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Benchmark Dose Modeling Approaches for Volatile Organic Chemicals using a Novel Air-Liquid Interface In Vitro Exposure System
Citation:
Speen, A., J. Murray, Todd Krantz, D. Davies, P. Evansky, J. Harrill, L. Everett, J. Bundy, L. Dailey, W. Zander, E. Carlsten, M. Monsees, J. Hill, J. Zavala, AND M. Higuchi. Benchmark Dose Modeling Approaches for Volatile Organic Chemicals using a Novel Air-Liquid Interface In Vitro Exposure System. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 188(1):88-107, (2022). https://doi.org/10.1093/toxsci/kfac040
Impact/Purpose:
The data from this project characterizes the impact volatile organic chemicals have on human airway epithelial cells. The data generated will be useful to state, federal, and other regulatory agencies in the development of hazard assessments for chemicals routinely used in volatile and aerosolized forms. The chemicals studied are comprised of biocide formulations, preservatives, fertilizers, pesticides, refrigerants, and combustion products. Importantly, the data presented here will be highly valuable for making scientifically based decisions on the variable and adverse effects of volatile chemicals on human inhalation health and inform future in vitro and in vivo toxicity studies.
Description:
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 molecularbased points-of-departure in human airway epithelial cell exposure to volatile chemicals.
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DOI: Benchmark Dose Modeling Approaches for Volatile Organic Chemicals using a Novel Air-Liquid Interface In Vitro Exposure System