Polybrominated Dibenzo-P-Dioxins – Natural Formation Mechanisms and Biota Retention, Maternal Transfer, and Effects

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Polybrominated Dibenzo-P-Dioxins – Natural Formation Mechanisms and Biota Retention, Maternal Transfer, and Effects Polybrominated dibenzo-p-dioxins – Natural formation mechanisms and biota retention, maternal transfer, and effects Kristina Arnoldsson Department of Chemistry Doctoral Thesis Umeå 2012 Kristina Arnnoldsson received her B.Sc. in Chemistry from Stockholm University. She began her graduate studies in Environmental Chemistry at the Department of Chemistry, Umeå University in 2007. Polybrominated dibenzo-p-dioxins (PBDD) and dibenzofurans (PBDF) are a group of compounds of emerging interest as potential environmental stressors. Their structures as well as toxic responses are similar to the highly characterized toxicants polychlorinated dibenzo-p-dioxins. High levels of PBDDs have been found in algae, shellfish and fish, even from remote areas in the Baltic Sea. The geographical and temporal variations of PBDD in biota samples suggests natural rather than anthropogenic origins. The work underlying this thesis investigated the retention and transfer behavior, as well as health and reproductive effects, of PBDD/Fs in fish, to further increase the knowledge on persistency, retention and effects of PBDD/Fs, specifically concerning influence of substitution pattern and physico-chemical properties. In addition, biotic and abiotic formation of PBDDs from naturally abundant phenolic precursors were explored, to evaluate whether the PBDD profiles found in Baltic Sea biota can be explained by natural formation processes. Department of Chemistry ISBN 978-91-7459-353-2 Umeå University, S-901 87 Umeå www.chemistry.umu.se Polybrominated dibenzo-p-dioxins – Natural formation mechanisms and biota retention, maternal transfer, and effects Kristina Arnoldsson Akademisk avhandling som med vederbörligt tillstånd av Rektor vid Umeå universitet för avläggande av filosofie doktorsexamen framläggs till offentligt försvar i hörsal KB3B1, KBC-huset, fredagen den 3 februari, kl. 10:00. Avhandlingen kommer att försvaras på engelska. Fakultetsopponent: Professor Walter Vetter, Institute of Food Chemistry, University of Hohenheim, Stuttgart, Tyskland. Kemiska institutionen Umeå universitet Umeå 2012 Organization Document type Date of publication Umeå University Doctoral thesis 13 January 2012 Department of Chemistry Author Kristina Arnoldsson Title Polybrominated dibenzo-p-dioxins – Natural formation mechanisms and biota retention, maternal transfer, and effects Abstract Polybrominated dibenzo-p-dioxins (PBDD) and dibenzofurans (PBDF) are a group of compounds of emerging interest as potential environmental stressors. Their structures as well as toxic responses are similar to the highly characterized toxicants polychlorinated dibenzo-p-dioxins. High levels of PBDDs have been found in algae, shellfish, and fish, also from remote areas in the Baltic Sea. This thesis presents studies on PBDD behavior in fish and offspring, and natural formation of PBDDs from naturally abundant phenolic precursors. The uptake, elimination, and maternal transfer of mono- to tetraBDD/Fs were investigated in an exposure study reported in Paper I. The effects of PBDDs in fish were examined in a dose-response study (Paper II). It was shown that fish can assimilate PBDD/Fs from their feed, although non- laterally substituted congeners were rapidly eliminated. Laterally substituted congeners were retained as was congeners without vicinal hydrogens to some extent. PBDD/Fs were transferred to eggs, and congeners that were rapidly eliminated in fish showed a higher transfer ratio to eggs. Exposure to the laterally substituted 2,3,7,8-TeBDD had significant effects on the health, gene expression and several reproduction end-points of zebrafish, even at the lowest dose applied. The geographical and temporal variations of PBDD in biota samples from the Baltic Sea suggest biogenic rather than anthropogenic origin. In Paper III, bromoperoxidase-mediated coupling of 2,4,6-tribromophenol yielded several PBDD congeners, some formed after rearrangement. The overall yield was low, but significantly higher at low temperature, and the product profile obtained was similar to congener profiles found in biota from the Swedish West Coast. In Paper IV, photo- chemically induced cyclization of hydroxylated polybrominated diphenyl ethers under natural conditions produced PBDDs at percentage yield. Rearranged products were not detected, and some abundant congeners do not seem to be formed this way. However, the product profile obtained was similar to congener profiles found in biota from the Baltic Proper. Since the PBDD congeners found in biota have a high turn-over in fish, the exposure must be high and continuous to yield the PBDD levels measured in wild fish. Thus, PBDDs must