Seventh International PCB Workshop:
May 27, 2012 Sunday
6.00 pm Sunday Evening Reception: Address to participants and
7.00 pm Honorary lecture by J.F. Narbonne in celebration of his retirement: “25 years of PCB risk assessment in France"
May 28, 2012 Monday
Chairs: Keri Hornbuckle (Iowa SRP) and Bruno Lebizec
9.00 am Dr. Amina Salamova "Polychlorinated Biphenyls (PCBs) in the Great Lakes’ Atmosphere"
9.30 am Dr. Geniece M. Lehmann "Evaluating non-cancer health risk from inhaled PCBs: Uncertainties and research needs"
10.00 am Dr. Benoit Van Aken (Iowa SRP) "Biodegradation of PCBs and their hydroxylated metabolites"
10.30 am Coffee break
11.00 am Dr. Keri Hornbuckle "Sources of PCB congeners in urban, industrial, rural and indoor environments"
11.30 am Dr. Bruno Le Bizec
12.00 pm Selected Posters Presentation
12:45 pm Lunch
Summary of the session: The goal of this session was to identify and quantify current sources of PCBs, levels in atmosphere, soil and water, transfer in the food web. Amina Salamova showed us, employing data from the longest running air monitoring program (IADN), that PCBs have very long environmental half lives - 17 years more. This is not because PCBs have no sinks. In fact, several speakers showed that PCBs can be degraded. For example, Benoit Van Aken demonstrated that PCBs can be degraded by plants common in our world. PCBs have many current sources from a wide variety of materials and sites. Keri Hornbuckle showed examples of contaminated water, indoor air, and current household paint as sources. Bruno Le Bizec demonstrated that even agricultural feed is a current source of PCBs. Geniece Lehmann showed that although there is strong evidence that air is an important route of exposure, there are many questions remaining about quantifying this route of human exposure to PCBs from our environment and challenges in assessing risk to human health.
Chairs: Michael Duffel (Iowa SRP) and Jean-Pierre Cravedi
2.00 pm Michael Duffel “Metabolism of PCBs with an Emphasis on the Potential Roles of Sulfation in Toxicity and Endocrine Disruption”
2.30 pm Jean Pierre Cravedi "Biotransformation of PBDEs and Other Polybrominated Compounds: Evidence for Bioactivation Pathways and Comparison with PCBs"
3.00 pm Coffee break
3.15 pm Bernhard Hennig "Influence of Nutrition in Mechanisms of PCB toxicity"
3.45 pm Gabriele Ludewig (Iowa SRP) “Genotoxic endpoints and exposure to PCBs: Unique effects by different PCBs and metabolites”
Summary of the session: This session addressed aspects of the metabolism and mechanism of action of polyhalogenated compounds. Presentations included studies on the roles of metabolism, metabolites, and parent compounds in receptor-binding, endocrine signaling, cardiovascular toxicity, and genotoxicity. Michael Duffel presented studies on the roles of sulfation in the metabolism of hydroxylated PCBs and related interactions with sulfotransferases that are important in steroid hormone signaling. Recent results on the high-affinity binding of PCB-sulfates to the thyroid hormone binding protein, transthyretin, were also discussed. Jean Pierre Cravedi made the connection between metabolism of polybrominated aromatics and PCBs and presented evidence that the hydroxylated metabolites of PBDEs alter endocrine action through thyroid and steroid hormone pathways. Moreover, sulfated metabolites of tetrabromobisphenol A were noted as agonists of the PPAR gamma receptor. Bernhard Hennig discussed the role of diet in modulating the effects of PCBs on the vascular endothelium through changes in cellular lipids, oxidative stress, and antioxidants. These concepts were carried into studies on caveolae and their role in endothelial changes mediated by co-planar PCBs. Finally, Gabriele Ludewig addressed the genotoxicity of the oxidized metabolites of lower-chlorinated PCBs, including point mutations and pre-neoplastic foci in the rat. She also presented new findings on the ability of these PCB metabolites to reduce the length of telomeres and to reduce the activity of telomerase.
