NPLK18000U Toxicology and Ecotoxicology

The course gives a basic overview on fundamentals in both human- and ecotoxicology. Basic toxicological processes encompass toxicokinetic (TK) and toxicodynamic (TD) descriptions of pollutants in organisms. The toxicokinetic processes are what the organism does to the chemical, and can be described through the understanding of Absorption, Distribution, Metabolism and Excretion (ADME) of chemical substances in organisms. The toxicodynamic processes are what the chemical does to the organism: the toxic mechanisms. Toxic mechanisms take place at different organizational levels and on different time scales, from chemical effects on the gene expression level, to effects on cell function, effects on organs, on organism health, growth, reproduction and survival and finally, in an ecotoxicological context also on the population of the organism and on the community of species in the environment. To comprehend toxic mechanisms and the impact of chemicals on humans and the environment, understanding of the whole chain of effects, also called Adverse Outcome Pathways, is important.

The principles of toxicokinetic and dynamic processes for major groups of pollutants will be taught through lectures, theoretical and practical exercises. The students will learn to use on-line databases and computational tools applied in toxicology and ecotoxicology to calculate Effect Concentrations (e.g. EC₅₀), No Observable Adverse Effect Concentrations (NOAECs), Lowest Observable Effect Concentrations (LOECs) and predicted no-effect concentrations (PNEC), and they will learn to critically interpret dose-response data and the parameters derived from them. In addition they will get an introduction to the use of TKTD models, their strengths and weaknesses compared to the more traditional dose-response assessments of toxicity and their use in human- and ecotoxicological research. Also, the students will learn how to predict the effect of chemical cocktails using standard mixture toxicity models, and how to identify potential synergists in a mixture toxicity scenario. Basic statistical considerations and tools to interpret toxicity data (as the pro’s and con’s of significance testing, use of power analysis, recognizing type 1 and type 2 errors, trade-offs between doses and replications in an experiment, weight of evidence approaches for quality assurance of experiments etc) will be introduced, used and discussed. The computational programs used will be Excel, R and OpenModel. The students will have to conduct two laboratory experiments: one in vitro study, investigating effects on an enzymatic or cellular level and one in vivo study, looking at chemical effects on the organismal level. For each of the experiments they will need to use the computational tools conducting either dose-response curves or parameterizing TKTD models. The data has to be interpreted in the theoretical framework of ADME and AOP for their specific toxicant and test, and the results will be presented for and evaluated by their peer students (poster and oral presentation, as well as a scientific manuscript).