Exposure and effects of naturally produced hydroxylated polybrominated diphenyl ethers in fish : Implications for Baltic Sea wildlife

Abstract: The aim of this thesis was to investigate if naturally produced hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are causing negative health effects for Baltic Sea wildlife. In the laboratory, OH-PBDEs have shown to be potent disrupters of energy metabolism as well as endocrine disruptors and neurotoxins. OH-PBDEs are naturally produced, for example, by filamentous macroalgae in the Baltic Sea but are also metabolites of the flame retardants polybrominated diphenyl ethers (PBDEs). High concentrations of OH-PBDEs have been detected in several species in the Baltic Sea, including the European perch (Perca fluviatilis). The concentrations of OH-PBDEs in perch, and some other species from the Baltic Sea, are within reported toxicological effect concentrations.In this thesis, perch were sampled approximately once a week during an exposure peak of OH-PBDEs between May and October in 2018. In Paper I, correlations between OH-PBDEs and several health biomarkers in perch were studied. A higher OH-PBDE concentration correlated with increased ethoxyresorufin-O-deethylase (EROD) activity, increased plasma lactate concentration, increased plasma glucose concentration, decreased lipid percentage in muscle, and decreased liver somatic index. These correlations indicate that OH-PBDEs might cause negative health effects in perch from the Baltic Sea.Many aquatic species in the Baltic Sea have been reported to suffer from thiamine (vitamin B1) deficiency. Thiamine deficiency could be a confounding factor when assessing potential in vivo effects of OH-PBDEs. Hence, in Paper II, the thiamine status of perch was investigated. Perch were found to have sufficient thiamine, thus thiamine deficiency is not a confounding factor when assessing potential effects of OH-PBDEs in perch from the Baltic Sea.In Paper III, metabolomics was performed on zebrafish (Danio rerio) embryos exposed to OH-PBDEs. The aim was to study the toxicity of OH-PBDEs at the metabolome level and to identify selective and sensitive biomarker(s) for energy disruption of OH-PBDEs. OH-PBDEs were found to cause diverse metabolic effects at environmentally relevant concentrations. Accumulation of succinic acid, a key metabolite for energy production and regulation of the immune system, was suggested as a potential biomarker for energy disruption due to OH-PBDEs. In Paper IV, lipids and 19 polar metabolites, including metabolites observed to be affected by OH-PBDEs in Paper III, were analysed in perch from the Baltic Sea. Among other findings, a correlation between increased OH-PBDE exposure and increased concentration of succinic acid was observed. The correlations observed in the perch to a large extent agreed with the metabolic effects seen in zebrafish embryos exposed to OH-PBDEs (Paper III), indicating potential causality between exposure to OH-PBDEs and effects in perch from the Baltic Sea.The correlations observed in this thesis between OH-PBDEs and biomarkers in perch should be interpreted with caution as the correlations could be spurious, for example caused by underlying environmental factors. However, taken together, the results support the hypothesis that naturally produced OH-PBDEs could cause negative health effects in perch from the Baltic Sea.