Inter-comparison of laboratory smog chamber and flow reactor systems on organic aerosol yield and composition. Atmos Meas Tech 8(6):2315–2332, 10.5194/amt-8-2315-2015. DOI

Burkholder JB, Abbatt JPD, Barnes I, Roberts JM, Melamed ML, Ammann M, et al. . 2017. The essential role for laboratory studies in atmospheric chemistry. Environ Sci Technol 51(5):2519–2528, PMID: , 10.1021/acs.est.6b04947. PubMed DOI

Canagaratna MR, Jimenez JL, Kroll JH, Chen Q, Kessler SH, Massoli P, et al. . 2015. Elemental ratio measurements of organic compounds using aerosol mass spectrometry: characterization, improved calibration, and implications. Atmos Chem Phys 15(1):253–272, 10.5194/acp-15-253-2015. DOI

Chan AWH, Kautzman KE, Chhabra PS, Surratt JD, Chan MN, Crounse JD, et al. . 2009. Secondary organic aerosol formation from photooxidation of naphthalene and alkylnaphthalenes: implications for oxidation of intermediate volatility organic compounds (IVOCs). Atmos Chem Phys 9(9):3049–3060, 10.5194/acp-9-3049-2009. DOI

Chen CL, Kacarab M, Tang P, Cocker DR III.. 2016. SOA formation from naphthalene, 1-methylnaphthalene, and 2-methylnaphthalene photooxidation. Atmos Environ 131:424–433, 10.1016/j.atmosenv.2016.02.007. DOI

Chow JC, Watson JG, Chen LWA, Chang MCO, Robinson NF, Trimble D, et al. . 2007. The IMPROVE_A temperature protocol for thermal/optical carbon analysis: maintaining consistency with a long-term database. J Air Waste Manag Assoc 57(9):1014–1023, PMID: , 10.3155/1047-3289.57.9.1014. PubMed DOI

Chowdhury PH, He Q, Carmieli R, Li C, Rudich Y, Pardo M. 2019. Connecting the oxidative potential of secondary organic aerosols with reactive oxygen species in exposed lung cells. Environ Sci Technol 53(23):13949–13958, PMID: , 10.1021/acs.est.9b04449. PubMed DOI

Chowdhury PH, He QF, Male TL, Brune WH, Rudich Y, Pardo M. 2018. Exposure of lung epithelial cells to photochemically aged secondary organic aerosol shows increased toxic effects. Environ Sci Technol Lett 5(7):424–430, 10.1021/acs.estlett.8b00256. DOI

Chughtai AR, Kim JM, Smith DM. 2003. The effect of temperature and humidity on the reaction of ozone with combustion soot: implications for reactivity near the tropopause. J Atmos Chem 45(3):231–243, 10.1023/A:1024250505886. DOI

Cohen AJ, Brauer M, Burnett R, Anderson HR, Frostad J, Estep K, et al. . 2017. Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution: an analysis of data from the Global Burden of Diseases Study 2015. Lancet 389(10082):1907–1918, PMID: , 10.1016/S0140-6736(17)30505-6. PubMed DOI PMC

DeCarlo PF, Kimmel JR, Trimborn A, Northway MJ, Jayne JT, Aiken AC, et al. . 2006. Field-deployable, high-resolution, time-of-flight aerosol mass spectrometer. Anal Chem 78(24):8281–8289, PMID: , 10.1021/ac061249n. PubMed DOI

Deng X, Zhang F, Rui W, Long F, Wang L, Feng Z, et al. . 2013. PM2.5-induced oxidative stress triggers autophagy in human lung epithelial A549 cells. Toxicol In Vitro 27(6):1762–1770, PMID: , 10.1016/j.tiv.2013.05.004. PubMed DOI

Dennis-Smither BJ, Marshall FH, Miles REH, Preston TC, Reid JP. 2014. Volatility and oxidative aging of aqueous maleic acid aerosol droplets and the dependence on relative humidity. J Phys Chem A 118(30):5680–5691, PMID: , 10.1021/jp504823j. PubMed DOI

Dergham M, Lepers C, Verdin A, Billet S, Cazier F, Courcot D, et al. . 2012. Prooxidant and proinflammatory potency of air pollution particulate matter (PM2.5–0.3) produced in rural, urban, or industrial surroundings in human bronchial epithelial cells (BEAS-2B). Chem Res Toxicol 25(4):904–919, PMID: , 10.1021/tx200529v. PubMed DOI

