associations between phthalates exposure and health outcomes of newborns, pregnant women and...
TRANSCRIPT
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Associations between phthalatesexposure and health outcomes of newborns,pregnant women and precocious puberty girls in Taiwan
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*Whats Phthalates (PAEs)?They are a family of chemical substances that have been in use for about 50 years, primarily to make polyvinyl chloride (PVC) soft and flexible.Phthalates look like clear vegetable oil.
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Physico-chemical properties of Phthalates
CompoundsDimethyl phthalate DMPDiethyl phthalate DEPDi-n-butyl phthalate DBPButyl benzyl phthalate BBzPDi(2-ethylhexyl) phthalate DEHP
Chemical formulaC10H10O4C12H14O4C16H22O4C19H20O4C24H38O4Molecular weight194.19222.23278.35312.35390.62Melting point (C)5.5- 40.5- 35- 35- 47Boiling point (C)282295~302340370386Vapor pressure (mmHg)1 (100C)1.6510-32.710-5610-7110-7Soubility (mg L-1, ) 40001000130.70.3Log Kow 1.62.54.54.97.5Log Koc1.9-2.61.8-2.73.1-4.23.2-4.24.9-6.0MetabolitesMMPMEPMBPMBzPMEHP,MEOHP, MEHHP
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Applications of phthalatesPersonal care products
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Application of phthalates
PAEs
DEHP
()(PVC)()()()PVC
DBP
(latex adhesive)(cellulose plastic)PVC(PVC)
BBP
(vinyl tile)(food conveyor belt)(carpet tile)(artificial leather)(tarpaulin)(automotive trim)(Weather stripping)(traffic cone)(adhesives)
DEP
DMP
DINP(Di-isononyl phthalate)
PVCPVCPVCPVCPVCPVCPVC
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Metabolic pathway of DEHP-Albro, et al., 1982; ATSDR, 1993, Schmid, et al., 1985c.DEHPMEHPHumanPrimarySecondary
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ObjectivesPart I: Association between Phthalate Exposure and Thyroid Hormone in Pregnant WomenTo determine the concentrations of urinary phthalate monoesters in pregnant women. To investigate the association between phthalate exposure and thyroid hormone during pregnancy.
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ObjectivesPart II: Association between Prenatal Exposure to Phthalates and the Health of NewbornsTo determine the concentrations of amniotic fluid phthalate monoesters in pregnant women. To evaluate the association between prenatal exposure of the fetus to phthalates in amniotic fluid and maternal urine and the health of newborns.
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To follow-up our previously established participants in order to determine the correlation between phthalate exposure and thyroid hormones in pregnant women and newborns. ObjectivesPart III: Phthalates may alter thyroid hormones in utero: A follow-up study
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Framework
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Newborns healthAnogenital distanceGestational age Urine samplePhthalate monoesters Serum &Cord bloodTSH,T3, T4, FT4Phthalate monoestersMaterials and MethodsInformed consent Amniotic fluidPhthalate monoesters Urine samplePhthalate monoestersCreatinineSerum sampleTSH,T3, T4, FT4 Urine samplePhthalate monoestersCreatinine Serum sampleTSH,T3, T4, FT4 QuestionnaireAge, BMI, gestationFood consumptionCosmetic usageFollow up-76 subjects Follow up-65 subjects Interview- 83 subjects alpha fetal protein (AFP) -free -hCG maternal age > 35 yrsundergo amniocentesis
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*Measured Parameters Phthalate monoestersmonomethyl phthalate (MMP)monoethyl phthalate (MEP)monobutyl phthalate (MBP)monobenzyl phthalate (MBzP)mono-2-ethylhexyl phthalate (MEHP)SampleUrine/ Amniotic fluidSerumAnalytical methodLC-MS/MS (Agilent 1100/API 3000)
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Measured Parameters Physical examinationAnogenital distance (AGD)Birth weightBirth heightGestational ageAnogenital index (AGI)AGI-W= AGD/ birth weight.AGI-L= AGD/ birth length.Thyroid hormonesThyroid stimulating hormone (TSH)Thyroxin (T4)Triiodotyronine (T3) Free thyroxin (FT4)QuestionnairesAge, BMI, gestation age, Smoking, Medical care etc.Food consumptionCosmetic usagePersonal care product usageBuilding characteristics
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Table I-1 Demographic characteristics of study participants (n = 76). Characteristics Mean SDAge (years)33.6 3.3Body mass index (BMI)20.9 2.5Duration of gestation (weeks)27.9 2.3Pregnancies and births Number of current pregnancy1.9 1.0 Number of current birth1.5 0.6Smoking status (n/%) Active smoker0/0 Passive smoker14/18.4 Non-smoker62/81.6Alcohol drinker (n/%)0/0New decoration of living/ working place during previous 1 year (n/%) aHome Moving to new decorated house7/9.2 Just decorated4/5.3Workplace Moving to new decorated workplace2/2.6 Just decorated6/7.9Medical care during previous 3 months (n/%) Blood transfusion3/3.9 Intravenous drip3/3.9 Oxygen mask1/1.3 a Moving to new decorated house or workplace means moved into a new building. Just decorated means the place you live or work have decorated recently such as painting or changing the floor.
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*Table I-2 Levels of five urinary phthalates monoester in pregnant Taiwanese women and comparison with other studies (g/g creatinine).
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Table I-3 Distribution of thyroid hormones in pregnant women. aThe analytic sensitivities of T3, T4, free T4, and TSH were 19.5 ng/dL, 0.42 g/dL, 0.023 ng/dL and 0.014 lU/mL, respectively; the coefficient variations of T3, T4, free T4, and TSH were 2.9%, 4.2%, 3.1%, and 3.0%, respectively.
Hormones aPercentileReference rangeMin5th50th95thMaxT3 (ng/dL)72.686.3132.0209.0246.084.6-202.0T4 (g/dL)4.395.318.8511.213.65.13-14.1Free T4 (ng/dL)0.460.690.931.251.350.93-1.7TSH ( IU/mL)0.220.311.063.45.190.27-4.2
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Table I-4 Spearman correlation coefficients a between thyroid hormone, age, BMI, duration of gestation and urinary phthalate monoester levels (n = 75). a Spearman correlation coefficients, *: p < 0.05.
