Construction of an In Vitro Air–Liquid Interface Exposure System to Assess the Toxicological Impact of Gas and Particle Phase of Semi-Volatile Organic Compounds

November 26, 2022

https://doi.org/10.3390/toxics10120730

Stephanie Binder 1,2, Narges Rastak 1,2, Erwin Karg 1, Anja Huber 1, Evelyn Kuhn 1, George C. Dragan 3, Christian Monsé 4, Dietmar Breuer 5, Sebastiano Di Bucchianico 1,2 , Mathilde N. Delaval 1, Sebastian Oeder 1, Martin Sklorz 1 and Ralf Zimmermann 1,2

1 Joint Mass Spectrometry Center (JMSC) at Comprehensive Molecular Analytics (CMA), Helmholtz Zentrum München, 85764 Neuherberg, Germany
2 Joint Mass Spectrometry Center (JMSC) at Analytical Chemistry, Institute of Chemistry, University of Rostock, 18051 Rostock, Germany
3 Berufsgenossenschaft Handel und Warenlogistik (BGHW), 80639 Munich, Germany
4 Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), 44789 Bochum, Germany
5 Institute of Occupational Safety of the German Social Accident Insurance (IFA), 53757 Sankt Augustin, Germany

Abstract
Anthropogenic activities and industrialization render continuous human exposure to semi-volatile organic compounds (SVOCs) inevitable. Occupational monitoring and safety implementations consider the inhalation exposure of SVOCs as critically relevant. Due to the inherent properties of SVOCs as gas/particle mixtures, risk assessment strategies should consider particle size-segregated SVOC association and the relevance of released gas phase fractions. We constructed an in vitro air–liquid interface (ALI) exposure system to study the distinct toxic effects of the gas and particle phases of the model SVOC dibutyl phthalate (DBP) in A549 human lung epithelial cells. Cytotoxicity was evaluated and genotoxic effects were measured by the alkaline and enzyme versions of the comet assay. Deposited doses were assessed by model calculations and chemical Analysis using liquid chromatography tandem mass spectrometry. The novel ALI exposure system was successfully implemented and revealed the distinct genotoxic effects of the gas and particle phases of DBP. The empirical measurements of cellular deposition and the model calculations of the DBP particle phase were concordant.The model SVOC DBP showed that inferred oxidative DNA Damage may be attributed to particle-related effects. While pure gas phase exposure may follow a distinct mechanism of genotoxicity, the contribution of the gas phase to total aerosol was comparably low.

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