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Introduction to Brominated Flame Retardants Linda S. Birnbaum Director, Experimental Toxicology Division NHEERL Research Triangle Park, NC Region 2 Science Day/Non-Regulated Pollutants Workshop NYC – October 25, 2005

Introduction to Brominated Flame Retardants

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Introduction to Brominated Flame Retardants. Linda S. Birnbaum Director, Experimental Toxicology Division NHEERL Research Triangle Park, NC Region 2 Science Day/Non-Regulated Pollutants Workshop NYC – October 25, 2005. Flame Retardants. - PowerPoint PPT Presentation

Text of Introduction to Brominated Flame Retardants

  • Introduction to Brominated Flame RetardantsLinda S. BirnbaumDirector, Experimental Toxicology DivisionNHEERLResearch Triangle Park, NC

    Region 2 Science Day/Non-Regulated Pollutants Workshop

    NYC October 25, 2005

  • Flame RetardantsFires kill >3000, injure >20,000, and cause damages exceeding $11 billion annually in US alone>175 different types of FRsHalogenated (~46%)Phosphorus-containing (24%)Melamines (4%)Inorganics (27%)

  • Brominated Flame RetardantsBFRs are the largest market group due to low cost and high efficiencyBFRs account for 38% global demand for bromine>75 BFRs recognized commerciallyBr-BPs, BDEs, CDs, phenols, phthalates,++Global, transboundary problemPersistencePotential for bioaccumulationLimited Data Base

  • Global Market Demand for Major BFRs in 2001 (metric tons) [BSEF]

  • TBBPA(Tetrabromobisphenol A)Reactive & additive Primary use - ElectronicsAcute tox data oral LD50: 5-10 g/kgLow chronic toxicityNot teratogenic or mutagenicLimited data in biotaDimethyl-TBBPA Metabolite eliminated in bile Little retained in tissues

  • Health Effects of TBBPAImmunotoxicInhibits T cell activation : blocks CD25 (
  • Health Effects of TBBPA (cont.)Endocrine DisruptionAhR EffectsNot relevant for commercial product (Contaminants? Combustion products?)ThyroidTBBPA>T4 in relation to binding to transthyretinBlocks T3 binding to TRPerturbations observed in vivoEstrogenicInhibits sulfotransferase (decreases estrogen clearance)Mostly in vitro data

  • Hexabromocylododecane(HBCD)AdditiveUsed in Electronics; Textile BackingsEcotox Algae, daphnia, NOEC = 3 ug/LFish, LC 50>water solubility; PNEC=.03ug/LGeneral ToxicityHigh absorption; mild irritant and skin sensitizer; liver effects after repeated exposures (rat LOAEL ~13 mg/kg/day)Need more info: repeated dose studies, repro tox

  • HBCD (cont.)NeurotoxicityDevelopmental neurotoxicantBlocks dopamine uptakeConcern for occupational settingsFound in human breast milk Persistent, bioaccumulative, toxic, long range transportIsomeric composition in environmental samples differs from commercial mixture

  • Polybrominated Diphenyl Ethers (PBDEs) Major Additive BFRs(~67 metric tons/yr)DBDE largest volume (75% in EU)97% DBDE; 3% NBDEPolymers, electronic equipment, textile backingOBDE6%HxBDE; 42%HpBDE;36% OBDE; 13%NBDE;2%DBDEmultiple congenersunclear if any PeBDE)Polymers, esp. office equipmentPeBDEFlexible polyurethane foam (up to 30%)Cushions; mattresses; carpet paddingMainly PeBDE+TeBDE, some HxBDEBrBr

  • PropertiesSolids with low solubility (< 1ug/kg), high log Kow (>5)Lower congeners - more bioaccumulative, persistentStrong adsorption to soil/sediment/sludgeNo significant biodegradation in air/waterBioaccumulation - BCF > 5000Long-range transport - Evidence of remote contamination (e.g., Arctic)Persistence- t 1/2 Atmospheric >2 days;Water >2 mos; Soil, sediment >6 mos

  • Sources of Environmental ReleasePolymer ProcessingFormulating/applying to textilesVolatilization and leaching during useParticulate losses over use/disposalIncinerationRecycling

  • Pathways of Exposure?Indoor air >> outdoor airMay account for ~4%, on average, of daily intake by inhalation (could be much higher for some)BDE209 as well as 47, 99, 100, 153, 154House dustRecent studies in Cape Cod, Northwest, Texas, EuropeWide rangeRecent study: N = 10. Range: 705-69,000 ppb; Mean: 12,100 ppb; Median: 2,500 ppb Levels in US, UK>>Europe, JapanPatterns resemble commercial products (Penta, Deca)

  • Breast Milk vs. Dust(BDE 47+99+100+153+154)r=0.76 (p=0.006);not confounded by diet; (T.Webster)

  • Daily US Adult PBDE Dietary Intake (A. Schecter)

    Chart1

    723.4315798677450.9270427389

    8882.1333333333

    101.020159067376.649426018

    20-39 Males

    20-39 Females

    PBDE intake pg/kg bw per day

    Sheet1

    Gram consumed per USDAmedian pg/g PBDE

    20-39 Males 70kg20-39 Females 60kg20-39 Males 70kg20-39 Females 60kg20-39 Males 70kg20-39 Females 60kg

    Ice Cream1710101.48218786261725.19719366411014.821878625924.645674195216.9136979771

    Total Milk2562067.92813502262029.60256578171633.195814652528.994322368327.2199302442

    Total Cheese342097.54739339023316.61137526581950.947867803447.380162503832.5157977967

    Total Chicken and Turkey4833282.6925729613569.24350208129328.8549076808193.846335744155.480915128

    Total Beef8038104.59375906778367.50072541793974.5628445735119.535724648866.2427140762

    Total Pork2313131.10312719943015.37192558571704.340653591943.076741794128.4056775599

    Total Bacon21105.1182534078210.2365068155105.11825340783.00337866881.7519708901

    Total Frankfruters and Lucheon Meats3215796.183060338725477.857930839611942.7459050811363.969399012199.0457650847

    Total Finfish108616616049288882.1333333333

    Total Eggs2215851870127526.714285714321.25

    Margarine22881761762.51428571432.9333333333

    Butter2148597048513.85714285718.0833333333

    Yogurt31.5526765681pg/kg bw.20-39 Males20-39 Females

    Ice cream171.4116991571Meat50640.210590739927055.622564335Meat723.4315798677450.9270427389

    101.4821878626Fish61604928Fish8882.1333333333

    Milk7.9105388097Dairy7071.41113471164598.9655610818Dairy101.020159067376.649426018

    Lowfat milk7.9457312355Eggs18701275Eggs26.714285714321.25

    7.9281350226Margarine176176Margarine2.51428571432.9333333333

    Cheese9.8365722899Butter970485Butter13.85714285718.0833333333

    41.5417042753

    81.0516515197

    114.0431352606

    182.0894598701

    683.0598574128

    97.5473933902

    Chicken129.2249706437

    282.69257296

    713.0113016642

    282.69257296

    Beef78.6653321624

    104.5937590677

    257.9725337634

    104.5937590677

    Pork40.8052398728

    221.401014526

    131.1031271994

    Bacon39.0129349921

    105.1182534078

    164.9699103454

    105.1182534078

    Sausage195.265972128

    244.0411273468

    1348.3249933306

    1378.0508719731

    796.1830603387

    Fish616

    Eggs85

    Margarine88

    Butter485

    Sheet1

    20-39 Males

    20-39 Females

    PBDE intake pg/kg bw per day

    Sheet2

    Sheet3

  • US Human Breast Milk PBDE levels, 2005, N=62. (A. Schecter)

