GC×GC; human metabolome; blood, plasma and serum; urinary metabolome; MOSH/MOAH; drinking water; air/particle
Abstract :
[en] In context of the exposome paradigm, the ‘exposure’ describes all individual and global environmental influences an individual throughout its entire lifetime. Cause, effect and their causality are the central research objectives, which require interdisciplinary research strategies. The core benefits of comprehensive two-dimensional gas chromatography (GC×GC) make it a versatile technique for both, exposure and response driven approaches, especially when combined with appropriate sample preparation and MS detection. In this article, the potentials and recent advances of GC×GC in the field of human exposome research is critically discussed.
Disciplines :
Environmental sciences & ecology Chemistry Forensic medicine
Niedzwiecki, M.M., Walker, D.I., Vermeulen, R., Chadeau-Hyam, M., Jones, D.P., Miller, G.W., The exposome: molecules to populations. Annu Rev Pharmacol Toxicol 59 (2019), 107–127.
Wild, C.P., Complementing the genome with an “exposome”: the outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol Biomark Prev 14 (2005), 1847–1850.
Wild, C.P., The exposome: from concept to utility. Int J Epidemiol 41 (2012), 24–32.
Hernández, F., Bakker, J., Bijlsma, L., de Boer, J., Botero-Coy, A.M., Bruinen de Bruin, Y., Fischer, S., Hollender, J., Kasprzyk-Hordern, B., Lamoree, M., et al. The role of analytical chemistry in exposure science: focus on the aquatic environment. Chemosphere, 2019, 10.1016/j.chemosphere.2019.01.118.
Jones, D.P., Sequencing the exposome: a call to action. Toxicol Rep 3 (2016), 29–45.
Liu, Z., Phillips, J.B., Comprehensive two-dimensional gas chromatography using an on-column thermal modulator interface. J Chromatogr Sci 29 (1991), 227–231.
Welthagen, W., Shellie, R.A., Spranger, J., Ristow, M., Zimmermann, R., Fiehn, O., Comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry (GC × GC-TOF) for high resolution metabolomics: biomarker discovery on spleen tissue extracts of obese NZO compared to lean C57BL/6 mice. Metabolomics 1 (2005), 65–73.
Higgins Keppler, E.A., Jenkins, C.L., Davis, T.J., Bean, H.D., Advances in the application of comprehensive two-dimensional gas chromatography in metabolomics. TrAC Trends Anal Chem (Reference Ed) 109 (2018), 275–286.
Misra, B.B., Bassey, E., Bishop, A.C., Kusel, D.T., Cox, L.A., Olivier, M., High-resolution gas chromatography/mass spectrometry metabolomics of non-human primate serum. Rapid Commun Mass Spectrom 32 (2018), 1497–1506.
Näsström, E., Jonsson, P., Johansson, A., Dongol, S., Karkey, A., Basnyat, B., Tran Vu Thieu, N., Trinh Van, T., Thwaites, G.E., Antti, H., et al. Diagnostic metabolite biomarkers of chronic typhoid carriage. PLoS Neglected Trop Dis, 12, 2018.
Silva, D., Arend, E., Rocha, S.M., Rudnitskaya, A., Delgado, L., Moreira, A., Carvalho, J., The impact of exercise training on the lipid peroxidation metabolomic profile and respiratory infection risk in older adults. Eur J Sport Sci 19 (2019), 384–393.
Stander, Z., Luies, L., Mienie, L.J., Keane, K.M., Howatson, G., Clifford, T., Stevenson, E.J., Loots, D.T., The altered human serum metabolome induced by a marathon. Metabolomics, 14, 2018.
Misra, B.B., Puppala, S.R., Comuzzie, A.G., Mahaney, M.C., VandeBerg, J.L., Olivier, M., Cox, L.A., Analysis of serum changes in response to a high fat high cholesterol diet challenge reveals metabolic biomarkers of atherosclerosis. PLoS One, 14, 2019.
Rist, M.J., Roth, A., Frommherz, L., Weinert, C.H., Krüger, R., Merz, B., Bunzel, D., Mack, C., Egert, B., Bub, A., et al. Metabolite patterns predicting sex and age in participants of the Karlsruhe Metabolomics and Nutrition (KarMeN) study. PLoS One, 12, 2017.
