DIOXIN%202003%20BOSTON%20SESSION%20SUMMARY%20REPORT%20Takeshi%20Nakano

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DIOXIN 2003 BOSTONSESSION SUMMARY
REPORTTakeshi Nakano
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DIOXIN 2003 Rapporteur Reports
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ltAnalyticalgt
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FASTER ANALYSIS AUTOMATED CLEANUP
SYSTEMSPressurized Fluid Extraction(ASE) with
silica cleanup in cellSemi-Automated
Comprehensive ExtractionMultiple
Fractionation(SACEMF)Fluid Management
SystemSFE-GC/MS BioassayMiniature and
disposable cleanup procedures
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FASTER ANALYSIS SAMPLE ANALYSISBioassays
Excellent agreement with GC/HRMS, Biased High,
Biased Low Minimal Cleanup, Full Cleanup
GC-TOF with Fast GC Combined analysis of
analyte groups Parallel Columns Analysis GC
Racer
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MORE SELECTIVE ANALYSISMultidimensional Gas
Chromatography-GC/GC-TOF for PCBs and
PBDEs-GC/GC-ECD for PCDDs and PCBsStopped Flow
ChromatographyAnalyte Specific ColumnsCongener
methods for source identification GC/MS/MS-QIT
and TQMS(PCDDs, PCBs)Additional Labeled
Standards13C12BDE 209, 13C-HBCD,PFOS
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MORE SENSITIVE ANALYSISREQUIRED FOR FOOD
ANALYSISBioassays Low fg/g TEQ
DLsChromatographic ModulationLarger sample
sizes or large volume injectionsRequires more
rigorous cleanup
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NEW TECHNIQUES FOR ANALYSISLC/MS-HBCD, TBBPA,
PFOS, PFOAPassive Sampling for Air-Window
sampling of Biofilms for Halogenated
Compounds-Mosses for samplingPassive sampling
of water samples-Semi permeable membranesSPME
for polar and non-polar compoundsGas Monitors
for Combustion Systems
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ENHANCED QUALITYPerformance Based Methods with
well defined quality standards-Ensure labs are
measuring the same thing the same wayEnsure
Quality is part of labs cultureAccreditation,
ISO 17025Participation in interlaboratory and
Performance Evaluation StudiesUse of Certified
Reference Materials and Standards
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ADDITIONAL QUALITYObtain Consensus and
Direction on Low Level Reporting-Control Lab
Contamination, e.g BFR material in labs-reduces
dust in lab, Teflon in LC/MS values and tubing
for PFOS-Blank Subtraction-no common protocol
Promote RD and continual improvement
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ltBrominated Flame Retardantsgt
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ltBrominated Flame RetardantsgtBackgroundFrom
late 1980s to 19971988 (15 papers)- 2002(30
papers)2003Plenary Lecture by Jacob de Boer
Over 110 presentations included BFRs 4
special sessions over two days Roundtable
discussion Two day workshop prior to Dioxin 2003
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Highlights of the BFR WorkshopPlenary
presentation by Åke BergmanFocused on other
BFRs that we are not currently investigatingReac
tivity of various Flame RetardantsKeynote
Presentations by Linda Birnbaum and Mehran
AlaeeSimilar presentations to Dioxin 2003,
however in smaller setting
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BFR SessionsBrominated Flame Retardants
Related Compunds,Åke Bergman, and Rob
LetcherLevels in human tissue Brominated Flame
Retardants and Related CompoundsMehran Alaee
and Janice HuweMetabolism and environmental
occurrencePBDEs Analysis and Environmental
LevelsDerek Muir and Shin-ichi SakaiPBDEs
Human Exposure and Biological EffectsLinda
Birnbaum and Andreas Sjödin
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Levels in Human TissueNew data of levels and
trends in human tissue from US. Retrospective
time trend study of PBDEs and PBB in human serum
from US PBDEs in maternal and fetal blood
samples Congener specific measurement of PBDEs
in individual milk samples from nursing mothers
in US BDE-209 was detected in breast
milkOther studies from UK, Northern Quebec, and
Sweden
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MetabolismDebromination of PBDEs particularly
BDE-209PBDE metabolites, chromatographic
characterization and environmental
occurrencePossibility of naturally occurring
hydroxy methoxy BDEs and tribromo-p-dibenzodioxi
n were discussed
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Environmental OccurrenceInformation on levels of
BFRs at this symposium was overwhelmingHBCDs
are widespread in the environment In some
instances the levels of HBCD was similar to PBDEs
in biota Levels of HBCD is on the rise in
Europe Isomer specific determination of HBCD
demonstrated isomer specific bio-magnification
Use of skipjack tuna as a global bio-indicator
for PBDEs was discussed Decabromodiphenyl
ethane was detected in the environment
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AnalysisBFRs are not just another PCBSynthesis
