Noncoding RNAs and Risk Assessment Science: an ECETOC/Cefic LRI Workshop Report

Brussels, August 2016

It is well understood that DNA is the basic instruction manual that explains how to make a living organism, such as a human body. RNA is a messenger sent from the coding DNA-sequences called genes to make proteins, the essential building bricks for cells. However, studies of cells also identified RNA that is not directly involved in protein synthesis. Initially these were thought to be “evolutionary junk” collected over the eon of time in evolution. It is now understood that these noncoding RNAs (ncRNAs) play an important role in gene regulation and disease and that exposure to man-made chemicals can affect how these small molecules work.

In March 2016, ECETOC organised a workshop in collaboration with the Cefic Long-range Research Initiative (LRI) to discuss the state-of-the-art research on ncRNAs as potential biomarkers in regulatory toxicology for the assessment of product safety. A promising avenue is using measurements of ncRNAs as markers of toxicity, particularly tumour induction, which is usually examined in high-tiered studies requiring the use of many experimental animals. Thus, such measurements hold the potential to significantly reduce animal testing for the carcinogenic potential of chemicals. It was however agreed that while significant progress has been achieved careful evaluation is still required to determine the utility of such biomarkers in assessing product safety.

The Workshop identified 3 focus areas for ECETOC to progress the application of ncRNAs for regulatory toxicology:

1. Comprehensive literature reviews to identify candidate ncRNAs for further assessment as potential biomarkers of toxicity;
2. Develop consensus on how to conduct and report ncRNA expression profiling in a toxicological context to support applicability for regulatory decision-making;
3. Conduct experimental projects to evaluate the toxicological relevance of the expression profiles of selected ncRNAs.

It was agreed technical advances in measuring biomarkers such as ncRNAs have the potential to enhance understanding of toxicological effects thereby improving chemical safety assessment and developing new products. ECETOC is encouraged to progress the understanding of how ncRNAs might be involved in toxicological pathogenicity and how measurements of such biomarkers can be used in a regulatory context.

The findings of the Workshop have been published as ECETOC Workshop Report no.32: Noncoding RNAs and Risk Assessment Science. 3 – 4 March 2016, Málaga.