NSCPHD1165 Dynamic modelling of toxic effects

Volume 2013/2014
Content
The toxicity of a chemical depends on chemical properties, the exposed species, exposure time, the endpoint measured and exposure conditions. Mathematical modelling is a powerful tool to interpret the results of laboratory toxicity tests and to make educated extrapolations. In this course, you will learn the basics of toxicokinetic and toxicodynamic modelling, and how they can be linked and learn how to analyse and interpret body residue and toxicity data on a mechanistic basis.

A detailed schedule for the content of the specific talks and exercises will be provided in spring.
The overall content is given in this summary:
The toxicity of a chemical depends on properties of the compound and of the species that is exposed, but also on the exposure time, the endpoint (e.g. growth, reproduction or survival), and the exposure conditions (temperature, food level, etc.). In ecotoxicology, the interdependencies of these factors are generally ignored by rigid standardisation of the tests and descriptive summary statistics such as EC50 and NOEC. However, we need a more mechanistic interpretation of toxicity to make an unbiased comparison of toxicity between species and chemicals, and to extrapolate the effects to untested exposure conditions. Because it is impossible to test all chemicals on all species under all possible exposure scenarios, extrapolation is of key importance for ecotoxicologists and environmental risk assessors.

Mathematical modelling is a powerful tool to interpret the results of laboratory toxicity tests and to make educated extrapolations. The process of mechanistically modelling toxicity can be divided into two steps: toxicokinetics (TK) and toxicodynamics (TD). TK deals with the uptake, biotransformation and distribution of a chemical into the body of an organism, whereas TD deals with the next step: from internal concentration of the active compound to effects on the organism over time.

In this course, you will learn the basics of TK and TD modelling, and how they can be linked, and you will learn to analyse and interpret toxicity data on a mechanistic basis. For TK modelling, we will focus on 1- and 2-compartment models; TD modelling will be based on a simple Dynamic Energy Budget model (DEBkiss). The course comprises a combination of lectures, computer exercises and discussions. In the computer exercises you will learn to build and use basic TKTD models yourself in Matlab or OpenModel, and work with advanced pre-programmed models (GUTS, DEBkiss) to fit more elaborate data sets. The output of the course will be individual reports where the students use their accomplished skills to fit TKTD models to their own and/or provided data, and to interpret the results.
Learning Outcome

In this course, students will:

  • Understand the concepts of TK and TD
  • Understand the basics of mechanistic effect modelling
  • Build TK and TD models to analyse and interpret toxicity data
  • Analyse example data, discuss and interpret the results
  • Use the software Matlab or OpenModel

Jager T, Heugens EHW, Kooijman SALM. 2006. Making sense of ecotoxicological test results: Towards application of process-based models. Ecotoxicology 15:305-314.

Ashauer R, Escher BI. 2010. Advantages of toxicokinetic and toxicodynamic modelling in aquatic ecotoxicology and risk assessment. Journal of Environmental Monitoring 12:2056-2061.

Jager T, Albert C, Preuss TG, Ashauer R. 2011. General Unified Threshold Model of Survival - a Toxicokinetic-Toxicodynamic Framework for Ecotoxicology. Environ Sci Technol 45:2529-2540.

Jager, T.; Martin, B. T.; Zimmer, E. I., DEBkiss or the quest for the simplest generic model of animal life history. Journal of Theoretical Biology 2013, 328, 9-18.

More information including references can be found on: www.debtox.info and www.ecotoxmodels.org.
Teaching will be a combination of lectures, computer exercises and discussions. Datasets will be provided for the hand-in report. Students can bring their own data for the report also, providing they are of a sufficient quality
Location & transport
The course will take place at Søminestationen (http:/​/​www.soeminestationen.dk/​). Transport to and from Søminestationen to Holbæk station on Tuesday 5th and Wednesday 13th and food and housing is included in the price.
  • Category
  • Hours
  • Lectures
  • 20
  • Practical exercises
  • 10
  • Preparation
  • 40
  • Project work
  • 40
  • Theory exercises
  • 26
  • Total
  • 136
Credit
5 ECTS
Type of assessment
Written assignment
The final report must be handed in in time and be accepted by the course convenors.
Exam registration requirements
We expect you to prepare for the course in advance and to hand in a report at September 1st at the latest to receive full credits.
Exam period
September 2014