presumably be formed by common precursors in general processes, such as via enzymatic oxidations, UV-initiated reactions or a combination of both. The presented pathways for formation of PBDDs are both likely sensitive to changes in climatic conditions. Keywords polybrominated dibenzo-p-dioxins, PBDDs, Baltic Sea, uptake, retention, maternal transfer, metabolism, bioavailability, natural formation, precursor, bromoperoxidase, bromophenol, photochemical transformation, oxidative coupling, hydroxylated polybrominated diphenyl ethers Language ISBN Number of pages English 978-91-7459-353-2 65 + 4 papers Polybrominated dibenzo-p-dioxins – Natural formation mechanisms and biota retention, maternal transfer, and effects Kristina Arnoldsson Department of Chemistry Doctoral Thesis Umeå 2012 © Kristina Arnoldsson ISBN: 978-91-7459-353-2 Front cover: “A day by the sea at Kont” Linnea Carlquist © Electronic version available at http://umu.diva-portal.org/ Printed by: VMC, KBC, Umeå University Umeå, Sweden 2012 Till Joel och Linnea – ni gör livet och arbetet värt! Abstract Polybrominated dibenzo‐p‐dioxins (PBDD) and dibenzofurans (PBDF) are a group of compounds of emerging interest as potential environmental stressors. Their structures as well as toxic responses are similar to the highly characterized toxicants polychlorinated dibenzo‐p‐dioxins. High levels of PBDDs have been found in algae, shellfish, and fish, also from remote areas in the Baltic Sea. This thesis presents studies on PBDD behavior in fish and offspring, and natural formation of PBDDs from naturally abundant phenolic precursors. The uptake, elimination, and maternal transfer of mono‐ to tetraBDD/Fs were investigated in an exposure study reported in Paper I. The effects of PBDDs in fish were examined in a dose‐response study (Paper II). It was shown that fish can assimilate PBDD/Fs from their feed, although non‐ laterally substituted congeners were rapidly eliminated. Laterally substituted congeners were retained, as was congeners without vicinal hydrogens to some extent. PBDD/Fs were transferred to eggs, and congeners that were rapidly eliminated in fish showed a higher transfer ratio to eggs. Exposure to the laterally substituted 2,3,7,8‐TeBDD had significant effects on the health, gene expressions and several reproduction end‐points of zebrafish, even at the lowest dose applied. The geographical and temporal variations of PBDD in biota samples from the Baltic Sea suggest biogenic rather than anthropogenic origin. In Paper III, bromoperoxidase‐mediated coupling of 2,4,6‐tribromophenol yielded several PBDD congeners, some formed after rearrangement. The overall yield was low, but significantly higher at low temperature, and the product profile obtained was similar to congener profiles found in biota from the Swedish West Coast. In Paper IV, photochemically induced cyclization of hydroxylated polybrominated diphenyl ethers under natural conditions produced PBDDs at percentage yield. Rearranged products were not detected, and some abundant congeners do not seem to be formed this way. However, the product profile obtained was similar to congener profiles found in biota from the Baltic Proper. Since the PBDD congeners found in biota have a high turn‐over in fish, the exposure must be high and continuous to yield the PBDD levels measured in wild fish. Thus, PBDDs must presumably be formed by common precursors in general processes, such as enzymatic oxidations, UV‐initiated reactions or a combination of both. The presented pathways for formation of PBDDs are both likely sensitive to changes in climatic conditions. - i - Sammanfattning (summary in Swedish) Bakgrund Östersjön är ett av jordens största brackvattenhav, med mycket speciell miljö, men det är också en av de mest förorenade havsmiljöerna i världen. Ett av de allvarligaste miljögifterna i Östersjön, som egentligen består av en grupp ämnen, är polyklorerade dibenso‐p‐dioxiner och dibensofuraner (PCDD/Fs). På senare tid har man hittat ämnen med liknande struktur och kemiska egenskaper; polybromerade dibenso‐p‐dioxiner (PBDDs), i bl.a. fisk och musslor från Östersjön. Halterna är högst i Egentliga Östersjön, framförallt vid kusten och i samma nivå som halterna av PCDD/Fs. I mussla har hittats 4 ng PBDDs/g färskvikt från en opåverkad lokal. Den toxiska mekanismen är samma för PCDD/Fs och PBDD/Fs och de ger samma toxiska effekter. Därför är det viktigt ur risksynpunkt att öka kunskapen om PBDD/Fs för att utröna om de kommer att ha en påverkan på miljö och/eller hälsa. Den geografiska spridningen av PBDDs tyder på att källorna är lokala i motsats till PCDD/Fs, och en hypotes är att PBDDs är naturligt producerade. En bildning av bromerade dioxiner skulle kunna ske genom reaktioner med enklare byggstenar (precursorer). Föreslagna precursorer är bromfenoler och bromerade hydroxy‐difenyletrar, som bägge har hittats i marin miljö. Målet
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