Bileck, A., Fluck, C.E., Dhayat, N., Groessl, M., How high-resolution techniques enable reliable steroid identification and quantification. J Steroid Biochem Mol Biol 186 (2019), 74–78.
Bileck, A., Verouti, S.N., Escher, G., Vogt, B., Groessl, M., A comprehensive urinary steroid analysis strategy using two-dimensional gas chromatography-time of flight mass spectrometry. Analyst 143 (2018), 4484–4494.
Eshima, J., Ong, S., Davis, T.J., Miranda, C., Krishnamurthy, D., Nachtsheim, A., Stufken, J., Plaisier, C., Fricks, J., Bean, H.D., et al. Monitoring changes in the healthy female metabolome across the menstrual cycle using GC × GC-TOFMS. J Chromatogr B Anal Technol Biomed Life Sci 1121 (2019), 48–57.
Bressanello, D., Liberto, E., Collino, M., Chiazza, F., Mastrocola, R., Reichenbach, S.E., Bicchi, C., Cordero, C., Combined untargeted and targeted fingerprinting by comprehensive two-dimensional gas chromatography: revealing fructose-induced changes in mice urinary metabolic signatures. Anal Bioanal Chem 410 (2018), 2723–2737.
Mack, C.I., Egert, B., Liberto, E., Weinert, C.H., Bub, A., Hoffmann, I., Bicchi, C., Kulling, S.E., Cordero, C., Robust markers of coffee consumption identified among the volatile organic compounds in human urine. Mol Nutr Food Res, 63, 2019 HS-SPME coupled to GC×GC–MS to the study of the volatile urinary metabolome and could identify six potential markers related to the dietary intake of coffee. Emphasizing the methods ruggedness and stability, this study illustrates the integration of GC×GC into controlled exposome research.
Beccaria, M., Bobak, C., Maitshotlo, B., Mellors, T.R., Purcaro, G., Franchina, F.A., Rees, C.A., Nasir, M., Black, A., Hill, J.E., Exhaled human breath analysis in active pulmonary tuberculosis diagnostics by comprehensive gas chromatography-mass spectrometry and chemometric techniques. J Breath Res, 13, 2019.
Beccaria, M., Mellors, T.R., Petion, J.S., Rees, C.A., Nasir, M., Systrom, H.K., Sairistil, J.W., Jean-Juste, M.A., Rivera, V., Lavoile, K., et al. Preliminary investigation of human exhaled breath for tuberculosis diagnosis by multidimensional gas chromatography – time of flight mass spectrometry and machine learning. J Chromatogr B Anal Technol Biomed Life Sci 1074–1075 (2018), 46–50.
Franchina, F.A., Mellors, T.R., Aliyeva, M., Wagner, J., Daphtary, N., Lundblad, L.K.A., Fortune, S.M., Rubin, E.J., Hill, J.E., Towards the use of breath for detecting mycobacterial infection: a case study in a murine model. J Breath Res, 12, 2018.
Mellors, T.R., Blanchet, L., Flynn, J.A.L., Tomko, J., O'Malley, M., Scanga, C.A., Lin, P.L., Hill, J.E., A new method to evaluate macaque health using exhaled breath: a case study of M. tuberculosis in a BSL-3 setting. J Appl Physiol 122 (2017), 695–701.
Purcaro, G., Nasir, M., Franchina, F.A., Rees, C.A., Aliyeva, M., Daphtary, N., Wargo, M.J., Lundblad, L.K.A., Hill, J.E., Breath metabolome of mice infected with Pseudomonas aeruginosa. Metabolomics, 15, 2019.
Nasir, M., Bean, H.D., Smolinska, A., Rees, C.A., Zemanick, E.T., Hill, J.E., Volatile molecules from bronchoalveolar lavage fluid can “rule-in” Pseudomonas aeruginosa and “rule-out” Staphylococcus aureus infections in cystic fibrosis patients. Sci Rep, 8, 2018.
Nizio, K.D., Perrault, K.A., Troobnikoff, A.N., Ueland, M., Shoma, S., Iredell, J.R., Middleton, P.G., Forbes, S.L., In vitro volatile organic compound profiling using GCGC-TOFMS to differentiate bacteria associated with lung infections: a proof-of-concept study. J Breath Res, 10, 2016.