TSHT3T4FT4AgeBMIGestationTSH1T30.1451T40.291*0.709*1FT40.1720.299*0.761*1Age0.2030.307*0.218*0.0081BMI0.0440.3090.1370.0100.1061Gestation0.1060.0180.0380.0570.0290.1311MBP0.0790.2340.248*0.368*0.0820.081*0.098MEP0.0820.0190.0390.0170.0800.095*0.199MEHP-0.0600.0670.1000.0900.1660.0300.030*MBzP0.0800.0840.0340.0070.0640.0270.118MMP0.0780.2590.0890.0070.0380.0060.004
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Figure I-1. Correlation between (A) free thyroxine (FT4), (B) thyroxine (T4) and log MBP (ppb) and MBP-c level in pregnant women at the 2nd trimester. AB
Origin Data
NAMEIDLog MBP (ppb)CreatinineFSHE2ProgTSHT4T3FT4Log MBP-c
E940216US0012.85916254126.90.1219915139.22.747.9972.570.6712.28581328
E940321US0011.6252631320.40.117730165.11.197.93108.30.8462.66480479
E940420US0012.2235165261.80.12060552.091.538.0797.291.012.43252805
E940421US0011.9852001650.50.119200182.70.619.131150.9752.26885973
E940423US0011.5842474543.30.114030101.30.4866.4485.840.7912.27511142
E940428US0011.95480207240.1151174053.410.3684.8180.970.782.68318627
E940513US0012.63396916185.60.10510480117.50.3666.3698.470.7742.36539119
E940518US0011.965558268.30.11043590.82.468.04129.30.8613.04648017
E940523US0012.3774377656.50.136975211.90.9476.7996.910.8172.62538932
E940524US0011.7614294110.40.1884568.53.2310.39132.71.222.74439607
E940524US0021.9524884812.90.10611875770.2167.71050.9372.84189877
E940526US0011.8349551314.70.117220111.21.049.91311.052.66763779
E940530US0011.8920988412.10.12747599.21.046.0892.310.812.80931347
E940601US0011.8058225176.50.11244069.10.5736.63126.30.8041.92216108
E940601US0022.0446067519.70.11244080.50.5068.77128.10.9322.75014053
E940602US0012.14612804132.90.127400114.90.8128.88131.81.012.02260305
E940602US0021.8984325915.10.112060111.91.078.01113.60.9512.89449735
E940602US0031.8810122840.1859070.60.8187.55128.80.8393.27895229
E940604US0011.5543879124.20.12215421570.6099.05127.51.042.63387059
E940606US0012.0999307534.80.1171265596.81.26.3790.890.8622.28403916
E940607US0012.2427301488.10.12913559.851.86.79106.90.7992.29775423
E940609US0011.9646494617.40.116106651311.055.71102.60.7872.72410021
E940613US0011.409296315.40.11590593.40.97.36120.40.832.22177557
E940614US0011.96106345111.80.12785079.750.4598.96135.10.9721.91262164
E940615US0011.6286399122.20.132625224.250.5049.651541.042.28228694
E940618US0011.7271646923.80.113673118.251.19.87131.60.9432.35058774
E940622US0011.9385301275.40.12070777.51.168.41109.20.9972.06115878
E940623US0012.2063528575.40.1012393883.51.366.38115.60.7352.3289815
E940623US0022.29330552310.18750137.40.8556.03130.70.72.80194382
E940627US0011.99537967131.80.125900191.51.577.47107.70.8161.87546426
E940628US0011.6575821536.50.1082602554.70.587.21108.80.792.09528929
E940704US0011.4457499216.60.112130154.31.199.77134.41.052.22564183
E940706US0012.3291443361.90.116570106.61.338.87180.40.8022.53745368
E940708US0011.5723709640.50.10816270145.61.39.5111.71.151.96491594
E940716US0011.238197978.50.1116290107.51.648.75131.40.922.30877905
E940723US0012.1206173746.90.113470103.90.75811.64207.61.032.44944453
E940725US0011.414160049.50.10918550150.41.8311.61147.21.122.43643643
E940725US0021.122000916.60.134090157.61.49.81117.21.162.30245698
E940730US0012.105799139.50.11810630154.63.068.39123.70.8782.509202
E940803US0011.5569544228.40.120920205.90.76411.23149.21.12.10363608
E940811US0012.0979983487.10.11513092.60.80510.48163.11.052.15798019
E940818US0011.6063754329.90.117270176.71.9210.43145.91.062.13070424
E940823US0012.1616583367.90.127700204.80.6439.08132.11.072.32978855
E940824US0011.5767190219.20.16118570115.72.1110.52152.51.012.29341779
E940902US0011.9139084330.50.128800202.70.2317.52122.40.9852.42960859
E940905US0012.1807961260.10.147820441.95.194.39145.10.462.40192165
E940905US0021.40356794250.123230307.10.9039.25139.90.9612.00562793
E940906US0012.5376305841.10.10930160206.61.178.31137.70.8892.92378875
E940923US0011.6032586417.20.10220540160.20.8848.31138.20.7952.36773019
E940928US0011.387990417.10.1116350112.51.6311.17148.50.9832.53673206
E940929US0012.10205118120.50.1694851.730.47810.9192.60.9182.02106414
E941003US0011.5994867540.50.13316980105.11.1210.43158.50.9611.99203172
E941006US0011.5932418134.80.1120160124.42.568.44126.60.82.05166257
E941006US0021.6767974330.60.10422480150.31.179.87159.30.9172.191076
E941007US0012.76327488119.80.1431367045.641.57.02110.80.7382.68481807
E941013US0011.49765853180.12210730761.797.65128.50.8382.24238602
E941020US0011.8939958695.40.128590140.70.9469.17122.20.8971.91444748
E941021US0011.6674779912.30.131258086.22.128.45169.60.7532.57757288
E941101US0012.30777007113.90.137100226.40.4627.62137.80.852.25124635
E941105US0012.1709947146.20.11485649.71.158.29110.41.182.00604733
E941107US0011.9109444164.10.11055085.70.7289.14140.40.9732.10408638
E941117US0012.31699717177.60.1151073054.50.87612.35204.60.9562.06755421
E941203US0012.2741809594.80.127280351.50.5567.06155.50.7662.29737261
E941205US0011.964636729.60.116770165.10.6197.54157.10.7262.49334499
E941207US0011.99659922450.11177053.870.4168.61137.90.9712.34338671
E941213US0012.40973029115.90.114376130.21.6710.23119.71.072.34564686
E941219US0011.6148972212.90.10310278151.20.7679.99133.81.042.50430751
E950103US0011.5174598315.20.19260881.2910.191540.8882.33561624
E950104US0011.9009676243.30.121520159.81.798.93157.10.7882.26447973
E950105US0012.13395384104.80.10219240106.41.7911.83245.80.8972.11359256
E950112US0011.8977919888.70.119180214.51.619.2165.30.9111.94986836
