Synthetic and Naturally Occurring Brominated
Compounds in the Marine Environment
John P. Giesy, Yi Wan, Steven B. Wiseman, Hong Chang,
Markus Hecker, M. H.W. Lam, and Paul D. Jones
City University
of Hong Kong
Affiliations
Emeritus Distinguished Professor of Zoology
Michigan State University
Chair Professor at Large
Dept. Biology and Chemistry
City University of Hong Kong
Concurrent Professor
School of the Environment
Nanjing University
Guest Professor
Xiamen University
Distinguished Visiting Professor
King Saud University
Organic Brominated Compounds

Halogenated organic compounds of environmental
concern: fluorinated, chlorinated, and brominated

Large amounts of brominated flame retardants have been
produced and used in globally

Many diverse types of naturally occurring organic
brominated compounds have been reported, especially in
the marine environment some with many bromines

Relationships, contributions and potential risks of the
anthropogenic and naturally occurring brominated
compounds?
Polybrominated diphenyl ethers (PBDEs)

Synthetic flame retardants





In many products, textiles, foam for seating and
electronics
Ubiquitous in the environment
Neurotoxins
Endocrine disruption
Moderately toxic at high concentrations
O
Brx
x+y=1-10
Bry
E-Waste handling
Polybrominated biphenyls (PBBs)




Synthetic flame retardants
Became of great concern after Michigan cattle
pollution accident in the U.S. in 1973
Widely detected in the environment
High bioaccumulation potential
Bry
Brx
x+y=1-10
Electrical products
Hydroxylated PBDEs

OH-PBDEs





Marine Sponge
Natural Products
2-OH-PBDE-47
6-OH-PBDE-47
Bio-transformation of PBDEs
Variety of Effects

Endocrine disruption

Disruption of oxidative phosphorylation

6-OH-PBDE is acutely toxic to Zebrafish
OH
O
Brx
x+y=2-9
Bry
Red algae
Bromophenols (BRPs)



Natural compounds: a key natural flavour
component of marine fish
Some are used as flame retardants (2,4,6-triBRP)
reported to be biotransformation products of
OH-PBDEs
OH
Brx
x=1-5
Marine fish
Flame Retardant
Methoxylated PBDEs

MeO-PBDEs


Concentrations sometimes greater than PBDE
Two abundant congeners are natural products




2-MeO-PBDE-68
6 MeO-PBDE-47
Suggested that they may be form from OH-PBDEs
Toxicity unknown
OCH3
O
Bry
Brx
x+y=2-9
Fish oil
Contribution of Synthetic and Naturally Occurring
Organo-bromine Compounds to Bromine Mass
Background

Some well-known synthetic organo-bromines such as
PBDEs have become ubiquitous environmental pollutants

There are a number of unidentified organo-bromines in
the environment

Mass balance studies: synoptic quantification of organobrominated compounds along with quantification of total
organically bond bromine

To estimate the contribution of identified and unidentified
organo-brominated compounds.
Wan Y., Jones P.D., Wiseman S., Chang H., Chorney D., Kannan K., Khim J.S., Tanabe S.,
Lam M.H.W., Giesy J.P., Contribution of Anthropogenic and Naturally Occurring
Organobromine Compounds to Bromine Mass in Marine Organisms Environmental
Science & Technology, Submitted.
Sample details
Collection
Date
1999
1992-1996
#
Species Name
1995-1996
10 Pacific tuna
6 Black-browed
albatross
3 Grey-headed
albatross
1 Light-mantled
sooty albatross
2 Shy albatross
1995-1996
3
1994-1996
1995
1993-2002
Yellow-nosed
albatross
10 Polar bear
Location
North Pacific Ocean
Indian Ocean, South
Pacific Ocean
Indian Ocean
South Atlantic Ocean
South Atlantic Ocean,
Indian Ocean
Indian Ocean
Arctic Ocean
Liver tissues
Analytical Method

Target compounds


QA/AC


21 PBDEs, 10 PBBs, 12 MeO-PBDEs, 10 OH-PBDEs and 16 BRPs
Recoveries for matrix spiked samples were 90-127%, 81-126%,
87-128%, 81-123% and 65-126% for PBBs, MeO-PBDEs, PBDEs,
OH-PBDEs, and BRPs respectively.
Derivatization