Pesesse, R., Stefanuto, P.H., Schleich, F., Louis, R., Focant, J.F., Multimodal chemometric approach for the analysis of human exhaled breath in lung cancer patients by TD-GC × GC-TOFMS. J Chromatogr B Anal Technol Biomed Life Sci 1114–1115 (2019), 146–153.
Schleich, F.N., Zanella, D., Stefanuto, P.-H., Bessonov, K., Smolinska, A., Dallinga, J.W., Henket, M., Paulus, V., Guissard, F., Graff, S., et al. Exhaled volatile organic compounds are able to discriminate between neutrophilic and eosinophilic asthma. Am J Respir Crit Care Med, 2019, 10.1164/rccm.201811-2210oc.
Bishop, A.C., Libardoni, M., Choudary, A., Misra, B., Lange, K., Bernal, J., Nijland, M., Li, C., Olivier, M., Nathanielsz, P.W., et al. Nonhuman primate breath volatile organic compounds associate with developmental programming and cardio-metabolic status. J Breath Res, 12, 2018 The authors differentiated between intrauterine growth restricted baboons and a control group as well as their corresponding gender based on breath gas analysis. Breath VOCs were quantified using a two-dimensional gas chromatography mass spectrometer. 27 VOCs were identified as statistically discriminatory. The 27 VOCs included 2-pentanone, 2-octanone, 2,2,7,7-tetramethyloctane and 3-methyl-1-heptene, which have not previously been associated with cardio-metabolic disease.
Gruber, B., Keller, S., Groeger, T., Matuschek, G., Szymczak, W., Zimmermann, R., Breath gas monitoring during a glucose challenge by a combined PTR-QMS/GC×GC-TOFMS approach for the verification of potential volatile biomarkers. J Breath Res, 10, 2016 036003.
Zhou, M., Sharma, R., Zhu, H., Li, Z., Li, J., Wang, S., Bisco, E., Massey, J., Pennington, A., Sjoding, M., et al. Rapid breath analysis for acute respiratory distress syndrome diagnostics using a portable two-dimensional gas chromatography device. Anal Bioanal Chem, 2019, 10.1007/s00216-019-02024-5.
Wilde, M.J., Cordell, R.L., Salman, D., Zhao, B., Ibrahim, W., Bryant, L., Ruszkiewicz, D., Singapuri, A., Free, R.C., Gaillard, E.A., et al. Breath analysis by two-dimensional gas chromatography with dual flame ionisation and mass spectrometric detection – method optimisation and integration within a large-scale clinical study. J Chromatogr A 1594 (2019), 160–172.
Gruber, B., Groeger, T., Harrison, D., Zimmermann, R., Vacuum ultraviolet absorption spectroscopy in combination with comprehensive two-dimensional gas chromatography for the monitoring of volatile organic compounds in breath gas: a feasibility study. J Chromatogr A 1464 (2016), 141–146.
Muscalu, A.M., Górecki, T., Comprehensive two-dimensional gas chromatography in environmental analysis. TrAC Trends Anal Chem (Reference Ed) 106 (2018), 225–245.
Gruber, B., Weggler, B.A., Jaramillo, R., Murrell, K.A., Piotrowski, P.K., Dorman, F.L., Comprehensive two-dimensional gas chromatography in forensic science: a critical review of recent trends. TrAC Trends Anal Chem (Reference Ed) 105 (2018), 292–301.
Sampat, A., Lopatka, M., Sjerps, M., Vivo-Truyols, G., Schoenmakers, P., van Asten, A., Forensic potential of comprehensive two-dimensional gas chromatography. TrAC Trends Anal Chem (Reference Ed) 80 (2016), 345–363.
Bayona, J.M., Domínguez, C., Albaigés, J., Analytical developments for oil spill fingerprinting. Trends Environ Anal Chem 5 (2015), 26–34.
Damavandi, H.G., Gupta, A Sen, Nelson, R.K., Reddy, C.M., Interpreting comprehensive two-dimensional gas chromatography using peak topography maps with application to petroleum forensics. Chem Cent J, 10, 2016.
Gros, J., Reddy, C.M., Nelson, R.K., Socolofsky, S.A., Arey, J.S., Simulating gas-liquid-water partitioning and fluid properties of petroleum under pressure: implications for deep-sea blowouts. Environ Sci Technol 50 (2016), 7397–7408.
