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J Appl Toxicol

Title:		Prediction of acute inhalation toxicity using cytotoxicity data from human lung epithelial cell lines
Author(s):		Lim SK; Yoo J; Kim H; Lim YM; Kim W; Shim I; Kim HR; Kim P; Eom IC;
Address:		"Environmental Health Research Department, National Institute of Environmental Research, Incheon, Republic of Korea. College of Pharmacy, Daegu Catholic University, Gyeongsan, Republic of Korea"
Journal Title:		J Appl Toxicol
Year:		2021
Volume:		20201021
Issue:		7
Page Number:		1038 - 1049
DOI:		10.1002/jat.4090
ISSN/ISBN:		1099-1263 (Electronic) 0260-437X (Linking)
Abstract:		"Recent research on in vitro systems has focused on mimicking the in vivo situation of cells within the respiratory system. However, few studies have predicted inhalation toxicity using conventional and simple submerged two-dimensional (2D) cell culture models. We investigated the conventional submerged 2-D cell culture model as a method for the prediction of acute inhalation toxicity. Median lethal concentration (LC(50) ) (rat, inhalation, 4 h) and half maximal inhibitory concentration (IC(50) ) (lung or bronchial cell, 24 h) data for 59 substances were obtained from the literature and by experiments. Cytotoxicity assays were performed on 44 substances with reported LC(50) , but without IC(50) , data to obtain the IC(50) values. A weak correlation was observed between the IC(50) and LC(50) of all substances. Semi-volatile organic compounds (SVOCs) and non-VOCs (NVOCs) (16 substances) with a water solubility of >/=1 g/L were strongly correlated between 24-h IC(50) and 4-h LC(50) , and this had an excellent predictive ability to distinguish between Categories 1-3 and 4 (Globally Harmonized System classification for acute inhalation toxicity). Our results suggest that the submerged 2-D cell culture model may be used to predict in vivo acute inhalation toxicity for substances with a water solubility of >/=1 g/L in SVOCs and NVOCs"
Keywords:		"Administration, Inhalation Animal Testing Alternatives Animals Cell Culture Techniques Cell Line Epithelial Cells/*drug effects Humans *Inhalation Exposure Lethal Dose 50 Lung/*drug effects Rats Toxicity Tests/*methods A549 cell line GHS category ROC curv;"
Notes:		"MedlineLim, Seong Kwang Yoo, Jean Kim, Haewon Lim, Yeon-Mi Kim, Woong Shim, Ilseob Kim, Ha Ryong Kim, Pilje Eom, Ig-Chun eng Research Support, Non-U.S. Gov't England 2020/10/22 J Appl Toxicol. 2021 Jul; 41(7):1038-1049. doi: 10.1002/jat.4090. Epub 2020 Oct 21"