Health risk assessment of dioxin-like compounds in complex samples

Abstract: There are several scientific as well as political and economic reasons why the risk assessment of dioxins in complex samples needs to be further refined. Today, there seems to be no margin of safety between doses that cause suspected effects and exposure. Therefore, uncertainties and gaps in the knowledge have to be minimized. This thesis work aims to provide novel scientific data on the toxicity of dioxin-like pollutants with focus on complex samples which address some of the present data gaps. Fish is a major source of human dioxin exposure. There is a concern that high intake of fish could cause adverse health effects. In addition to dioxin exposure, there is a concern as yet unidentified pollutants, other than dioxin, could pose a significant hazard to man. To further investigate the relevance of these issues to human health a study investigating the subchronic toxicity of Baltic herring oil or fractions was performed in rats (Study I and II). No adverse effects were observed after exposure of up to 34.4 kg fish/week (expressed as corresponding human intake). No effects could be linked to any unidentified organohalogens. Importantly, dioxin-like biochemical effects were observed at a daily intake of 0. 15 pg TEQ/kg and above. Kinetic data are essential for extrapolation from laboratory animals to humans; these aspects are not adequately addressed in most assessments. To deliver congener specific kinetic data on PCBs in a low dose range, a kinetic study was performed (Study III). Half-lives and partition coefficients were reported for several PCBs, as well as concentration data of one major PCB- metabolite. Briefly, the results showed that halflives seem to be longer than previously reported and that PCB77 has a liver specific retention. Today, the concept of toxic equivalency factors (TEF) in combination with chemical analysis is used to summarize some of the dioxin-like potency of a sample. However, this concept has many drawbacks. There is a need for efficient biological screening tools for dioxin-like compounds to complement the chemical analysis. In this thesis, the MH1C1-EROD-assay was shown to readily assess dioxin-like potency in various complex samples (Study IV). In addition, the use of a clean-up procedure with sulphuric acid was shown to be important for result interpretation. Finally, a study was performed to investigate how light can influence AhR mediated EROD- activity in vitro (Study V). A photoproduct of tryptophan, which has been suggested as the endogenous ligand, namely formylindolo[3,2-b]carbazole (FICZ) was identified as a causative mediator.