PBPK models for the accumulation of microcontaminants and immunological effects in harbour seals and porpoises

Introduction and objectives:
During the last decades, it has been shown that microcontaminants are able to reach considerable concentrations in organisms feeding higher up in the food chain, like harbour seals (Phoca vitulina) and harbour porpoises (Phocoena phocoena). Both species are considered to be toppredators in the North Sea-ecosystem and therefore bioaccumulate microcontaminants, such as heavy metals and persistent organic pollutants, in their tissues. Due to their physical and chemical characteristics, these chemicals have often different distribution-and accumulationpatterns and other toxicological mechanisms. As a consequence, the accumulation of contaminants may lead to effects on several systems, such as the reproduction (Reijnders, 1986), the endocrine (Beineke et al., 2005) and the immune system (Ross et al., 1996). Disorders of the immune system are considered to be one of the most important consequences of exposure to microcontaminants in marine mammals.

Therefore, the objectives of this project are:
- Development and evaluation of a theoretical physiologically based pharmacokinetic (PBPK) bioaccumulation model to gain knowledge about the uptake, biotransformation and elimination of contaminants in both species
- Examination of immunological condition of the animals using ‘classical’ and modern biomarkers
- Investigation of the relationship between possible immunological problems, the presence of microcontaminants and other external factors (maybe induced by global change?!)

Methods:
The immunological condition of the harbour seals and porpoises will be tested using fresh bloodsamples (obtained in a non-destructive way according to the European guidelines for sampling (marine) mammals). Several blood parameters, known for their reaction in a immune response will be measured with modern methods, such as flow cytometry, enzyme linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR) (Beineke et al., 2004; Mos et al., 2006).
To gain knowledge about the relation between uptake, distribution and elimination, a theoretical bioaccumulationmodel will be developed. The theoretical model will be evaluated with data found in databases (CEFAS: Centre for Environment, Fisheries and Aquaculture Science), in the literature and with own results from analyses, performed on tissue samples (dead animals) and, if possible, also on biopsy-samples (living animals).

Collaboration:
This project will happen in a close collaboration with the research team of the University of Liège (Laboratoire d’Océanologie, ULg). Research teams of the University of St. Andrews, Schotland (Sea Mammals Research Unit) and the University of Kiel, Germany will also, if possible, take part of this project. Analyses of microcontaminants will be done in collaboration with the Toxicological Centre (University of Antwerp). Tissue samples (dead animals), biopsies and bloodsamples will be received from the Dolfinarium of Harderwijk (the Netherlands), Sea Life in Blankenberge and the Zoo in Antwerp.

References:
Beineke, A. et al., 2004. Veterinary Immunology and Immunopathology, 98, 59 – 68; Beineke, A. et al., 2005. Environmental Science & Technology, 39, 3933 – 3938; Mos, L. et al., 2006. Environmental Toxicology & Chemistry, 25 (12), 3110 – 3117; Reijnders, P.J.H., 1986. Nature, 324, 456 – 457; Ross, P.J. et al., 1996. Aquatic Toxicology, 34, 71 – 84.