Di Bucchianico S, Cappellini F, Le Bihanic F, Zhang Y, Dreij K, Karlsson HL. 2017. Genotoxicity of TiO2 nanoparticles assessed by mini-gel comet assay and micronucleus scoring with flow cytometry. Mutagenesis 32(1):127–137, PMID: , 10.1093/mutage/gew030. PubMed DOI PMC

Drwal E, Rak A, Gregoraszczuk EL. 2019. Review: polycyclic aromatic hydrocarbons (PAHs)—action on placental function and health risks in future life of newborns. Toxicology 411:133–142, PMID: , 10.1016/j.tox.2018.10.003. PubMed DOI

Eaves LA, Smeester L, Hartwell HJ, Lin YH, Arashiro M, Zhang Z, et al. . 2020. Isoprene-derived secondary organic aerosol induces the expression of microRNAs associated with inflammatory/oxidative stress response in lung cells. Chem Res Toxicol 33(2):381–387, PMID: , 10.1021/acs.chemrestox.9b00322. PubMed DOI PMC

Ehn M, Thornton JA, Kleist E, Sipilä M, Junninen H, Pullinen I, et al. . 2014. A large source of low-volatility secondary organic aerosol. Nature 506(7489):476–479, PMID: , 10.1038/nature13032. PubMed DOI

Evans SJ, Clift MJD, Singh N, Wills JW, Hondow N, Wilkinson TS, et al. . 2019. In vitro detection of in vitro secondary mechanisms of genotoxicity induced by engineered nanomaterials. Part Fibre Toxicol 16(1):8, PMID: , 10.1186/s12989-019-0291-7. PubMed DOI PMC

Faiola CL, Jobson BT, VanReken TM. 2015. Impacts of simulated herbivory on volatile organic compound emission profiles from coniferous plants. Biogeosciences 12(2):527–547, 10.5194/bg-12-527-2015. DOI

Feng S, Gao D, Liao F, Zhou F, Wang X. 2016. The health effects of ambient PM2.5 and potential mechanisms. Ecotoxicol Environ Saf 128:67–74, PMID: , 10.1016/j.ecoenv.2016.01.030. PubMed DOI

Gaspari L, Chang SS, Santella RM, Garte S, Pedotti P, Taioli E. 2003. Polycyclic aromatic hydrocarbon-DNA adducts in human sperm as a marker of DNA damage and infertility. Mutat Res 535(2):155–160, PMID: , 10.1016/S1383-5718(02)00297-8. PubMed DOI

Gminski R, Tang T, Mersch-Sundermann V. 2010. Cytotoxicity and genotoxicity in human lung epithelial A549 cells caused by airborne volatile organic compounds emitted from pine wood and oriented strand boards. Toxicol Lett 196(1):33–41, PMID: , 10.1016/j.toxlet.2010.03.015. PubMed DOI

Guenther A, Hewitt CN, Erickson D, Fall R, Geron C, Graedel T, et al. . 1995. A global model of natural volatile organic compound emissions. J Geophys Res 100(D5):8873–8892, 10.1029/94JD02950. DOI

Guenther AB, Jiang X, Heald CL, Sakulyanontvittaya T, Duhl T, Emmons LK, et al. . 2012. The Model of Emissions of Gases and Aerosols from Nature version 2.1 (MEGAN2.1): an extended and updated framework for modeling biogenic emissions. Geosci Model Dev 5(6):1471–1492, 10.5194/gmd-5-1471-2012. DOI

Halappanavar S, van den Brule S, Nymark P, Gaté L, Seidel C, Valentino S, et al. . 2020. Adverse outcome pathways as a tool for the design of testing strategies to support the safety assessment of emerging advanced materials at the nanoscale. Part Fibre Toxicol 17(1):16, PMID: , 10.1186/s12989-020-00344-4. PubMed DOI PMC

Hallquist M, Wenger JC, Baltensperger U, Rudich Y, Simpson D, Claeys M, et al. . 2009. The formation, properties and impact of secondary organic aerosol: current and emerging issues. Atmos Chem Phys 9(14):5155–5236, 10.5194/acp-9-5155-2009. DOI

Han J, Wang S, Yeung K, Yang D, Gu W, Ma Z, et al. . 2020. Proteome-wide effects of naphthalene-derived secondary organic aerosol in BEAS-2B cells are caused by short-lived unsaturated carbonyls. Proc Natl Acad Sci U S A 117(41):25386–25395, PMID: , 10.1073/pnas.2001378117. PubMed DOI PMC

