Since 1 September 2021, Nynke Kramer is associate professor in toxicology at the Toxicology Division of the Agrotechnology and Food Sciences group of Wageningen University. She teaches toxicology, toxicokinetics and (eco)toxicological risk assessment at undergraduate, graduate, and postgraduate level. Before starting at Wageningen University, she was assistant professor in toxicology at the Institute for Risk Assessment Sciences (IRAS) of Utrecht University, where she also obtained her PhD in 2010. Her research focusses on enhancing the uptake of in vitro models in chemical safety assessment by developing models extrapolating toxic concentrations in in vitro cell assays to toxic doses relevant to humans and animals. Her research has led to over seventy peer-reviewed publications identifying physiological and chemical parameters underlying the accumulation of toxicants in cells in the body and in in in vitro toxicity assays. Illustratively, Nynke’s research has been awarded the SETAC Procter and Gamble Fellowship for Doctoral Research in Environmental Sciences. She used the prize money to do part of her research at the Swiss Federal Institute for Aquatic Science and Technology, Eawag, Dübendorf, Switzerland. Before starting her PhD, Nynke obtained her BSc degree in Life Sciences at University College Utrecht and her MSc degree in Environmental Change and Management at the University of Oxford. She currently is board member of in2TOX specialty section of EUROTOX, the Federation of European Toxicologist, and member of the Society of Toxicology (SOT) Scientific Committee.
OpenTox Summer School 2026
Next-generation risk assessment (NGRA) aims to evaluate chemical safety using mechanistic, human-relevant evidence while reducing reliance on animal testing. This lecture explains how quantitative in vitro–in vivo extrapolation (QIVIVE) provides the kinetic bridge required to translate concentrations causing effects in vitro into external human doses relevant for risk assessment. In vitro assays can reveal mechanisms and concentration-response relationships. However, commonly used nominal effect concentrations in vitro may poorly represent biologically effective exposure because chemicals bind to serum proteins in exposure medium and well plate plastic plastic, evaporate, metabolise, or accumulate in cells. In vitro distribution models can be used to estimate freely dissolved and cell-associated concentrations in vitro as more relevant dose metrics for NGRA. Physiologically based kinetic (PBK) models subsequently describe absorption, distribution, metabolism and excretion (ADME) through interconnected tissue compartments and mass-balance equations. Chemical-specific parameters, including permeability, plasma binding, tissue partitioning, metabolic clearance and renal excretion, are combined with human physiological parameters to predict target-tissue concentration–time profiles. Using reverse dosimetry, the PBK model identifies the external dose that produces an internal concentration equivalent to the in vitro point of departure (POD). This enables derivation of bioequivalent administered doses, comparison with anticipated exposure, and estimation of margins of safety. QIVIVE thereby integrates toxicodynamics with toxicokinetics and supports more mechanistic, transparent and human-relevant decision-making within NGRA.