E950112US0021.9444333252.60.112889964.42.2811.7141.71.212.22344757
E950112US0031.377124043.90.11720270170.30.9018.83108.41.072.78605944
E950112US0041.299289337.80.112880154.20.9016.24162.30.7312.40719473
E950121US0011.9382694848.90.117786.7452.179.39140.90.9622.24896062
E950124US0011.6402826375.60.1152221095.10.94813.37224.31.231.76176083
E950126US0011.7209857439.40.19955211.20.87212.47144.21.292.12548952
E950126US0021.5737995836.90.1219501703.8213.59225.31.352.00677322
MBP-FT4
NAMEIDFT4T4Log MBP (ppb)Log MBP-cTSHT3CreatinineFSHE2Prog
E940216US0010.6717.992.859162542.285813282.7472.57126.90.1219915139.2
E940420US0011.018.072.223516522.432528051.5397.2961.80.12060552.09
E940421US0010.9759.131.985200162.268859730.6111550.50.119200182.7
E940423US0010.7916.441.584247452.275111420.48685.8443.30.114030101.3
E940428US0010.784.811.954802072.683186270.36880.97240.1151174053.41
E940513US0010.7746.362.633969162.365391190.36698.47185.60.10510480117.5
E940518US0010.8618.041.965558263.046480172.46129.38.30.11043590.8
E940523US0010.8176.792.377437762.625389320.94796.9156.50.136975211.9
E940524US0011.2210.391.761429412.744396073.23132.710.40.1884568.5
E940524US0020.9377.71.952488482.841898770.21610512.90.1061187577
E940526US0011.059.91.834955132.667637791.0413114.70.117220111.2
E940530US0010.816.081.892098842.809313471.0492.3112.10.12747599.2
E940601US0010.8046.631.805822511.922161080.573126.376.50.11244069.1
E940601US0020.9328.772.044606752.750140530.506128.119.70.11244080.5
E940602US0011.018.882.146128042.022603050.812131.8132.90.127400114.9
E940602US0020.9518.011.898432592.894497351.07113.615.10.112060111.9
E940602US0030.8397.551.881012283.278952290.818128.840.1859070.6
E940604US0011.049.051.554387912.633870590.609127.524.20.1221542157
E940606US0010.8626.372.099930752.284039161.290.8934.80.1171265596.8
E940607US0010.7996.792.242730142.297754231.8106.988.10.12913559.85
E940609US0010.7875.711.964649462.724100211.05102.617.40.11610665131
E940613US0010.837.361.40929632.221775570.9120.415.40.11590593.4
E940614US0010.9728.961.961063451.912621640.459135.1111.80.12785079.75
E940615US0011.049.651.628639912.282286940.50415422.20.132625224.25
E940618US0010.9439.871.727164692.350587741.1131.623.80.113673118.25
E940622US0010.9978.411.938530122.061158781.16109.275.40.12070777.5
E940623US0010.7356.382.206352852.32898151.36115.675.40.1012393883.5
E940623US0020.76.032.293305522.801943820.855130.7310.18750137.4
E940627US0010.8167.471.995379671.875464261.57107.7131.80.125900191.5
E940628US0010.797.211.657582152.095289290.58108.836.50.1082602554.7
E940704US0011.059.771.445749922.225641831.19134.416.60.112130154.3
E940706US0010.8028.872.329144332.537453681.33180.461.90.116570106.6
E940708US0011.159.51.572370961.964915941.3111.740.50.10816270145.6
E940723US0011.0311.642.120617372.449444530.758207.646.90.113470103.9
E940725US0011.1211.611.414160042.436436431.83147.29.50.10918550150.4
E940725US0021.169.811.122000912.302456981.4117.26.60.134090157.6
E940730US0010.8788.392.10579912.5092023.06123.739.50.11810630154.6
E940803US0011.111.231.556954422.103636080.764149.228.40.120920205.9
E940811US0011.0510.482.097998342.157980190.805163.187.10.11513092.6
E940818US0011.0610.431.606375432.130704241.92145.929.90.117270176.7
E940823US0011.079.082.161658332.329788550.643132.167.90.127700204.8
E940824US0011.0110.521.576719022.293417792.11152.519.20.16118570115.7
E940902US0010.9857.521.913908432.429608590.231122.430.50.128800202.7
E940905US0010.464.392.180796122.401921655.19145.160.10.147820441.9
E940905US0020.9619.251.403567942.005627930.903139.9250.123230307.1
E940906US0010.8898.312.537630582.923788751.17137.741.10.10930160206.6
E940923US0010.7958.311.603258642.367730190.884138.217.20.10220540160.2
E940928US0010.98311.171.387990412.536732061.63148.57.10.1116350112.5
E940929US0010.91810.92.102051182.021064140.478192.6120.50.1694851.73
E941003US0010.96110.431.599486751.992031721.12158.540.50.13316980105.1
E941006US0010.88.441.593241812.051662572.56126.634.80.1120160124.4
E941006US0020.9179.871.676797432.1910761.17159.330.60.10422480150.3
E941007US0010.7387.022.763274882.684818071.5110.8119.80.1431367045.64
E941013US0010.8387.651.497658532.242386021.79128.5180.1221073076
E941020US0010.8979.171.893995861.914447480.946122.295.40.128590140.7
E941021US0010.7538.451.667477992.577572882.12169.612.30.131258086.2
E941101US0010.857.622.307770072.251246350.462137.8113.90.137100226.4
E941105US0011.188.292.17099472.006047331.15110.4146.20.11485649.7
E941107US0010.9739.141.910944412.104086380.728140.464.10.11055085.7
E941117US0010.95612.352.316997172.067554210.876204.6177.60.1151073054.5
E941203US0010.7667.062.274180952.297372610.556155.594.80.127280351.5
E941205US0010.7267.541.96463672.493344990.619157.129.60.116770165.1
E941207US0010.9718.611.996599222.343386710.416137.9450.11177053.87
E941213US0011.0710.232.409730292.345646861.67119.7115.90.114376130.2
E941219US0011.049.991.614897222.504307510.767133.812.90.10310278151.2
E950103US0010.88810.191.517459832.335616241.2915415.20.1926088
E950104US0010.7888.931.900967622.264479731.79157.143.30.121520159.8
E950105US0010.89711.832.133953842.113592561.79245.8104.80.10219240106.4
E950112US0010.9119.21.897791981.949868361.61165.388.70.119180214.5
E950112US0021.2111.71.944433322.223447572.28141.752.60.112889964.4
E950112US0031.078.831.377124042.786059440.901108.43.90.11720270170.3
E950112US0040.7316.241.299289332.407194730.901162.37.80.112880154.2
