Practical considerations in selecting appropriate reference chemicals in setting new in vitro test systems for cardiotoxicity testing

The exposure of humans to various chemical compounds, such as pesticides, drugs, and their mixtures might have a negative health impact. Indeed, several studies highlighted a relationship between chemicals and cardiovascular disease (CVD), one of the leading causes of world mortality. However, the evaluation of the potential cardiotoxic effects of chemicals is poorly addressed and regulated except for drugs. To address some of the current gaps, valuable support can arise from in vitro testing methodologies involving innovative biomaterials and addressing, at the same time, the regulatory needs during their development1. There are several critical aspects in the development of new in vitro methods for regulatory testing, and among them, the identification of golden standard compounds to properly assess the response of the new test system to known stressors is crucial to understand the behavior of the new test method and facilitate its regulatory acceptance2. Here we will present the rationale and the process used to identify the control chemicals selected to support the development of a new in vitro system to address cardiotoxicity.