Harbor porpoises; Metabolism; PBPK models; PCBs; Time trends
Abstract :
[en] In the last decade, physiologically based pharmacokinetic (PBPK) models have increasingly been developed to explain the kinetics of environmental pollutants in wildlife. For marine mammals specifically, these models provide a new, non-destructive tool that enables the integration of biomonitoring activities and in vitro studies. The goals of the present study were firstly to develop PBPK models for several environmental relevant PCB congeners in harbor porpoises (Phocoena phocoena), a species that is sensitive to pollution because of its limited metabolic capacity for pollutant transformation. These models were tested using tissue data of porpoises from the Black Sea. Secondly, the predictive power of the models was investigated for time trends in the PCB concentrations in North Sea harbor porpoises between 1990 and 2008. Thirdly, attempts were made to assess metabolic capacities of harbor porpoises for the investigated PCBs. In general, results show that parameter values from other species (rodents, humans) are not always suitable in marine mammal models, most probably due to differences in physiology and exposure. The PCB 149 levels decrease the fastest in male harbor porpoises from the North Sea in a time period of 18†years, whereas the PCB 101 levels decrease the slowest. According to the models, metabolic breakdown of PCB 118 is probably of lesser importance compared to other elimination pathways. For PCB 101 and 149 however, the presence of their metabolites can be attributed to bioaccumulation of metabolites from the prey and to metabolic breakdown of the parent compounds in the harbor porpoises.
Research center :
MARE - Centre Interfacultaire de Recherches en Océanologie - ULiège
Anthony D.C., Montine T.J., Graham D.G. Toxic responses of the nervous system. Casarett & Doull's Toxicology: The Basic Science of Poisons 1996, 463-486. The McGraw-Hill Companies, Inc. C.D. Klaassen, M.O. Amdur, J. Doull (Eds.).
Bachour G., Failing K., Georgii S., Elmadfa I., Brunn H. Species and organ dependence of PCB contamination in fish, foxes, roe deer, and humans. Arch. Environ. Contam. Toxicol. 1998, 35:666-673.
Beckmen K.B., Ylitalo G.M., Towell R.G., Krahn M.M., O'Hara T.M., Blake J.E. Factors affecting organochlorine contaminant concentrations in milk and blood of northern fur seal (Callorhinus ursinus) dams and pups from St. George Island, Alaska. Sci. Total Environ. 1999, 231:183-200.
Boon J.P., van der Meer J., Allchin C.R., Law R.J., Klungsøyr J., Leonards P.E.G., Spliid H., Storr-Hansen E., Mckenzie C., Wells D.E. Concentration-dependent changes of PCB patterns in fish-eating mammals: structural evidence for induction of cytochrome P450. Arch. Environ. Contam. Toxicol. 1997, 33:298-311.
Borrell A., Garcia-Solà A., Aguilar A., Garcia N.A., Crespo E.A. Organochlorine residues in South American sea lions, Otaria flavescens (Shaw, 1800): bioaccumulation and time trends. Bull. Environ. Contam. Toxicol. 2010, 84:731-737.
Bossart G.D., Reidarson T.H., Dierauf L.A., Duffield D.A. Clinical Pathology. CRC Handbook of Marine Mammal Medicine 2001, 383-436. CRC Press LCC, Florida, USA. Second Edition. L.A. Dierauf, F.M.D. Gulland (Eds.).
Chu S., Covaci A., Haraguchi K., Voorspoels S., Van de Vijver K., Das K., Bouquegneau J.M., De Coen W., Blust R., Schepens P. Levels and enantiomeric signatures of methyl sulfonyl PCB and DDE metabolites in livers of harbor porpoises (Phocoena phocoena) from the Southern North Sea. Environ. Sci. Technol. 2003, 37:4573-4578.
Clewell R.A., Clewell H.J. Development and specification of physiologically based pharmacokinetic models for use in risk assessment. Regul. Toxicol. Pharmacol. 2008, 50:129-143.
