title: The virtual cell based assay: Current status and future perspectives.
abstract: In order to replace the use of animals in toxicity testing, there is a need to predict in vivo toxic doses from concentrations that cause toxicological effects in relevant in vitro systems. The Virtual Cell Based Assay (VCBA) estimates time-dependent concentration of a test chemical in the cell and cell culture for a given in vitro system. The concentrations in the different compartments of the cell and test system are derived from ordinary differential equations, physicochemical parameters of the test chemical and properties of the cell line. The VCBA has been developed for a range of cell lines including BALB/c 3T3 cells, HepG2, HepaRG, lung A459 cells, and cardiomyocytes. The model can be used to design and refine in vitro experiments and extrapolate in vitro effective concentrations to in vivo doses that can be applied in risk assessment. In this paper, we first discuss potential applications of the VCBA: i) design of in vitro High Throughput Screening (HTS) experiments; ii) hazard identification (based on acute systemic toxicity); and iii) risk assessment. Further extension of the VCBA is discussed in the second part, exploring potential application to i) manufactured nanomaterials, ii) additional cell lines and endpoints, and considering iii) other opportunities.
authors.affiliation: Chemical Safety and Alternative Methods Unit incorporating EURL ECVAM, Directorate Health, Consumers and Reference Materials, European Commission, Joint Research Centre, Ispra, Italy.
authors.forename: Rabea
authors.initials: R
authors.lastname: Graepel
authors.affiliation: Chemical Safety and Alternative Methods Unit incorporating EURL ECVAM, Directorate Health, Consumers and Reference Materials, European Commission, Joint Research Centre, Ispra, Italy. Electronic address: lara.lamon@ec.europa.eu.
authors.forename: Lara
authors.initials: L
authors.lastname: Lamon
authors.affiliation: Chemical Safety and Alternative Methods Unit incorporating EURL ECVAM, Directorate Health, Consumers and Reference Materials, European Commission, Joint Research Centre, Ispra, Italy.
authors.forename: David
authors.initials: D
authors.lastname: Asturiol
authors.affiliation: Chemical Safety and Alternative Methods Unit incorporating EURL ECVAM, Directorate Health, Consumers and Reference Materials, European Commission, Joint Research Centre, Ispra, Italy.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Berggren
authors.affiliation: Chemical Safety and Alternative Methods Unit incorporating EURL ECVAM, Directorate Health, Consumers and Reference Materials, European Commission, Joint Research Centre, Ispra, Italy.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Joossens
authors.affiliation: Chemical Safety and Alternative Methods Unit incorporating EURL ECVAM, Directorate Health, Consumers and Reference Materials, European Commission, Joint Research Centre, Ispra, Italy.
authors.forename: Alicia
authors.initials: A
authors.lastname: Paini
authors.affiliation: Chemical Safety and Alternative Methods Unit incorporating EURL ECVAM, Directorate Health, Consumers and Reference Materials, European Commission, Joint Research Centre, Ispra, Italy.
authors.forename: Pilar
authors.initials: P
authors.lastname: Prieto
authors.affiliation: Chemical Safety and Alternative Methods Unit incorporating EURL ECVAM, Directorate Health, Consumers and Reference Materials, European Commission, Joint Research Centre, Ispra, Italy.
authors.forename: Maurice
authors.initials: M
authors.lastname: Whelan
authors.affiliation: Chemical Safety and Alternative Methods Unit incorporating EURL ECVAM, Directorate Health, Consumers and Reference Materials, European Commission, Joint Research Centre, Ispra, Italy.
authors.forename: Andrew
authors.initials: A
authors.lastname: Worth
mesh_terms: D000818:Animals; D002460:Cell Line; D057166:High-Throughput Screening Assays; D006801:Humans; D008954:Models, Biological; D018570:Risk Assessment
keywords: Chemical fate; In vitro; Nanomaterial; Toxicity; VCBA; Virtual cell