E950121US0010.9629.391.938269482.248960622.17140.948.90.117786.745
E950124US0011.2313.371.640282631.761760830.948224.375.60.1152221095.1
E950126US0011.2912.471.720985742.125489520.872144.239.40.19955211.2
E950126US0021.3513.591.573799582.006773223.82225.336.90.121950170
Fig-MBP-FT4
2.859162542.28581328
2.223516522.43252805
1.985200162.26885973
1.584247452.27511142
1.954802072.68318627
2.633969162.36539119
1.965558263.04648017
2.377437762.62538932
1.761429412.74439607
1.952488482.84189877
1.834955132.66763779
1.892098842.80931347
1.805822511.92216108
2.044606752.75014053
2.146128042.02260305
1.898432592.89449735
1.881012283.27895229
1.554387912.63387059
2.099930752.28403916
2.242730142.29775423
1.964649462.72410021
1.40929632.22177557
1.961063451.91262164
1.628639912.28228694
1.727164692.35058774
1.938530122.06115878
2.206352852.3289815
2.293305522.80194382
1.995379671.87546426
1.657582152.09528929
1.445749922.22564183
2.329144332.53745368
1.572370961.96491594
2.120617372.44944453
1.414160042.43643643
1.122000912.30245698
2.10579912.509202
1.556954422.10363608
2.097998342.15798019
1.606375432.13070424
2.161658332.32978855
1.576719022.29341779
1.913908432.42960859
2.180796122.40192165
1.403567942.00562793
2.537630582.92378875
1.603258642.36773019
1.387990412.53673206
2.102051182.02106414
1.599486751.99203172
1.593241812.05166257
1.676797432.191076
2.763274882.68481807
1.497658532.24238602
1.893995861.91444748
1.667477992.57757288
2.307770072.25124635
2.17099472.00604733
1.910944412.10408638
2.316997172.06755421
2.274180952.29737261
1.96463672.49334499
1.996599222.34338671
2.409730292.34564686
1.614897222.50430751
1.517459832.33561624
1.900967622.26447973
2.133953842.11359256
1.897791981.94986836
1.944433322.22344757
1.377124042.78605944
1.299289332.40719473
1.938269482.24896062
1.640282631.76176083
1.720985742.12548952
1.573799582.00677322
Log MBP (ppb)
Log MBP-c
FT4
Urinary MBP
Fig-MBP-T4
2.859162542.28581328
2.223516522.43252805
1.985200162.26885973
1.584247452.27511142
1.954802072.68318627
2.633969162.36539119
1.965558263.04648017
2.377437762.62538932
1.761429412.74439607
1.952488482.84189877
1.834955132.66763779
1.892098842.80931347
1.805822511.92216108
2.044606752.75014053
2.146128042.02260305
1.898432592.89449735
1.881012283.27895229
1.554387912.63387059
2.099930752.28403916
2.242730142.29775423
1.964649462.72410021
1.40929632.22177557
1.961063451.91262164
1.628639912.28228694
1.727164692.35058774
1.938530122.06115878
2.206352852.3289815
2.293305522.80194382
1.995379671.87546426
1.657582152.09528929
1.445749922.22564183
2.329144332.53745368
1.572370961.96491594
2.120617372.44944453
1.414160042.43643643
1.122000912.30245698
2.10579912.509202
1.556954422.10363608
2.097998342.15798019
1.606375432.13070424
2.161658332.32978855
1.576719022.29341779
1.913908432.42960859
2.180796122.40192165
1.403567942.00562793
2.537630582.92378875
1.603258642.36773019
1.387990412.53673206
2.102051182.02106414
1.599486751.99203172
1.593241812.05166257
1.676797432.191076
2.763274882.68481807
1.497658532.24238602
1.893995861.91444748
1.667477992.57757288
2.307770072.25124635
2.17099472.00604733
1.910944412.10408638
2.316997172.06755421
2.274180952.29737261
1.96463672.49334499
1.996599222.34338671
2.409730292.34564686
1.614897222.50430751
1.517459832.33561624
1.900967622.26447973
2.133953842.11359256
1.897791981.94986836
1.944433322.22344757
1.377124042.78605944
1.299289332.40719473
1.938269482.24896062
1.640282631.76176083
1.720985742.12548952
1.573799582.00677322
Log MBP (ppb)
Log MBP-c
T4
Urinary MBP
y = -0.0544x + 2.3782R2 = 0.0892
Sheet2
Sheet3
Origin Data
NAMEIDLog MBP (ppb)CreatinineFSHE2ProgTSHT4T3FT4Log MBP-c
E940216US0012.85916254126.90.1219915139.22.747.9972.570.6712.28581328
E940321US0011.6252631320.40.117730165.11.197.93108.30.8462.66480479
E940420US0012.2235165261.80.12060552.091.538.0797.291.012.43252805
E940421US0011.9852001650.50.119200182.70.619.131150.9752.26885973
E940423US0011.5842474543.30.114030101.30.4866.4485.840.7912.27511142
E940428US0011.95480207240.1151174053.410.3684.8180.970.782.68318627
E940513US0012.63396916185.60.10510480117.50.3666.3698.470.7742.36539119
E940518US0011.965558268.30.11043590.82.468.04129.30.8613.04648017
E940523US0012.3774377656.50.136975211.90.9476.7996.910.8172.62538932
E940524US0011.7614294110.40.1884568.53.2310.39132.71.222.74439607
E940524US0021.9524884812.90.10611875770.2167.71050.9372.84189877
E940526US0011.8349551314.70.117220111.21.049.91311.052.66763779
E940530US0011.8920988412.10.12747599.21.046.0892.310.812.80931347
E940601US0011.8058225176.50.11244069.10.5736.63126.30.8041.92216108
E940601US0022.0446067519.70.11244080.50.5068.77128.10.9322.75014053
E940602US0012.14612804132.90.127400114.90.8128.88131.81.012.02260305
E940602US0021.8984325915.10.112060111.91.078.01113.60.9512.89449735
E940602US0031.8810122840.1859070.60.8187.55128.80.8393.27895229
E940604US0011.5543879124.20.12215421570.6099.05127.51.042.63387059
E940606US0012.0999307534.80.1171265596.81.26.3790.890.8622.28403916
E940607US0012.2427301488.10.12913559.851.86.79106.90.7992.29775423
E940609US0011.9646494617.40.116106651311.055.71102.60.7872.72410021
E940613US0011.409296315.40.11590593.40.97.36120.40.832.22177557
E940614US0011.96106345111.80.12785079.750.4598.96135.10.9721.91262164
E940615US0011.6286399122.20.132625224.250.5049.651541.042.28228694
E940618US0011.7271646923.80.113673118.251.19.87131.60.9432.35058774
E940622US0011.9385301275.40.12070777.51.168.41109.20.9972.06115878
