Toxicological Mechanisms of Non-Dioxinlike Persistant Organic Pollutants: Tools for Risk Evaluation

Norway is a major producer of farmed fish, and produces about 650 000 ton yearly. 95% of this is exported. Recently, the levels of persistant organic pollutants (POP) in farmed salmon has raised concerns. Allthough levels of dioxins and dioxin-like PCBs i n Norwegian farmed salmon are well below EU-regulated thresholds, fat fish is a main source of these pollutants. WHO and EU recomend that dioxin and PCB levels in EU is lowered. Thus, the application of techniques to reduce POP levels in farmed fish feed willbe welcomed and and may represent a marketing advantage. Strict thresholds have been introduced for dioxins and dioxin-like PCBs, but not for the large group of non-dioxinlike PCBs or brominated flame retardants. From experimental investigation we k now that these substances are carcinogenic and have deleterious effects on mental development. Some cohort studies from US and EU indicate that present levels of non-dioxinlike PCBs in EU and US populations are associated with neurotoxic effects. Our lack of knowledge of the molecular targets and mechanisms of these pollutants has made it impossible to define thresholds for complex mixtures (such as PCBs) based on animal experiments. This project aims at identification of the toxicological mechanisms of n on.dioxinlike PCBs, and to evaluate if this approach can be used to create models of risk evaluation for non-dioxinlike PCBs. PCB153 will be used as a prototype, non-dioxinlike PCB. Primary rat hepatocytes will be exposed, and effects on proliferation, ce ll death and differentiation examined. Microarray techniques will be used to examine alterations in gene expression profiles. Alterations in membrane flow and intracellular signalling will be explored, and cell cycle progression will be investigated.