of isotope labeled HBCD, hydroxy-BDEs and
nona-BDEs GC conditions such as injection
technique plays an important role in the
determination of BDE-209Comprehensive GC/GC
method showed some promising data Some
information of chromatographic behavior of PBDD
and PBDF was presented, however there was lack of
discussion on mixed bromochloro dioxins
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Human Exposure and Biological EffectsCo-exposure
of BDE-99 and CB-52 enhanced developmental
neurotoxic effectsPBDEs have low dioxin-like
activitiesEstrogenic activity of PBDEs and other
BFRs were evaluated both in-vivo BDE-99 and
in-vitro (TBBPA, HBCDD, TBP, HO-BDE)Exprosure to
6-HO-BDE 47, resulted in significant reduction in
aromatase enzyme activity
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ltFormation and Remediationgt
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FormationIntroduction of X-ray absorption fine
structure spectroscopy (XAFS) provides new
aspects to de novo synthesis.Identification of
chemical state of copper in fly ashCu, Cu2O,
CuCl, CuCl2, CuO, Cu(OH)2, CuS,
CuCO3/Cu(OH)2/H2OStrong correlation between
copper oxides and CBs/PCBsFurther application
produces more information
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Thermal DestructionIn Situ Thermal
DesorptionVacuum Heating ProcessIndirect
HeatingSuper Critical Water OxidationHigh
destruction rate of dioxins in soil/fly
ashFurther investigation for the best available
and cost effective technology is necessary.
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Interest to Non-Stationary Combustion(Reduction
of Soot Formation)Optimization of Cold Start-up
ConditionsOptimization of burner Reduction
of air supply Prevention of air leakage
Strictly control of the CO level Activated
carbon injectionImprovement of Shut-downStop
of waste feed until back-up burner is
firedBurner operation till burn out
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Bioremediation1.Bacteria Bacillus,
Sphingomonas, mixed culture2.Fungi
PseudallescheriaIt will be a low cost
technology.Destruction of highly chlorinated
dioxins?Establishment of application method in
large scale treatment is needed.
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ltToxicologygt
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ltToxicologygtTopics in ToxicologyBFRsAh
ReceptorsPharmacokinetics/ModelingEndocrine
DisruptorsTEFsDevelopmental and reproductive
Toxicoogy
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Rats and mice vs EcotoxicologyWhy do we
differentiate these two groups?All species we
examine have-Endocrine systems-Reproductive
systems-Immune systems-Ah receptorsSuggestion
-Have sessions on toxicology topics
(reproductive, endocrine, etc.)It would make the
rapporteur job easier
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Ah ReceptorNon-halogenated LigandsWhat is the
role of the Ah receptor? Biosensor for
light, environmental chemicals (natural products
and POPs)Ah receptor in C. Elegans to humans
Fish have multiple Ah receptors Mammals
have one Ah receptorAhR Response Elements may
have ligand specific effects
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TEFsExpanding the methodology to other
chemicalsWhy the broad range in REPs for a
single chemical -Different systems (MCF-7 vs
MCF-10A cells)-Different methods of estimating
REPs-Chemical impurities-Pharmacokinetics/study
design Frameworks for evaluating data used to
derive TEFs or RPFs.
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EDCsEDCs more complicated that we
thought-Chemicals act on more than ER, AR and
TR Alter synthesis and catabolism of
hormones -Chemicals act on more than one
system TCDD and DDE influence/disrupt both
estrogen and androgen pathways -Interactions
between Endocrine, Immune and Nervous system
Impossible to effect one of these systems and
not the others Call for more holistic
approach to understanding the effects of
environmental chemicals
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ToxicologyPharmacokinetics Animal and Human data
matching up-Influence of disease states (animal
and human concurrence)-Dose dependant
elimination rates.Mixtures of POPs-Particular
focus in wildlife studies
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ltLevelgt
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Food levelsFood still can be a matter of concern
for human uptake of chlorinated components as
reportedSchecter et al. Presented new findings
for TCDD contamination of food, recently
collected at a HOT SPOT north of
Saigon/Vietnam, close to a former air base. For
individuals consuming this food regularly
elevated blood levels were reported even 30 years
after the Vietnam war.First dioxin and PCB data
in food were reported for Greece by Papadopulus
The levels were found to be quite similar as
reported for other southern European countries.
