RESUMEN
Toxicokinetic-toxicodynamic (TKTD) modeling has received increasing attention in terms of the regulatory environmental risk assessment of chemicals. This type of mechanistic model can integrate all available data from individual-level bioassays into a single framework and enable refined risk assessments by extrapolating from laboratory results to time-variable exposure scenarios, based, for instance, on surface water exposure modeling (e.g., FOCUS). Dynamic energy budget (DEB) models coupled with TKTD modules (DEB-TKTD) constitute the leading approach to assess and predict sublethal effects of chemicals on individual organisms. However, thorough case studies are rare. We provide a state-of-the-art example with the standard aquatic test species Ceriodaphnia dubia and the fungicide azoxystrobin, including all steps, from bespoke laboratory toxicity tests to model calibration and validation, through to environmental risk assessment. Following the framework proposed in the European Food Safety Authority Scientific Opinion from 2018, we designed bespoke good laboratory practice-compliant laboratory toxicity studies based on test guideline 211 of the Organisation for Economic Co-operation and Development and then identified robust parameter values from those data for all relevant model parameters through model calibration. The DEB-TKTD model, DEBtox2019, then informed the design of the validation experiment. Once validated, the model was used to perform predictions for a time-variable exposure scenario generated by FOCUS. A moving time-window approach was used to perform the environmental risk assessment. This assessment method reduces uncertainty in the risk assessment while maintaining consistency with the traditional measures of risk. Environ Toxicol Chem 2024;00:1-13. © 2024 Syngenta Crop Protection AG. ibacon GmbH and The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
RESUMEN
The extrapolation of effects from controlled standard laboratory tests to real environmental conditions is a major challenge facing ecological risk assessment (ERA) of chemicals. Toxicokinetic-toxicodynamic (TKTD) models, such as those based on dynamic energy budget (DEB) theory, can play an important role in filling this gap. Through the years, different practical TKTD models have been derived from DEB theory, ranging from the full "standard" DEB animal model to simplified "DEBtox" models. It is currently unclear what impact a different level of model complexity can have on the regulatory risk assessment. In the present study, we compare the performance of two DEB-TKTD models with different levels of complexity, focusing on model calibration on standard test data and on forward predictions for untested time-variable exposure profiles. The first model is based on the standard DEB model with primary parameters, whereas the second is a reduced version with compound parameters, based on DEBkiss. After harmonization of the modeling choices, we demonstrate that these two models can achieve very similar performances both in the calibration step and in the forward prediction step. With the data presented in the present study, selection of the most suitable TKTD model for ERA therefore cannot be based alone on goodness-of-fit or on the precision of model predictions (within current ERA procedures for pesticides) but would likely be based on the trade-off between ease of use and model flexibility. We also stress the importance of modeling choices, such as how to fill gaps in the information content of experimental toxicity data and how to accommodate differences in growth and reproduction between different data sets for the same chemical-species combination. Environ Toxicol Chem 2024;43:440-449. © 2023 ibacon GmbH. Bayer AG and The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.