Search

Endocrine screening assays not only provide mechanistic information on the potential of a substance to interact with the endocrine system, but also data potentially relevant for risk assessment. However, these screening assays have a number of limitations that should be considered before the direct use of such data for risk assessment purposes. This paper discusses the limitations that should be considered for both human and environmental risk assessment. A proposal is made to provide an objective and transparent process in order to consider which endpoint(s) might be incorporated into a risk assessment, and when more definitive studies may be of value. The proposal is complemented with an easy-to-follow flowchart to aid industry scientists and regulators when evaluating the relevance of these data. Such an approach is necessary to ensure the appropriate use of screening data to further our understanding of the eco/toxicological profile of substances undergoing screening. [ABSTRACT FROM AUTHOR]

An important goal in toxicology is the development of new ways to increase the speed, accuracy, and applicability of chemical hazard and risk assessment approaches. A promising route is the integration of in vitro assays with biological pathway information. We examined how the adverse outcome pathway (AOP) framework can be used to develop pathway‐based quantitative models useful for regulatory chemical safety assessment. By using AOPs as initial conceptual models and the AOP knowledge base as a source of data on key event relationships, different methods can be applied to develop computational quantitative AOP models (qAOPs) relevant for decision making. A qAOP model may not necessarily have the same structure as the AOP it is based on. Useful AOP modeling methods range from statistical, Bayesian networks, regression, and ordinary differential equations to individual‐based models and should be chosen according to the questions being asked and the data available. We discuss the need for toxicokinetic models to provide linkages between exposure and qAOPs, to extrapolate from in vitro to in vivo, and to extrapolate across species. Finally, we identify best practices for modeling and model building and the necessity for transparent and comprehensive documentation to gain confidence in the use of qAOP models and ultimately their use in regulatory applications. Environ Toxicol Chem 2019;38:1850–1865. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. [ABSTRACT FROM AUTHOR]