E940623US0012.2063528575.40.1012393883.51.366.38115.60.7352.3289815
E940623US0022.29330552310.18750137.40.8556.03130.70.72.80194382
E940627US0011.99537967131.80.125900191.51.577.47107.70.8161.87546426
E940628US0011.6575821536.50.1082602554.70.587.21108.80.792.09528929
E940704US0011.4457499216.60.112130154.31.199.77134.41.052.22564183
E940706US0012.3291443361.90.116570106.61.338.87180.40.8022.53745368
E940708US0011.5723709640.50.10816270145.61.39.5111.71.151.96491594
E940716US0011.238197978.50.1116290107.51.648.75131.40.922.30877905
E940723US0012.1206173746.90.113470103.90.75811.64207.61.032.44944453
E940725US0011.414160049.50.10918550150.41.8311.61147.21.122.43643643
E940725US0021.122000916.60.134090157.61.49.81117.21.162.30245698
E940730US0012.105799139.50.11810630154.63.068.39123.70.8782.509202
E940803US0011.5569544228.40.120920205.90.76411.23149.21.12.10363608
E940811US0012.0979983487.10.11513092.60.80510.48163.11.052.15798019
E940818US0011.6063754329.90.117270176.71.9210.43145.91.062.13070424
E940823US0012.1616583367.90.127700204.80.6439.08132.11.072.32978855
E940824US0011.5767190219.20.16118570115.72.1110.52152.51.012.29341779
E940902US0011.9139084330.50.128800202.70.2317.52122.40.9852.42960859
E940905US0012.1807961260.10.147820441.95.194.39145.10.462.40192165
E940905US0021.40356794250.123230307.10.9039.25139.90.9612.00562793
E940906US0012.5376305841.10.10930160206.61.178.31137.70.8892.92378875
E940923US0011.6032586417.20.10220540160.20.8848.31138.20.7952.36773019
E940928US0011.387990417.10.1116350112.51.6311.17148.50.9832.53673206
E940929US0012.10205118120.50.1694851.730.47810.9192.60.9182.02106414
E941003US0011.5994867540.50.13316980105.11.1210.43158.50.9611.99203172
E941006US0011.5932418134.80.1120160124.42.568.44126.60.82.05166257
E941006US0021.6767974330.60.10422480150.31.179.87159.30.9172.191076
E941007US0012.76327488119.80.1431367045.641.57.02110.80.7382.68481807
E941013US0011.49765853180.12210730761.797.65128.50.8382.24238602
E941020US0011.8939958695.40.128590140.70.9469.17122.20.8971.91444748
E941021US0011.6674779912.30.131258086.22.128.45169.60.7532.57757288
E941101US0012.30777007113.90.137100226.40.4627.62137.80.852.25124635
E941105US0012.1709947146.20.11485649.71.158.29110.41.182.00604733
E941107US0011.9109444164.10.11055085.70.7289.14140.40.9732.10408638
E941117US0012.31699717177.60.1151073054.50.87612.35204.60.9562.06755421
E941203US0012.2741809594.80.127280351.50.5567.06155.50.7662.29737261
E941205US0011.964636729.60.116770165.10.6197.54157.10.7262.49334499
E941207US0011.99659922450.11177053.870.4168.61137.90.9712.34338671
E941213US0012.40973029115.90.114376130.21.6710.23119.71.072.34564686
E941219US0011.6148972212.90.10310278151.20.7679.99133.81.042.50430751
E950103US0011.5174598315.20.19260881.2910.191540.8882.33561624
E950104US0011.9009676243.30.121520159.81.798.93157.10.7882.26447973
E950105US0012.13395384104.80.10219240106.41.7911.83245.80.8972.11359256
E950112US0011.8977919888.70.119180214.51.619.2165.30.9111.94986836
E950112US0021.9444333252.60.112889964.42.2811.7141.71.212.22344757
E950112US0031.377124043.90.11720270170.30.9018.83108.41.072.78605944
E950112US0041.299289337.80.112880154.20.9016.24162.30.7312.40719473
E950121US0011.9382694848.90.117786.7452.179.39140.90.9622.24896062
E950124US0011.6402826375.60.1152221095.10.94813.37224.31.231.76176083
E950126US0011.7209857439.40.19955211.20.87212.47144.21.292.12548952
E950126US0021.5737995836.90.1219501703.8213.59225.31.352.00677322
MBP-FT4
NAMEIDFT4T4Log MBP (ppb)Log MBP-cTSHT3CreatinineFSHE2Prog
E940216US0010.6717.992.859162542.285813282.7472.57126.90.1219915139.2
E940420US0011.018.072.223516522.432528051.5397.2961.80.12060552.09
E940421US0010.9759.131.985200162.268859730.6111550.50.119200182.7
E940423US0010.7916.441.584247452.275111420.48685.8443.30.114030101.3
E940428US0010.784.811.954802072.683186270.36880.97240.1151174053.41
E940513US0010.7746.362.633969162.365391190.36698.47185.60.10510480117.5
E940518US0010.8618.041.965558263.046480172.46129.38.30.11043590.8
E940523US0010.8176.792.377437762.625389320.94796.9156.50.136975211.9
E940524US0011.2210.391.761429412.744396073.23132.710.40.1884568.5
E940524US0020.9377.71.952488482.841898770.21610512.90.1061187577
E940526US0011.059.91.834955132.667637791.0413114.70.117220111.2
E940530US0010.816.081.892098842.809313471.0492.3112.10.12747599.2
E940601US0010.8046.631.805822511.922161080.573126.376.50.11244069.1
E940601US0020.9328.772.044606752.750140530.506128.119.70.11244080.5
E940602US0011.018.882.146128042.022603050.812131.8132.90.127400114.9
E940602US0020.9518.011.898432592.894497351.07113.615.10.112060111.9
E940602US0030.8397.551.881012283.278952290.818128.840.1859070.6
E940604US0011.049.051.554387912.633870590.609127.524.20.1221542157
E940606US0010.8626.372.099930752.284039161.290.8934.80.1171265596.8
E940607US0010.7996.792.242730142.297754231.8106.988.10.12913559.85
E940609US0010.7875.711.964649462.724100211.05102.617.40.11610665131
E940613US0010.837.361.40929632.221775570.9120.415.40.11590593.4
E940614US0010.9728.961.961063451.912621640.459135.1111.80.12785079.75
E940615US0011.049.651.628639912.282286940.50415422.20.132625224.25
E940618US0010.9439.871.727164692.350587741.1131.623.80.113673118.25
E940622US0010.9978.411.938530122.061158781.16109.275.40.12070777.5
E940623US0010.7356.382.206352852.32898151.36115.675.40.1012393883.5
E940623US0020.76.032.293305522.801943820.855130.7310.18750137.4
E940627US0010.8167.471.995379671.875464261.57107.7131.80.125900191.5