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Food, cont. Human exposure to PCDD/Fs and PCBs
for Japanese infants and adults were given in 2
papersThe intake for infants was found to be
25times higher than the WHO-TDI, even after the?.
delivery as reported by Uehara et al.For adults
the estimated intake was reported by Suzuki et
al., at 1.5 pg TEQ/kg BW/day. 97 resulted from
the diet.
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Food, cont.Of specific help may be a paper of
Focant et al. from University Liege. They
analyzed Fast Food samples from 8 locations
worldwide for PCDD/Fs and PCBs. Resulting from
this we can expect the same dose of about 2
pgTEQ/g fat in Sidney, Atlanta, Zurich or other
places when consuming a Hamburger or Pizza.
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Human LevelsAdditional results of the
WHO-coordinated exposure study on the levels of
PCBs, PCDDs and PCDFs in human milk were reported
by Malisch and v. Leeuwen. Lowest values were
found for countries from the southern
hemisphere e.g. Brazil, New Zealand, Australia,
Fiji. The 2 samples from US (east/west coast)
were found to be below the world median value
of 28 samples.3 papers gave information on
special consumption habits on the Faroe Island
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Human Levels, cont.D. Barr et al. reported on
the successful application of new analytical
methodology on PCBs and OC pesticides for 900
serum samples from children from the F. Isld.
Correlations between selected PCBs and blubber
consumption and nursing could be
demonstrated.Weihe et al. reported on the
sustained high concentration of Faroese pregnant
woman despite dietary intervention while Heilmann
et al. gave information on decreased childhood
vaccine response in children exposed to PCBs
from maternal seafood diet at the F. Isld.
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Levels other than Dioxins and
PCBsFluorochemicals are used in a wide variety
of industrial and consumer products. Increasing
interest in these components is reflected by 7
oral presentations.
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Important findings were given on
perfluoroalkylated compounds in human blood by
Kannau et al., NY Health. PFOS (Perfluoro
octanesulfonat) is one of the metabolic end
products of these components in the human
body. This and similar end products were reported
for background exposed population in USA,
Italy and India. The values found were up to 10
times higher than corresponding PCBs.
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Levels other than Dioxins and PCBs, cont.PFOS
was also reported from Keller et al. to be
present in the blood of Loggerhead sea turtles
from North Carolina at values up to 28
ng/ml.Triclosan is a persistent and lipophilic
component that is acutely toxic to biota. Mehran
Alaee et al. presented the first evidence for
Triclosan in fish plasma from 13 different
species of fish collected in the Great Lakes
area (Detroit River).
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Soil LevelsFirst background levels of PCDD/Fs
in 42 soil samples of Beijing area, China were
reported by Chen et al. at a mean of 0.8 pg
TEQ/g. Data are comparable to West- European
soils.For site of a former PCP producing plant
in Taiwan, Chung et al. referred on highly
contaminated soil and sediment samples of up to
2000 ng TEQ/g. The former industrial field will
be used as urban residential area. First
successes in cleaning activities could be
reported at.
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Sediment Levels The occurrence of elevated POP
levels in sediments can often be seen in
association with adverse biological
effects.Vosolo et al. provide first data for
PCDD/Fs and PCBs in sediments from South Africa.
In general the values are relatively low. Levels
were highest in urban and industrial areas and
occur at lower values in pristine areas.Knoth et
al. reported on the potential effect of a
historical flood of the river Elbe in 2002 on
dioxin concentration of sediments of the river.
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Sediment Levels, cont. Contaminated landfills
and chemical factoriescould have leaked out.
Leaking of a highly dioxin contaminated plant
area in Czechia could not be proved. Historical
and projected surficial sediment concentration if
dioxins and PCBs in Lower Passaic River, New
Jersey were given by Su and Finley. Rates of 50
decline were calculated from the historical trend
for most of 30 congeners at about 20 years.
