title: Predicting GHS toxicity using RTCA and discrete-time Fourier transform.
abstract: In order to promote the acceptance of cell-based toxicity testings, the accuracy of cytotoxicity test must be determined when compared to in vivo results. Traditional methods of cytotoxicity analysis, such as LC[Formula: see text] (concentration where 50% of the cells are killed) can be problematic since they have been found to vary with time. Technological advances in cytotoxicity testing make it easy to record the dynamic data on changes in cell proliferation, morphology, and damage. To effectively and reasonably analyze the dynamic data, we present a new in vitro toxicity assessed method using the discrete-time Fourier transform (DTFT) which maps the measured cell index from the time domain to the frequency domain. The direct current (DC) component of the DTFT is extracted as a feature which reflects the intensity of cytotoxicity. The smaller the value, the higher the cytotoxicity. Then, a novel toxicity index, as expressed in terms of DC[Formula: see text], is calculated. Results generated with selected test chemicals are compared favorably with data obtained from The Interagency Coordinating Committee on the Validation of Alternative Method (ICCVAM) report concerning the prediction of acute systemic toxicity in rodents. The method can be applied with the standard and high throughput to estimate acute rodent oral toxicity which reduces the number of animals required in subsequent pharmacological/toxicological studies.
authors.affiliation: * School of Electrical & Information Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China.|† Changzhou College of Information Technology, Changzhou, Jiangsu 213164, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Chen
authors.affiliation: * School of Electrical & Information Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
authors.forename: Tianhong
authors.initials: T
authors.lastname: Pan
authors.affiliation: * School of Electrical & Information Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
authors.forename: Tianqing
authors.initials: T
authors.lastname: Pu
authors.affiliation: ‡ Department of Chemical & Materials Engineering, University of Alberta, Edmonton, Alberta, T6G 2G6, Canada.
authors.forename: Biao
authors.initials: B
authors.lastname: Huang
authors.affiliation: § Alberta Centre for Toxicology, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.
authors.forename: Dorothy Yu
authors.initials: DY
authors.lastname: Huang
authors.affiliation: ¶ Alberta Health, Edmonton, Alberta, T5J 1S6, Canada.
authors.forename: Weiping
authors.initials: W
authors.lastname: Zhang
authors.affiliation: ∥ Division of Analytical and Environmental Toxicology, University of Alberta, Edmonton, Alberta, T6G 2G3, Canada.
authors.forename: Stephan
authors.initials: S
authors.lastname: Gabos
authors.affiliation: ** Department of Biology, ACEA Biosciences, San Diego, CA 92121, USA.
authors.forename: Can
authors.initials: C
authors.lastname: Jin
mesh_terms: D000284:Administration, Oral; D000465:Algorithms; D002460:Cell Line; D019295:Computational Biology / Q000379:methods*; D017097:Electric Impedance; D005583:Fourier Analysis; D006801:Humans; D007928:Lethal Dose 50; D018675:Toxicity Tests / Q000295:instrumentation / Q000379:methods*
keywords: Discrete-time Fourier transform (DTFT); globally harmonized system (GHS); high-throughput screening (HTS); in vitro toxicity assay; registry of cytotoxicity (RC); time-dependent cellular response curve (TCRC)