Nelson, R.K., Gosselin, K.M., Hollander, D.J., Murawski, S.A., Gracia, A., Reddy, C.M., Radović, J.R., Exploring the complexity of two iconic crude oil spills in the gulf of Mexico (Ixtoc i and deepwater Horizon) using comprehensive two-dimensional gas chromatography (GC × GC). Energy Fuels 33 (2019), 3925–3933.
Alexandrino, G.L., Tomasi, G., Kienhuis, P.G.M., Augusto, F., Christensen, J.H., Forensic investigations of diesel oil spills in the environment using comprehensive two-dimensional gas chromatography-high resolution mass spectrometry and chemometrics: new perspectives in the absence of recalcitrant biomarkers. Environ Sci Technol 53 (2019), 550–559.
Kopperi, M., Parshintsev, J., Ruiz-Jiménez, J., Riekkola, M.L., Nontargeted evaluation of the fate of steroids during wastewater treatment by comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry. Environ Sci Pollut Res 23 (2016), 17008–17017.
Kopperi, M., Riekkola, M.L., Non-targeted evaluation of selectivity of water-compatible class selective adsorbents for the analysis of steroids in wastewater. Anal Chim Acta 920 (2016), 47–53.
Blum, K.M., Gallampois, C., Andersson, P.L., Renman, G., Renman, A., Haglund, P., Comprehensive assessment of organic contaminant removal from on-site sewage treatment facility effluent by char-fortified filter beds. J Hazard Mater 361 (2019), 111–122.
Blum, K.M., Andersson, P.L., Renman, G., Ahrens, L., Gros, M., Wiberg, K., Haglund, P., Non-target screening and prioritization of potentially persistent, bioaccumulating and toxic domestic wastewater contaminants and their removal in on-site and large-scale sewage treatment plants. Sci Total Environ 575 (2017), 265–275.
Li, C., Wang, D., Xu, X., Xu, M., Wang, Z., Spatial variations in the occurrence of potentially genotoxic disinfection by-products in drinking water distribution systems in China. Environ Pollut 231 (2017), 1463–1468.
Li, C., Wang, D., Xu, X., Xu, M., Wang, Z., Xiao, R., Tracking changes in composition and amount of dissolved organic matter throughout drinking water treatment plants by comprehensive two-dimensional gas chromatography–quadrupole mass spectrometry. Sci Total Environ 609 (2017), 123–131.
Relić, D., Popović, A., Đorđević, D., Čáslavský, J., Occurrence of synthetic musk compounds in surface, underground, waste and processed water samples in Belgrade, Serbia. Environ Earth Sci, 76, 2017.
Wanda, E.M.M., Mamba, B.B., Msagati, T.A.M., Hydrochemical modelling of water quality in terms of emerging micropollutants in Mpumalanga, Gauteng and North West Provinces. Phys Chem Earth, Parts A/B/C 100 (2017), 143–157.
Cordero, C., Guglielmetti, A., Bicchi, C., Liberto, E., Baroux, L., Merle, P., Tao, Q., Reichenbach, S.E., Comprehensive two-dimensional gas chromatography coupled with time of flight mass spectrometry featuring tandem ionization: challenges and opportunities for accurate fingerprinting studies. J Chromatogr A 1597 (2019), 132–141.
Stefanuto, P.H., Perrault, K.A., Dubois, L.M., L'Homme, B., Allen, C., Loughnane, C., Ochiai, N., Focant, J.F., Advanced method optimization for volatile aroma profiling of beer using two-dimensional gas chromatography time-of-flight mass spectrometry. J Chromatogr A 1507 (2017), 45–52.
Cordero, C., Kiefl, J., Reichenbach, S.E., Bicchi, C., Characterization of odorant patterns by comprehensive two-dimensional gas chromatography: a challenge in omic studies. TrAC Trends Anal Chem (Reference Ed) 113 (2019), 364–378.
Biedermann, M., Munoz, C., Grob, K., Update of on-line coupled liquid chromatography – gas chromatography for the analysis of mineral oil hydrocarbons in foods and cosmetics. J Chromatogr A 1521 (2017), 140–149.
