Prediction of acute inhalation toxicity using cytotoxicity data from human lung epithelial cell lines. Issue 7 (21st October 2020)

• Record Type: Journal Article
• Authors: Lim, Seong Kwang; Yoo, Jean; Kim, Haewon; Lim, Yeon‐Mi; Kim, Woong; Shim, Ilseob; Kim, Ha Ryong; Kim, Pilje; Eom, Ig‐chun
• Is Part Of: Journal of applied toxicology. Volume 41:Issue 7(2021)
• Page Start: 1038
• Page End: 1049
• Publication Date: 2020-10-21
• Subjects: A549 cell line -- acute inhalation toxicity -- cytotoxicity -- GHS category -- in vitro–in vivo correlation -- linear regression -- ROC curve analysis; Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.4090
• Languages: English
• ISSNs: 0260-437X

Abstract

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 (LC50 ) (rat, inhalation, 4 h) and half maximal inhibitory concentration (IC50 ) (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 LC50, but without IC50, data to obtain the IC50 values. A weak correlation was observed between the IC50 and LC50 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 IC50 and 4‐h LC50, 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. Abstract : We investigated the submerged 2‐D cell culture model as a method to predict acute inhalation toxicity. LC50 and IC50 data for 59 substances were obtained from the literature and by experiments. We observed a strong correlation and predictive ability between IC50 and LC50 in substances with high water solubility and low vapor pressure. This suggests that simple submerged 2‐D cell culture models may be used as an indicator of in vivo acute inhalation toxicity for these types of substances.