    Chart1

    6.2

    6.2

    6.9

    8

    11.8

    12.5

    12.916

    13.3

    14.5

    14.7

    15.2

    15.6

    16.2

    16.216

    16.3

    16.37

    17.81

    17.813

    18.1

    18.3

    18.6

    19.1

    19.138

    21.1

    22.4

    22.8

    23.5

    23.5

    24.097

    24.1

    26.2

    27.3

    28.2

    28.207

    28.3

    29.6

    30.1

    33.691

    33.7

    34

    34.1

    36.1

    36.1

    36.566

    36.8

    42.4

    45.5

    45.69

    45.7

    46

    47

    49.6

    53.9

    54.6

    63.8

    65.1

    65.101

    75.8

    75.9

    75.914

    81.9

    98.2

    98.2

    103.1

    141.6

    204.3

    248.5

    296.9

    376.7

    385.5

    418.8

    PBDEs ng/g or ppb, lipid

    original mother milk

    NumberLipidAgeNursing (wks)17284766778599100138153154183209Sum BDE

    %

    4.8313n.d.0.22.90.02n.d.0.080.70.7n.d.1.50.06n.d.n.d.6.2

    1.3293n.d.0.33.5n.d.n.d.0.080.70.5n.d.0.90.060.06n.d.6.2

    2.12374n.d.0.23.90.06n.d.0.111.50.6n.d.0.40.08n.d.n.d.6.9

    4.83221--0.33.50.14--0.081.60.70.091.40.090.04--8

    2.622400.010.36.30.05n.d.0.232.81.2n.d.0.70.20.05n.d.11.8

    3.636109n.d.0.47.80.09n.d.0.232.41.10.010.40.11n.d.n.d.12.5

    1.93220n.d.0.78.20.04n.d.0.221.31.7n.d.0.90.120.08n.d.13.3

    6.3252n.d.0.47.90.02n.d.0.382.32.7n.d.0.80.150.06n.d.14.7

    2.13529--0.78.80.19--0.171.51.70.1620.060.03--15.2

    5.53230n.d.0.480.01n.d.0.442.92n.d.0.90.140.240.4815.6

    52020.011.110.90.05n.d.0.1822.4n.d.1.30.170.04n.d.18.1

    3.42330.010.480.03n.d.0.353.12.7n.d.20.210.610.9318.3

    1.33216--0.810.5n.d.--0.352.52.20.1920.120.03--18.6

    3.425n.a.0.021.1120.13n.d.0.232.51.8n.d.1.30.150.081.8521.1

    2.921290.030.510.70.09n.d.0.275.52.1n.d.0.90.350.072.7422.4

    3.53030--0.76.9n.d.--0.121.34.60.418.50.190.06--22.8

    1232n.d.0.914.20.11n.d.0.373.72.6n.d.1.30.240.09n.d.23.5

    3.72319--0.713.20.57--0.293.72.50.291.90.170.06--23.5

    3.2262n.d.1.317.40.19n.d.0.3542.1n.d.0.70.18n.d.n.d.26.2

    3.53422--114.30.29--0.465.73.60.251.40.20.1--27.3

    3.13360--1.418.4n.d.--0.254.11.80.092.10.160.06--28.3

    4.93826--1.217.4n.d.--0.347.12.30.140.60.30.12--29.6

    3.43020.010.715.20.06n.d.0.424.22.3n.d.30.220.033.9730.1

    5.128530.011.1200.18n.d.0.535.13.90.012.70.320.11n.d.34

    4.735n.a.--1.320.90.56--0.316.32.90.141.20.220.17--34.1

    1.141380.021.519.50.11n.d.0.413.43.3n.d.7.70.18n.d.n.d.36.1

    6.13725--7.617.21.19--0.356.12.30.181.70.270.05--36.8

    32751--1.428.2n.d.--0.517.52.90.250.70.20.75--42.4

    4.825n.a.--1.821.60.94--0.59.44.40.475.80.60.06--45.5

    2.23911--1.126.8n.d.--0.758.95.30.5820.450.1--46

    5.634n.a.--2.731.8n.d.--0.427.83.10.090.80.220.1--47

    3.42710--2.630.10.75--0.575.96.50.322.50.340.09--49.6

    2.820130.021.131.30.17n.d.0.1310.25.90.021.50.480.112.9653.9

    42013--3.433.52.32--0.495.85.80.272.60.320.06--54.6

    3.32617--1.432.30.7--0.669.65.70.4612.40.510.05--63.8

    2.22016--1.425.50.75--0.76818.31.7518.30.940.08--75.8

    1.122510.042.244.30.550.030.6410.88.10.0214.70.56n.d.n.d.81.9

    4.32938--5.234.80.61--1.949.829.21.214.50.960.1--98.2

    126220.021.754.70.54n.d.1.6323.610n.d.4.81.150.07n.d.98.2

    4.93238--3.449.71.21--1.27.721.11.416.30.930.15--103.1

    3.4309--3.963.13.13--2.8130.116.23.2917.21.940.08--141.6

    1.22120.110.1120.91.680.062.6430.320.10.1316.42.07n.d.n.d.204.3

    1.23315--8139.6n.d.--4.1244.6234.4721.82.760.18--248.5

    12320.063.6172.41.14n.d.6.2869.831.90.088.43.070.16n.d.296.9

    2.13413--7.5199.66.67--7.73108.531.74.126.93.620.36--376.7

    1.733470.186.1196.22.070.166.46111310.2715.57.211.328.24385.5

    5.12928--16.1271.53.16--6.2950.447.46.8614.12.870.12--418.8

    Mean28.6424.560.022.440.80.650.011.15148.20.65.30.760.130.9273.9

    Median29200.011.218.40.14n.a.0.415.72.90.0920.220.07n.a.34

    SD5.722.260.043.159.41.190.041.8924.610.81.376.11.30.231.96103.3

    Min202n.d.0.22.9n.d.n.d.0.080.70.5n.d.0.40.06n.d.n.d.6.2

    7.23

    18.45

    34

    69.8

    352.76

    Max411090.1816.1271.56.670.167.7311147.46.8621.87.211.328.24418.8

    select congeners

    Concentrations of PBDE congeners in human milk from nursing mothers in US. 2001-2004. (ng/g ppb lipid)

    personLipid %AgeNursing (wks)284799100153154183209Sum BDE

    4.83130.22.90.70.71.50.06n.d.n.d.6.06

    1.32930.33.50.70.50.90.060.06n.d.6.02

    2.123740.23.91.50.60.40.08n.d.n.d.6.68

    4.832210.33.51.60.71.40.090.04--7.63

    2.622400.36.32.81.20.70.20.05n.d.11.55

    3.6361090.47.82.41.10.40.11n.d.n.d.12.21

    1.932200.78.21.31.70.90.120.08n.d.13

    6.32520.47.92.32.70.80.150.06n.d.14.31

    9a2.135290.78.81.51.720.060.03--14.79

    5.532300.482.920.90.140.240.4815.06

    52021.110.922.41.30.170.04n.d.17.91

    3.42330.483.12.720.210.610.9317.95

    1.332160.810.52.52.220.120.03--18.15

    3.425n.a.1.1122.51.81.30.150.081.8520.78

    2.921290.510.75.52.10.90.350.072.7422.86

    3.530300.76.91.34.68.50.190.06--22.25

    12320.914.23.72.61.30.240.09n.d.23.03

    3.723190.713.23.72.51.90.170.06--22.23

    3.22621.317.442.10.70.18n.d.n.d.25.68

    3.53422114.35.73.61.40.20.1--26.3

    3.133601.418.44.11.82.10.160.06--28.02

    4.938261.217.47.12.30.60.30.12--29.02

    3.43020.715.24.22.330.220.033.9729.62

    5.128531.1205.13.92.70.320.11n.d.33.23

    4.735n.a.1.320.96.32.91.20.220.17--32.99

    1.141381.519.53.43.37.70.18n.d.n.d.35.58

    6.137257.617.26.12.31.70.270.05--35.22

    327511.428.27.52.90.70.20.75--41.65

    4.825n.a.1.821.69.44.45.80.60.06--43.66

    2.239111.126.88.95.320.450.1--44.65

    5.634n.a.2.731.87.83.10.80.220.1--46.52

    3.427102.630.15.96.52.50.340.09--48.03

    2.820131.131.310.25.91.50.480.112.9653.55

    420133.433.55.85.82.60.320.06--51.48

    3.326171.432.39.65.712.40.510.05--61.96

    2.220161.425.5818.318.30.940.08--72.52

    1.122512.244.310.88.114.70.56n.d.n.d.80.66

    4.329385.234.89.829.214.50.960.1--94.56

    126221.754.723.6104.81.150.07n.d.96.02

    4.932383.449.77.721.116.30.930.15--99.28

    3.43093.963.130.116.217.21.940.08--132.52

    1.221210.1120.930.320.116.42.07n.d.n.d.199.87

    1.233158139.644.62321.82.760.18--239.94

    12323.6172.469.831.98.43.070.16n.d.289.33

    2.134137.5199.6108.531.76.93.620.36--358.18

    1.733476.1196.21113115.57.211.328.24376.57

    5.1292816.1271.550.447.414.12.870.12--402.49

    483.18na0.69.92.71.30.620.130.0722.417.722

    493.28na1.225114.53.10.570.092045.462

    503.9na4.44111116.10.710.14074.35

    513.12na2.3376.76.9110.390.11064.4

    526.31na1.8142.92.92.10.170.1023.97

    537.04370.71165.82.52.20.280.0570.0227.567

    543.29330.7691.52.12.60.0940.0510.04516.15

    552.44381.21952.72.40.270.0512.533.121

    566.5na0.96.111.26.70.0770.0290.02516.031

    575.55na0.96.111.23.40.0770.0290.02512.731

    586.75na1.5244.82.72.10.220.570.0535.94

    593.08na1.21021.340.150.0960.118.846

    Mean3.509152542428.6424.562.192711864436.144067796612.0864406787.22372881364.97830508470.6620.14571153851.386052631664.8190184073