Zoccali, M., Tranchida, P.Q., Mondello, L., On-line liquid chromatography-comprehensive two dimensional gas chromatography with dual detection for the analysis of mineral oil and synthetic hydrocarbons in cosmetic lip care products. Anal Chim Acta 1048 (2019), 221–226.
Bartsch, N., Hutzler, C., Vieth, B., Luch, A., Target analysis of polycyclic aromatic hydrocarbons (PAHs) in consumer products and total content of polycyclic aromatic compounds (PACs). Polycycl Aromat Comp 37 (2017), 114–121.
Walzl, A., Kopacic, S., Bauer, W., Leitner, E., Characterization of natural polymers as functional barriers for cellulose-based packaging materials. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 36 (2019), 976–988 The authors conducted parallel migration and permeation experiments in migration cells using deuterated alkanes. GC-FID, GC-MS, HPLC-GC-FID-MS and GC×GC MS were used for the parallel study of contaminant migration with and without application of a protective biopolymer layer. Migration of mineral oil hydrocarbons could be prevented by up to 90% using an alginate-based polymer.
Barp, L., Biedermann, M., Grob, K., Blas-Y-Estrada, F., Nygaard, U.C., Alexander, J., Cravedi, J.P., Accumulation of mineral oil saturated hydrocarbons (MOSH) in female Fischer 344 rats: comparison with human data and consequences for risk assessment. Sci Total Environ 575 (2017), 1263–1278 The authors investigated the bioaccumulation of the MOSH and MOAH uptake by food in liver spleen and adipose tissue in Fischer. In liver and spleen tissue, the maximum retention of the MOSH in terms of molecular mass was at n-C29, in adipose tissue, it was found to be at nC15/16. The authors concluded that the differentiation between MOSH below and above n-C25 (Class I versus Class II and III oils), used for present regulation, is not supported by their data on accumulation.
Wang, R., Gao, L., Zheng, M., Li, J., Zhang, L., Wu, Y., Wang, G., Xiong, L., Ding, D., Lu, D., et al. Characterization of short- and medium-chain chlorinated paraffins in cereals and legumes from 19 Chinese provinces. Chemosphere, 2019, 10.1016/j.chemosphere.2019.03.148.
Xia, D., Gao, L.R., Zheng, M.H., Li, J.G., Zhang, L., Wu, Y.N., Qiao, L., Tian, Q.C., Huang, H.T., Liu, W Bin, et al. Health risks posed to infants in rural China by exposure to short- and medium-chain chlorinated paraffins in breast milk. Environ Int 103 (2017), 1–7.
Wang, R., Gao, L., Zheng, M., Tian, Y., Li, J., Zhang, L., Wu, Y., Huang, H., Qiao, L., Liu, W., et al. Short- and medium-chain chlorinated paraffins in aquatic foods from 18 Chinese provinces: occurrence, spatial distributions, and risk assessment. Sci Total Environ 615 (2018), 1199–1206.
Qiao, L., Gao, L., Zheng, M., Xia, D., Li, J., Zhang, L., Wu, Y., Wang, R., Cui, L., Xu, C., Mass fractions, ccongener group patterns, and placental transfer of short- and medium-chain chlorinated paraffins in paired maternal and cord serum. Environ Sci Technol 52 (2018), 10097–10103.
Fernando, S., Renaguli, A., Milligan, M.S., Pagano, J.J., Hopke, P.K., Holsen, T.M., Crimmins, B.S., Comprehensive analysis of the Great Lakes top predator fish for novel halogenated organic contaminants by GC×GC-HR-ToF mass spectrometry. Environ Sci Technol 52 (2018), 2909–2917 The authors used a non-targeted screening methodology for the identification of halogenate chemicals in Great Lakes top predator fish. Besides from the U.S. Environmental Protection Agency's Great Lakes Fish Monitoring and Surveillance Program currently targeted species, 60 additional halogenated compounds were identified. Thereby, the most abundant class was found to be halomethoxyphenols accounting for more than 60% of the total concentration of halogenated compounds in top predator fish from all five Great Lakes.
Savareear, B., Escobar-Arnanz, J., Brokl, M., Saxton, M.J., Wright, C., Liu, C., Focant, J.F., Non-targeted analysis of the particulate phase of heated tobacco product aerosol and cigarette mainstream tobacco smoke by thermal desorption comprehensive two-dimensional gas chromatography with dual flame ionisation and mass spectrometric detection. J Chromatogr A, 2019, 10.1016/j.chroma.2019.06.057.
