RNA interference (RNAi) is a biological process in which small ribonucleic acid (RNA) molecules inhibit gene expression, typically by causing the enzymatic destruction of specific messenger RNA (mRNA) molecules, which are the templates for the synthesis of proteins. This process is commonly referred to as post-transcriptional gene silencing (PTGS); that is, mRNA is transcribed from the DNA gene but before the message is translated into proteins by ribosomes, the mRNA is blocked or otherwise destroyed by an enzymatic process guided by a specific non-coding small interfering RNA (siRNA) or microRNA (miRNA). The purpose of the OECD work leading to this paper was to develop a broad set of recommendations relating to risk assessment considerations for exogenously-applied dsRNA-based products, with a focus on issues relating to data requirements for determining the environmental fate of sprayable RNA molecules and for examining the potential risks to non-target organisms.