Methyl chloroformate (MCF) was used for OH-PBDE analysis
Exhibits excellent reproducibility and fewer background
interferences compared to diazomethane
Fractionation of TBr, EOBr and
Identified EOBr
Sample
Freeze dried (water content %)
ASE with n-hexane/DCM (1:1)
and n-hexane/MTBE (1:1) for two
cycles
Non-extractable bromine (NEBr) Extractable organic bromine (EOBr)
Weight (lipid content %)
Dissolved
Total bromine (TBr)
0.5 M KOH in 50% ethanol
Neutral fraction
Phenolic fraction
Treated with H2SO4 Silica gel column Derivatized with MCF
Silica gel column
Alumina column
Silica gel column
PBBs PBDEs and MeO-PBDEsOH-PBDEs and BRPs
Identified EOBr
Bromine Analysis

INAA



Samples were activated at a neutron flux of 5.0 × 1011
(n/cm2)/s in the SLOWPOKE 2 nuclear reactor
Quantification was based on γ-peaks from 80-Br (t1/2 = 17.6
min, Eγ = 616 keV). Count duration 15 min.
GC-HRMS Analysis




Chromatographic separation was achieved on a DB-5MS
fused silica capillary (30 m length, 0.25 mm ID, 0.1 μm film
thickness)
Resolution > 7,000
Injector temperature: 285 ℃; Ion source: 285 ℃.
Electron ionization energy: 37 eV, ion current: 750 μA.
Concentrations of
Identified EOBr


The naturally occurring
compounds were prevalent
in tuna and albatross
The identifiable extractable
organic-bromine (EOBr)
consisted primarily of
synthetic compounds in
polar bears
400
200
0
1000
Albatross
750
500
250
0
600
Polar bear
400
200
0
PBB-153
PBB-18
PBB-15
BDE-183
BDE-153
BDE-154
BDE-99
BDE-100
BDE-47
BDE-28
BRP-246
BRP-24
2'-OH-BDE-68
6-OH-BDE-47
5'-MeO-BDE-100
6-MeO-BDE-47
2'-MeO-BDE-68
Concentrations of EOBr are
species- and locationspecific
Tuna
Bromine Concentrations (pg/g ww)

600
Naturally occurring EOBr
Synthetic EOBr
Contribution of identified EOBr, EOBr
and NEBr to TBr



The majority of the
bromine was nonextractable or inorganic
(NEBr)
Extractable’ organic
bromine (EOBr)
accounted for 10 to 28%
of the total bromine (TBr)
0.08-0.11% and 0.0080.012% of EOBr and TBr,
respectively, could be
identified
Great diversity of naturally
occurring organo-bromine
compounds
Polar Bear
MeO-PBDEs
OH-PBDEs
BRPs
PBDEs
PBBs
Albatross
Tuna
0%
20%
40%
60%
80%
100%
0.008-0.012%
Polar Bear
Identified EOBr
EOBr
NEBr
Albatross
Tuna
0%
20%
40%
60%
80%
100%
Contributions of identified organo-halogens
to extractable organic halogens (%)
Bond Energies vs Identified EOX/EOX
100

More than half of the known
naturally occurring organohalogen compounds contained
bromine

As the bonds become stronger,
they become less likely to be
derived naturally and also less
likely to be degraded natually

Potential natural sources and
impact(s) of organic brominated
compounds should not be
neglected: What are they? What
do they do? Might they have
beneficial uses?
C-F
75
50
C-Cl
25
C-Br
0
50
75
100
125
150
Bond Energy (kcal/mole)
Summary

Methods were developed for identification and
quantification of TBr, EOBr and five classes of identified
EOBr.

The majority of the bromine in marine organisms was nonextractable or inorganic, with EOBr accounting for 10 to
28% of the TBr.

Overall, 0.08-0.11% and 0.008-0.012% of EOBr and TBr,
respectively, could be identified, based on prevalent
classes of brominated compounds.

The small proportion of identified EOBr was related to the
great diversity of naturally occurring organo-bromine
compounds
Origins and Relationships of PBDE Structurally Related
Compounds
Sources and Relationships

Formation of OH-PBDEs is of considerable concern due to
their greater toxicities relative to PBDEs and MeO-PBDEs.