    Med3.3529201.217.45.12.72.10.220.080.129.62

    SD1.5092219665.722.262.818475272953.949396056822.32398939779.94358810885.64554543731.17793505760.21928317592.107789507690.9342449864

    Min12020.22.90.70.50.40.06n.d.n.d.6.02

    5%1.092020.33.721.30.70.6110.0710.03207.2025

    25%2.223.59.50.79.452.52.051.30.150.059250.022517.93

    50%3.429.5201.217.45.12.72.10.220.080.129.62

    75%4.833342.2532.059.156.26.80.5350.11252.4557.755

    95%6.3293859.37.64174.7852.3431.0716.482.890.5884.397296.215

    Max7.044110916.1271.511147.421.87.211.328.24402.49

    95/5 ratio5.80642201831.929.6525.466666666746.983870967740.261538461544.385714285726.972176759440.704225352118.375na41.1

    max/min7.042.0554.580.593.6206896552158.571428571494.854.5120.1666666667nana66.8588039867

    n.a., not available. n.d., not detected. a: Dallas samples. b: Austin samples.

    select congeners

    6.2

    7.6694

    18.15

    31.9

    61.5

    294.48

    418.8

    max/min ratio=68

    PBDEs sum

    percentile

    PBDEs (ng/g lipid)

    Total PBDEs in human milk from US nursing mothers. 2003. (n=59. ng/g lipid)

    lipid based

    Concentrations of PBDE congeners in human milk from nursing mothers in US. 2001-2004. (ng/g ppb lipid)

    PBDE congener

    Lipid %AgeNursing (wks)17284766778599100138153154183209Sum BDE

    4.8313n.d.0.22.90.02n.d.0.080.70.7n.d.1.50.06n.d.n.d.6.2

    1.3293n.d.0.33.5n.d.n.d.0.080.70.5n.d.0.90.060.06n.d.6.2

    2.12374n.d.0.23.90.06n.d.0.111.50.6n.d.0.40.08n.d.n.d.6.9

    4.83221--0.33.50.14--0.081.60.70.091.40.090.04--8

    2.622400.010.36.30.05n.d.0.232.81.2n.d.0.70.20.05n.d.11.8

    3.636109n.d.0.47.80.09n.d.0.232.41.10.010.40.11n.d.n.d.12.5

    1.93220n.d.0.78.20.04n.d.0.221.31.7n.d.0.90.120.08n.d.13.3

    6.3252n.d.0.47.90.02n.d.0.382.32.7n.d.0.80.150.06n.d.14.7

    9a2.13529--0.78.80.19--0.171.51.70.1620.060.03--15.2

    5.53230n.d.0.480.01n.d.0.442.92n.d.0.90.140.240.4815.6

    52020.011.110.90.05n.d.0.1822.4n.d.1.30.170.04n.d.18.1

    3.42330.010.480.03n.d.0.353.12.7n.d.20.210.610.9318.3

    1.33216--0.810.5n.d.--0.352.52.20.1920.120.03--18.6

    3.425n.a.0.021.1120.13n.d.0.232.51.8n.d.1.30.150.081.8521.1

    2.921290.030.510.70.09n.d.0.275.52.1n.d.0.90.350.072.7422.4

    3.53030--0.76.9n.d.--0.121.34.60.418.50.190.06--22.8

    1232n.d.0.914.20.11n.d.0.373.72.6n.d.1.30.240.09n.d.23.5

    3.72319--0.713.20.57--0.293.72.50.291.90.170.06--23.5

    3.2262n.d.1.317.40.19n.d.0.3542.1n.d.0.70.18n.d.n.d.26.2

    3.53422--114.30.29--0.465.73.60.251.40.20.1--27.3

    3.13360--1.418.4n.d.--0.254.11.80.092.10.160.06--28.3

    4.93826--1.217.4n.d.--0.347.12.30.140.60.30.12--29.6

    3.43020.010.715.20.06n.d.0.424.22.3n.d.30.220.033.9730.1

    5.128530.011.1200.18n.d.0.535.13.90.012.70.320.11n.d.34

    4.735n.a.--1.320.90.56--0.316.32.90.141.20.220.17--34.1

    1.141380.021.519.50.11n.d.0.413.43.3n.d.7.70.18n.d.n.d.36.1

    6.13725--7.617.21.19--0.356.12.30.181.70.270.05--36.8

    32751--1.428.2n.d.--0.517.52.90.250.70.20.75--42.4

    4.825n.a.--1.821.60.94--0.59.44.40.475.80.60.06--45.5

    2.23911--1.126.8n.d.--0.758.95.30.5820.450.1--46

    5.634n.a.--2.731.8n.d.--0.427.83.10.090.80.220.1--47

    3.42710--2.630.10.75--0.575.96.50.322.50.340.09--49.6

    2.820130.021.131.30.17n.d.0.1310.25.90.021.50.480.112.9653.9

    42013--3.433.52.32--0.495.85.80.272.60.320.06--54.6

    3.32617--1.432.30.7--0.669.65.70.4612.40.510.05--63.8

    2.22016--1.425.50.75--0.76818.31.7518.30.940.08--75.8

    1.122510.042.244.30.550.030.6410.88.10.0214.70.56n.d.n.d.81.9

    4.32938--5.234.80.61--1.949.829.21.214.50.960.1--98.2

    126220.021.754.70.54n.d.1.6323.610n.d.4.81.150.07n.d.98.2

    4.93238--3.449.71.21--1.27.721.11.416.30.930.15--103.1

    3.4309--3.963.13.13--2.8130.116.23.2917.21.940.08--141.6

    1.22120.110.1120.91.680.062.6430.320.10.1316.42.07n.d.n.d.204.3

    1.23315--8139.6n.d.--4.1244.6234.4721.82.760.18--248.5

    12320.063.6172.41.14n.d.6.2869.831.90.088.43.070.16n.d.296.9

    2.13413--7.5199.66.67--7.73108.531.74.126.93.620.36--376.7

    1.733470.186.1196.22.070.166.46111310.2715.57.211.328.24385.5

    5.12928--16.1271.53.16--6.2950.447.46.8614.12.870.12--418.8

    483.18na0.0110.69.90.058nd(0.01)na2.71.30.0220.620.130.0722.417.81Ivana Arriaga

    493.28na0.0161.2250.12nd(0.01)na114.50.0923.10.570.092nd(0.3)45.7Ivana Arriaga

    503.9na0.0164.4410.098nd(0.01)1.311110.156.10.710.14nd(0.2)75.9Ivana Arriaga

    513.12na0.0152.3370.11nd(0.01)0.496.76.90.086110.390.11nd(0.3)65.1Ivana Arriaga

    526.31na0.011.8140.084nd(0.01)na2.92.90.0332.10.170.1nd(0.1)24.1Ivana Arriaga

    537.04370.020.7160.13na0.465.82.5nd(0.06)2.20.280.06nd(0.04)28.2Heidi Franklin

    543.29330.010.7690.06na0.141.52.1nd(0.02)2.60.090.05nd(0.09)16.3Gina Wilson

    552.44380.021.2190.18na0.3552.7nd(0.04)2.40.270.052.533.7Lucretia Woodruff

    565.1nd(0.01)0.96.10.09na0.0811.2nd(0.02)6.70.070.03nd(0.05)16.2Rebecca Stolz

    576.5nd(0.01)0.629.10.08na0.171.71.2nd(0.02)1.30.120.11nd(0.1)14.5Sarah Ackerly

    585.80.051.5240.2na0.44.82.7nd(0.04)2.10.220.06nd(0.1)36.1Florence Williams

    593.080.021.2100.09na0.1821.3nd(0.02)40.150.1nd(0.2)19.1Christina Mena

    603.360.0423.173nd(0.2)na2.513310.37201.80.28nd(0.07)145.542Jill Kaiser

    610.41nd(0.01)0.363.4nd(0.02)na0.0710.620.66nd(0.02)1.50.0610.110.87.652Mrs Wellwer

    621.640.0171.115nd(0.01)na0.272.92.70.038320.140.0940.1554.414Sarah Frieson

    Mean3.404032258128.6424.560.03026923082.15548387135.91774193550.63740.08333333331.026118644111.77935483877.42838709680.75792105265.56645161290.66275806450.13887272732.456363636466.0293225806