May 29, 2012 Tuesday
Chairs: Jean François Narbonne and Isaac Pessah
9.00 am Ellen Fritsche "Pathway-and Species-specific Effects of Different POPS on Neurosphere Development in vitro"
9.30 am Pamela Lein “Polychlorinated Biphenyls (PCBs) Modulate Neuronal Connectivity via Ryanodine Receptor Dependent Mechanisms”
10.00 am Remco Westerink “Modulation of neutrotransmitter-and voltage-gated ion channels by PCBs and other POPs”
10.30 am Coffee break
11.00 am Rich Seegal “Sexually Dimorphic Effects of PCBs -From Neurodevelopment to Neurodegeneration”
11.30 am Isaac Pessah "Strategic Models for Understanding Gene X Environment Interactions Conferring PCB Susceptibility"
12.00 pm Miroslav Machala et al "In vitro assessment of toxic potencies of PCBs - old and novel mechanisms"
12.30 pm Rachid Soulimani " Methodology for the neurotoxic effects assessment of exposure to low doses of NDL-PCB mixtures in the early stages of development"
13.00 pm Lunch
Summary of the Session: Session III entitled Health effects/critical limits was chaired by Jean François Narbonne (Univ Bordeaux) and Isaac Pessah (UC Davis). The session brought together a truly trans disciplinary group of researchers that are taking innovative approaches to understand how NDL PCBs alter cellular signaling and contribute to developmental neurotoxicity. Dr. Ellen Fritsche presented her latest work developing a human neurosphere model with which to investigate the influence of PCBs and related toxicants on the early differentiation of neural precursor cells, extension of dendrites and axons. Dr. Pam Lein presented her work in rodent models that investigate how PCBs alter activity dependent dendritic growth and complexity both in vitro and in vivo. She implicated a ryanodine receptor dependent mechanism for PCB developmental neurotoxicity that alters the CaM kinase II – CREB- Wnt2 signaling pathway. Dr. Remco Westerink presented a detailed structure-activity relationship by which PCBs, PBDEs and their hydroxylated metabolites alter GABAergic, cholinergic, and voltage-gated ion channels constitutively expressed in PC12 cells or heterologously expressed in Xenopus oocytes. Dr. Rich Seegal presented evidence for sexually dimorphic influences of PCBs on several neurotransmitter systems, including dopamine. These differences measured in animal models appear to mirror the sex bias he has identified in aging capacitor workers, where women appear to be preferentially impacted by occupational exposures to PCBs earlier in their lives. Dr. Isaac Pessah presented unpublished data showing that mice expressing mutations in ryanodine receptor type 1 significantly increases the susceptibility of primary myotubes (embryonic muscle cells) to Ca2+ dysregulation and contractility to very low-level PCB exposures. He hypothesized a pronounced gene X environment interaction may be contributing to impairments in individuals that express malignant hyperthermia mutations whose prevalence is now estimated at greater than 1:3000. Dr. Miroslav Machala presented in vitro assessments of toxic potencies of PCBs based on what is currently known about their mechanism of action. Finally, Dr. Rachid Soulimani presented a broad spectrum of research results, both in vitro and in vivo investigating the neurotoxic effects of low doses of NDL PCB mixtures, with a particular focus on early stages of development. Interestingly one of the primary targets promoting dysregulation appears to involve ryanodine receptor mediated impairment in Ca2+ dynamics. Overall the talks in the session were well integrated, each providing mechanistic information that will be useful to setting biological limits for critical health effects for general and at risk (susceptible) populations.
Chairs: Jean Charles Leblanc, Nadine Fréry
2.00 pm Fanny Héraud "PCB exposure via food in Europe"
2.30 pm Rainer Malisch “Results of WHO/UNEP-coordinated exposure studies on levels of PCDD/F and PCBs (dioxin-like and non dioxin-like) and in human milk"
3.00 pm Nadine Fréry & Jean-Charles Leblanc French studies: "PCB biomonitoring in general and specific populations in France"
3.30 pm Coffee break
4.00 pm Peter S. Thorne (Iowa SRP) "The AESOP Study: Assessing Exposure to PCBs in Children and their Mothers in At-Risk and Baseline Communities"
4.30 pm Mohamed Ridha Driss “PCB levels in the Tunisian population”
5.00 - 6.30 pm Selected Posters Presentation (sessions II, III, IV)
Summary of the session: Monitoring programs on dioxins and PCBs in food have been conducted in 26 European countries between 1995 and 2010. They show that eels and fish liver are the most highly contaminated food products to both dioxins and PCBs. The dietary exposure assessment conducted by EFSA (European Food Safety Authority) confirms the three main food contributors to the dietary intake of PCBs and dioxins we already know: fish, meat and dairy products. Their relative importance to the total intake depends on age and country. The most exposed population groups (when expressing the intake on a body weight basis) are the toddlers and the other children (<10 years old). The dietary intake of dioxins and PCBs has decreased during those last ten years. The decrease trend seems to be less important for the NDL-PCBs than for the sum of dioxins and DL-PCBs. This might be explained by a higher decrease of contamination of the terrestrial food chain compared to the aquatic food chain, which must be further investigated.
