Fit Reduced GUTS Models Online: From Theory to Practice

Abstract

Abstract Mechanistic modeling approaches, such as the toxicokinetic-toxicodynamic (TKTD) framework, are promoted by international institutions such as the European Food Safety Authority and the Organization for Economic Cooperation and Development to assess the environmental risk of chemical products generated by human activities. TKTD models can encompass a large set of mechanisms describing the kinetics of compounds inside organisms (e.g., uptake and elimination) and their effect at the level of individuals (e.g., damage accrual, recovery, and death mechanism). Compared to classical dose–response models, TKTD approaches have many advantages, including accounting for temporal aspects of exposure and toxicity, considering data points all along the experiment and not only at the end, and making predictions for untested situations as realistic exposure scenarios. Among TKTD models, the general unified threshold model of survival (GUTS) is within the most recent and innovative framework but is still underused in practice, especially by risk assessors, because specialist programming and statistical skills are necessary to run it. Making GUTS models easier to use through a new module freely available from the web platform MOSAIC (standing for MOdeling and StAtistical tools for ecotoxIClogy) should promote GUTS operability in support of the daily work of environmental risk assessors. This paper presents the main features of MOSAIC_GUTS: uploading of the experimental data, GUTS fitting analysis, and LCx estimates with their uncertainty. These features will be exemplified from literature data. Integr Environ Assess Manag 2018;14:625–630. © 2018 SETAC Key Points GUTS models (both reduced versions, SD and IT) can be fitted to survival data collected under either constant or time-variable exposure profiles, through a user-friendly web interface available for free at http://pbil.univ-lyon1.fr/software/mosaic/guts. Any x% lethal concentration at the end of the experiment is provided, which can account for the uncertainty in the GUTS parameter estimates and can be used to better address risks of time-variable exposures. Without wasting time on extensive mathematical and statistical technicalities, users are given the most advanced and innovative methods for a valuable quantitative environmental risk assessment based on TKTD models for survival (GUTS). Considering the recommendations from authorities, there is no doubt that GUTS models will be more widely used to assess the safety of chemicals; the GUTS module of the web platform MOSAIC will support risk assessors in their daily work.