    Med3.3329200.021.217.40.1550.060.385.052.70.1852.10.220.092.431.9

    SD1.62522781225.722.260.0366546672.766493713553.02556304091.15354277720.06806859291.725596809221.841731741810.21169984621.48166353526.78245158461.1620348840.2057494932.252710690492.8343772052

    Min0.41202n.d.0.22.90.010.030.0710.620.50.010.40.060.030.156.2

    5%1.0052020.010.33.520.02450.0330.081.0150.70.01850.6240.061450.030.3157.6694

    25%2.12523.59.50.010250.79.30.08550.0450.232.52.0250.091.30.150.060.86518.15

    50%3.3329.5200.021.217.40.1550.060.385.052.70.1852.10.220.092.431.9

    75%4.833340.02752.27532.1750.67750.110.659.2756.350.44757.50.54750.112.8561.5

    95%6.293859.30.097.595170.762.76550.156.28150.11314.172518.2452.86450.4356.105294.48

    Max7.04411090.1816.1271.56.670.167.7311147.46.86327.211.328.24418.8

    95/5 ratio6.25870646771.929.65925.316666666748.5113636364112.8775510204na78.512549.369458128144.2857142857225.540540540529.238782051346.615134255514.5na38.4

    max/min17.17073170732.0554.5na80.593.6206896552nanana179.032258064594.8na80120.1666666667nana67.5483870968

    n.a., not available. n.d., not detected. a: Dallas samples. b: Austin samples.

    personLipid %AgeNursing (wks)17284766778599100138153154183209Sum BDE

    x4.8313n.d.0.22.90.02n.d.0.080.70.7n.d.1.50.06n.d.n.d.6.2

    x1.3293n.d.0.33.5n.d.n.d.0.080.70.5n.d.0.90.060.06n.d.6.2

    x2.12374n.d.0.23.90.06n.d.0.111.50.6n.d.0.40.08n.d.n.d.6.9

    x4.83221--0.33.50.14--0.081.60.70.091.40.090.04--8

    x2.622400.010.36.30.05n.d.0.232.81.2n.d.0.70.20.05n.d.11.8

    x3.636109n.d.0.47.80.09n.d.0.232.41.10.010.40.11n.d.n.d.12.5

    x5.55na0.0050.96.10.088na0.08211.20.013.40.0770.0290.02512.916

    x1.93220n.d.0.78.20.04n.d.0.221.31.7n.d.0.90.120.08n.d.13.3

    x6.5nd(0.01)0.629.10.08na0.171.71.2nd(0.02)1.30.120.11nd(0.1)14.5

    x6.3252n.d.0.47.90.02n.d.0.382.32.7n.d.0.80.150.06n.d.14.7

    x2.13529--0.78.80.19--0.171.51.70.1620.060.03--15.2

    x5.53230n.d.0.480.01n.d.0.442.92n.d.0.90.140.240.4815.6

    x5.1nd(0.01)0.96.10.09na0.0811.2nd(0.02)6.70.070.03nd(0.05)16.2

    x6.5na0.0050.96.10.088na0.08211.20.016.70.0770.0290.02516.216

    x3.29330.010.7690.06na0.141.52.1nd(0.02)2.60.090.05nd(0.09)16.3

    x3.29330.0140.7690.056na0.141.52.10.012.60.0940.0510.04516.37

    x3.18na0.0110.69.90.058nd(0.01)na2.71.30.0220.620.130.0722.417.81

    x3.18na0.0110.69.90.058002.71.30.0220.620.130.0722.417.813

    x52020.011.110.90.05n.d.0.1822.4n.d.1.30.170.04n.d.18.1

    x3.42330.010.480.03n.d.0.353.12.7n.d.20.210.610.9318.3

    x1.33216--0.810.5n.d.--0.352.52.20.1920.120.03--18.6

    x3.080.021.2100.09na0.1821.3nd(0.02)40.150.1nd(0.2)19.1

    x3.08na0.0161.2100.086na0.1821.30.0140.150.0960.119.138

    x3.425n.a.0.021.1120.13n.d.0.232.51.8n.d.1.30.150.081.8521.1

    x2.921290.030.510.70.09n.d.0.275.52.1n.d.0.90.350.072.7422.4

    x3.53030--0.76.9n.d.--0.121.34.60.418.50.190.06--22.8

    x1232n.d.0.914.20.11n.d.0.373.72.6n.d.1.30.240.09n.d.23.5

    x3.72319--0.713.20.57--0.293.72.50.291.90.170.06--23.5

    x6.31na0.011.8140.084002.92.90.0332.10.170.1024.097

    x6.31na0.011.8140.084nd(0.01)na2.92.90.0332.10.170.1nd(0.1)24.1

    x3.2262n.d.1.317.40.19n.d.0.3542.1n.d.0.70.18n.d.n.d.26.2

    x3.53422--114.30.29--0.465.73.60.251.40.20.1--27.3

    x7.04370.020.7160.13na0.465.82.5nd(0.06)2.20.280.06nd(0.04)28.2

    x7.04370.020.71160.13na0.465.82.50.032.20.280.0570.0228.207

    x3.13360--1.418.4n.d.--0.254.11.80.092.10.160.06--28.3

    x4.93826--1.217.4n.d.--0.347.12.30.140.60.30.12--29.6

    x3.43020.010.715.20.06n.d.0.424.22.3n.d.30.220.033.9730.1

    x2.44380.021.2190.18na0.3552.70.022.40.270.0512.533.691

    x2.44380.021.2190.18na0.3552.7nd(0.04)2.40.270.052.533.7

    x5.128530.011.1200.18n.d.0.535.13.90.012.70.320.11n.d.34

    x4.735n.a.--1.320.90.56--0.316.32.90.141.20.220.17--34.1

    x1.141380.021.519.50.11n.d.0.413.43.3n.d.7.70.18n.d.n.d.36.1

    x5.80.051.5240.2na0.44.82.7nd(0.04)2.10.220.06nd(0.1)36.1

    x6.75na0.0461.5240.18na0.384.82.70.022.10.220.570.0536.566

    x6.13725--7.617.21.19--0.356.12.30.181.70.270.05--36.8

    x32751--1.428.2n.d.--0.517.52.90.250.70.20.75--42.4

    x4.825n.a.--1.821.60.94--0.59.44.40.475.80.60.06--45.5

    x3.28na0.0161.2250.1200114.50.0923.10.570.092045.69

    x3.28na0.0161.2250.12nd(0.01)na114.50.0923.10.570.092nd(0.3)45.7

    x2.23911--1.126.8n.d.--0.758.95.30.5820.450.1--46

    x5.634n.a.--2.731.8n.d.--0.427.83.10.090.80.220.1--47

    x3.42710--2.630.10.75--0.575.96.50.322.50.340.09--49.6

    x2.820130.021.131.30.17n.d.0.1310.25.90.021.50.480.112.9653.9

    x42013--3.433.52.32--0.495.85.80.272.60.320.06--54.6

    x3.32617--1.432.30.7--0.669.65.70.4612.40.510.05--63.8

    x3.12na0.0152.3370.11nd(0.01)0.496.76.90.086110.390.11nd(0.3)65.1

    x3.12na0.0152.3370.1100.496.76.90.086110.390.11065.101

    x2.22016--1.425.50.75--0.76818.31.7518.30.940.08--75.8

    x3.9na0.0164.4410.098nd(0.01)1.311110.156.10.710.14nd(0.2)75.9

    x3.9na0.0164.4410.09801.311110.156.10.710.14075.914

    x1.122510.042.244.30.550.030.6410.88.10.0214.70.56n.d.n.d.81.9

    x4.32938--5.234.80.61--1.949.829.21.214.50.960.1--98.2

    x126220.021.754.70.54n.d.1.6323.610n.d.4.81.150.07n.d.98.2

    x4.93238--3.449.71.21--1.27.721.11.416.30.930.15--103.1

    x3.4309--3.963.13.13--2.8130.116.23.2917.21.940.08--141.6

    x1.22120.110.1120.91.680.062.6430.320.10.1316.42.07n.d.n.d.204.3

    x1.23315--8139.6n.d.--4.1244.6234.4721.82.760.18--248.5

    x12320.063.6172.41.14n.d.6.2869.831.90.088.43.070.16n.d.296.9

    x2.13413--7.5199.66.67--7.73108.531.74.126.93.620.36--376.7

    x1.733470.186.1196.22.070.166.46111310.2715.57.211.328.24385.5

    x5.12928--16.1271.53.16--6.2950.447.46.8614.12.870.12--418.8

    lipid based

    max/min ratio=68

    PBDEs sum

    percentile

    PBDEs (ng/g lipid)

