Details zur Publikation

Kategorie Textpublikation
Referenztyp Zeitschriften
DOI 10.1002/etc.4505
Lizenz creative commons licence
Titel (primär) Building and applying quantitative adverse outcome pathway models for chemical hazard and risk assessment
Autor Perkins, E.J.; Ashauer, R.; Burgoon, L.; Conolly, R.; Landesmann, B.; Mackay, C.; Murphy, C.A.; Pollesch, N.; Wheeler, J.R.; Zupanic, A.; Scholz, S.
Journal / Serie Environmental Toxicology and Chemistry
Erscheinungsjahr 2019
Department BIOTOX
Band/Volume 38
Heft 9
Seite von 1850
Seite bis 1865
Sprache englisch
Abstract 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 for this is the integration of in vitro assays with biological pathway information. Here we examine 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 identified best practices for modeling, model building and the necessity for transparent and comprehensive documentation to gain confidence in the use of a quantitative AOP models and ultimately their use in regulatory applications.
dauerhafte UFZ-Verlinkung
Perkins, E.J., Ashauer, R., Burgoon, L., Conolly, R., Landesmann, B., Mackay, C., Murphy, C.A., Pollesch, N., Wheeler, J.R., Zupanic, A., Scholz, S. (2019):
Building and applying quantitative adverse outcome pathway models for chemical hazard and risk assessment
Environ. Toxicol. Chem. 38 (9), 1850 - 1865