Corley R.A., Mendrala A.L., Smith F.A., Staats D.A., Gargas M.L., Conolly R.B., Andersen M.E., Reitz R.H. Development of a physiologically based pharmacokinetic model for chloroform. Toxicol. Appl. Pharmacol. 1990, 103:512-527.
Covaci A., Van de Vijver K., De Coen W., Das K., Bouquegneau J.M., Blust R., Schepens P. Determination of organohalogenated contaminants in liver of harbour porpoises (Phocoena phocoena) stranded on the Belgian North Sea coast. Mar. Pollut. Bull. 2002, 44:1157-1169.
Debier C., Pomeroy P.P., Dupont C., Joiris C., Comblin V., Le Boulengé E., Larondelle Y., Thomé J.P. Dynamics of PCB transfer from mother to pup during lactation in UK grey seals Halichoerus grypus: differences in PCB profile between compartments of transfer and changes during the lactation period. Mar. Ecol. Prog. Ser. 2003, 247:249-256.
Dietz R., Riget F.F., Sonne C., Letcher R., Born E.W., Muir D.C.G. Seasonal and temporal trends in polychlorinated biphenyls and organochlorine pesticides in East Greenland polar bears (Ursus maritimus), 1990-2001. Sci. Total Environ. 2004, 331:107-124.
Doolittle N.D., Petrillo A., Bell S., Cummings P., Eriksen S. Blood-brain barrier disruption for the treatment of malignant brain tumors: the national program. J. Neurosci. Nurs. 1998, 30:81-90.
Dufresne M.M., Frouin H., Pillet S., Lesage V., De Guise S., Fournier M. Comparative sensitivity of harbour and grey seals to several environmental contaminants using in vitro exposure. Mar. Pollut. Bull. 2010, 60:344-349.
Grandjean P., Budtz-Jørgensen E., Barr D.B., Needham L.L., Weihe P., Heinzow B. Elimination half-lives of polychlorinated biphenyl congeners in children. Environ. Sci. Technol. 2008, 42:6991-6996.
Hickie B.E., Mackay D., de Koning J. Lifetime pharmacokinetic model for hydrophobic contaminants in marine mammals. Environ. Toxicol. Chem. 1999, 18:2622-2633.
Hirakawa S., Iwata H., Takeshita Y., Kim E.Y., Sakamoto T., Okajima Y., Amano M., Miyazaki N., Petrov E.A., Tanabe S. Molecular characterization of cytochrome P450 1A1, 1A2, and 1B1, and effects of polychlorinated dibenzo-p-dioxin, dibenzofuran, and biphenyl congeners on their hepatic expression in Baikal seal (Pusa sibirica). Toxicol. Sci. 2007, 97:318-335.
Kajiwara N., Ueno D., Takahashi A., Baba N., Tanabe S. Polybrominated diphenyl ethers and organochlorines in archived Northern fur seal samples from the Pacific coast of Japan, 1972-1998. Environ. Sci. Technol. 2004, 38:3804-3809.
Koopman H.N. Phylogenetic, ecological, and ontogenetic factors influencing the biochemical structure of the blubber of Odontocetes. Mar. Biol. 2007, 151:277-291.
Law R.J., Bersuder P., Barry J., Deaville R., Reid R.J., Jepson P.D. Chlorobiphenyls in the blubber of harbour porpoises (Phocoena phocoena) from the UK: Levels and trends 1991-2005. Mar. Pollut. Bull. 2010, 60:470-473.
Lebeuf M., Noël M., Trottier S., Measures L. Temporal trends (1987-2002) of persistent, bioaccumulative and toxic (PBT) chemicals in beluga whales (Delphinapterus leucas) from the St. Lawrence Estuary, Canada. Sci. Total Environ. 2007, 383:216-231.
Lee S.K., Ou Y.C., Yang R.S.H. Comparison of pharmacokinetic interactions and physiologically based pharmacokinetic modeling of PCB 153 and PCB 126 in nonpregnant mice, lactating mice, and suckling pups. Toxicol. Sci. 2002, 65:26-34.