    Total PBDEs in human milk from US nursing mothers. 2003. (n=59. ng/g lipid)

    Sheet1

    PBDEs ng/g or ppb, lipid

    wet wt

    Dallas NumberLipidAgeNursing (wks)17284766778599100138153154183209Sum BDE

    %

    4.8313n.d.0.22.90.02n.d.0.080.70.7n.d.1.50.06n.d.n.d.6.2

    1.3293n.d.0.33.5n.d.n.d.0.080.70.5n.d.0.90.060.06n.d.6.2

    2.12374n.d.0.23.90.06n.d.0.111.50.6n.d.0.40.08n.d.n.d.6.9

    2.622400.010.36.30.05n.d.0.232.81.2n.d.0.70.20.05n.d.11.8

    3.636109n.d.0.47.80.09n.d.0.232.41.10.010.40.11n.d.n.d.12.5

    1.93220n.d.0.78.20.04n.d.0.221.31.7n.d.0.90.120.08n.d.13.3

    6.3252n.d.0.47.90.02n.d.0.382.32.7n.d.0.80.150.06n.d.14.7

    5.53230n.d.0.480.01n.d.0.442.92n.d.0.90.140.240.4815.6

    52020.011.110.90.05n.d.0.1822.4n.d.1.30.170.04n.d.18.1

    3.42330.010.480.03n.d.0.353.12.7n.d.20.210.610.9318.3

    3.425n.a.0.021.1120.13n.d.0.232.51.8n.d.1.30.150.081.8521.1

    2.921290.030.510.70.09n.d.0.275.52.1n.d.0.90.350.072.7422.4

    1232n.d.0.914.20.11n.d.0.373.72.6n.d.1.30.240.09n.d.23.5

    3.2262n.d.1.317.40.19n.d.0.3542.1n.d.0.70.18n.d.n.d.26.2

    3.43020.010.715.20.06n.d.0.424.22.3n.d.30.220.033.9730.1

    5.128530.011.1200.18n.d.0.535.13.90.012.70.320.11n.d.34

    1.141380.021.519.50.11n.d.0.413.43.3n.d.7.70.18n.d.n.d.36.1

    2.820130.021.131.30.17n.d.0.1310.25.90.021.50.480.112.9653.9

    1.122510.042.244.30.550.030.6410.88.10.0214.70.56n.d.n.d.81.9

    126220.021.754.70.54n.d.1.6323.610n.d.4.81.150.07n.d.98.2

    12320.063.6172.41.14n.d.6.2869.831.90.088.43.070.16n.d.296.9

    1.733470.186.1196.22.070.166.46111310.2715.57.211.328.24385.5

    Mean2.918181818226.863636363626.04761904760.03384615381.190909090930.69545454550.27190476190.0950.9112.43181818185.48181818180.06833333333.28636363640.70045454550.198753.024285714356.0636363636

    Median2.8525.5200.020.811.450.090.0950.353.252.350.021.30.190.082.7421.75

    Minimum12020.010.22.90.010.030.080.70.50.010.40.060.030.486.2

    Maximum6.3411090.186.1196.22.070.166.4611131.90.2715.57.211.328.24385.5

    Austin NumberLipidAgeNursing (wks)17284766778599100138153154183209Sum BDE

    %

    4.83221--0.33.50.14--0.081.60.70.091.40.090.04--8

    2.13529--0.78.80.19--0.171.51.70.1620.060.03--15.2

    1.33216--0.810.5n.d.--0.352.52.20.1920.120.03--18.6

    3.53030--0.76.9n.d.--0.121.34.60.418.50.190.06--22.8

    3.72319--0.713.20.57--0.293.72.50.291.90.170.06--23.5

    3.53422--114.30.29--0.465.73.60.251.40.20.1--27.3

    3.13360--1.418.4n.d.--0.254.11.80.092.10.160.06--28.3

    4.93826--1.217.4n.d.--0.347.12.30.140.60.30.12--29.6

    4.735n.a.--1.320.90.56--0.316.32.90.141.20.220.17--34.1

    6.13725--7.617.21.19--0.356.12.30.181.70.270.05--36.8

    32751--1.428.2n.d.--0.517.52.90.250.70.20.75--42.4

    4.825n.a.--1.821.60.94--0.59.44.40.475.80.60.06--45.5

    2.23911--1.126.8n.d.--0.758.95.30.5820.450.1--46

    5.634n.a.--2.731.8n.d.--0.427.83.10.090.80.220.1--47

    3.42710--2.630.10.75--0.575.96.50.322.50.340.09--49.6

    42013--3.433.52.32--0.495.85.80.272.60.320.06--54.6

    3.32617--1.432.30.7--0.669.65.70.4612.40.510.05--63.8

    2.22016--1.425.50.75--0.76818.31.7518.30.940.08--75.8

    4.32938--5.234.80.61--1.949.829.21.214.50.960.1--98.2

    4.93238--3.449.71.21--1.27.721.11.416.30.930.15--103.1

    3.4309--3.963.13.13--2.8130.116.23.2917.21.940.08--141.6

    1.22120.110.1120.91.680.062.6430.320.10.1316.42.07n.d.n.d.204.3

    1.23315--8139.6n.d.--4.1244.6234.4721.82.760.18--248.5

    2.13413--7.5199.66.67--7.73108.531.74.126.93.620.36--376.7

    5.12928--16.1271.53.16--6.2950.447.46.8614.12.870.12--418.8

    Mean3.53630.223.13636363640.13.42849.6041.4623529412na1.364415.36810.6121.1047.0040.82040.125na90.404

    Median3.532200.11.426.80.750.060.57.54.60.292.50.320.085na46

    Minimum1.22020.10.33.50.140.060.081.30.70.090.60.060.0308

    Maximum6.139600.116.1271.56.670.067.73108.547.46.8621.83.620.750418.8

    Sheet2

    PBDE concentration in US human milk. 2002. Wet wt. Ng/g

    NumberLipid %AgeNursing (wks)17284766778599100138153154183209Sum BDE

    4.8313n.d.0.00960.13920.0010n.d.0.00380.03360.0336n.d.0.07200.0029n.d.n.d.0.2957

    1.3293n.d.0.00390.0455n.d.n.d.0.00100.00910.0065n.d.0.01170.00080.0008n.d.0.0793

    2.12374n.d.0.00420.08190.0013n.d.0.00230.03150.0126n.d.0.00840.0017n.d.n.d.0.1439

    4.83221--0.01440.16800.0067--0.00380.07680.03360.00430.06720.00430.0019--0.3811

    2.622400.00030.00780.16380.0013n.d.0.00600.07280.0312n.d.0.01820.00520.0013n.d.0.3078

    3.636109n.d.0.01440.28080.0032n.d.0.00830.08640.03960.00040.01440.0040n.d.n.d.0.4514

    1.93220n.d.0.01330.15580.0008n.d.0.00420.02470.0323n.d.0.01710.00230.0015n.d.0.2519

    6.3252n.d.0.02520.49770.0013n.d.0.02390.14490.1701n.d.0.05040.00950.0038n.d.0.9267

    9a2.13529--0.01470.18480.0040--0.00360.03150.03570.00340.04200.00130.0006--0.3215

    5.53230n.d.0.02200.44000.0006n.d.0.02420.15950.1100n.d.0.04950.00770.01320.02640.8531

    52020.00050.05500.54500.0025n.d.0.00900.10000.1200n.d.0.06500.00850.0020n.d.0.9075

    3.42330.00030.01360.27200.0010n.d.0.01190.10540.0918n.d.0.06800.00710.02070.03160.6236

    1.33216--0.01040.1365n.d.--0.00460.03250.02860.00250.02600.00160.0004--0.2430

    3.425n.a.0.00070.03740.40800.0044n.d.0.00780.08500.0612n.d.0.04420.00510.00270.06290.7194

    2.921290.00090.01450.31030.0026n.d.0.00780.15950.0609n.d.0.02610.01020.00200.07950.6743

