Heritable hazards of smoking: Applying the "clean sheet" framework to further science and policy

All the cells in our bodies are derived from the germ cells of our parents, just as our own germ cells become the bodies of our children. The integrity of the genetic information inherited from these germ cells is of paramount importance in establishing the health of each generation and perpetuating our species into the future. There is a large and growing body of evidence strongly suggesting the existence of substances that may threaten this integrity by acting as human germ cell mutagens. However, there generally are no absolute regulatory requirements to test agents for germ cell effects. In addition, the current regulatory testing paradigms do not evaluate the impacts of epigenetically mediated intergenerational effects, and there is no regulatory framework to apply new and emerging tests in regulatory decision making. At the 50th annual meeting of the Environmental Mutagenesis and Genomics Society held in Washington, DC, in September 2019, a workshop took place that examined the heritable effects of hazardous exposures to germ cells, using tobacco smoke as the example hazard. This synopsis provides a summary of areas of concern regarding heritable hazards from tobacco smoke exposures identified at the workshop and the value of the Clean Sheet framework in organizing information to address knowledge and testing gaps.