Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Abstract

SummaryModels of the outer epithelia of the human body -namely the skin, the intestine and the lung -have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report.

Small Size Silver Nanoparticle’s Corrosive and Hazardous Manifestations on Mature and Developing Kidney Following Accumulation in Pregnant Mice and Offspring’s after Serial Oral Bolus Experimental Application: A New Chapter in Teratogenicity and Toxicity Search

“…They also found toxic sequence in kidney cell line in this experiment [30]. Gordon et al recently researched non-animal models of epithelial barriers (skin, kidney, intestine and lung) in research, industrial applications and found regulatory toxicology dilemma in these vital organs in histological and gross view [31].…”

The need for strategic development of safety sciences

“…CAAT has started a number of collaborative programs to advance safety sciences, which include the Human Toxome Collaboration (see above), the Evidence-based Toxicology Collaboration (see below), the Good Cell Culture Practice Collaboration (Pamies et al, 2017) building on earlier work steered by ECVAM (Coecke et al, 2005), the Good ReadAcross Practice Collaboration (Patlewicz et al, 2014, Ball et al, 2016Zhu et al, 2016), the Refinement Collaboration (Zurlo and Hutchinson, 2014) and others. CAAT's transatlantic think tank for toxicology (t 4 ) has organized more than 30 workshops to advance concepts of toxicology such as integrated testing strategies (Hartung et al, 2013b;Rovida et al, 2015b), epithelial barrier models (Gordon et al, 2015), 3D cell cultures (Alépée et al, 2014), microphysiological systems (Marx et al, 2016), high-content imaging (van Vliet et al, 2014), and has commissioned a number of white papers. (Andersen et al, 2011.…”

Opinion versus evidence for the need to move away from animal testing

“…We can analyze the kinetics of substances in different species, including man, and improve our extrapolation to humans (Bale et al, 2014;Tsaioun et al, 2016), especially by integrating information from in vitro epithelial barrier models (Gordon et al, 2015). We can use and properly report the right statistics, which in turn will strongly increase the necessary animal group sizes.…”