Hartikainen A, Tiitta P, Ihalainen M, Yli-Pirilä P, Orasche J, Czech H, et al. . 2020. Photochemical transformation of residential wood combustion emissions: dependence of organic aerosol composition on OH exposure. Atmos Chem Phys 20(11):6357–6378, 10.5194/acp-20-6357-2020. DOI

Heidemann J, Ogawa H, Dwinell MB, Rafiee P, Maaser C, Gockel HR, et al. . 2003. Angiogenic effects of interleukin 8 (CXCL8) in human intestinal microvascular endothelial cells are mediated by CXCR2. J Biol Chem 278(10):8508–8515, PMID: , 10.1074/jbc.M208231200. PubMed DOI

Heyder J. 2004. Deposition of inhaled particles in the human respiratory tract and consequences for regional targeting in respiratory drug delivery. Proc Am Thorac Soc 1(4):315–320, PMID: , 10.1513/pats.200409-046TA. PubMed DOI

Hilton G, Barosova H, Petri-Fink A, Rothen-Rutishauser B, Bereman M. 2019. Leveraging proteomics to compare submerged versus air-liquid interface carbon nanotube exposure to a 3D lung cell model. Toxicol In Vitro 54:58–66, PMID: , 10.1016/j.tiv.2018.09.010. PubMed DOI

Hohaus T, Gensch I, Kimmel J, Worsnop DR, Kiendler-Scharr A. 2015. Experimental determination of the partitioning coefficient of β-pinene oxidation products in SOAs. Phys Chem Phys 17(22):14796–14804, PMID: , 10.1039/c5cp01608h. PubMed DOI

Huang RJ, Zhang Y, Bozzetti C, Ho KF, Cao JJ, Han Y, et al. . 2014. High secondary aerosol contribution to particulate pollution during haze events in China. Nature 514(7521):218–222, PMID: , 10.1038/nature13774. PubMed DOI

IARC (IARC Working Group on the Evaluation of Carcinogenic Risks to Humans). 2010. Some non-heterocyclic polycyclic aromatic hydrocarbons and some related exposures. IARC Monogr Eval Carcinog Risks Hum 92:1–853, PMID: . PubMed PMC

Ihantola T, Di Bucchianico S, Happo M, Ihalainen M, Uski O, Bauer S, et al. . 2020. Influence of wood species on toxicity of log-wood stove combustion aerosols: a parallel animal and air-liquid interface cell exposure study on spruce and pine smoke. Part Fibre Toxicol 17(1):27, PMID: , 10.1186/s12989-020-00355-1. PubMed DOI PMC

Janssen NAH, Hoek G, Simic-Lawson M, Fischer P, van Bree L, ten Brink H, et al. . 2011. Black carbon as an additional indicator of the adverse health effects of airborne particles compared with PM10 and PM2.5. Environ Health Perspect 119(12):1691–1699, PMID: , 10.1289/ehp.1003369. PubMed DOI PMC

Jayne JT, Leard DC, Zhang XF, Davidovits P, Smith KA, Kolb CE, et al. . 2000. Development of an aerosol mass spectrometer for size and composition analysis of submicron particles. Aerosol Sci Technol 33(1–2):49–70, 10.1080/027868200410840. DOI

Jia C, Batterman S. 2010. A critical review of naphthalene sources and exposures relevant to indoor and outdoor air. Int J Environ Res Public Health 7(7):2903–2939, PMID: , 10.3390/ijerph7072903. PubMed DOI PMC

Jiang H, Jang M. 2018. Dynamic oxidative potential of atmospheric organic aerosol under ambient sunlight. Environ Sci Technol 52(13):7496–7504, PMID: , 10.1021/acs.est.8b00148. PubMed DOI

Käfer U, Gröger T, Rüger CP, Czech H, Saraji-Bozorgzad M, Wilharm T, et al. . 2019. Direct inlet probe–high-resolution time-of-flight mass spectrometry as fast technique for the chemical description of complex high-boiling samples. Talanta 202:308–316, PMID: , 10.1016/j.talanta.2019.05.030. PubMed DOI

Kaminski M, Fuchs H, Acir IH, Bohn B, Brauers T, Dorn HP, et al. . 2017. Investigation of the β-pinene photooxidation by OH in the atmosphere simulation chamber SAPHIR. Atmos Chem Phys 17(11):6631–6650, 10.5194/acp-17-6631-2017. DOI

Kang E, Root MJ, Toohey DW, Brune WH. 2007. Introducing the concept of potential aerosol mass (PAM). Atmos Chem Phys 7(22):5727–5744, 10.5194/acp-7-5727-2007. DOI

