Characterizing the marine mammal exposome by iceberg modeling, linking chemical analysis and in vitro bioassays

The present study complements work on mixture effects measured with in vitro bioassays of passive equilibrium sampling extracts using the silicone polydimethylsiloxane (PDMS) in organs from marine mammals with chemical profiling. Blubber, liver, kidney and brain tissues of harbor porpoise (Phocoena phocoena), harbor seal (Phoca vitulina), ringed seal (Phoca hispida) and orca (Orcinus orca) from the North and Baltic Seas were investigated. We analyzed 117 chemicals including legacy and emerging contaminants using gas chromatography-high resolution mass spectrometry and quantified 70 of those chemicals in at least one sample. No systematic differences between the organs were found. Only for single compounds a clear distribution pattern was observed. For example, 4,4'-dichlorodiphenyltrichloroethane, enzacamene and etofenprox were mainly detected in blubber, whereas tonalide and the hexachlorocyclohexanes were more often found in liver. Furthermore, we compared the chemical profiling with the bioanalytical results using an iceberg mixture model, evaluating how much of the biological effect could be explained by the analyzed chemicals. The mixture effect predicted from the quantified chemical concentrations explained 0.014-83% of the aryl hydrocarbon receptor activating effect (AhR-CALUX), but less than 0.13% for the activation of the oxidative stress response (AREc32) and peroxisome-proliferator activated receptor (PPARγ). The quantified chemicals also explained between 0.044-45% of the cytotoxic effect measured with the AhR-CALUX. The largest fraction of the observed effect was explained for the orca, which was the individuum with the highest chemical burden. This study underlines that chemical analysis and bioassays are complementary to comprehensively characterize the mixture exposome of marine mammals.