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Toxicol Sci

Title:		Benchmark Dose Modeling Approaches for Volatile Organic Chemicals Using a Novel Air-Liquid Interface In Vitro Exposure System
Author(s):		Speen AM; Murray JR; Krantz QT; Davies D; Evansky P; Harrill JA; Everett LJ; Bundy JL; Dailey LA; Hill J; Zander W; Carlsten E; Monsees M; Zavala J; Higuchi MA;
Address:		"Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, Tennessee 37830, USA. CPHEA, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27709, USA. CCTE, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27709, USA. Oak Ridge Associated Universities (ORAU), Oak Ridge, Tennessee 37830, USA. MedTec BioLab Inc., Hillsborough, North Carolina 27278, USA"
Journal Title:		Toxicol Sci
Year:		2022
Volume:		188
Issue:		1
Page Number:		88 - 107
DOI:		10.1093/toxsci/kfac040
ISSN/ISBN:		1096-0929 (Electronic) 1096-6080 (Print) 1096-0929 (Linking)
Abstract:		"Inhalation is the most relevant route of volatile organic chemical (VOC) exposure; however, due to unique challenges posed by their chemical properties and poor solubility in aqueous solutions, in vitro chemical safety testing is predominantly performed using direct application dosing/submerged exposures. To address the difficulties in screening toxic effects of VOCs, our cell culture exposure system permits cells to be exposed to multiple concentrations at air-liquid interface (ALI) in a 24-well format. ALI exposure methods permit direct chemical-to-cell interaction with the test article at physiological conditions. In the present study, BEAS-2B and primary normal human bronchial epithelial cells (pHBEC) are used to assess gene expression, cytotoxicity, and cell viability responses to a variety of volatile chemicals including acrolein, formaldehyde, 1,3-butadiene, acetaldehyde, 1-bromopropane, carbon tetrachloride, dichloromethane, and trichloroethylene. BEAS-2B cells were exposed to all the test agents, whereas pHBECs were only exposed to the latter 4 listed above. The VOC concentrations tested elicited only slight cell viability changes in both cell types. Gene expression changes were analyzed using benchmark dose (BMD) modeling. The BMD for the most sensitive gene set was within one order of magnitude of the threshold-limit value reported by the American Conference of Governmental Industrial Hygienists, and the most sensitive gene sets impacted by exposure correlate to known adverse health effects recorded in epidemiologic and in vivo exposure studies. Overall, our study outlines a novel in vitro approach for evaluating molecular-based points-of-departure in human airway epithelial cell exposure to volatile chemicals"
Keywords:		Acetaldehyde *Air Pollutants Benchmarking Formaldehyde Humans *Volatile Organic Compounds/analysis in vitro Voc benchmark dose cell culture exposure system inhalation transcriptomics;
Notes:		"MedlineSpeen, Adam M Murray, Jessica R Krantz, Quentin Todd Davies, David Evansky, Paul Harrill, Joshua A Everett, Logan J Bundy, Joseph L Dailey, Lisa A Hill, Jazzlyn Zander, Wyatt Carlsten, Elise Monsees, Michael Zavala, Jose Higuchi, Mark A eng EPA999999/ImEPA/Intramural EPA/ EPA/EPA/ Research Support, U.S. Gov't, Non-P.H.S. 2022/04/16 Toxicol Sci. 2022 Jun 28; 188(1):88-107. doi: 10.1093/toxsci/kfac040"