    3.53030--0.02450.2415n.d.--0.00420.04550.16100.01440.29750.00670.0021--0.7973

    1232n.d.0.00900.14200.0011n.d.0.00370.03700.0260n.d.0.01300.00240.0009n.d.0.2351

    3.72319--0.02590.48840.0211--0.01070.13690.09250.01070.07030.00630.0022--0.8651

    3.2262n.d.0.04160.55680.0061n.d.0.01120.12800.0672n.d.0.02240.0058n.d.n.d.0.8390

    3.53422--0.03500.50050.0102--0.01610.19950.12600.00880.04900.00700.0035--0.9555

    3.13360--0.04340.5704n.d.--0.00780.12710.05580.00280.06510.00500.0019--0.8792

    4.93826--0.05880.8526n.d.--0.01670.34790.11270.00690.02940.01470.0059--1.4455

    3.43020.00030.02380.51680.0020n.d.0.01430.14280.0782n.d.0.10200.00750.00100.13501.0237

    5.128530.00050.05611.02000.0092n.d.0.02700.26010.19890.00050.13770.01630.0056n.d.1.7320

    4.735n.a.--0.06110.98230.0263--0.01460.29610.13630.00660.05640.01030.0080--1.5980

    1.141380.00020.01650.21450.0012n.d.0.00450.03740.0363n.d.0.08470.0020n.d.n.d.0.3973

    6.13725--0.46361.04920.0726--0.02140.37210.14030.01100.10370.01650.0031--2.2533

    32751--0.04200.8460n.d.--0.01530.22500.08700.00750.02100.00600.0225--1.2723

    4.825n.a.--0.08641.03680.0451--0.02400.45120.21120.02260.27840.02880.0029--2.1874

    2.23911--0.02420.5896n.d.--0.01650.19580.11660.01280.04400.00990.0022--1.0116

    5.634n.a.--0.15121.7808n.d.--0.02350.43680.17360.00500.04480.01230.0056--2.6337

    3.42710--0.08841.02340.0255--0.01940.20060.22100.01090.08500.01160.0031--1.6888

    2.820130.00060.03080.87640.0048n.d.0.00360.28560.16520.00060.04200.01340.00310.08291.5089

    42013--0.13601.34000.0928--0.01960.23200.23200.01080.10400.01280.0024--2.1824

    3.32617--0.04621.06590.0231--0.02180.31680.18810.01520.40920.01680.0017--2.1047

    2.22016--0.03080.56100.0165--0.01670.17600.40260.03850.40260.02070.0018--1.6672

    1.122510.00040.02420.48730.00610.00030.00700.11880.08910.00020.16170.0062n.d.n.d.0.9013

    4.32938--0.22361.49640.0262--0.08340.42141.25560.05160.62350.04130.0043--4.2273

    126220.00020.01700.54700.0054n.d.0.01630.23600.1000n.d.0.04800.01150.0007n.d.0.9821

    4.93238--0.16662.43530.0593--0.05880.37731.03390.06860.79870.04560.0074--5.0514

    3.4309--0.13262.14540.1064--0.09551.02340.55080.11190.58480.06600.0027--4.8195

    1.22120.00120.12121.45080.02020.00070.03170.36360.24120.00160.19680.0248n.d.n.d.2.4538

    1.23315--0.09601.6752n.d.--0.04940.53520.27600.05360.26160.03310.0022--2.9824

    12320.00060.03601.72400.0114n.d.0.06280.69800.31900.00080.08400.03070.0016n.d.2.9689

    2.13413--0.15754.19160.1401--0.16232.27850.66570.08650.14490.07600.0076--7.9107

    1.733470.00310.10373.33540.03520.00270.10981.88700.52700.00460.26350.12260.02240.14016.5571

    5.12928--0.821113.84650.1612--0.32082.57042.41740.34990.71910.14640.0061--21.3588

    483.180.00030.01910.31480.00180.00000.00000.08590.04130.00070.01970.00410.00230.07630.0000

    493.280.00050.03940.82000.00390.00000.00000.36080.14760.00300.10170.01870.00300.00000.0000

    503.90.00060.17161.59900.00380.00000.05070.42900.42900.00590.23790.02770.00550.00000.0000

    513.120.00050.07181.15440.00340.00000.01530.20900.21530.00270.34320.01220.00340.00000.0000

    526.310.00060.11360.88340.00530.00000.00000.18300.18300.00210.13250.01070.00630.00000.0000

    Mean3.315192307728.638297872324.55813953490.00065145260.07828038461.11905230770.0227403442000.33809019230.23823288460.0260950750.14930780770.01888740380.0045717600

    Median3.3529200.000510.03670.56570.00540.0000000.1893950.1230.006720.069150.0100250.0027200

    SD1.5092219665.696778387522.25533892670.00062929930.13018014681.97518987470.0376937794000.51644171320.39015163430.06131082190.18657323530.02798291440.005289998200

    Min12020.00020.00390.04550.00055000.00910.00650.000220.00840.000780.0003900

    5%1.0552020.0002180.008460.1379850.000966000.03150.027430.00047250.013770.0016260.00071600

    25%2.1239.50.00034490.0168750.3029250.00227000.0862650.0596250.00262990.0420.0051750.0018600

    50%3.3529200.000510.03670.56570.0054000.1893950.1230.006720.069150.0100250.0027200

    75%4.72533340.00062750.09031.0880250.0243000.36150.216710.01455750.1704750.01729650.005600

    95%5.82537.759.30.0013860.1952.8403450.105058001.412020.831390.0928550.6022150.0704870.01923200

    Max6.31411090.003060.821113.84650.16116002.57042.41740.349860.79870.146370.022500

    95/5 ratio5.52132701421.88529.656.357798165123.049645390120.5844475849108.7556935818na044.82603174630.3095151294196.518518518543.733841684843.349938499426.8603351955na0

    Sheet2

    0

    0

    0

    0

    0

    0

    0

    95/5 percent ratio = 24

    percentile

    PBDE ng/g wet wt.

    PBDE concentrations in US human milk samples from 2002 by percentile. (n=52, ng/g wet wt)

