Over the past decade, regulatory bodies such as the World Health Organisation (WHO) and the U.S. Food and Drug Administration (FDA) have been working towards regulation to support harm reduction for smokers. It was proposed to introduce ceilings on specific compounds in tobacco smoke which are believed to be harmful or potentially harmful. Different lists of compounds have been proposed. Unfortunately, many of these compounds are negatively correlated and to reach these ceilings no real solution exists by breeding or by blending.

In recent years, WHO and FDA have worked towards developing regulation to lower nicotine in tobacco products. While WHO proposes to reach the limit of feasibility, the FDA is working on the non-addictive limit. Lowering nicotine content in tobacco products may prove counterproductive with the increase of illicit trade and the composition of products escaping all control.

However, with the development of new genetic tools, another risk reduction strategy can be considered in a comprehensive way. Toxicogenomics and transcriptomics by high-throughput sequencing (RNAseq) enable the assessment of cigarette smoke toxicity on human cells. This type of analysis could be integrated into an association mapping approach in the tobacco plant. It can be expected to identify molecular makers related to global mutagenicity of cigarette smoke. New tobacco cultivars could be developed taking into consideration the reduction of risk for the smoker.