Regulatory toxicology in the twenty-first century: challenges, perspectives and possible solutions

Abstract

The advent of new testing systems and "omics"-technologies has left regulatory toxicology facing one of the biggest challenges for decades. That is the question whether and how these methods can be used for regulatory purposes. The new methods undoubtedly enable regulators to address important open questions of toxicology such as species-specific toxicity, mixture toxicity, low-dose effects, endocrine effects or nanotoxicology, while promising faster and more efficient toxicity testing with the use of less animals. Consequently, the respective assays, methods and testing strategies are subject of several research programs worldwide. On the other hand, the practical application of such tests for regulatory purposes is a matter of ongoing debate. This document summarizes key aspects of this debate in the light of the European "regulatory status quo", while elucidating new perspectives for regulatory toxicity testing.

A guide to nanosafety testing: Considerations on cytotoxicity testing in different cell models

“…Furthermore, skin and lung models may be exposed at the airliquid interface (Stoehr et al 2015) while ingestion models could include a more realistic digestion fluid on one side. Finally, cell models are being refined, and new developments such as microfluidic systems and organoids promise to allow more realistic models and to eliminate the species differences in toxicological data by using human cells (Esch et al 2014;Tralau et al 2015).…”

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

“…In the case of the cosmetic industry, efforts to establish alternative testing models have been driven considerably by the introduction of the Cosmetics Regulation (EU, 2009a), which banned animal experiments and literally forced this sector to investigate (and to invest!) in alternative testing methods; likewise, the REACH legislation with its aim to reduce live animal testing has been proven to be a driver for the development and regulatory application of alternative testing approaches (EU, 2006;Hartung, 2010;Tralau et al, 2015). Together with the fact that there had already been quite some progress in reconstructing skin equivalents as an alternative to native human skin transplants for treating severe burns, this has led to the advanced status of non-animal models for safety testing of cosmetics and other topically applied chemicals.…”

Air–Liquid InterfaceIn VitroModels for Respiratory Toxicology Research: Consensus Workshop and Recommendations

“…Their use may also provide better information on in vivo processes in humans and allow investigations into mechanisms that occur in humans (some of which might differ or do not exist in animal models due to variations in physiology). 14 Their increasing use in EU-funded projects (e.g., FUTURE-NANONEEDS, npSCOPE, SPOTVIEW, NANOREG, NANOREG2, PneumoNP) highlights the levels of interest in ALI models and potential realms of application. While their increased use is starting to provide novel information on endpoints and potential mechanisms, stakeholders at the EU level have raised questions about levels of validation and standardization of the methods and concerns about how much information coming from the projects in particular can actually be compared.…”