Schwanz, T.G., Bokowski, L.V.V., Marcelo, M.C.A., Jandrey, A.C., Dias, J.C., Maximiano, D.H., Canova, L.S., Pontes, O.F.S., Sabin, G.P., Kaiser, S., Analysis of chemosensory markers in cigarette smoke from different tobacco varieties by GC×GC-TOFMS and chemometrics. Talanta 202 (2019), 74–89.
Savareear, B., Escobar-Arnanz, J., Brokl, M., Saxton, M.J., Wright, C., Liu, C., Focant, J.F., Comprehensive comparative compositional study of the vapour phase of cigarette mainstream tobacco smoke and tobacco heating product aerosol. J Chromatogr A 1581–1582 (2018), 105–115.
Booyens, W., Van Zyl, P.G., Beukes, J.P., Ruiz-Jimenez, J., Kopperi, M., Riekkola, M.-L., Vakkari, V., Josipovic, M., Kulmala, M., Laakso, L., Characterising particulate organic nitrogen at a savannah-grassland region in South Africa. Atmosphere, 10, 2019, 492 (Basel).
Chibwe, L., Manzano, C.A., Muir, D., Atkinson, B., Kirk, J.L., Marvin, C.H., Wang, X., Teixeira, C., Shang, D., Harner, T., et al. Deposition and source identification of nitrogen heterocyclic polycyclic aromatic compounds in snow, sediment, and air samples from the athabasca oil sands region. Environ Sci Technol 53 (2019), 2981–2989.
Hatch, L.E., Jen, C.N., Kreisberg, N.M., Selimovic, V., Yokelson, R.J., Stamatis, C., York, R.A., Foster, D., Stephens, S.L., Goldstein, A.H., et al. Highly speciated measurements of terpenoids emitted from laboratory and mixed-conifer forest prescribed fires. Environ Sci Technol 53 (2019), 9418–9428.
Hatch, L.E., Rivas-Ubach, A., Jen, C.N., Lipton, M., Goldstein, A.H., Barsanti, K.C., Measurements of I/SVOCs in biomass-burning smoke using solid-phase extraction disks and two-dimensional gas chromatography. Atmos Chem Phys 18 (2018), 17801–17817.
Weggler, B.A., Ly-Verdu, S., Jennerwein, M., Sippula, O., Reda, A.A., Orasche, J., Gröger, T., Jokiniemi, J., Zimmermann, R., Untargeted identification of wood type-specific markers in particulate matter from wood combustion. Environ Sci Technol 50 (2016), 10073–10081.
Lebedev, A.T., Polyakova, O.V., Mazur, D.M., Artaev, V.B., Canet, I., Lallement, A., Vaïtilingom, M., Deguillaume, L., Delort, A.M., Detection of semi-volatile compounds in cloud waters by GC×GC-TOF-MS. Evidence of phenols and phthalates as priority pollutants. Environ Pollut 241 (2018), 616–625.
Brits, M., Gorst-Allman, P., Rohwer, E.R., De Vos, J., de Boer, J., Weiss, J.M., Comprehensive two-dimensional gas chromatography coupled to high resolution time-of-flight mass spectrometry for screening of organohalogenated compounds in cat hair. J Chromatogr A 1536 (2018), 151–162.
Oeder, S., Kanashova, T., Sippula, O., Sapcariu, S.C., Streibel, T., Arteaga-Salas, J.M., Passig, J., Dilger, M., Paur, H.-R.R., Schlager, C., et al. 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, 2015, 10.1371/journal.pone.0126536 The authors investigate the biological effect on human health induced by aerosol particles from ship fuel combustion (diesel and heavy-duty oil). Thereby, comprehensive chemical and physical characterization of the aerosols properties was linked to effects observed in a lung model. Despite a lower content of known toxic compounds, combustion particles from the clean shipping diesel influenced several essential pathways of lung cell metabolism more strongly than particles from the unrefined heavy-duty oil. Thereby, the study correlated findings of different analytical chemical methods to the results from a biological lung model, showing the exposome character and suitability of GC×GC.
