Current standing and future prospects for the technologies proposed to transform toxicity testing in the 21st century

The National Academy of Sciences publication, Toxicity Testing in the 21st Century: A Vision and a Strategy, proposes a paradigm shift in toxicology from current animal-based testing towards the application of emerging technologies, i.e., assays based on human cells or non-mammalian models, high throughput testing, omics approaches, systems biology, and computational modeling. These technologies should be used to identify how chemicals interact with cellular response networks and alter them to toxicity pathways. According to the authors, such a new paradigm would provide a better scientific understanding and more adequate data to predict the adverse effects of chemicals on human health. As expected from a vision document, the report enthusiastically and optimistically describes a radical transformation of toxicology from current practices to a new approach. Several toxicologists have commented on the report, and although they generally confirm the importance of the vision, they pose critical questions regarding its feasibility. Unlike the theoretical concepts, which are carefully described, many practical aspects of how to establish the vision are less well defined. Today's technologies provide great opportunities, although many challenges remain regarding their development, implementation, and validation to adequately assess human health effects. To bring the envisioned toxicology closer to concrete implementation, it is important to identify the current knowledge gaps in the vision and develop solutions. The goal of this review is to evaluate the technologies proposed as to their maturation to transform toxicity testing in the 21st century. This paper will provide an overview of the current standing by defining advantages, limitations, and developmental needs. In doing so, I do not intend to point out obstacles but, rather, to focus on current opportunities to advance toxicity testing for human risk assessment.