Conceptual model of formation of OH-BDEs and MeO-BDEs
that has been proposed in the literature
O
Brx
PBDEs
Bry
Biotransformation
OH
OCH3
Methylation
O
O
Bry
Brx
MeO-PBDEs
OH
Br
Bry
Brx
OH-PBDEs
BRPs
PBDEs as Precursors of OH-PBDEs ?

Exposure concentrations of PBDEs during in vitro or in vivo studies
were large (ppm), but OH-PBDEs occurred at trace levels (<0.01-1%
of PBDEs) (Environ. Sci. Technol. 2005, 39, 5342-5348; Mol. Nutr. Food
Res. 2008, 52, 284-298; Environ. Health Persp. 2009, 117, 197-202.)

Relatively large concentrations of OH-PBDEs have been detected in
marine organisms. (Environ. Sci. Technol. 2005, 39, 2990-2997)

These results are consistent with existence of sources of OH-BDE
other than synthetic PBDEs
What are the sources of OH-PBDEs, MeO-BDEs ?
What is the relationships between PBDEs, MeO-PBDEs and
OH-PBDEs?
Experimental Goals -1

Determine concentrations of PBDEs, MeO-PBDEs, OHPBDEs and bromo-phenols in liver of tuna, five albatross
species and polar bear collected from remote marine
locations

Investigate relationships among PBDEs, MeO-PBDEs, OHPBDEs and bromo-phenols in wildlife
Wan, Y., S. Wiseman, H. Chang, X. Zhang, P.D. Jones, M, Hecker, K. Kannan,
S. Tanabe, J. Hu, M.H.W. Lam, and J.P. Giesy. 2009. Origin of Hydroxylated
Brominated Dophenyl Ethers: Natural Compounds of Man-Made Flame
Retardants. Environ. Sci. Technol. 43:7536-7542. (DOI:10.1021/es901357u)
Concentrations of PBDEs, MeO-PBDEs, OHPBDEs and BRPs in Marine Organisms
Total concentration (ng/g ww)
2.4
PBDE
MeO-PBDEs
OH-PBDEs
BRP
1.9
Observations
Concentration of ΣPBDEs not
related to those of ΣOH-PBDEs
1.4
0.9
Possible relationships between
MeO-PBDEs and OH-PBDEs
0.4
0
Tuna
Albatross
Polar bear
Correlations between MeO-PBDEs, OH-PBDEs
and BRPs
10000
ƩOH-PBDEs+ƩBRPs
ƩOH-PBDEs
10000
1000
100
10
1
1000
100
10
1
10
100
1000 10000
1
10
Conc. of ƩMeO-PBDEs (pg/g ww)
100
1000 10000
No significant correlation between ΣPBDEs and ΣOH-PBDEs
Significant correlation between ΣMeO-PBDEs and ΣOH-PBDEs
More significant correlation between ΣMeO-PBDEs and ΣOH-PBDEs+ΣBRPs
Profiles
5’-MeO-BDE-100
6-MeO-BDE-47
2’ -MeO-BDE-68
4’-OH-BDE-49
6-OH-BDE-47
2’-OH-BDE-68
Percentage (%)
Variations
in patterns among species similar for MeO and OH100%
BDE-183
PBDEs.
BDE-153
75%
BDE-154
Significant correlations for compounds with similar structures
BDE-99
consistent with relationship between OH-PBDEs and MeO-PBDEs.
50%
BDE-119
BDE-100
BDE-47
25%
BDE-49
0%
BDE-28
T
A
PB
497
1051 23.4
T
A
PB
T
A
PB
25.1
541
11.8
191
269
736
Species (Sum Conc. pg/g ww)
Experimental Goals -2

Investigate in vitro biotransformation of PBDEs, MeOPBDEs, and OH-PBDEs in hepatic microsomes
Wan, Y., S. Wiseman, H. Chang, X. Zhang, P.D. Jones, M, Hecker, K. Kannan, S. Tanabe, J. Hu,
M.H.W. Lam, and J.P. Giesy. 2009. Origin of Hydroxylated Brominated Dophenyl Ethers:
Natural Compounds of Man-Made Flame Retardants. Environ. Sci. Technol. 43:7536-7542.
(DOI:10.1021/es901357u).