Karg EW, Ferron GA, Bauer S, Di Bucchianico S, Zimmermann R. 2020. Is the particle deposition in a cell exposure facility comparable to the lungs? A computer model approach. Aerosol Sci Technol 54(6):668–684, 10.1080/02786826.2020.1724868. DOI

Karki P, Birukov KG. 2020. Oxidized phospholipids in healthy and diseased lung endothelium. Cells 9(4):981, PMID: , 10.3390/cells9040981. PubMed DOI PMC

Kenseth CM, Huang Y, Zhao R, Dalleska NF, Hethcox JC, Stoltz BM, et al. . 2018. Synergistic O3 + OH oxidation pathway to extremely low-volatility dimers revealed in β-pinene secondary organic aerosol. Proc Natl Acad Sci U S A 115(33):8301–8306, PMID: , 10.1073/pnas.1804671115. PubMed DOI PMC

Keyte IJ, Harrison RM, Lammel G. 2013. Chemical reactivity and long-range transport potential of polycyclic aromatic hydrocarbons—a review. Chem Soc Rev 42(24):9333–9391, PMID: , 10.1039/c3cs60147a. PubMed DOI

Kim YW, Byzova TV. 2014. Oxidative stress in angiogenesis and vascular disease. Blood 123(5):625–631, PMID: , 10.1182/blood-2013-09-512749. PubMed DOI PMC

Klein SG, Serchi T, Hoffmann L, Blömeke B, Gutleb AC. 2013. An improved 3D tetraculture system mimicking the cellular organisation at the alveolar barrier to study the potential toxic effects of particles on the lung. Part Fibre Toxicol 10:31, PMID: , 10.1186/1743-8977-10-31. PubMed DOI PMC

Kleist E, Mentel TF, Andres S, Bohne A, Folkers A, Kiendler-Scharr A, et al. . 2012. Irreversible impacts of heat on the emissions of monoterpenes, sesquiterpenes, phenolic BVOC and green leaf volatiles from several tree species. Biogeosciences 9(12):5111–5123, 10.5194/bg-9-5111-2012. DOI

Kouassi KS, Billet S, Garçon G, Verdin A, Diouf A, Cazier F, et al. . 2010. Oxidative damage induced in A549 cells by physically and chemically characterized air particulate matter (PM2.5) collected in Abidjan, Côte D’Ivoire. J Appl Toxicol 30(4):310–320, PMID: , 10.1002/jat.1496. PubMed DOI

Kroll JH, Donahue NM, Jimenez JL, Kessler SH, Canagaratna MR, Wilson KR, et al. . 2011. Carbon oxidation state as a metric for describing the chemistry of atmospheric organic aerosol. Nat Chem 3(2):133–139, PMID: , 10.1038/nchem.948. PubMed DOI

Künzi L, Krapf M, Daher N, Dommen J, Jeannet N, Schneider S, et al. . 2015. Toxicity of aged gasoline exhaust particles to normal and diseased airway epithelia. Sci Rep 5:11801, PMID: , 10.1038/srep11801. PubMed DOI PMC

Lacroix G, Koch W, Ritter D, Gutleb AC, Larsen ST, Loret T, et al. . 2018. Air–liquid interface in vitro models for respiratory toxicology research: consensus workshop and recommendations. Appl In Vitro Toxicol 4(2):91–106, PMID: , 10.1089/aivt.2017.0034. PubMed DOI PMC

Låg M, Øvrevik J, Refsnes M, Holme JA. 2020. Potential role of polycyclic aromatic hydrocarbons in air pollution-induced non-malignant respiratory diseases. Respir Res 21(1):299, PMID: , 10.1186/s12931-020-01563-1. PubMed DOI PMC

Lan Y, Ng CT, Ong RXS, Muniasamy U, Baeg GH, Ong CN, et al. . 2020. Urban PM2.5 reduces angiogenic ability of endothelial cells in an alveolar-capillary co-culture lung model. Ecotoxicol Environ Saf 202:110932, PMID: , 10.1016/j.ecoenv.2020.110932. PubMed DOI

Landar A, Zmijewski JW, Dickinson DA, Le Goffe C, Johnson MS, Milne GL, et al. . 2006. Interaction of electrophilic lipid oxidation products with mitochondria in endothelial cells and formation of reactive oxygen species. Am J Physiol Heart Circ Physiol 290(5):H1777–H1787, PMID: , 10.1152/ajpheart.01087.2005. PubMed DOI