E940628US0010.797.211.657582152.095289290.58108.836.50.1082602554.7
E940704US0011.059.771.445749922.225641831.19134.416.60.112130154.3
E940706US0010.8028.872.329144332.537453681.33180.461.90.116570106.6
E940708US0011.159.51.572370961.964915941.3111.740.50.10816270145.6
E940723US0011.0311.642.120617372.449444530.758207.646.90.113470103.9
E940725US0011.1211.611.414160042.436436431.83147.29.50.10918550150.4
E940725US0021.169.811.122000912.302456981.4117.26.60.134090157.6
E940730US0010.8788.392.10579912.5092023.06123.739.50.11810630154.6
E940803US0011.111.231.556954422.103636080.764149.228.40.120920205.9
E940811US0011.0510.482.097998342.157980190.805163.187.10.11513092.6
E940818US0011.0610.431.606375432.130704241.92145.929.90.117270176.7
E940823US0011.079.082.161658332.329788550.643132.167.90.127700204.8
E940824US0011.0110.521.576719022.293417792.11152.519.20.16118570115.7
E940902US0010.9857.521.913908432.429608590.231122.430.50.128800202.7
E940905US0010.464.392.180796122.401921655.19145.160.10.147820441.9
E940905US0020.9619.251.403567942.005627930.903139.9250.123230307.1
E940906US0010.8898.312.537630582.923788751.17137.741.10.10930160206.6
E940923US0010.7958.311.603258642.367730190.884138.217.20.10220540160.2
E940928US0010.98311.171.387990412.536732061.63148.57.10.1116350112.5
E940929US0010.91810.92.102051182.021064140.478192.6120.50.1694851.73
E941003US0010.96110.431.599486751.992031721.12158.540.50.13316980105.1
E941006US0010.88.441.593241812.051662572.56126.634.80.1120160124.4
E941006US0020.9179.871.676797432.1910761.17159.330.60.10422480150.3
E941007US0010.7387.022.763274882.684818071.5110.8119.80.1431367045.64
E941013US0010.8387.651.497658532.242386021.79128.5180.1221073076
E941020US0010.8979.171.893995861.914447480.946122.295.40.128590140.7
E941021US0010.7538.451.667477992.577572882.12169.612.30.131258086.2
E941101US0010.857.622.307770072.251246350.462137.8113.90.137100226.4
E941105US0011.188.292.17099472.006047331.15110.4146.20.11485649.7
E941107US0010.9739.141.910944412.104086380.728140.464.10.11055085.7
E941117US0010.95612.352.316997172.067554210.876204.6177.60.1151073054.5
E941203US0010.7667.062.274180952.297372610.556155.594.80.127280351.5
E941205US0010.7267.541.96463672.493344990.619157.129.60.116770165.1
E941207US0010.9718.611.996599222.343386710.416137.9450.11177053.87
E941213US0011.0710.232.409730292.345646861.67119.7115.90.114376130.2
E941219US0011.049.991.614897222.504307510.767133.812.90.10310278151.2
E950103US0010.88810.191.517459832.335616241.2915415.20.1926088
E950104US0010.7888.931.900967622.264479731.79157.143.30.121520159.8
E950105US0010.89711.832.133953842.113592561.79245.8104.80.10219240106.4
E950112US0010.9119.21.897791981.949868361.61165.388.70.119180214.5
E950112US0021.2111.71.944433322.223447572.28141.752.60.112889964.4
E950112US0031.078.831.377124042.786059440.901108.43.90.11720270170.3
E950112US0040.7316.241.299289332.407194730.901162.37.80.112880154.2
E950121US0010.9629.391.938269482.248960622.17140.948.90.117786.745
E950124US0011.2313.371.640282631.761760830.948224.375.60.1152221095.1
E950126US0011.2912.471.720985742.125489520.872144.239.40.19955211.2
E950126US0021.3513.591.573799582.006773223.82225.336.90.121950170
Fig-MBP-FT4
2.859162542.28581328
2.223516522.43252805
1.985200162.26885973
1.584247452.27511142
1.954802072.68318627
2.633969162.36539119
1.965558263.04648017
2.377437762.62538932
1.761429412.74439607
1.952488482.84189877
1.834955132.66763779
1.892098842.80931347
1.805822511.92216108
2.044606752.75014053
2.146128042.02260305
1.898432592.89449735
1.881012283.27895229
1.554387912.63387059
2.099930752.28403916
2.242730142.29775423
1.964649462.72410021
1.40929632.22177557
1.961063451.91262164
1.628639912.28228694
1.727164692.35058774
1.938530122.06115878
2.206352852.3289815
2.293305522.80194382
1.995379671.87546426
1.657582152.09528929
1.445749922.22564183
2.329144332.53745368
1.572370961.96491594
2.120617372.44944453
1.414160042.43643643
1.122000912.30245698
2.10579912.509202
1.556954422.10363608
2.097998342.15798019
1.606375432.13070424
2.161658332.32978855
1.576719022.29341779
1.913908432.42960859
2.180796122.40192165
1.403567942.00562793
2.537630582.92378875
1.603258642.36773019
1.387990412.53673206
2.102051182.02106414
1.599486751.99203172
1.593241812.05166257
1.676797432.191076
2.763274882.68481807
1.497658532.24238602
1.893995861.91444748
1.667477992.57757288
2.307770072.25124635
2.17099472.00604733
1.910944412.10408638
2.316997172.06755421
2.274180952.29737261
1.96463672.49334499
1.996599222.34338671
2.409730292.34564686
1.614897222.50430751
1.517459832.33561624
1.900967622.26447973
2.133953842.11359256
1.897791981.94986836
1.944433322.22344757
1.377124042.78605944
1.299289332.40719473
1.938269482.24896062
1.640282631.76176083
1.720985742.12548952
1.573799582.00677322
Log MBP (ppb)
Log MBP-c
FT4
Urinary MBP
y = -0.8073x + 2.6508R2 = 0.1328
Fig-MBP-T4
2.859162542.28581328
2.223516522.43252805
1.985200162.26885973
1.584247452.27511142
1.954802072.68318627
2.633969162.36539119
1.965558263.04648017
2.377437762.62538932
1.761429412.74439607
1.952488482.84189877
1.834955132.66763779
1.892098842.80931347
1.805822511.92216108
2.044606752.75014053
2.146128042.02260305
1.898432592.89449735
1.881012283.27895229
1.554387912.63387059
2.099930752.28403916
2.242730142.29775423
1.964649462.72410021
1.40929632.22177557
1.961063451.91262164
1.628639912.28228694
1.727164692.35058774
1.938530122.06115878
