Intuitive toxicology in the 21st century-Bridging the perspectives of the public and risk assessors in Europe.

Three decades ago, several articles on the subjectivity in chemical risk judgments (i.e., labeled "intuitive toxicology") measured the divide between the public and toxicologists with different backgrounds regarding the validity of predicting health effects based on in vivo studies. Similar divides with impacts on societal discourse and chemical risk assessment practices might exist concerning alternative toxicity testing methods (i.e., in vitro and in silico). However, studies to date have focused either on the public's views of in vivo or stem cell testing or on experts' views of in vivo testing and potential alternatives (i.e., toxicologists and medical students), which do not allow for a direct investigation of potential divides. To fill this knowledge gap, we conducted two online surveys, involving members of the German-speaking public in Switzerland and European human health risk assessors, respectively. This article presents the results of these two surveys regarding the divide in the public's and risk assessors' perspectives on risk assessment based on in vivo, in vitro, and in silico testing. Particularly, the survey with the risk assessors highlights that, beyond scientific and regulatory barriers, alternatives to in vivo testing may encounter individual hurdles, such as higher uncertainty associated with them. Understanding and addressing these hurdles will be crucial to facilitate the integration of new approach methodologies into chemical risk assessment practices as well as a successful transition toward next-generation risk assessment, bringing us closer to a fit-for-purpose and more efficient regulatory landscape.

Protocol for designing INVITES-IN, a tool for assessing the internal validity of in vitro studies.

This protocol describes the design and development of a tool for evaluation of the internal validity of in vitro studies, which is needed to include the data as evidence in systematic reviews and chemical risk assessments. The tool will be designed specifically to be applied to cell culture studies, including, but not restricted to, studies meeting the new approach methodology (NAM) definition. The tool is called INVITES-IN (IN VITro Experimental Studies INternal validity). In this protocol, three of the four studies that will be performed to create the release version of INVITES-IN are described. In the first study, evaluation of existing assessment tools will be combined with focus group discussions to identify how characteristics of the design or conduct of an in vitro study can affect its internal validity. Bias domains and items considered to be of relevance for in vitro studies will be identified. In the second study, group agreement on internal validity domains and items of importance for in vitro studies will be identified via a modified Delphi methodology. In the third study, the draft version of the tool will be created, based on the data on relevance and importance of bias domains and items collected in Studies 1 and 2. A separate protocol will be prepared for the fourth study, which includes the user testing and validation of the tool, and collection of users' experience.