Lenz AG, Karg E, Brendel E, Hinze-Heyn H, Maier KL, Eickelberg O, et al. . 2013. Inflammatory and oxidative stress responses of an alveolar epithelial cell line to airborne zinc oxide nanoparticles at the air-liquid interface: a comparison with conventional, submerged cell-culture conditions. Biomed Res Int 2013:652632, PMID: , 10.1155/2013/652632. PubMed DOI PMC

Li D, Li Y, Li G, Zhang Y, Li J, Chen H. 2019. Fluorescent reconstitution on deposition of PM2.5 in lung and extrapulmonary organs. Proc Natl Acad Sci U S A 116(7):2488–2493, PMID: , 10.1073/pnas.1818134116. PubMed DOI PMC

Lim CY, Browne EC, Sugrue RA, Kroll JH. 2017. Rapid heterogeneous oxidation of organic coatings on submicron aerosols. Geophys Res Lett 44(6):2949–2957, 10.1002/2017GL072585. DOI

Lin YH, Arashiro M, Clapp PW, Cui T, Sexton KG, Vizuete W, et al. . 2017. Gene expression profiling in human lung cells exposed to isoprene-derived secondary organic aerosol. Environ Sci Technol 51(14):8166–8175, PMID: , 10.1021/acs.est.7b01967. PubMed DOI PMC

Liu F, Saavedra MG, Champion JA, Griendling KK, Ng NL. 2020. Prominent contribution of hydrogen peroxide to intracellular reactive oxygen species generated upon exposure to naphthalene secondary organic aerosols. Environ Sci Technol Lett 7(3):171–177, 10.1021/acs.estlett.9b00773. DOI

Löndahl J, Möller W, Pagels JH, Kreyling WG, Swietlicki E, Schmid O. 2014. Measurement techniques for respiratory tract deposition of airborne nanoparticles: a critical review. J Aerosol Med Pulm Drug Deliv 27(4):229–254, PMID: , 10.1089/jamp.2013.1044. PubMed DOI PMC

Longhin E, Holme JA, Gutzkow KB, Arlt VM, Kucab JE, Camatini M, et al. . 2013. Cell cycle alterations induced by urban PM2.5 in bronchial epithelial cells: characterization of the process and possible mechanisms involved. Part Fibre Toxicol 10:63, PMID: , 10.1186/1743-8977-10-63. PubMed DOI PMC

LoPachin RM, Gavin T. 2014. Molecular mechanisms of aldehyde toxicity: a chemical perspective. Chem Res Toxicol 27(7):1081–1091, PMID: , 10.1021/tx5001046. PubMed DOI PMC

Loret T, Peyret E, Dubreuil M, Aguerre-Chariol O, Bressot C, le Bihan O, et al. . 2016. Air-liquid interface exposure to aerosols of poorly soluble nanomaterials induces different biological activation levels compared to exposure to suspensions. Part Fibre Toxicol 13(1):58, PMID: , 10.1186/s12989-016-0171-3. PubMed DOI PMC

Lucci F, Castro ND, Rostami AA, Oldham MJ, Hoeng J, Pithawalla YB, et al. . 2018. Characterization and modeling of aerosol deposition in Vitrocell ® exposure systems—exposure well chamber deposition efficiency. J Aerosol Sci 123:141–160, 10.1016/j.jaerosci.2018.06.015. DOI

Ma I, Allan AL. 2011. The role of human aldehyde dehydrogenase in normal and cancer stem cells. Stem Cell Rev Rep 7(2):292–306, PMID: , 10.1007/s12015-010-9208-4. PubMed DOI

Mills IC, Atkinson RW, Kang S, Walton H, Anderson HR. 2015. Quantitative systematic review of the associations between short-term exposure to nitrogen dioxide and mortality and hospital admissions. BMJ Open 5(5):e006946, PMID: , 10.1136/bmjopen-2014-006946. PubMed DOI PMC

Møller P, Danielsen PH, Karottki DG, Jantzen K, Roursgaard M, Klingberg H, et al. . 2014. Oxidative stress and inflammation generated DNA damage by exposure to air pollution particles. Mutat Res Rev Mutat Res 762:133–166, PMID: , 10.1016/j.mrrev.2014.09.001. PubMed DOI

Moore RH, Ziemba LD, Dutcher D, Beyersdorf AJ, Chan K, Crumeyrolle S, et al. . 2014. Mapping the operation of the miniature combustion aerosol standard (Mini-CAST) soot generator. Aerosol Sci Technol 48(5):467–479, 10.1080/02786826.2014.890694. DOI

Mülhopt S, Dilger M, Diabaté S, Schlager C, Krebs T, Zimmermann R, et al. . 2016. Toxicity testing of combustion aerosols at the air–liquid interface with a self-contained and easy-to-use exposure system. J Aerosol Sci 96:38–55, 10.1016/j.jaerosci.2016.02.005. DOI

National Academies of Sciences, Engineering, and Medicine. 2016. The Future of Atmospheric Chemistry Research: Remembering Yesterday, Understanding Today, Anticipating Tomorrow. Washington, DC: National Academies Press.

