A framework for algae modelling in regulatory risk assessment.

The use of toxicokinetic-toxicodynamic (TKTD) modelling in regulatory risk assessment of plant protection products is increasingly popular, especially since the 2018 EFSA opinion on TKTD modelling announced that several established models are ready for use in risk assessment. With careful adherence to the guidelines laid out by EFSA we present a stepwise approach to validation and use of the SAM-X algae model for regulatory submission in Tier 2C. We demonstrate how the use of moving time windows across time-variable exposure profiles can generate thousands of virtual laboratory mimic simulations that seamlessly predict the effects of time variable exposures across a full exposure profile while maintaining the laboratory conditions of the standard OECD growth inhibition test. Thus, every virtual laboratory test has a duration of 72 hours, with OECD medium and constant light and temperature conditions. The only deviation from the standard test setup is the replacement of constant exposure conditions for time variable concentrations. The present work demonstrates that for simulation of 72h toxicity tests, the nutrient dynamics in the SAM-X model are not required, and we propose the alternative use of a simplified model version. For risk assessment, in accordance with the EFSA guidelines we use a EP 50 of 10 as a threshold, meaning that if a time window within the exposure profile causes 50% growth inhibition when magnified by a factor of 10, the threshold will have been exceeded. We here present a simplified example for chlorotoluron and isoproturon. This case study brings to life our proposed framework for TKTD modelling of algae to establish whether a given exposure can be considered low risk.