2.206352852.3289815
2.293305522.80194382
1.995379671.87546426
1.657582152.09528929
1.445749922.22564183
2.329144332.53745368
1.572370961.96491594
2.120617372.44944453
1.414160042.43643643
1.122000912.30245698
2.10579912.509202
1.556954422.10363608
2.097998342.15798019
1.606375432.13070424
2.161658332.32978855
1.576719022.29341779
1.913908432.42960859
2.180796122.40192165
1.403567942.00562793
2.537630582.92378875
1.603258642.36773019
1.387990412.53673206
2.102051182.02106414
1.599486751.99203172
1.593241812.05166257
1.676797432.191076
2.763274882.68481807
1.497658532.24238602
1.893995861.91444748
1.667477992.57757288
2.307770072.25124635
2.17099472.00604733
1.910944412.10408638
2.316997172.06755421
2.274180952.29737261
1.96463672.49334499
1.996599222.34338671
2.409730292.34564686
1.614897222.50430751
1.517459832.33561624
1.900967622.26447973
2.133953842.11359256
1.897791981.94986836
1.944433322.22344757
1.377124042.78605944
1.299289332.40719473
1.938269482.24896062
1.640282631.76176083
1.720985742.12548952
1.573799582.00677322
Log MBP (ppb)
Log MBP-c
T4
Urinary MBP
Sheet2
Sheet3
- Table I-5. Multivariate linear regression between serum FT4 and T4 levels, and their corresponding urinary phthalate monoesters (FT4: R-square= 0.240; T4: R-square= 0.187)a. a One outlier was excluded because of hypothyroidism (n=75).Multiple regression: FT4 = -0.110, R2=0.24, p|t|Intercept1.2700.0132.3620.001Age0.0240.886-0.3210.177BMI0.0880.5790.3480.120Gestational age-0.1170.598-0.0660.831MBP-0.110
-
Table II-1 Physical examination of male and female newborns (n = 65).1 The AGD of two girls and boys, respectively, were not available.2 AGI=ano-genital index; AGI-W= AGD/birth weight; AGI-L=AGD/ birth length.3 *: p
Health statusMales (n=33)Females (n=32)P-value3Birth weight (g)3171 (1678-4260)3002(2000-3935)0.156Birth length (cm)49.6 (42.0-56.0)48.3 (42.5-53.5)0.023*Gestational age (weeks)39.0 (35.3-41.7)38.4 (33.6-40.3)0.020*Ano-genital distance (AGD) (mm)123 (10-36)16 (7-23)
-
Table II-2 Concentrations of five phthalate monoesters in amniotic fluid from female and male infants (ng/mL, n=64)1.1One amniotic fluid sample was failed during analysis. 2ND=not detected, detection limit of MMP, MEP, MBP, MBzP and MEHP were as follow: 1.4, 1.0, 1.4, 1.4, 0.9 ng/mL
Female infantsMin10th50th90thMaxMBP39.345.685.5134.6192.0MEHPND25.024.091.1148.0MEPNDNDND3.96.5MBzPNDNDND84.1233.0MMPNDNDNDND2.92Male infantsMin10th50th90thMaxMBP28.444.381.3127.8145.0MEHPND22.622.1100.6110.0MEPNDNDND4.47.7MBzPNDNDND87.9104.0MMPNDNDNDNDND
-
Figure II-1 Distribution plot of MBP levels in maternal urine and amniotic fluid (n=59). All the data were log-transformed.It is indicated that current levels of exposure to phthalate in pregnant women may only partly represent in utero fetal exposure
-
Table II-3 Distribution of health status in females categorized by median levels of phthalate monoester in amniotic fluid (-AF) (n = 31).1Wilcoxon Rank Sum Test, *: p < 0.05;2AGD data were lacking for one female newborn in each group.3AGD data were lacking for two female newborns in the high MEHP-AF group.4Median levels of amniotic fluid MBP in low and high group were 67 and 104 ng/mL, respectively; those of MEHP were 9.5 and 38.8 ng/mL, respectively.
Health status in female infantsMBP-AF2MEHP-AF3Low4(n=15)High4(n=16)P-value1Low4(n=15)High4(n=16)P-value1Birth weight (g)281043931723980.031*291844830614670.527Birth length (cm)47.32.349.21.70.018*48.12.148.62.40.138Gestational age (weeks)38.11.538.71.00.20538.40.938.41.60.591AGD (mm)17.64.013.93.80.024*17.04.114.24.10.109AGI-W (mm/kg)6.21.64.51.50.007*6.01.44.71.80.016*AGI-L (103)3.70.92.80.80.008*3.60.82.90.90.015*
-
Table II-4. Distribution of health status in boys category by median levels of phthalate monoester in amniotic fluid. (n = 33).1 One male infant of each group in MBP-AF and MEHP-AF, respectively, were lack of AGD.
Health status in male infantsMBPMEHPLow(n=16)High(n=17)P-valueLow(n=16)High(n=17)P-valueBirth weight (g)314648131944690.640321344031315150.815Birth length (cm)49.22.550.02.80.70549.42.449.73.00.971Gestational age (weeks)39.11.038.91.40.39639.10.938.91.50.787AGD (mm)21.26.524.15.70.23423.36.822.25.60.606AGI-W (mm/kg)6.62.17.72.20.2067.42.66.91.70.635AGI-L (103)4.31.24.81.20.3044.71.44.41.00.649
- Table II-5 Spearman correlation coefficients1 between birth weight, birth length, gestational age, AGD, AGI-W, AGI-L, and phthalate monoester levels in amniotic fluid in female infants (n = 29)2. 1 *:p< 0.05; #: p
-
Figure II-2 (A) Linear regressions between MBP in amniotic fluid and AGI-W in females at birth (n=29, R2=0.14, p=0.043); (B) Linear regressions between MBP in amniotic fluid and AGI-L in females at birth (n=29, R2=0.16, p=0.032).Negative associations among amniotic fluid MBP and AGI
-
Figure III-3 Multiple regression of AGI, MBP in amniotic fluid and gestational age adjustment of gestational age and other phthalate monoesters (amniotic fluid MBP: = 2.73, p = 0.041; gestational age: = 0.899, p = 0.006) .
-
Table III-1 Concentrations of phthalate monoesters in urine, serum and cord blood at delivery (ng/mL, n=61).aMBP = monobutyl phthalate; MBzP = monobenzyl phthalate; MEP = monoethyl phthalate; MEHP = mono-2-ethylhexyl phthalate; MMP = monomethyl phthalate. bDetection limit (LOD) of phthalate monoesters were: MBP, 1.4; MBzP, 1.4; MEP, 1.0; MEHP, 0.9; MMP, 1.4 ng/mL, respectively. Half of LOD was calculated as the detected value below the LOD.