Ng NL, Canagaratna MR, Jimenez JL, Chhabra PS, Seinfeld JH, Worsnop DR. 2011. Changes in organic aerosol composition with aging inferred from aerosol mass spectra. Atmos Chem Phys 11(13):6465–6474, 10.5194/acp-11-6465-2011. DOI

Ng NL, Canagaratna MR, Zhang Q, Jimenez JL, Tian J, Ulbrich IM, et al. . 2010. Organic aerosol components observed in Northern Hemispheric datasets from Aerosol Mass Spectrometry. Atmos Chem Phys 10(10):4625–4641, 10.5194/acp-10-4625-2010. DOI

Oeder S, Kanashova T, Sippula O, Sapcariu SC, Streibel T, Arteaga-Salas JM, et al. . 2015. Particulate matter from both heavy fuel oil and diesel fuel shipping emissions show strong biological effects on human lung cells at realistic and comparable in vitro exposure conditions. PLoS One 10(6):e0126536, PMID: , 10.1371/journal.pone.0126536. PubMed DOI PMC

Papazian D, Würtzen PA, Hansen SWK. 2016. Polarized airway epithelial models for immunological co-culture studies. Int Arch Allergy Immunol 170(1):1–21, PMID: , 10.1159/000445833. PubMed DOI

Park M, Joo HS, Lee K, Jang M, Kim SD, Kim I, et al. . 2018. Differential toxicities of fine particulate matters from various sources. Sci Rep 8(1):17007, PMID: , 10.1038/s41598-018-35398-0. PubMed DOI PMC

Paur HR, Cassee FR, Teeguarden J, Fissan H, Diabate S, Aufderheide M, et al. . 2011. In-vitro cell exposure studies for the assessment of nanoparticle toxicity in the lung—a dialog between aerosol science and biology. J Aerosol Sci 42(10):668–692, 10.1016/j.jaerosci.2011.06.005. DOI

Peng Z, Day DA, Ortega AM, Palm BB, Hu W, Stark H, et al. . 2016. Non-OH chemistry in oxidation flow reactors for the study of atmospheric chemistry systematically examined by modeling. Atmos Chem Phys 16(7):4283–4305, 10.5194/acp-16-4283-2016. DOI

Perera F, Hemminki K, Jedrychowski W, Whyatt R, Campbell U, Hsu Y, et al. . 2002. In utero DNA damage from environmental pollution is associated with somatic gene mutation in newborns. Cancer Epidemiol Biomark Prev 11(10 pt 1):1134–1137, PMID: . PubMed

Peters A, Nawrot TS, Baccarelli AA. 2021. Hallmarks of environmental insults. Cell 184(6):1455–1468, PMID: , 10.1016/j.cell.2021.01.043. PubMed DOI PMC

Peterson LA. 2013. Reactive metabolites in the biotransformation of molecules containing a furan ring. Chem Res Toxicol 26(1):6–25, PMID: , 10.1021/tx3003824. PubMed DOI PMC

Pieber SM, Kumar NK, Klein F, Comte P, Bhattu D, Dommen J, et al. . 2018. Gas-phase composition and secondary organic aerosol formation from standard and particle filter-retrofitted gasoline direct injection vehicles investigated in a batch and flow reactor. Atmos Chem Phys 18(13):9929–9954, 10.5194/acp-18-9929-2018. DOI

Pope CA III, Bhatnagar A, McCracken JP, Abplanalp W, Conklin DJ, O’Toole T. 2016. Exposure to fine particulate air pollution is associated with endothelial injury and systemic inflammation. Circ Res 119(11):1204–1214, PMID: , 10.1161/CIRCRESAHA.116.309279. PubMed DOI PMC

Pope CA III, Coleman N, Pond ZA, Burnett RT. 2020. Fine particulate air pollution and human mortality: 25+ years of cohort studies. Environ Res 183:108924, PMID: , 10.1016/j.envres.2019.108924. PubMed DOI

Prinn RG, Huang J, Weiss RF, Cunnold DM, Fraser PJ, Simmonds PG, et al. . 2001. Evidence for substantial variations of atmospheric hydroxyl radicals in the past two decades. Science 292(5523):1882–1888, PMID: , 10.1126/science.1058673. PubMed DOI

