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.
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Environ Toxicol Chem
January 2025
Osnabrück University, Osnabrück, Lower Saxony, Germany.
In regulatory aquatic risk assessment, toxicokinetic-toxicodynamic (TKTD) methods, such as the generalized unified threshold model of survival (GUTS), are already established and considered ready for use, whereas TKTD methods for aboveground terrestrial species, like arthropods, are less developed and currently not intended for risk assessment. This could be due to the fact that exposure in aboveground terrestrial systems is more event-based (feeding, contact, overspray, etc.), whereas exposure in aquatic systems is simply related to substance concentrations in the surrounding water.
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January 2025
Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
bioRxiv
December 2024
Department of Molecular and Cellular Physiology and Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Injured epithelial organs must rapidly replace damaged cells to restore barrier integrity and physiological function. In response, injury-born stem cell progeny differentiate faster compared to healthy-born counterparts, yet the mechanisms that pace differentiation are unclear. Using the adult Drosophila intestine, we find that injury speeds cell differentiation by altering the lateral inhibition circuit that transduces a fate-determining Notch signal.
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