    Sheet3

    Lipid basedLipid %AgeNursing (wks)17284766778599100138153154183209Sum BDE

    4.8313n.d.0.22.90.02n.d.0.080.70.7n.d.1.50.06n.d.n.d.6.2

    1.3293n.d.0.33.5n.d.n.d.0.080.70.5n.d.0.90.060.06n.d.6.2

    2.12374n.d.0.23.90.06n.d.0.111.50.6n.d.0.40.08n.d.n.d.6.9

    4.83221--0.33.50.14--0.081.60.70.091.40.090.04--8

    2.622400.010.36.30.05n.d.0.232.81.2n.d.0.70.20.05n.d.11.8

    3.636109n.d.0.47.80.09n.d.0.232.41.10.010.40.11n.d.n.d.12.5

    1.93220n.d.0.78.20.04n.d.0.221.31.7n.d.0.90.120.08n.d.13.3

    6.3252n.d.0.47.90.02n.d.0.382.32.7n.d.0.80.150.06n.d.14.7

    9a2.13529--0.78.80.19--0.171.51.70.1620.060.03--15.2

    5.53230n.d.0.480.01n.d.0.442.92n.d.0.90.140.240.4815.6

    52020.011.110.90.05n.d.0.1822.4n.d.1.30.170.04n.d.18.1

    3.42330.010.480.03n.d.0.353.12.7n.d.20.210.610.9318.3

    1.33216--0.810.5n.d.--0.352.52.20.1920.120.03--18.6

    3.425n.a.0.021.1120.13n.d.0.232.51.8n.d.1.30.150.081.8521.1

    2.921290.030.510.70.09n.d.0.275.52.1n.d.0.90.350.072.7422.4

    3.53030--0.76.9n.d.--0.121.34.60.418.50.190.06--22.8

    1232n.d.0.914.20.11n.d.0.373.72.6n.d.1.30.240.09n.d.23.5

    3.72319--0.713.20.57--0.293.72.50.291.90.170.06--23.5

    3.2262n.d.1.317.40.19n.d.0.3542.1n.d.0.70.18n.d.n.d.26.2

    3.53422--114.30.29--0.465.73.60.251.40.20.1--27.3

    3.13360--1.418.4n.d.--0.254.11.80.092.10.160.06--28.3

    4.93826--1.217.4n.d.--0.347.12.30.140.60.30.12--29.6

    3.43020.010.715.20.06n.d.0.424.22.3n.d.30.220.033.9730.1

    5.128530.011.1200.18n.d.0.535.13.90.012.70.320.11n.d.34

    4.735n.a.--1.320.90.56--0.316.32.90.141.20.220.17--34.1

    1.141380.021.519.50.11n.d.0.413.43.3n.d.7.70.18n.d.n.d.36.1

    6.13725--7.617.21.19--0.356.12.30.181.70.270.05--36.8

    32751--1.428.2n.d.--0.517.52.90.250.70.20.75--42.4

    4.825n.a.--1.821.60.94--0.59.44.40.475.80.60.06--45.5

    2.23911--1.126.8n.d.--0.758.95.30.5820.450.1--46

    5.634n.a.--2.731.8n.d.--0.427.83.10.090.80.220.1--47

    3.42710--2.630.10.75--0.575.96.50.322.50.340.09--49.6

    2.820130.021.131.30.17n.d.0.1310.25.90.021.50.480.112.9653.9

    42013--3.433.52.32--0.495.85.80.272.60.320.06--54.6

    3.32617--1.432.30.7--0.669.65.70.4612.40.510.05--63.8

    2.22016--1.425.50.75--0.76818.31.7518.30.940.08--75.8

    1.122510.042.244.30.550.030.6410.88.10.0214.70.56n.d.n.d.81.9

    4.32938--5.234.80.61--1.949.829.21.214.50.960.1--98.2

    126220.021.754.70.54n.d.1.6323.610n.d.4.81.150.07n.d.98.2

    4.93238--3.449.71.21--1.27.721.11.416.30.930.15--103.1

    3.4309--3.963.13.13--2.8130.116.23.2917.21.940.08--141.6

    1.22120.110.1120.91.680.062.6430.320.10.1316.42.07n.d.n.d.204.3

    1.23315--8139.6n.d.--4.1244.6234.4721.82.760.18--248.5

    12320.063.6172.41.14n.d.6.2869.831.90.088.43.070.16n.d.296.9

    2.13413--7.5199.66.67--7.73108.531.74.126.93.620.36--376.7

    1.733470.186.1196.22.070.166.46111310.2715.57.211.328.24385.5

    5.12928--16.1271.53.16--6.2950.447.46.8614.12.870.12--418.8

    483.18na0.0110.69.90.0580.005na2.71.30.0220.620.130.0722.417.81

    493.28na0.0161.2250.120.005na114.50.0923.10.570.0920.1545.7

    503.9na0.0164.4410.0980.0051.311110.156.10.710.140.175.9

    513.12na0.0152.3370.110.0050.496.76.90.086110.390.110.1565.1

    526.31na0.011.8140.0840.005na2.92.90.0332.10.170.10.0524.1

    537.04370.020.7160.13na0.465.82.50.032.20.280.060.0228.2

    543.29330.010.7690.06na0.141.52.10.012.60.090.050.04516.3

    552.44380.021.2190.18na0.3552.70.022.40.270.052.533.7

    565.10.0050.96.10.09na0.0811.20.016.70.070.030.02516.2

    576.50.0050.629.10.08na0.171.71.20.011.30.120.110.0514.5

    585.80.051.5240.2na0.44.82.70.022.10.220.060.0536.1

    593.080.021.2100.09na0.1821.30.0140.150.10.119.1

    603.360.0423.1730.1na2.513310.37201.80.280.035145.642

    610.410.0050.363.40.01na0.0710.620.660.011.50.0610.110.87.677

    621.640.0171.1150.005na0.272.92.70.038320.140.0940.1554.419

    wet wt pg/gLipid %AgeNursing (wks)17284766778599100138153154183209Sum BDE

    4.8313na9.6139.20.96na3.8433.633.6na722.88nana297.6

    1.3293na3.945.5nana1.049.16.5na11.70.780.78na80.6

    2.12374na4.281.91.26na2.3131.512.6na8.41.68nana144.9

    4.83221na14.41686.72na3.8476.833.64.3267.24.321.92na384

    2.622400.267.8163.81.3na5.9872.831.2na18.25.21.3na306.8

    3.636109na14.4280.83.24na8.2886.439.60.3614.43.96nana450

    1.93220na13.3155.80.76na4.1824.732.3na17.12.281.52na252.7

    6.3252na25.2497.71.26na23.94144.9170.1na50.49.453.78na926.1

    9a2.13529na14.7184.83.99na3.5731.535.73.36421.260.63na319.2

    5.53230na224400.55na24.2159.5110na49.57.713.226.4858

    52020.5555452.5na9100120na658.52na905

    3.42330.3413.62721.02na11.9105.491.8na687.1420.7431.62622.2

    1.33216na10.4136.5nana4.5532.528.62.47261.560.39na241.8

    3.425n.a.0.6837.44084.42na7.828561.2na44.25.12.7262.9717.4

    2.921290.8714.5310.32.61na7.83159.560.9na26.110.152.0379.46649.6

    3.53030na24.5241.5nana4.245.516114.35297.56.652.1na798

    1232na91421.1na3.73726na132.40.9na235

    3.72319na25.9488.421.09na10.73136.992.510.7370.36.292.22na869.5

    3.2262na41.6556.86.08na11.212867.2na22.45.76nana838.4

    3.53422na35500.510.15na16.1199.51268.754973.5na955.5

    3.13360na43.4570.4nana7.75127.155.82.7965.14.961.86na877.3

    4.93826na58.8852.6nana16.66347.9112.76.8629.414.75.88na1450.4

    3.43020.3423.8516.82.04na14.28142.878.2na1027.481.02134.981023.4

    5.128530.5156.110209.18na27.03260.1198.90.51137.716.325.61na1734

    4.735n.a.na61.1982.326.32na14.57296.1136.36.5856.410.347.99na1602.7

    1.141380.2216.5214.51.21na4.5137.436.3na84.71.98nana397.1

    6.13725na463.61049.272.59na21.35372.1140.310.98103.716.473.05na2244.8

    32751na42846nana15.3225877.521622.5na1272

    4.825n.a.na86.41036.845.12na24451.2211.222.56278.428.82.88na2184

    2.23911na24.2589.6nana16.5195.8116.612.76449.92.2na1012

    5.634n.a.na151.21780.8nana23.52436.8173.65.0444.812.325.6na2632

    3.42710na88.41023.425.5na19.38200.622110.888511.563.06na1686.4

    2.820130.5630.8876.44.76na3.64285.6165.20.564213.443.0882.881509.2

    42013na136134092.8na19.623223210.810412.82.4na2184

    3.32617na46.21065.923.1na21.78316.8188.115.18409.216.831.65na2105.4

    2.22016na30.856116.5na16.72176402.638.5402.620.681.76na1667.6

    1.122510.4424.2487.36.050.337.04118.889.10.22161.76.16nana900.9

    4.32938na223.61496.426.23na83.42421.41255.651.6623.541.284.3na4222.6

    126220.2175475.4na16.3236100na4811.50.7na982

    4.93238na166.62435.359.29na58.8377.31033.968.6798.745.577.35na5051.9

    3.4309na132.62145.4106.42na95.541023.4550.8111.86584.865.962.72na4814.4

    1.22121.2121.21450.820.160.7231.68363.6241.21.56196.824.84nana2451.6

    1.23315na961675.2nana49.44535.227653.64261.633.122.16na2982

    12320.636172411.4na62.86983190.88430.71.6na2969

    2.13413na157.54191.6140.07na162.332278.5665.786.52144.976.027.56na7910.7

    1.733473.06103.73335.435.192.72109.8218875274.59263.5122.5722.44140.086553.5

    5.12928na821.113846.5161.16na320.792570.42417.4349.86719.1146.376.12na21358.8

    483.18na0.349819.08314.821.84440.159na85.8641.340.699619.7164.1342.289676.32566.358

    493.28na0.524839.368203.9360.164na360.8147.63.0176101.6818.6963.01764.921498.96

    503.9na0.624171.615993.8220.19550.74294295.85237.927.695.463.92960.1

    513.12na0.46871.761154.43.4320.15615.288209.04215.282.6832343.212.1683.4324.682031.12

    526.31na0.631113.58883.45.30040.3155na182.99182.992.0823132.5110.7276.313.1551520.71

    537.04371.40849.281126.49.152na32.384408.321762.112154.8819.7124.2241.4081985.28

    543.29330.32925.004296.11.974na4.60649.3569.090.32985.542.9611.6451.4805536.27

    552.44380.48829.28463.64.392na8.5412265.880.48858.566.5881.2261822.28

    565.10.25545.9311.14.59na4.085161.20.51341.73.571.531.275826.2

    576.50.32540.3591.55.2na11.05110.5780.6584.57.87.153.25942.5

    585.82.987139211.6na23.2278.4156.61.16121.812.763.482.92093.8

    593.080.61636.963082.772na5.54461.640.040.308123.24.623.083.08588.28

    603.361.4112104.162452.83.36na84436.81041.612.43267260.489.4081.1764893.5712

    610.410.02051.47613.940.041na0.29112.5422.7060.0416.150.25010.4513.2831.4757

    621.640.278818.042460.082na4.42847.5644.280.6232524.82.2961.54162.46892.4716

    n=62 Median pg/g ww0.537.18558.94.760.2552514.57167.75114.654.45584.258.9752.724.29968.75

  • Median Levels of PBDE 47, 99, 153 in Human Milk from Different Countries.

