Towards tailored assays for cell-based approaches to toxicity testing

Consensus report on the future of animal-free systemic toxicity testing

“…4). the combination of high throughput screening assays with traditional cellular assays has been supplemented by in vitro-in vivo mathematical extrapolations, systems biology (computer models of cell regulation) and other approaches by many leading academic and governmental organizations to provide integrated testing strategies (leist et al, 2012a,b;Sturla et al, 2014;Hartung et al, 2013b;Kavlock et al, 2012;Andersen et al, 2011;Hartung and McBride, 2011;Bouhifd et al, 2014;Rossini and Hartung, 2012).…”

“…Only few programs use simple assays of elementary biochemical and cellular function (e.g., ToxcCast TM Program). Over time, more and more critical biomarkers of toxicity may be identified by the application of HCS (highcontent screening) and omics technologies to the complex systems, and simple test systems may suffice to measure key processes (Rossini and Hartung, 2012). Case studies, e.g., from PBPK (physiologically based pharmacokinetic modeling) and skin sensitization fields, could be used as learning models for the transition.…”

In vitro-ex vivo model systems for nanosafety assessment

“…Industrial nanomaterials are regulated under the REACH and OECD guidelines following the tracks of chemicals with toxicity testing for product fillings. In addition, within the EU there are considerable efforts to replace the expensive and controversial discussed animal testing with in vitro alternatives (5)(6)(7). Despite the fact that changing this regulation is a long process, first efforts have been successful within the EU with a ban on animal testing for skin allergies of cosmetics (80).…”

“…A full assessment of the safety of such materials following traditional regulations would be extremely cost-intensive and time-consuming. Moreover the outcome of animal testing regarding its predictive power for human beings poorly correlated, due to physiological and biochemical species dissimilarities (7). Furthermore, the principle of the 3Rs -replacement, reduction and refinement -became an increasing public and legal demand which for ethical reasons supports the replacement of animal use with more human-relevant alternatives (8).…”

Advanced humanin vitromodels to assess metal oxide nanoparticle-cell interactions

“…A full assessment of the potential side effects according to today's regulations would be extremely cost intensive and time consuming, and its relevance for human beings is still doubtful. 4 Therefore new concepts for more effi cient, cost-effective, and evidence-based testing strategies toward mechanistical-based understanding of the nanoparticlebiology interaction are proposed. 5 Despite the broad use of traditional cell-based in vitro cell monocultures, it is recognized that these models lack phenotypic details, physiological functions, or depict the complex cross-talks between different cells only partly or not at all.…”