Qian Z, Chen Y, Liu Z, Han Y, Zhang Y, Feng Y, et al. . 2021. Intermediate volatile organic compound emissions from residential solid fuel combustion based on field measurements in rural China. Environ Sci Technol 55(9):5689–5700, PMID: , 10.1021/acs.est.0c07908. PubMed DOI

Raes F, Van Dingenen R, Vignati E, Wilson J, Putaud JP, Seinfeld JH, et al. . 2000. Formation and cycling of aerosols in the global troposphere. Atmos Environ 34(25):4215–4240, 10.1016/S1352-2310(00)00239-9. DOI

Rebollido-Rios R, Venton G, Sánchez-Redondo S, Iglesias I Felip C, Fournet G, González E, et al. . 2020. Dual disruption of aldehyde dehydrogenases 1 and 3 promotes functional changes in the glutathione redox system and enhances chemosensitivity in nonsmall cell lung cancer. Oncogene 39(13):2756–2771, PMID: , 10.1038/s41388-020-1184-9. PubMed DOI PMC

Riediker M, Zink D, Kreyling W, Oberdörster G, Elder A, Graham U, et al. . 2019. Particle toxicology and health—where are we? Part Fibre Toxicol 16(1):19, PMID: , 10.1186/s12989-019-0302-8. PubMed DOI PMC

Rodriguez-Torres M, Allan AL. 2016. Aldehyde dehydrogenase as a marker and functional mediator of metastasis in solid tumors. Clin Exp Metastasis 33(1):97–113, PMID: , 10.1007/s10585-015-9755-9. PubMed DOI PMC

Rothen-Rutishauser B, Blank F, Mühlfeld C, Gehr P. 2008. In vitro models of the human epithelial airway barrier to study the toxic potential of particulate matter. Expert Opin Drug Metab Toxicol 4(8):1075–1089, PMID: , 10.1517/17425255.4.8.1075. PubMed DOI

Sarrafzadeh M, Wildt J, Pullinen I, Springer M, Kleist E, Tillmann R, et al. . 2016. Impact of NOx and OH on secondary organic aerosol formation from β-pinene photooxidation. Atmos Chem Phys 16(17):11237–11248, 10.5194/acp-16-11237-2016. DOI

Sato K, Jia T, Tanabe K, Morino Y, Kajii Y, Imamura T. 2016. Terpenylic acid and nine-carbon multifunctional compounds formed during the aging of β-pinene ozonolysis secondary organic aerosol. Atmos Environ 130:127–135, 10.1016/j.atmosenv.2015.08.047. DOI

Schwöbel JAH, Koleva YK, Enoch SJ, Bajot F, Hewitt M, Madden JC, et al. . 2011. Measurement and estimation of electrophilic reactivity for predictive toxicology. Chem Rev 111(4):2562–2596, PMID: , 10.1021/cr100098n. PubMed DOI

Shakya KM, Griffin RJ. 2010. Secondary organic aerosol from photooxidation of polycyclic aromatic hydrocarbons. Environ Sci Technol 44(21):8134–8139, PMID: , 10.1021/es1019417. PubMed DOI

Sýkorová B, Kucbel M, Raclavský K. 2016. Composition of airborne particulate matter in the industrial area versus mountain area. Perspect Sci (Neth) 7:369–372, 10.1016/j.pisc.2015.12.006. DOI

Tǎbǎran AF, O’Sullivan MG, Seabloom DE, Vevang KR, Smith WE, Wiedmann TS, et al. . 2019. Inhaled furan selectively damages club cells in lungs of A/J mice. Toxicol Pathol 47(7):842–850, PMID: , 10.1177/0192623319869306. PubMed DOI PMC

Tuet WY, Chen YL, Xu L, Fok S, Gao D, Weber RJ, et al. . 2017. Chemical oxidative potential of secondary organic aerosol (SOA) generated from the photooxidation of biogenic and anthropogenic volatile organic compounds. Atmos Chem Phys 17(2):839–853, 10.5194/acp-17-839-2017. DOI

U.S. EPA (Environmental Protection Agency). 2021a. EPA CompTox Chemicals Dashboard: Beta-pinene. https://comptox.epa.gov/dashboard/dsstoxdb/results?search=beta-pinene#toxicity-values [accessed 3 December 2021].

U.S. EPA. 2021b. EPA CompTox Chemicals Dashboard: Naphthalene. https://comptox.epa.gov/dashboard/dsstoxdb/results?search=DTXSID8020913#toxicity-values [accessed 3 December 2021].