Letcher R.J., Norstrom R.J., Muir D.C.G. Biotranformation versus bioaccumulation: sources of methyl sulfone PCB and 4,4'-DDE metabolites in the polar bear food chain. Environ. Sci. Technol. 1998, 32:1656-1661.
Li H., Boon J.P., Lewis W.E., van den Berg M., Nyman M., Letcher R.J. Hepatic microsomal cytochrome P450 enzyme activity in relation to in vitro metabolism/inhibition of polychlorinated biphenyls and testosterone in Baltic grey seal (Halichoerus grypus). Environ. Toxicol. Chem. 2003, 22:636-644.
Maervoet J., Beck V., Roelens S.A., Covaci A., Voorspoels S., Geuns J.M.C., Darras V.M., Schepens P. Uptake and tissue-specific distribution of selected polychlorinated biphenyls in developing chicken embryos. Environ. Toxicol. Chem. 2005, 24:597-602.
Marsili L., Gaggi C., Bortolotto A., Stanzani L., Franchi A., Renzoni A., Bacci E. Recalcitrant organochlorine compounds in captive bottlenose dolphins (Tursiops truncatus): biomagnification or bioaccumulation?. Chemosphere 1995, 31:3919-3932.
Maruyama W., Aoki Y. Estimated cancer risk of dioxins to humans using a bioassay and physiologically based pharmacokinetic model. Toxicol. Appl. Pharmacol. 2006, 214:188-198.
McKinney M.A., De Guise S., Martineau D., Béland P., Arukwe A., Letcher R.J. Biotransformation of polybrominated diphenyl ethers and polychlorinated biphenyls in beluga whale (Delphinapterus leucas) and rat mammalian model using an in vitro hepatic microsomal assay. Aquat. Toxicol. 2006, 77:87-97.
Miller K.A., Assunção M.G.L., Dangerfield N.J., Bandiera S.M., Ross P.S. Assessment of cytochrome P450 1A in harbour seals (Phoca vitulina) using a minimally-invasive biopsy approach. Mar. Environ. Res. 2005, 60:153-169.
Mos L., Tabuchi M., Dangerfield N., Jeffries S.J., Koop B.F., Ross P.S. Contaminant-associated disruption of vitamin A and its receptor (retinoic acid receptor ?) in free-ranging harbour seals (Phoca vitulina). Aquat. Toxicol. 2007, 81:319-328.
Mourente G., Tocher D.R. Lipid class and fatty acid composition of brain lipids from Atlantic herring (Clupea harengus) at different stages of development. Mar. Biol. 1992, 112:553-558.
Parham F.M., Kohn M.C., Matthews H.B., DeRosa C., Portier C.J. Using structural information to create physiologically based pharmacokinetic models for all polychlorinated biphenyls. I. Tisue:blood partition coefficients. Toxicol. Appl. Pharmacol. 1997, 144:340-347.
Redding L.E., Sohn M.D., McKone T.E., Chen J.W., Wang S.L., Hsieh D.P.H., Yang R.S.H. Population physiologically based pharmacokinetic modeling for the human lactational transfer of PCB-153 with consideration of worldwide human biomonitoring results. Environ. Health Perspect. 2008, 116:1629-1634.
Reddy M., Yang R.S.H., Clewell H.J., Andersen M.E. Physiologically Based Pharmacokinetics: Science and Applications 2005, John Wiley & Sons, 420 pp.
Reijnders P.J.H. Reproductive failure in common seals feeding on fish from polluted coastal waters. Nature 1986, 324:456-457.
Reitz R.H., McDougal J.N., Himmelstein M.W., Nolan R.J., Schumann A.M. Physiologically based pharmacokinetic modeling with methylchloroform: implications for interspecies, high dose/low dose, and dose route extrapolations. Toxicol. Appl. Pharmacol. 1988, 95:185-199.