Investigate in vivo biotransformation of PBDEs, MeOPBDEs, and OH-PBDEs in Japanese Medaka

Biotransformation of each compound

Gain insight into source(s) of each compound
Wan Y., Liu F.Y., Wiseman S., Zhang X.W., Chang H., Hecker M., Jones P.D., Lam M.H.W.,
Giesy J.P., Toxic Hydroxylated PBDEs: New Evidence for Natural Origins. PNAS, Submitted
Purity Tests
6-OH-BDE-47 6-MeO-BDE-47 BDE-47
Spiked foods
Control
N.D.
0.1
N.D.
6-OH-BDE-47
900
0.2
1.5
6-MeO-BDE-47
N.D.
8,000
28.3
BDE-47
N.D.
0.2
21,000
1500,000
4.3
1,900
N.D.
1300,000
4,800
N.D.
N.D.
50,000
Stock standard 6-OH-BDE-47
solutions
6-MeO-BDE-47
BDE-47
N.D.: not detected.
Presence of none of the contaminants in stock solutions
affected conclusions drawn from the studies
In vitro metabolism of PBDEs, MeO-PBDEs
and OH-PBDEs

Microsomes


Rainbow trout, chicken, and rat
Exposed groups


BDE-99
PBDE mix: BDE-28, BDE-49, BDE-47, BDE-66, BDE-100, BDE-119, BDE99, BDE-85, BDE-154, BDE-153, and BDE-183


6-MeO-BDE-47
MeO-PBDE mix: 2’-MeO-BDE-68, 6-MeO-BDE-47, 5-MeO-BDE-47, 4’MeO-BDE-49, 5’-MeO-BDE-100, 4’-MeO-BDE-103, 4’-MeO-BDE-99, and 4’MeO-BDE-101


6-OH-BDE-47
OH-PBDE mix: OH-BDE-47, 4’-OH-BDE-49, 6-OH-BDE-90 and 2-OHBDE123
Microsomal Incubations
Liver tissue
Homogenized with cold
phosphate buffer
Centrifuged for 15
min at 9000 g
Chicken
Take the supernatant
Centrifuged for 60 min
at 100,000 g
Rat
Dissolve in
phosphate buffer
Microsomes
Incubation with target
compounds
Rainbow trout
Percentage of OH-PBDEs and BRPs in PBDE and
MeO-PBDE exposed microsomes

OH-PBDEs and BRPs not detected in PBDE exposures
6-MeO-BDE-47
Percentage(%)
10
8
80
MeO-PBDE mixtures
60
Observations
6
No OH-BDEs formed from PBDE!
40
4
245-TriBRP
246-TriBRP
24-DiBRP
4'-OH-BDE103
6-OH-BDE-90
4’-OH-BDE-49
6-OH-BDE-47
245-TriBRP
246-TriBRP
24-DiBRP
4'-OH-BDE103
6-OH-BDE-90
4’-OH-BDE-49
6-OH-BDE-47
Significant amounts of 6-OH-BDE-47 were
20 generated from 6-MeO-BDE-47,
2
and more OH-PBDE
congeners were detected when additional MeO-PBDE
congeners were
incubated with microsomes.
0
0
Demonstrates biotransformation of MeO-PBDEs to OH-PBDEs at
environmentally relevant concentrations.
Percentage of OH-PBDE and BRP in OH-PBDEs
exposed microsomes

MeO-PBDEs were not detected in OH-PBDE exposed microsomes
6-OH-BDE-47
120
320
OH-PBDE mixtures
Percentage(%)
100
240
80
2,4-DiBRP was
the major BRP congener of OH-PBDE metabolism
60
160
40 of 4’-OH-BDE-49 were greater than the original exposure
Concentrations
80
concentrations,
suggesting the debromination
of OH-PentaBDE congeners
20
245-TriBRP
246-TriBRP
24-DiBRP
4'-OH-BDE103
6-OH-BDE-90
4’-OH-BDE-49
0
6-OH-BDE-47
245-TriBRP
246-TriBRP
24-DiBRP
4'-OH-BDE103
6-OH-BDE-90
6-OH-BDE-47
4’-OH-BDE-49
0
In vivo biostransformtion of PBDEs, MeOPBDEs and OH-PBDEs in Japanese Medaka

