Toxicokinetic Models to Interpret Contaminant Exposure Levels in Marine Wildlife: Dugongs as Model Organisms
Physiologically based pharmacokinetic (PBPK) or toxicokinetic (PBTK) modeling is an in silico or computer-based technique that allows evaluation of the distribution and kinetics of chemicals in the body of an organism. Divided into several compartments, the body represents a mass-balanced system in which the contaminant moves according to the biochemical properties of the compound and the physiological characteristics of the organism of interest. Usually, such a model follows on or is strongly attached to a controlled exposure experiment in organisms like rodents for which both compound-specific and species-specific parameters are largely deduced from the experimental set-up. For marine mammals, however, this scenario is not possible as in vivo exposure experiments are undesired or prohibited in these animals. For decades, toxicological research in marine mammals has focused mainly on the analyses of chemicals in tissues of dead, stranded animals and sometimes also in blood taken from live animals. However, these results fail to inform on contaminant kinetics and are only snapshots taken at a certain point in the exposure time window. On the other hand, recent advances using in vitro exposure experiments in blood or liver cell lines of marine mammals provide deeper insights into the toxic mechanisms of contaminants. However, they lack the ability to put the observed effects into a broader perspective as they focus on one tissue only. For marine mammals, PBPK models can be seen as a non-destructive addition to the in vivo and in vitro approaches, and can combine results of toxicity experiments and biomonitoring efforts. The focus of the present study was to develop such models for dugongs, focusing initially on dioxins as the contaminant group. Dugongsare herbivorous, coastal marine mammals that are listed as 'vulnerable' on the IUCN (International Union for Conservation of Nature) list. They are threatened by anthropogenic activities and past biomonitoring research has shown that they can accumulate high levels of dioxins in their tissues. Understanding the fate and dynamics of these contaminants in dugongs or even in marine mammals in general is key to evaluate the impact of environmental pollution on this important group of marine animals. By combining the outcomes of in vitro research and ongoing biomonitoring efforts, these models allow to assess past and current exposures, but also to predict future exposure scenarios. As such, they can be useful tools for risk assessment and conservation of dugongs.
This study utilised dugong tissues that were archived from numerous sampling events over the last decade. We would like to thank all the dedicated veterinarians and biologists who have assisted with this, particularly Dr David Haynes, Prof Paul Mills, Prof Colin Limpus, Darren Burns and Dr Wendy Blanchard, and are grateful for the in-kind support with sampling, necropsies, or expert advice by the Department of Environment and Heritage Protection, Great Barrier Reef Marine Park Authority, Quandamooka, Queensland Health, and Sea World.
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