Workshop Report 32


Wrapping up the workshop, Helmut Greim, Munich Technical University, Germany, recollected that ncRNAs play important roles in maintaining cellular homeostasis and in the evolvement of phenotypic alterations. To make available ncRNAs as biomarkers for regulatory toxicology and RA, normal and adverse ncRNA profiles and dose-response relationships of effects should be determined, and ncRNA expression profiles should be linked to phenotypic alterations. Further, it should be determined whether ncRNA levels in specific body fluids reflect levels in specific target tissues. Even though a number of research projects demonstrated a lack of toxicologically relevant uptake and activity of ingested RNAs, bioavailability of ingested ncRNAs and potential impacts to the consuming organism may merit further investigation.

In the long-term, knowledge of ncRNAs may serve to understand specific mechanisms of toxicity, e.g. to assess genotoxic and non-genotoxic carcinogenicity, reproductive / transgenerational toxicity, mixture toxicology, and long-term low-dose effects. All ncRNA methodologies should be standardised and validated and guidance for the reporting of data should be established. NcRNA analysis tools can be incorporated into standardised in vitro assays and in vivo repeated-dose studies used for RA applying a holistic approach that may take epigenetic mechanisms, gene methylation and acetylation and ‘-omics’ technologies into account. Importantly, all those involved in regulatory toxicology and the RA of substances should be continuously informed on the potential applicability of ncRNA data for RA. In the long term, ncRNA expression profiling may improve RA by enhancing hazard predictions at earlier stages, and it may serve the goals to reduce animal testing as well as reduce the costs and time required to market innovative products.