Fish


Exposed groups





Freshwater Japanese Medaka (Oryzias latipes)
Control
BDE-47:
6-MeO-BDE-47
6-OH-BDE-47
Exposure duration

Exposure via food for 2 weeks
6-MeO-BDE-47 Conc. 6-OH-BDE-47 Conc
ng/g ww
ng/g ww
600
Concentrations of Target
Compounds in Exposed
Medaka
Whole Fish - Liver
Liver
400
200
0
6000
Control
6-MeO-BDE-47

Significant concentrations of 6OH-BDE-47 were detected in
medaka exposed to 6-MeOBDE-47, but not BDE-47

6-MeO-BDE-47 was formed
from 6-OH-BDE-47 in medaka

BDE-47 observed in medaka
exposed to 6-MeO-BDE-47 and
6-OH-BDE-47 is likely due to
BDE-47 impurities in the stock
standard solutions.
40
3000
30
20
10
BDE-47 Conc.
ng/g ww
0
8000
Control
6-MeO-BDE-47
2000
80
60
40
20
0
Control
BDE-47
6-MeOBDE-47
Treatments
6-OH-BDE47
Percentages of exposed compounds
relative to the dosing concentration (%)
Accumulation in Eggs
25

Significant assimilation
efficiencies were observed for
6-MeO-BDE-47 and BDE-47
compared to 6-OH-BDE-47 as
indicated by the steep slopes
for accumulation.

Depuration rate of BDE-47 is
likely less than that of 6-MeOBDE-47 based on the slow
assimilation rate and large
concentration ratios between
fish and their diet.
6-OH-BDE-47
6-MeO-BDE-47
20
BDE-47
15
10
5
0
0
2
4
6
Time (days)
8
10
12
14
5
Concentrations of 6-MeO-BDE47 ng/g ww
Concentrations of 6-OH-BDE47 ng/g ww
Biotransformation Products in Eggs
10
Control
6-MeO-BDE-47
BDE-47
4
3
2
1
0
0
2
4
6
8
Time (days)
10
12
14
Control
6-OH-BDE-47
BDE-47
8
6
4
2
0
0
2
4
6
8
10
12
14
Time (days)
Direct in vivo evidence of biotransformation of 6-MeO-BDE-47
to 6-OH-BDE-47
Biotransformation of 6-OH-BDE-47 to 6-MeO-BDE-47 did not
occur in hepatic microsomal fraction
Proposed metabolic relationships among
brominated compounds
MeO-PBDEs
O
PBDEs
Br
OCH3
O
OMeBr5
Br
MeO-PentaBDEs
O
Br
Br
Br
OH
BDE-47
Br
O
Br
Br
Br
Br
Br
OH
(5)
OH
Br
(6)
6-OH-BDE-47
(3)
Br
BRPs
Br
OH-PentaBDEs
Br
(4)
OH-PBDEs
OHBr5
Br Br
BDE-99
(1)
O
O
Br
Br
6-MeO-BDE-47
(2)
Br
Br
Br
2,4-DiBRP
Br
2,4,6-TriBRP
Br
O
PBDDs
Br
OH
Br
4’-OH-BDE-49
OH-TetraBDEs
Br
(7)
Br
O
Br
O
1,3,7-TrBDD
Br
Br
O
O
1,3,8-TrBDD
Br
Summary

Hydroxylation of synthetic PBDEs to OH-PBDEs was
negligible

Biotransformation of 6-OH-BDE-47 to 6-MeO-BDE-47 did not
occur in the hepatic microsomal fraction

Significant production of OH-PBDEs from biotransformation
MeO-PBDEs

MeO-PentaBDE congeners could be an important contributor
of para-substituted OH-PBDEs

Human exposure to MeO-PBDEs that occur naturally in
marine organisms should be considered
Toxic Hydroxylated Polybrominated Diphenyl Ethers
in Pregnant Women and Their Matching Fetuses
Background

OH-PBDEs have various biological effects including disruption
of thyroid hormone homeostasis, disruption of sex hormone
steroidogenesis, and neurotoxicity.