Ross P.S. Marine mammals as sentinels in ecological risk assessment. Hum. Ecol. Risk Assess. 2000, 6:1-18.
Ross P.S., De Swart R.L., Timmerman H.H., Reijnders P.J.H., Vos J.G., Van Loveren H., Osterhaus A.D.M.E. Suppression of natural killer cell activity in harbour seals (Phoca vitulina) fed Baltic Sea herring. Aquat. Toxicol. 1996, 34:71-84.
Routti H., Letcher R.J., Arukwe A., Van Bavel B., Yoccoz N.G., Chu S., Gabrielsen G.W. Biotransformation of PCBs in relation to phase I and phase II xenobiotic-metabolizing enzyme activities in ringed seals (Phoca hispida) from Svalbard and the Baltic Sea. Environ. Sci. Technol. 2008, 42:8952-8958.
Sandermann H. Differential lipid affinity of xenobiotics and natural compounds. FEBS Lett. 2003, 554:165-168.
SCANS II Small Cetaceans in the European Atlantic and North Sea Final report available at:. http://biology.st-andrews.ac.uk/scans2/inner-furtherInfo.html.
Skåre J.U., Stenersen J., Kveseth N., Polder A. Time trends of organochlorine chemical residues in seven sedentary marine fish species from a Norwegian fjord during the period 1972-1982. Arch. Environ. Contam. Toxicol. 1985, 14:33-41.
Sonne C., Gustavson K., Rigét F.F., Dietz R., Birkved M., Letcher R.J., Bossi R., Vorkamp K., Born E.W., Petersen G. Reproductive performance in East Greenland polar bears (Ursus maritimus) may be affected by organohalogen contaminants as shown by physiologically-based pharmacokinetic (PBPK) modeling. Chemosphere 2009, 77:1558-1568.
Szlinder-Richert J., Barska I., Mazerski J., Usydus Z. PCBs in fish from the southern Baltic Sea: levels, bioaccumulation features, and temporal trends during the period from 1997 to 2006. Mar. Pollut. Bull. 2009, 58:85-92.
Tanabe S., Madhusree B., Oztürk A.A., Tatsukawa R., Miyazaki N., Ozdamar E., Aral O., Samsun O., Oztürk B. Isomer-specific analysis of polychlorinated biphenyls in harbour porpoise (Phocoena phocoena) from the Black Sea. Mar. Pollut. Bull. 1997, 34:712-720.
Tanabe S., Niimi S., Binh Minh T., Miyazaki N., Petrov E.A. Temporal trends of persistent organochlorine contamination in Russia: a case study of Baikal and Caspian seal. Arch. Environ. Contam. Toxicol. 2003, 44:533-545.
Thomas G.O., Moss S.E.W., Asplund L., Hall A. Absorption of decabromodiphenyl ether and other organohalogen chemicals by grey seals (Halichoerus grypus). Environ. Pollut. 2005, 133:581-586.
Tilbury K.L., Stein J.E., Meador J.P., Krone C.A., Chan S.L. Chemical contaminants in harbor porpoise (Phocoena phocoena) from the North Atlantic coast: tissue concentrations and intra-and interorgan distribution. Chemosphere 1997, 34:2159-2181.
Tilbury K.L., Adams N.G., Krone C.A., Meador J.P., Early G., Varanasi U. Organochlorines in stranded pilot whales (Globicephala melaena) from the coast of Massachusetts. Arch. Environ. Contam. Toxicol. 1999, 37:125-134.
Tilley R.E., Kemp G.D., Teramitsu I., Hall A.J. Isolation of two cytochrome P450 cDNAs, CYP1A1 and CYP1A2, from harp seal (Phoca groenlandica) and grey seal (Halichoerus grypus). Comp. Biochem. Physiol. C 2002, 132:181-191.
