SETAC Globe - Environmental Quality Through Science
  10 May 2012
Volume 13 Issue 5

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Toxicokinetic-Toxicodynamic Modelling Gains Momentum

Roman Ashauer, Swiss Federal Institute of Aquatic Science and Technology; Eawag

Recent activities in toxicokinetic-toxicodynamic modelling (TKTD modelling) indicate that interest is growing in line with the increasing number of tools and information available. For those unfamiliar with TKTD modelling, it's a powerful approach to quantify toxic effects of chemicals on organisms. TKTD models integrate concentration and time to quantify toxicity as an effect in a dynamic system. Websites such as and have plenty of information, links and material on the topic.

Summer school
Tjalling Jager of VU Amsterdam, along with Andreas Kretschmann and Nina Cedergreen of the University of Copenhagen, is organising a summer school on TKTD modelling, which is already fully booked. Even if it is too late to join for this session in August, interested scientists can download the course material from the course website and express their interest in another course to the organisers via email.

New version of R-package for GUTS
The recently published General Unified Threshold model of Survival (GUTS; see ES&T critical review abstract) for the first time unifies models for different mechanisms of toxicity into one framework where particular mechanisms of action emerge as special cases. The current version of the freely available R-package for GUTS has been updated with a new version. The new version is more robust, and detailed instructions as well as more example scripts should be uploaded by the end of May 2012. Exploring is highly recommended! A command line version is also in production.

Beta version of e-book "Making sense of chemical stress"
Recently, Tjalling Jager has published a beta version of his e-book "Making sense of chemical stress." I discovered it late one evening and was so captivated that I immediately read half of it. It's exciting, easy to read and eye-opening. The book has an easy to understand introduction, because it does not use any equations, but still reveals really important insights to the reader. How complex should a useful model for chemical stress be? The conceptual thinking connecting biology, toxicology, and model building is convincing and should be required reading for anyone interested in the science of ecotoxicology. Colleagues contemplating modelling adverse outcome pathways might find this book inspiring. It's also a thought-provoking read for scientists who apply omics approaches to questions in ecotoxicology!

"Killer app" on the horizon
The breakthrough for pesticide fate models to be used in regulatory environmental risk assessments came when the fate models provided a "killer app", in that case the ability to simulate leaching of pesticides through soil columns. Many thanks to Gerhard Görlitz for sharing that insight at the last SETAC Europe annual meeting. For TKTD models, it becomes more and more evident that their killer app will provide the ability to simulate toxic effects of fluctuating or pulsed exposure concentrations, including possible carry-over effects and delayed toxicity. Research within the European Union-funded research project CREAM has received great interest from industry and regulators alike, and abstract submissions for the upcoming SETAC World Congress in Berlin showcase some exciting developments bringing TKTD modelling closer and closer to applications in regulatory environmental risk assessment of chemicals. Even though I find the scientific opportunities that TKTD models create at least as exciting (e.g., in vitro to in vivo extrapolation or discovering fundamental relationships between TKTD model parameters, chemical properties and species traits), it is very motivating to see the day come closer when TKTD models are employed routinely by risk assessment practitioners.

Sessions at SETAC World Congress in Berlin
TKTD and other mechanistic effect models can be found in a number of sessions, including: RA01-Applying models to risk assessments: from the organism to the ecosystem level (10:50—12:50, 23 May, Estrel Hall A), RA15-Linking exposure to effects in environmental risk assessment (14:00—16:00, 23 May, Estrel Hall A) and MeMoRisk session on ecological modelling in support of terrestrial risk assessments (16:00—18:30, 22 May, SS07).

About the author: Roman Ashauer is a scientist at Eawag, the Swiss Federal Institute of Aquatic Science and Technology. He has been developing TKTD models for the past eight years and in 2011 he created

Graphic reprinted with permission from Ashauer R, Hintermeister A, O'Connor I, Elumelu M, Hollender J, Escher B. 2012. Significance of xenobiotic metabolism for bioaccumulation kinetics of organic chemicals in Gammarus pulex. Environ Sci Technol. 46(6):3498–3508. Copyright 2012 American Chemical Society.

Author's contact information:

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