MeO-PBDEs, as a precursor of OH-PBDEs, generally
accumulated to large concentrations in marine organisms.

Pregnant women might take nutritional supplements, such as
fish oil which can contain very great concentrations of MeOPBDEs

People living close to the ocean may hade greater
concentrations OH-PBDEs, and their fetuses may be at risks
due to exposure to these compounds ?
Area of populations
Maternal blood was drawn
during the third trimester of
pregnancy
S: Seoul
Cord blood was drawn at
delivery from the umbilical
cord vein of the matching
fetuses
C: Cheongju
G: Gumi
Characteristics of mothers and infants
Variable
Pregnant women (n=26)
Age (year)
Pre-pregnancy weight (kg)
Height (cm)
BMI (kg/m2)
Parity
Gestational age at delivery (weeks)
Gestational age at blood sampling (wk)
Infants (n=28)*
Sex
Birth weight (kg)
N
Range
Mean SD
Median
26
24
24
24
24
24
21
22-39
45.0-80.0
148.0-171.0
17.4-31.0
1-3
36-41
20-40
31
55.8
161.0
21.6
2
39
36
4.7
9.8
5.1
4.2
0.7
1.3
5.1
31
28
26
Male:13, Female:15
2.22-4.10
3.11
0.46
3.15
50.5
161.0
20.0
1
39
37
* Including 3 twins. One cord blood sample was missing from one of one twin.
LC-MS/MS chromatographic profiles of
OH-Tetra-BDEs and BPA
3.4e4
2.6e5
2.0e5
BPA standard solution
OH-Tetra-BDEs
standard solution
2.6e4
1.8e4
Abundance
1.4e5
1.0e4
8.0e4
2.0e3
2.0e4
13.0
2.2e3
1.6e3
15.0
17.0
19.0
13.0
21.0
6-OH-BDE-47 detected
in blood serum
3.0e4
15.0
17.0
19.0
21.0
BPA detected in
blood serum
2.2e4
1.0e3
1.4e4
0.4e3
6.0e3
13.0
15.0
17.0
19.0
21.0
13.0
Retention time (min)
15.0
17.0
19.0
21.0
Concentrations of 6-OH-BDE47 in people
worldwide
6-OH-BDE-47
n n>LOD Mean ± SD Range
Fetal
Median
Region
Ref
25
20
30.2±27.1
<4-127
26
2008-2009, Korea
This study
16
16
44.6a
-
4.5
2003-2004, USA
Qiu et al. 2009
6
4
1.4±2.0
<0.6-5.2
0.6
2005-2006, Japan
Kawashiro et al. 2008
OH-PBDEs
pregnant
women
originating
primarilyMeijer
fromet natural
9
0in Korean
2001-2002,
Netherlands
al. 2008
sources (marine food)
26
11
17.5±26.3
<4-117
a
<4
2008-2009, Korea
This study
a
4 South
2003-2004,
USA
4
0.9 exposed
Qiu et al. 2009
1.4
Pregnant
Korean
women
are
to relatively
great
Maternal
8.5±12
2.1
6
<1-27 compared
2005-2006,
Japanin other
4
Kawashiro
et al. 2008
concentrations
of
OH-PBDEs
with
people
geographical
regions90 0
2001-2002, Netherlands
Meijer et al. 2008
4
4
7.4±4.1
4.1-12.9
6.3
2002, Nicaragua
Athanasiadou et al. 2008
Children 10
10
8.9±8.7
1.7-25.7
6.8
2002, Nicaragua
Athanasiadou et al. 2008
Placental transfer of 6-OH-BDE-47
140
The placental transfer ratio
between fetal and maternal
serum (F/M ratio) was 1.4±1.1 for
6-OH-BDE-47
120
Fetal
100
80
The ratios were greater than that
of BPA (<1)
Due to high affinities to TTR?
60
40
20
0
0
20
40
60 80
Maternal
100 120 140
Y=15.02 + 0.81 X (r=0.625, p=0.001).
when the circled outlier was removed,
Y=17.94 + 0.55 X (r=0.567, p=0.005).
The ratios were greater than that
of OH-PCBs (Netherlands: 0.6-0.7,
and Japan: 0.1-0.9).
Due to high affinities to TBG?
Potential effects

The mean concentration of 6-OH-BDE-47 detected in fetal
serum was 30.2 ± 27.1 pg/g ww, or 0.06 nM, while the maximum
detected concentration was 127 pg/g ww or 0.25 nM.