Levels of PCBs and PCDD/Fs in human milk were determined in WHO-coordinated exposure studies since 1987. As suitable indicator for bioaccumulation of POPs, human milk was selected by UNEP as one of two matrices for evaluation of the effectiveness (Art.16) of the Stockholm Convention. Samples of more than 60 countries were submitted for the jointly organised WHO/UNEP studies. A comprehensive protocol and performance of analyses in the WHO/UNEP Reference Laboratory should contribute to the reliability of results. The decrease observed in food is in accordance with the one observed in human milk. Results of samples collected between 2001 and 2011 show a wide difference of dioxin and PCB levels among countries (range of individual pools: 2 - 50 pg WHO-PCDD/F(1998)-TEQ/g fat; 1 - 30 pg WHO-PCB(1998)-TEQ/g fat; 4-1000 ng/g fat for NDL-PCBs), with the highest levels observed in Europe (Czech Rep) for NDL-PCBs. Low or middle levels of PCDD/Fs and PCBs are mostly observed in Australia and Pacific Islands (such as in Fiji), Asia (except for India with high levels of dioxins) and in Caribbean, Central and South American countries. In Africa, the contamination with dioxins is characterized by two extremes: i) Some countries are in the group with the lowest dioxin levels in breast milk and ii) some cases show highest levels. The highest levels might have two reasons: i) in one country, dioxin emissions and production of food are quite close together in a densely populated country and ii) in two other countries, related to contaminated clay ingestion (geophagy; dioxin-contaminated clays assumed to be formed by geological processes over time). It seems relevant to study PCB levels in new countries being parties to the Stockholm Convention. With regard to the situation in European countries being in the middle and upper third with regard to PCDD/F and in particular PCBs, follow-up is recommended.
Some new data have been obtained from Tunisia as part of a national programme (in serum and human milk). The decrease at international level was also seen at national level, in particularly in France where serum NDL-PCB levels were divided by three in 20 years (1986 -2006/07) and breast milk dioxin levels were decreased by 40 % in 10 years (1998-2007). The French NDL-PCB levels remain relatively higher than those of other countries, except Czech Republic or Slovakia. The French results underline the importance of individual characteristics on PCB levels, such as age and recent loss of weight. When the NDL-PCB levels were studied in general or specific populations, such as in people living in the vicinity of incinerators or in anglers, no big difference was observed among populations, except for anglers who are high consumers of fish which accumulate PCBs.
The AESOP Study, a project within the Iowa SRP, is examining congener-specific exposures to PCBs among an urban cohort of children and their mothers in East Chicago, Indiana, an area contaminated with industrial pollutants, including PCBs. These exposures are being compared to a rural cohort without recognized industrial sources of PCBs (Columbus Junction, Iowa). The combination of annual blood samples and concurrent air samples at subjects’ homes and schools, both indoors and outdoors, along with detailed questionnaire data, provide a unique study from which to determine the contribution of inhalation exposure to the body burden of PCBs. The AESOP study shows that indoor levels of PCBs contribute more to the body burden than outdoor levels in both communities. The rural site PCB congener profiles have more di- to tetra-chlorinated biphenyls compared to the urban homes which show a higher proportion of penta- to hexa-chloro congeners. Blood samples collected in the first two years demonstrate congener profiles indicative of exposure to the more-volatile lower molecular weight congeners than most prior studies. Mothers exhibit higher levels of serum PCBs than their children with a profile skewed toward more chlorinated congeners. This suggests that inhalation exposures represent an important PCB exposure pathway and are especially important for children. So, if until now we have focused the study of PCB exposure on food exposure, it seems relevant today to study if indoor air exposure to PCBs can be an important source ignored until now.
May 30, 2012 Wednesday
Chairs: Rosalinda Gioia, Annie Sasco
9.00 am Rosalinda Gioia "Introduction of the topic"
9.10 am Abidemi Akindele "Persistent Organic Pollutants in Africa: Environmental and Human Health Considerations"
9.40 am Kwadwo Ansong Asante "Contamination by PCBs and BFRs and Human Health Risk Assessment in Fish and Human Breast Milk in Ghana"
10.10 am Coffee break
10.40 am Sunday Adebusoye "Metabolic potentials of PCB-degrading organisms from Nigerian contaminated systems: thus far, where further"
11.10 am Alfons Buekens "Technical, environmental and social factors in PCB management"
11.40 am Annie Sasco "Conclusions/Needs/Directions"
12.00 pm Selected Posters Presentation (sessions V, VI)
13.00 pm Lunch
Summary of the session: The goal of the session was to present data on stockpiles of PCBs in African and southern countries in terms of risk evaluation, environmental and public health consequences, solutions for elimination and remediation. There are indications of a continuing shift in primary emission sources of PCBs to the countries of the South including Africa. This is supported by air, milk and fish concentrations data of PCBs in Africa which clearly show an increase of PCBs during the last 5-10 years, suggesting potential health risks especially for the newborns. There is a growing of potential PCB sources in Africa including transformers, continuing import of e-waste from countries of the North, shipwreck and biomass burning.