    Chart1

    254.510.1

    17.45.12.1

    1331.3

    1.40.50.3

    0.80.20.5

    1.70.20.5

    10.40.3

    0.20.060.09

    BDE 47

    BDE 99

    BDE 153

    PBDE levels (ng/g. ppb. lipid)

    17

    Sheet1

    Results for individual PBDE congeners (parts per billion in breast millk lipid)

    PBDE CongenerNumber of brominesClass of PBDEPercent of samples with detectable levelsMinimum valueMedian valueAverage valueMaximum value

    31mono10%0.10.150.150.2USA EWG 2003 (n = 20)USA, TX, 2004 (n = 59)Canada 2002 (n = 92)Canada 1992 (n = 72)Germany 2000 (n = 7)Sweden 2000 (n = 40)Finland 1994-98 (n = 11)Hanoi, Vietnam 2004 (n = 2)

    72di35%0.0030.010.010.04BDE 472517.4131.40.81.710.2

    8 + 112di45%0.0050.010.020.06BDE 994.55.130.50.20.20.40.06

    122di5%0.010.010.010.01BDE 15310.12.11.30.30.50.50.30.09

    132di5%0.010.010.010.01

    152di100%0.190.431.4617.7

    173tri100%0.020.060.10.47

    253tri90%0.0020.010.020.06

    28 + 333tri100%0.351.896.2443.8

    353tri5%0.020.020.020.02

    373tri95%0.010.020.060.4

    474tetra100%5.5324.884.94589

    494tetra100%0.040.210.573.69

    664tetra100%0.060.261.138.37

    714tetra90%0.0040.020.050.33

    754tetra100%0.010.020.070.43

    855penta100%0.050.432.2717.1

    995penta100%0.764.4720.93200

    1005penta100%0.574.9118.43171

    1195penta35%0.0040.020.060.22

    1265penta50%0.0050.010.040.22

    138 + 1666hexa90%0.020.070.261.76

    1406hexa100%0.010.070.211.93

    1536hexa100%1.0710.0619.79122

    1546hexa100%0.040.321.4611.7

    1556hexa95%0.010.080.332.5

    1837hepta100%0.050.090.150.46

    1907hepta5%0.010.010.010.01

    2069nona40%0.0040.010.010.04

    2079nona75%0.020.040.060.13

    2089nona35%0.0050.010.010.04

    20910deca80%0.080.150.241.23

    48.68

    Sheet1

    000

    000

    000

    000

    000

    000

    000

    000

    BDE 47

    BDE 99

    BDE 153

    PBDE levels (ng/g. ppb. lipid)

    Sheet2

    Sheet3

  • PBDEs in Human SamplesPattern of congeners is different from commercial mixtures (and food)47>99 (others: 100,153,183, 209,)In some people (and biota)153>47Large inter-individual differencesPeople as high as PBDEs ~10 ppm lipid!!!!Increasing time trends levels doubling every 2-5 yearsPBDEs and PCBs levels are not correlated different sources and/or time sequenceNorth American levels ~ 10X Europe/Japan

    WHY?

  • (Petreas et al., 2002)

  • EcotoxicityPeBDE>>OBDE>DBDEPeBDE - Highly toxic to invertebrates Larval development, LOECs in low g/l rangeDE71 developmentally toxic to fish (1ng/l) Tail asymmetry; delayed hatching; behavioral changes; learning deficitsPBDEs associated with die-off of Baltic porpoise Lymphoid depletion BDE99 - depletion of Vitamin E in duck eggsBDE 47, 99, 100 - decreases in T4/retinoids, increases in oxidative stress in Kestrals

  • Ecotoxicity (cont.)DBDE/OBDEMay be low risk to surface water organism and top predatorsConcern for waste water, sediment, and soil organismsConcerns for lower brominated congeners in OBDE, potential for debromination, and generation of PBDDs/PBDFs

  • Mammalian Toxicity in Adult RodentsHepatotoxicEnzyme inductionUDP-glucuronyl transferaseWeak inducerCytochrome P450Induction of CYP2B,3APurified BDEs are NOT CYP1A inducersDBDE hepatocarcinogen (high dose)

  • Endocrine Disrupting EffectsAhR Effects Contamination of commercial PBDEsCombustion can produce PBDDs/PBDFsThyroid HomeostasisDecrease in T4OH-PBDE metabolites bind to transthyretin in vitroParent PBDEs - Effects on T4 seen in vivo Induction of UDP-glucuronyl transferaseNot a low dose effect

  • Endocrine Disrupting Effects (cont.)ProgestinsIn vitro Anti-progesteroneEstrogensIn vivoBDE99 decreased E2In vitroOH-PBDEs may be anti-estrogenicSulfotransferase inhibition could be estrogenic

  • Endocrine Disrupting Effects (cont.)AndrogensIn vivoDE71 decreased weight of seminal vesicles and ventral prostate, decreased LHBDE99 decreased TestosteroneIn vitroDE71, BDE100, BDE47 antiandrogenic (non-competitive inhibition)

  • Developmental Reproductive EffectsDE71 pubertal exposuresDelay in pubertyEffects on male organsAnti-androgenic in vitro esp BDEs100, 47BDE-99/47 in utero exposuresDelay in pubertyOvarian toxicityMale organ effects and decreased sperm

  • Developmental NeurotoxicityDE-71 RatsDeficits in sensory and cognitive functionAltered sex-dependent behaviorsEffects on thyroid, cholinergic, and dopaminergic systemsBDE-99 (47,153,206,208,209) - Mice and ratsInfantile exposure (Rapid Brain Growth) - Permanent effects on learningPerinatal exposure Delay in sensory-motor developmentBDE-99+PCB-52 MiceEffects may be more than additive

  • Developmental Neurotoxicity of PBDEs

    Mechanisms? Depression in serum T4 Anti-cholinergicAnti-dopamingergicPBDEs alter cell signaling in vitroDE71, BDEs 47, 99, 153Altered PKC and calcium homeostasis (associated with learning and memory) Alter phorbol ester binding

  • BDE 47 Toxicokinetics?BDE47 - Major PBDE in most people and wildlifeWell Absorbed (Oral~Inhalation>Dermal)Distribution dictated by lipophilicity-FatLimited Metabolism -Hydroxylation, DebrominationExcretion mice and rats differLong Half-life-Potential for Bioaccumulation

  • Comparative Urinary Excretion of PBDEs

  • PK of BDE 47,99, 100, and 153Well absorbedHigher urinary elimination in mice than ratsUrine elimination decreases as #Bromine atoms increaseBDE99 is most metabolized

    What does this all mean for people?

  • New Information on Deca

    Deca is major PBDE in outdoor air (Butt et al., 2004)Deca can break down in the environmentPhotolytic Debromination (Soderstrom et al, 2003) Matrices affect time course but not outcomeBDE 154 and 183 found in all matrices; BE47 only in silica gelDeca can break down in fishDetection of BDE-181 and 190 in carp (congeners not in commercial products) (Rice et al, 2002)7 penta to octa metabolites found (Stapleton et al, 2003)Deca can be absorbed (>10%) and break down in rodentsDebrominated, Hydroxylated, MethoxylatedReactive Intermediates - Covalent bindingDeca MAY BE developmentally neurotoxic

  • DBDE in Human SamplesRarely Measured but its there!SerumLevels as high as 200ppb lipid in occupational exposed workers Breast MilkMean~0.9 ppb lipidAnalytical IssuesHigh background levels in dust lead to laboratory contamination

  • Potential Health Risk of PBDEsTop 5% of current human exposure in US - >400 ng/g lipid If humans are 25% lipid, then their dose is ~0.1 mg/kg body weightSignificant dose causing DNT Mice < 0.8 mg BDE99/kg Rats
  • ConclusionsGrowing international concernP, B, and TPresence in biotaPresence in human tissuesNorth American levels much higher than Europe or JapanRelative Biotic levels are very different from commercial mixturesIncreasing potential for health effects

  • With Special ThanksNHEERLDaniele Staskal, Janet Diliberto, Mike Devito, Vicki Richardson, Kevin Crofton, Tammy Stoker, Prasada KodavantiEPA HQDan Axelrad, Tala Henry, Hend Galal-GorchevNIEHSTom Burka, Mike Sanders, Ed Lebetkin, John PrichardUSDAHeldur Hakk, Janice HuweUTArnie SchecterBUTom WebsterCal EPATom McDonaldDukeHeather Stapleton

    And all of my colleagues worldwide!