Wang G, Zhang X, Liu X, Zheng J, Chen R, Kan H. 2019. Ambient fine particulate matter induce toxicity in lung epithelial-endothelial co-culture models. Toxicol Lett 301:133–145, PMID: , 10.1016/j.toxlet.2018.11.010. PubMed DOI

Wang L, Atkinson R, Arey J. 2007. Dicarbonyl products of the OH radical-initiated reactions of naphthalene and the Cl- and C2-alkylnaphthalenes. Environ Sci Technol 41(8):2803–2810, PMID: , 10.1021/es0628102. PubMed DOI

Wang M, Li S, Zhu R, Zhang R, Zu L, Wang Y, et al. . 2020. On-road tailpipe emission characteristics and ozone formation potentials of VOCs from gasoline, diesel and liquefied petroleum gas fueled vehicles. Atmos Environ 223:117294, 10.1016/j.atmosenv.2020.117294. DOI

Watne ÅK, Westerlund J, Hallquist ÅM, Brune WH, Hallquist M. 2017. Ozone and OH-induced oxidation of monoterpenes: changes in the thermal properties of secondary organic aerosol (SOA). J Aerosol Sci 114:31–41, 10.1016/j.jaerosci.2017.08.011. DOI

Weitekamp CA, Stevens T, Stewart MJ, Bhave P, Gilmour MI. 2020. Health effects from freshly emitted versus oxidatively or photochemically aged air pollutants. Sci Total Environ 704:135772, PMID: , 10.1016/j.scitotenv.2019.135772. PubMed DOI PMC

Welch BL. 1947. The generalisation of ‘Student’s’ problems when several different population variances are involved. Biometrika 34(1–2):28–35, PMID: , 10.2307/2332510. PubMed DOI

Williams BJ, Goldstein AH, Kreisberg NM, Hering SV. 2010. In situ measurements of gas/particle-phase transitions for atmospheric semivolatile organic compounds. Proc Natl Acad Sci USA 107(15):6676–6681, PMID: , 10.1073/pnas.0911858107. PubMed DOI PMC

Williams J, de Reus M, Krejci R, Fischer H, Ström J. 2002. Application of the variability-size relationship to atmospheric aerosol studies: estimating aerosol lifetimes and ages. Atmos Chem Phys 2(2):133–145, 10.5194/acp-2-133-2002. DOI

Wragg FPH, Fuller SJ, Freshwater R, Green DC, Kelly FJ, Kalberer M. 2016. An automated online instrument to quantify aerosol-bound reactive oxygen species (ROS) for ambient measurement and health-relevant aerosol studies. Atmos Meas Tech 9(10):4891–4900, 10.5194/amt-9-4891-2016. DOI

Wu J, Wang Y, Liu G, Jia Y, Yang J, Shi J, et al. . 2017a. Characterization of air-liquid interface culture of A549 alveolar epithelial cells. Braz J Med Biol Res 51(2):e6950, PMID: , 10.1590/1414-431X20176950. PubMed DOI PMC

Wu X, Lintelmann J, Klingbeil S, Li J, Wang H, Kuhn E, et al. . 2017b. Determination of air pollution-related biomarkers of exposure in urine of travellers between Germany and China using liquid chromatographic and liquid chromatographic-mass spectrometric methods: a pilot study. Biomarkers 22(6):525–536, PMID: , 10.1080/1354750X.2017.1306753. PubMed DOI

Wyzga RE, Rohr AC. 2015. Long-term particulate matter exposure: attributing health effects to individual PM components. J Air Waste Manag Assoc 65(5):523–543, PMID: , 10.1080/10962247.2015.1020396. PubMed DOI

Xavier C, Rusanen A, Zhou PT, Dean C, Pichelstorfer L, Roldin P, et al. . 2019. Aerosol mass yields of selected biogenic volatile organic compounds—a theoretical study with nearly explicit gas-phase chemistry. Atmos Chem Phys 19(22):13741–13758, 10.5194/acp-19-13741-2019. DOI

Xu J, Hu W, Liang D, Gao P. 2022. Photochemical impacts on the toxicity of PM2.5. Crit Rev Environ Sci Technol 52(1):130–156, 10.1080/10643389.2020.1816126. DOI

Yan Z, Jin Y, An Z, Liu Y, Samet JM, Wu W. 2016. Inflammatory cell signaling following exposures to particulate matter and ozone. Biochim Biophys Acta 1860(12):2826–2834, PMID: , 10.1016/j.bbagen.2016.03.030. PubMed DOI