The potential for detrimental effects on environmental and human health due to long range transport (LRT) of PCBs by air, water and waste or by any other means should be of equal concern when managing POP-like chemicals. Further efforts are needed to mitigate export of obsolete products and waste from the countries of the North to the countries of the South as well as sound waste management and solution for elimination and remediation of PCBs from the environment.
Chairs: David Osterberg (Iowa SRP) and Pierre-Marie Badot
2.00 pm Pierre-Marie Badot "State of the art and rationalization on the variety of risk/regulatory approaches used in different countries to access mixtures of chemicals: the case-study of PCB"
2.30 pm Nancy Hopf "Concentration-dependent Half-Lives of Polychlorinated Biphenyl in Sera from an Occupational Cohort"
3.00 pm Geniece M. Lehmann "Evaluating non-cancer health risk from inhaled PCBs: current U.S. perspectives"
3.30 pm Coffee break
4.00 pm Takeshi Nakano "The way Japan deals with PCBs regulations and risk"
4.30 pm Niklas Johansson "The PCB Elimination Network (PEN) initiative of the Stockholm Convention: Recent Activity"
5.00 pm Beatrice Sécrétan "Plans for the IARC monograph on PCBs"
5.15 pm Closing comments
Summary of the session: The goal of this session was to discuss various approaches for risk assessment. What the best methodology for mixtures evaluation? Pierre-Marie Badot of CNRS (National Scientific Research Center), workshop session co-chair, began the discussion of evaluating PCB mixtures with the statement “we find no single chemical in the real world.” His presentation set the stage for one by Nancy Hopf (Institute for Occupational Health at Lausanne University) who presented research on the half-lives of various PCB congeners. Her new worker blood data gathered at the US National Institute of Occupational Safety and Health and analyzed while she was on the staff there, demonstrated the decrease over time in PCB levels in the same workers in a US electrical capacitor factory. Geniece Lehmann (US Environmental Protection Agency) discussed the levels of PCBs found in three New York City schools. She noted the lack of information on which to base an advisory level for PCBs in air. The US EPA used data from PCB levels found in schools in Germany to find levels that could serve as standards.
After the coffee break, Takeshi Nakano (Graduate School of Engineering, Osaka University) demonstrated the great strides in PCB disposal in Japan during the last ten years. A government corporation (JESCO) is using new chemical techniques to destroy PCBs in modern beautiful buildings designed to blend in with modern Japan and avoid the NIMBY problem. While worker protection within the company seemed of a high standard, his slides demonstrated that the transportation company bringing PCB contaminated materials to the plants did not have similar worker protection. The two standards of worker protection provide opportunities to monitor worker exposure. Niklas Johnson (Swedish Environmental Protection Agency) explained the PCB Elimination Network (PEN) and the progress this organization has made over the last four years. His presentation was the first of three designed to allow conference attendees to use their knowledge of PCB science to cooperate to expand knowledge. Niklas invited the audience to join the 700 present members of the PEN network. Beatrice Sécrétan (International Agency for Research on Cancer) described the IARC monograph process and the deadlines for researchers to become part of the new PCB panel and have their research considered in its deliberations. The last of the series to action steps was from Philippe Garrigues, editor of Environmental Science and Pollution Research. He described plans for a special issue of the Journal prepared from the papers of the Workshop.
J.-F. Narbonne, (University of Bordeaux)
Helene Budzinski, (University of Bordeaux)
Niklas Johansson (Swedish Environmental Protection Agency)
Larry W. Robertson (University of Iowa Superfund Research Program)
Jacob de Boer (Free University of Amsterdam and QUASIMEME)
Keri Hornbuckle (University of Iowa Superfund Research Program)
Dieter Schrenk (University of Kaiserslautern and ATHON)
Rolaf van Leeuwen (National Institute of Public Health & Environment, Bilthoven)
Claudia Heppner, (European Food Safety Authority)
Richard Seegal (New York State Department of Health)
Stuart Harrad (University of Birmingham)
Michael Denison (UC Davis Superfund Research Program)
Bernhard Hennig (University of Kentucky Superfund Research Program)
Jean Charles Leblanc (Agency for Food, Environmental & Occupational Health & Safety Paris)
Nadine Frery (French Institute for public health surveillance InVS Paris)
Marc Babut (Cemagref Lyon)
Bruno Lebizec (LABERCA, National Reference Laboratory for PCBs & PHAHs, Nantes)
Jean Pierre Cravedi (UMR1331 Inra/INP/UPS ToxAlim, Inra, Toulouse)
J.-F. Narbonne (U Bordeaux)
Helene Budzinski (U Bordeaux)
Jerome Cachot (University of Bordeaux)
Magalie Baudrimont (University of Bordeaux)
Pierre Labadie (University of Bordeaux)
Veronique Loizeau (IFREMER, Dept Biogeochim & Ecotoxicol)