Editorial: Five grand challenges in toxicology

The well-known dictum “the dose makes the poison” is familiar to every student of toxicology, though it is important to add that there is no risk of adverse effects without exposure. This essential point is sometimes overlooked when new and emerging risks such as engineered nanomaterials are being discussed (Fadeel, 2019). The question of the dose of a poisonous substance or toxicant relates to the question of toxicology as a scientific discipline–is toxicology the science of poisons, or has toxicology evolved into a “science of safety”? (Collins et al., 2008). Furthermore, are we ready to shed the predominantly observational science of the past and usher in a new predictive toxicological science of the future? Fifteen years ago, Thomas Hartung lamented that toxicological studies search for rare events using imperfect models–usually addressing one substance at a time (Hartung, 2009). He then listed scientific and strategic developments that are required to implement a new regulatory toxicology including the need for standardization and validation of new approaches, as well as the systematic integration of these approaches into testing strategies (Hartung, 2009). The question is, what should serve as the benchmark given that conventional validation processes often rely on animal tests that may lack adequate validation themselves (Nel and Malloy, 2017). Notwithstanding, it is evident from these discussions that toxicology is both a basic and an applied science. The objectives are thus two-fold: to uncover mechanisms of adverse effects of substances on biological systems while also leveraging this knowledge to protect human health and the environment. To facilitate this translation of knowledge into practice, the flow of information should be bidirectional. Indeed, to promote the field, a dialogue between researchers and regulators is required to identify the kind of knowledge that is needed.