The median inhibitory concentrations (IC50s) of r 6-OH-BDE-47
were 22.3-107.8 nM for TTR, and 100-867 nM for TBG in in vitro
studies of human cells.

Concentrations of OH-PBDEs of 100-1000 nM cause estrogenic
activities, concentrations of 1000-5000 nM can cause
neurotoxic effects, and concentrations of 5000-10000 nM can
inhibit human placental aromatase activity.

Thyroid and estrogen homone effects??
6-OH-BDE-47 vs E2 and T4 in Fetal Serum
12
12
A
10
10
T4 (ng/dL)
E2 (ng/ml)
Associations between concentrations of 6-OH-BDE-47 and E2 or T4 in
cord8 serum were not statistically significant
8
6
After6 corrected for the covariates age and
BMI of the mother, the
relationships were still not statistically significant
4
4
The 2concentration of 6-OH-BDE-47 in foetal
serum was closer to the
2
effect concentration for TTR or TBG binding than other potential effects
0
0
0
20 40 60 80 100 120 140
6-OH-BDE-47 (pg/g ww)
0
20 40 60 80 100 120 140
6-OH-BDE-47 (pg/g ww)
Summary

Only 6-OH-BDE-47, a naturally occurring OH-PBDE, was detected,
and the exposure was related to diets of Korean women

The placental transfer ratio between foetal and maternal blood
serum for 6-OH-BDE-47 (F/M ratio: 1.4±1.1).

The F/M ratio of 6-OH-BDE-47 was different than those of BPA and
OH-PCBs, possibly due to large affinities to T4 transport proteins.

A major effect of OH-PBDE exposure might be a decrease in
serum T4 concentrations.

Potential risks associated with disruption of T4 transport to the
developing foetus (e.g negative consequences for fetal neurological
development ) should be considered in further studies.
Thank You!!!!! Questions????








John P. Giesy, Ph.D.
Professor & Canada Research Chair in Environmental Toxicology
Dept. Veterinary Biomedical Sciences & Toxicology Centre
University of Saskatchewan
Saskatoon, SK, Canada
Tel: (306) 966-2096
Fax: (306) 931-1664
Email: John.Giesy@usask.ca
Web Site:
http://ww.usask.ca/toxicology/faculty_profiles/giesy_john.html
Related Publications

Wan Y., Wiseman S., Chang H., Zhang X.W., Jones P.D., Hecker M., Kannan K., Tanabe S.,
Hu J.Y., Lam M.H.W., Giesy J.P. Origin of hydroxylated brominated diphenyl ethers: natural
compounds or man-made flame retardants? Environmental Science & Technology 43,
7536-7542, 2009.

Wan Y., Choi K., Kim S., Ji K., Chang H., Wiseman S., Jones P.D., Khim J., Park S., Park J.,
Giesy J.P. Hydroxylated polybrominated diphenyl ethers and bisphenol A in pregnant
women and their matching fetuses: placental transfer and potential risks. Environmental
Science & Technology, In press.

Chang H., Wan Y., Naile J., Zhang X.W., Wiseman S., Hecker M., Lam M.H.W., Giesy J.P.,
Jones P.D. Simultaneous quantification of multiple classes of phenolic compounds in blood
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
Wan Y., Jones P.D., Wiseman S., Chang H., Chorney D., Kannan K., Khim J.S., Tanabe S.,
Lam M.H.W., Giesy J.P., Contribution of Anthropogenic and Naturally Occurring
Organobromine Compounds to Bromine Mass in Marine Organisms Environmental Science
& Technology, Submitted.

Wan Y., Liu F.Y., Wiseman S., Zhang X.W., Chang H., Hecker M., Jones P.D., Lam M.H.W.,
Giesy J.P., Toxic Hydroxylated PBDEs: New Evidence for Natural Origins. PNAS, Submitted.