Cefic-lri Programme | European Chemical Industry Council

ECO39 & 39.2: Review, ring-test and guidance for TKTD modelling

Principal Investigator

Dr Roman Ashauer
Environment Department
Wentworth Way
University of York
Heslington
York, YO10 5NG
United Kingdom
roman.ashauer@york.ac.uk
Tel: +44-(0)-1904-324052

Collaborators

Dr Tjalling Jager, DEBtox Research, tjalling@debtox.nl

Description

Stressors, such as toxicants, can cause mortality among organisms. Interestingly, not all individuals will die at the same time in the same exposure treatment, and the number of deaths will change with exposure time. The pattern of mortality will also depend on the exposure profile (e.g., constant versus pulsed exposure, fluctuating or time-variable exposure).

Making sense of these issues requires mechanism-based models, known as toxicokinetic-toxicodynamic (TKTD) models. For mortality, almost all published TKTD models can now be viewed as members of an over-arching framework: the General Unified Threshold model of Survival (GUTS). The additional information and insight gained through the application of toxicokinetic-toxicodynamic (TKTD) modelling can strengthen the environmental risk assessment of chemicals 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 consists of two 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 in the context of REACH. In order to ease the use of GUTS and increase trust and acceptability we recently released an extensive e-book and carried out a ring-test of different implementations of GUTS (ECO39).

The results from CEFIC-LRI ECO39 suggested that we needed a user-friendly, robust, freely-available and open-source software for standard GUTS applications. The ECO39.2 extension will produce such a tool.

Related Publications

Publications:

Tjalling Jager & Roman Ashauer. Modelling survival under chemical stress. LeanPub Ebook, 2018 Jan 18, ISBN 978-1-9999705-0-5.

Tjalling Jager & Roman Ashauer. How to evaluate the quality of toxicokinetic – toxicodynamic models in the context of environmental risk assessment. Integr Environ Assess Manag. 2018 Mar 24; 14(5): 604-614.

Roman Ashauer & Tjalling Jager. Physiological modes of action across species and toxicants: the key to predictive ecotoxicology. Environ Sci Process Impacts, 2018 Jan 24; 20(1):48-57.

Presentations:

Tjalling Jager. Applying criteria for model evaluation to TKTD models. 27th SETAC Europe Conference, May 2017, Brussels, Belgium.

Posters:

Roman Ashauer, Tjalling Jager. Review, ring-test and guidance for TKTD modelling. 18th Annual CEFIC-LRI Workshop, November 2016, Brussels, Belgium.

Roman Ashauer, Tjalling Jager. Review, ring-test and guidance for TKTD modelling. 27th SETAC Europe Conference, May 2017, Brussels, Belgium.

Tjalling Jager, Roman Ashauer. Modelling survival under chemical stress. A comprehensive guide to the GUTS framework. 28th SETAC Europe Conference, May 2018, Rome, Italy.

Roman Ashauer, Tjalling Jager. Ring-test of different implementations of the General Unified Threshold model of Survival (GUTS). 28th SETAC Europe Conference, May 2018, Rome, Italy.

Timeline:

ECO39 February 2017 > January 2018
ECO39.2 July 2018 > December 2019

LRI funding: € 80 000 for ECO39 | € 118 583 for ECO39.2

Cefic-Lri Programme Responsible Care

© Copyright 2017 Cefic | European Chemical Industry Council. All rights reserved | Terms and Conditions of Use