Verner M.A., Charbonneau M., Lopez-Carrillo L., Haddad S. Physiologically based pharmacokinetic modeling of persistent organic pollutants for lifetime exposure assessment: a new tool in breast cancer epidemiologic studies. Environ. Health Perspect. 2008, 116:886-892.
Voorspoels S., Covaci A., Maervoet J., De Meester I., Schepens P. Levels and profiles of PCBs and OCPs in marine benthic species from the Belgian North Sea and the Western Scheldt Estuary. Mar. Pollut. Bull. 2004, 49:393-404.
Walker C.H., Hopkin S.P., Sibly R.M., Peakall D.B. Chapter 6: Toxicity testing. Principles of Ecotoxicology 2006, 87-108. CRC Press, Taylor & Francis Group, USA. Third Edition. C.H. Walker, S.P. Hopkin, R.M. Sibly, D.B. Peakall (Eds.).
Weijs L., Dirtu A.C., Das K., Gheorghe A., Reijnders P.J.H., Neels H., Blust R., Covaci A. Inter-species differences for polychlorinated biphenyls and polybrominated diphenyl ethers in marine top predators from the Southern North Sea: Part 1. Accumulation patterns in harbour seals and harbour porpoises. Environ. Pollut. 2009, 157:437-444.
Weijs L., Dirtu A.C., Das K., Gheorghe A., Reijnders P.J.H., Neels H., Blust R., Covaci A. Inter-species differences for polychlorinated biphenyls and polybrominated diphenyl ethers in marine top predators from the Southern North Sea: Part 2. Biomagnification in harbour seals and harbour porpoises. Environ. Pollut. 2009, 157:445-451.
Weijs L., Das K., Neels H., Blust R., Covaci A. Occurrence of anthropogenic and naturally-produced organohalogenated compounds in tissues of Black Sea harbour porpoises. Mar. Pollut. Bull. 2010, 60:725-731.
Weijs L., Yang R.S.H., Covaci A., Das K., Blust R. Physiologically based pharmacokinetic models for lifetime exposure to PCB 153 in male and female harbour porpoises (Phocoena phocoena): model development and validation. Environ. Sci. Technol. 2010, 44:7023-7030.
Weijs L., van Elk N., Das K., Neels H., Blust R., Covaci A. Persistent organic pollutants and methoxylated PBDEs in harbour porpoises from the North Sea from 1990 until 2008: young wildlife at risk?. Sci. Total Environ. 2010, 409:228-237.
Weijs, L., Covaci, A., Yang, R.S.H., Das, K., Blust, R. Computational Toxicology: Physiologically based pharmacokinetic models (PBPK) for lifetime exposure and bioaccumulation of polybrominated diphenyl ethers (PBDEs) in marine mammals. Environ. Pol. (submitted for publication).
Weisbrod A.V., Shea D., Moore M.J., Stegeman J.J. Organochlorine exposure and bioaccumulation in the endangered Northwest Atlantic right whale (Eubalaena glacialis) population. Environ. Toxicol. Chem. 2000, 19:654-666.
Wilson J.Y., Moore M.J., Stegeman J.J. Catalytic and immunochemical detection of hepatic and extrahepatic microsomal cytochrome P450 1A1 (CYP1A1) in white-sided dolphin (Lagenorhynchus acutus). Aquat. Toxicol. 2010, 96:216-224.
Wolkers J., Burkow I.C., Lydersen C., Dahle S., Monshouwer M., Witkamp R.F. Congener specific PCB and polychlorinated camphene (toxaphene) levels in Svalbard ringed seals (Phoca hispida) in relation to sex, age, condition and cytochrome P450 enzyme activity. Sci. Total Environ. 1998, 216:1-11.
Yordy J.E., Wells R.S., Balmer B.C., Schwacke L.H., Rowles T.K., Kucklick J.R. Life history as a source of variation for persistent organic pollutant (POP) patterns in a community of common bottlenose dolphins (Tursiops truncatus) resident to Sarasota Bay, FL. Sci. Total Environ. 2010, 408:2163-2172.