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Levels ? Olaf Paepke and Susan Shaw Total
number of papers 139 (18 ) Session -POPs in
Arctic SS-POPs in Marine mammals SS-POPs in
Sediments and Aquatic Environments Wildlife
SS Fish SS
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POPs in the ArcticAMAP Update Muir et al.
presented new data on POP levels and trends. POPs
in wildlife are highest in the European Arctic
and lowest in the North American Arctic (except
for HCHs). Legacy POPs in biota declined until
1990, then began to stabilize. PBDEs are
increasing exponentially in beluga and ringed
seals.Novel Compounds New chemicals detected in
the Arctic environment are PBDEs, PCNs,
short-chain chlorinated paraffins (SCCPs) and
planar PCBs (Bidleman et al.). Planar PCBs and
PCDD/Fs were detected in Canadian birds (Braune
and Simon). TEQs were highest in reindeer on the
Kola Peninsula (Amirova et al.).
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POPs in the Arctic, cont.Polar Bear Results
Findings of a long-term study by Janneche Ume
Skaare et al. indicate that the high levels of
PCBs in polar bears at Svalbard are associated
with polar bear endocrine disruption and
immune suppression, placing the health of the
population at risk. Levels in Humans (AMAP and
New Russian Study)Indigenous human populations
who consume marine mammals have high levels of
POPs. Data on the Russians at Chukotka (Sandanger
et al.), the Inuit, and the Faroe Islanders
(Hansen et al.) indicate the Inuit of east
Greenland have highest levels due to their polar
bear diet. Subtle POP-related effects are
reported in some of these groups and there is a
need to reduce exposure.
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POPs in Marine MammalsLevels and Trends High
levels of POPs in marine mammals inhabiting
industrialized areas are linked with adverse
effects and mass mortalities and are a continuing
focus of research.Law et al. reported levels of
OCs and PBDEs in marine mammals stranded or
bycaught in the UK. The data will feed into
on-going risk assessments on flame retardants
within the EU. Novel flame retardants
hexabromocyclododecane (HBCD) and
tetrabromobisphenol-A (TBBP-A) were recently
detected in blubber of harbour porpoises.
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POPs in Marine Mammals, cont.Kajiwara et al.
reported temporal trends for PBDE residue levels
as well as changes in congener profiles of
PBDEs in blubber of northern fur seals collected
between 1972 and 1997 from Asian waters.Lebeuf
et al. used patterns of PBDEs and PCBs in blubber
of harbor seals to distinguish colonies in
Atlantic Canada. This study concluded that seals
collected from three sampling sites were
adequately classified into distinct colonies on
the basis of their patterns of POPs.
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POPs in Marine mammals, cont.Linking Levels and
Effects To access the sensitivity of marine
mammals to POPs, new studies are identifying
species-specific metabolic pathways. The
potential for planar PCBs and PCDD/Fs to modulate
expression of the AhR and CYP subfamilies was
examined in Baikal seals (Iwata et al.) and in
belugas from the St. Lawrence estuary and Arctic
Canada (Letcher, et al.).An unusual field study
in Sarasota Bay, Florida (Wells et al.) is
integratinf data on history, health and
reproductive success to examine effects of POPs
on a local population of free-ranging
bottlenose dolphins.
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POPs in Marine mammals, cont.A new approach
(Shaw et al.) applied reporter gene technology
(CALUX) to assess relationships between the
induction potency (TEQ) of planar PCBs and
PCDD/Fs and immune function in free-ranging
harbor seals along the US Atlantic coast. A
positive correlation between lymphocyte
mitogenesis and CALUX-TEQs was found, suggesting
an immunomodulatory effect of dioxin-like
compounds.
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POPs in Sediments Aquatic Environments
Reports on POPs in fish from the Baltic Sea
suggest that the occurrence of dioxins and other
persistent chemicals continues to be of
concern in the Nordic countries.Isosaari et al.
concluded from monitoring studies in Finland that
the levels in pelagic fish younger than 3-5
years old are below maximum permissible limits (4
pg WHO TEQ/g fw).Bjerselius et al. reported
similar findings in fish from the Baltic Sea and
along the Swedish coast.
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POPs in Sediments Aquatic Environments,
Monitoring studies of fish conducted over the
past few years suggest that PCDD/Fs and other
POPs are approaching levels of concern, and more
data is needed. Abalos et al. reported on
dioxins and PCBs monitored in fish and shellfish
consumed in Spain. Munschy et al. provide one
of the few reports on PCDD/F levels in bottom
fish from French coastal waters along the East
English Channel. Vojinovic-Miloradov et al.
present the only paper on PCB and OC pesticide
levels in amphibians. Levels in the liver of
frogs in Montenegro suggest that atmospheric
deposition is a major source.
