Mechanistic modelling for ecotoxicology and ecology

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Review, ring-test and guidance for TKTD modelling


URL
http://cefic-lri.org/projects/eco39-review-ring-test-and-guidance-for-tktd-modelling/
Funding
CEFIC/LRI ECO 39
Duration
2017
Project leader
University of York, UK (Dr. Roman Ashauer)

Description

The additional information and insight gained through the application of toxicokinetic-toxicodynamic (TKTD) modelling can strengthen the environmental risk assessment of chemicals, such as those applied in consumer products or plant protection products (PPPs). For the endpoint survival the most suitable and powerful tool is currently the General Unified Threshold model of Survival (GUTS), which unifies almost all of the previously published TKTD models for survival. Specific models can be derived as special cases of GUTS. The simples cases comprise the complimentary models: GUTS-SD (stochastic death) and GUTS-IT (individual tolerance). GUTS has been submitted as part of the environmental risk assessment of PPPs, but it can also be used within the context of REACH and other risk assessment frameworks. In order to facilitate application of GUTS and increase trust and acceptability we need to compare and test the range of software implementations available and generate guidance on how to use GUTS in Environmental Risk Assessment of chemicals. Beyond the endpoint survival, and beyond GUTS, TKTD models have broader applicability for sub-lethal endpoints, assessment of multiple stressors and reverse dosing for high-throughput toxicity testing. Reviewing the state of the science of TKTD modelling will enable development of a roadmap towards wider use of TKTD models in environmental risk assessment of chemicals in general and highlight synergies and differences with human safety evaluation methods.

Objectives:
1. Review the state of the science of TKTD modelling in general and develop a roadmap towards broader applicability in chemical risk assessment.
2. Carry out a ring test of different software implementations of the General Unified Threshold model of Survival (GUTS).
3. Develop guidance on how to use GUTS for environmental risk assessment of chemicals.

My role

Contribute to the objectives listed above. I am particularly looking forward to prepare an extensive e-book on GUTS, and the ring testing of the various software implementations.





Output: Publications (as first or co-author)

  • Jager T and Ashauer R (in prep.). Modelling survival under chemical stress. A comprehensive guide to the GUTS framework. E-book in preparation. More information.
  • Ashauer R and Jager T (acc.). Physiological modes of action across species and toxicants: The key to predictive ecotoxicology. Accepted in Environ. Sci. Processes Impacts.
  • Jager T and Ashauer R (in prep.). How to evaluate the quality of toxicokinetic-toxicodynamic models.
  • ...

Output: Presentations (as presenter and as contributor)

Output: Related publications (as first or co-author)

  • Jager T (2017). Comment on “Robust Fit of Toxicokinetic–Toxicodynamic Models Using Prior Knowledge Contained in the Design of Survival Toxicity Tests”. Environ, Sci, Technol. 51(14):8200-8201. http://dx.doi.org/10.1021/acs.est.7b02001 
  • ...

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