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ltTransport and Fategt
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OVERVIEWIn total, over 40 papers presented,
from all corners of the worldAppropriate that
several studies examined the regional global
fate and cycling of PCDD/Fs and PCBsIn the
Eastern Mediterranean, ca 4 t SPCB/yr eliminated
as a result of the major removal mechanism - OH
radical attackExtrapolated to a global scale,
and OH radical attack remains the predominant
mechanism for lower MW PCBs. For higher MW
congeners like 153 180, the dominant removal
process is burial in continental shelf sediments.
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OVERVIEWMean residence times in the global
environment for such higher MW congeners are ca
50-100 years, confirming the longevity of the PCB
legacyFor PCDD/Fs, the oceans and the atmosphere
(principally via OH radical reaction) shown to be
equally important global sinks for
ST4-O8-CDD/Fs. Steady state assumption estimates
total global emissions to equal ca 20 t/yr
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ltEpidemiology and Human EffectgtEndocrine and
Reproductive Effects FemalesSeveso women
healths study (Eskenazi et al.) -Doubling of
endometriosis but not significant dose response
-Longer menstrual cycle but only in women
exposed pre-menarche -No increase in
spontaneous abortion or birth defects (numbers
too small)
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Endocrine and Reproductive Effects Females,
cont. -No change in age of menarche -Possible
small association with birth weight/SGA
-Increasede breast cancer incidence Could be an
underestimate of effects due to potentially high
background Longer menstrual cycle length showed
also in Yucheng women by Leon Guo et al.
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Endocrine and Reproductive Effects Males
-Reduction of sperm motility in men exposed pre
and post natally to PCBs both in the Yucheng
cohort (Leon Guo et al.) And in Swedish fisherman
(Hagman et al.) -No casual relationship between
paternal TCDD exposure and lowered birthweight
(Lawson et al.)
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A Special Mention Needs the Ranch Hand Study1000
exp. (0-4000ppt) 1300 contr. (0-10)Increase
ofOverall cancer, Prostate cancer, Melanoma,
Diabetes, Probable peripheral neuropathyDecrease
ofLogical memory score (Michalek et al.)
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ConclusionsI regret not quoting other
interesting papers (time!!!) Much important new
information was presented We have still a lot
of work to do Thank to all, Best wishes SEE
YOU IN BERLIN!!
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ltEmerging POPsgtEmerging POPs Variety of New
Compounds-PBFRs (covered in separate
presentation)-Perfluorinated CompoundsNot all
POPs are created equal-Perfluorinated compounds
have new properties that need to be
consideredRe-Emerging POPs-PBFRs, PBDEs, some
OC pesticides
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Analytical Still poses many challengesA range
of compounds -Polar (PFOS)-Non-polar
(sulfonamides)Extraction techniques GC/MS
methods LC MS methods Different methods work for
different compounds
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Analytical, cont.Still lack of analytical
standards.Need standards of the compounds - many
labs using different commercial materials as
standardsNeed stable isotope standards - some
groups are now having these specially synthesized
so we can expect some advance on this front in
the near future.
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ToxicologyRelatively few toxicological studies
Biochemical studies suggest affects on
membranes.Physical properties also suggest
effects on membranes.As well as short term
affects on membranes also long term alterations
on gene expression.
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Human Exposure Detected in human serum and milk
Still determining the range of specific
compounds that should be monitored PFOS, PFOSA
Net-FOS-OH, PFOACompounds measured in Fast Food
Survey in CanadaConcentrations of sulfonates
seem to have declined in the last few years(US
production ceased in 2000)
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Environmental Levels Study looking at food chain
accumulation Showing biomagnification but
these compounds accumulate in blood and
liver.Our standard BMF model may need to be
modified for these compounds as they do not
accumulate in lipids.Concentrate in some marine
mammals (whales) but not others (walrus)
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Environmental Levels, cont. Several PFCS found
in near shore and open ocean waters in
AsiaBlanks a problem-Contamination in lab
equipment (plastics)-Contamination in
instruments (Teflon)Measured in open ocean
waters at pg/LPFOA gt PFOSShowed greater
concentrations nearer to the surface than at
depth -Still detectable in deep waters
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Conclusions Still identifying key environmental
compartmentsBetter understanding of
toxicological effectsPFCs are POPs of a
different color