Mono-PAEsUrineSerumCord bloodMedian (Range)10-90thMedian (Range)10-90thMedian (Range)10-90thMBPa114(25.4-1830)36.9-550.6158.0(59.6-1080)64.9-413.0256.0(65.2-815)97.4-604.8MEHP40.2(3.6-958)8.4-152.021.0(9.2-99.2)11.7-37.124.7(11.0-665.0)14.2-65.9MEP36.4(NDb-1980)4.6-236.82.8(ND-26.5)ND-6.3ND(ND-9.3)ND-3.4MBzP5.7(ND-218.0)1.9-49.2ND(ND-10.1)ND-2.8ND(ND-26.8)ND-3.6MMP8.3(ND-169)1.7-38.0ND(ND-3.7)ND-2.4ND(ND-13.3)ND-ND
-
Table III-2 Concentrations of thyroid hormones1 in maternal serum during pregnancy and cord blood at delivery (n=61).1Reference values for thyroid hormones in Taiwan: TSH: 0.27-4.2; T3: 84.6-202.0; T4: 5.13-14.1; FT4: 0.93-1.7. The analytic sensitivities of T3, T4, free T4, and TSH were 19.5 ng/dL, 0.42 g/dL, 0.023 ng/dL and 0.014 lU/mL, respectively. The coefficient variations of T3, T4, free T4, and TSH were 3.0%, 4.1%, 3.2%, and 2.9%, respectively.
Serum Thyroid HormonesFirst-trimesterSecond-trimesterThird-trimesterCord bloodMedianRangeMedianRangeMedianRangeMedianRangeTSH (IU/mL)1.130.01-4.381.060.23-5.192.080.38-6.077.051.63-289T3 (ng/dL)12370.2-23013472.6-24614082.4-27756.335.1-84.6T4 (g/dL)8.263.37-12.19.014.39-13.49.623.60-16.97.663.65-11.7FT4 (ng/dL)0.950.62-1.290.930.46-1.290.990.33-1.311.130.49-1.45
- Table III-3 Correlation a coefficients between fetal thyroid hormones and phthalate monoesters in cord blood samples (n=60)a.a Spearman correlation: **p
-
Figure III-2 Linear correlation between log MBP levels and TSHT4 in cord blood samples (R2=0.081, p=0.028, n=60).
Log MBP-T4-cord
7.66
9.04
5.38
5.44
11.73
5.56
7.23
6.68
6.24
5.89
10.19
8.24
7.67
6.35
7.46
9.09
6.35
7
9.7
8.57
9.01
7.57
10.66
4.16
8.58
8.85
8.56
5.3
10.71
11.36
11.15
10.64
5.83
7.32
5.88
7.88
7.71
7.96
6.83
6
9.53
10.19
8.38
7.3
6.56
7.29
5.27
7.2
8.86
8.29
7.7
8.61
6.26
8.96
8.97
5.65
9.37
5.54
Log MBP (ng/mL)
Thyroxine (T4) (g/dL)
y = -1.4656x + 11.315R2 = 0.055
Log MBP-TSH-cord
0.66181269
0.9380191
0.80955971
0.54157924
1.02938378
0.32221929
1.0211893
0.99078269
0.5390761
0.89597473
0.88705438
1.05115252
1.11327469
1.02653326
0.60959441
1.08062649
1.22427401
1.05918462
0.81090428
0.95808585
1.01452054
0.64542227
1.16106839
0.2121876
0.75511227
0.63042788
0.93043959
0.53402611
0.79588002
0.78175537
0.89762709
1.10311925
0.78532984
0.91115761
1.19617619
0.71096312
0.7176705
0.84818912
1.33984878
0.79448805
0.58771097
1.01828431
1.21404868
0.83058867
0.72181062
1.00475116
0.83122969
0.83122969
1.0733517
0.84509804
1.03941412
0.71600334
0.7363965
0.84010609
1.38632057
0.64836001
1.20384846
0.75358306
Log MBP (ng/mL)
TSH (IU/mL)
y = -0.2124x + 1.3707R2 = 0.060
Log MBP-T4-cord-1
7.66
9.04
5.38
5.44
11.73
5.56
7.23
6.68
6.24
5.89
10.19
8.24
7.67
6.35
7.46
9.09
3.65
6.35
7
9.7
8.57
7.57
9.01
7.57
10.66
4.16
8.58
8.85
8.56
5.3
10.71
11.36
11.15
10.64
5.83
7.32
5.88
7.88
7.71
7.96
6.83
6
9.53
10.19
8.38
7.3
6.56
7.29
5.27
7.2
8.86
8.29
7.7
8.61
6.26
8.96
8.97
5.65
9.37
5.54
Log MBP (ng/mL)
Thyroxine (T4) (g/dL)
Log MBP-TSH-Cord-1
0.66181269
0.9380191
0.80955971
0.54157924
1.02938378
0.32221929
1.0211893
0.99078269
0.5390761
0.89597473
0.88705438
1.05115252
1.11327469
1.02653326
0.60959441
1.08062649
2.4619485
1.22427401
1.05918462
0.81090428
0.95808585
1.21774707
1.01452054
0.64542227
1.16106839
0.2121876
0.75511227
0.63042788
0.93043959
0.53402611
0.79588002
0.78175537
0.89762709
1.10311925
0.78532984
0.91115761
1.19617619
0.71096312
0.7176705
0.84818912
1.33984878
0.79448805
0.58771097
1.01828431
1.21404868
0.83058867
0.72181062
1.00475116
0.83122969
0.83122969
1.0733517
0.84509804
1.03941412
0.71600334
0.7363965
0.84010609
1.38632057
0.64836001
1.20384846
0.75358306
TSH-log
Log MBP (ng/mL)
TSH (IU/mL)
Chart1
35.1594
78.3768
34.701
18.9312
125.511
11.676
75.915
65.3972
21.5904
46.3543
78.5649
92.7
99.5566
67.5005
30.3622
109.4436
106.426
80.22
62.759
77.8156
124.9807
93.1634
33.4594
154.4634
6.7808
48.8202
37.7895
72.9312
18.126
66.9375
68.728
88.085
134.9152
35.563
59.658
92.3748
40.5032
40.2462
56.118
149.3721
37.38
36.8811
106.2817
137.1806
49.421
34.5712
73.7019
35.7306
48.816
104.9024
58.03
84.315
44.772
34.117
62.0032
218.3298
25.1425
149.8263
31.4118
13.9293
TSHxT4
Log MBP in cord blood (ng/mL)
TSH(IU/mL)T4(g/dL)
y = -42.792x + 171.39R2 = 0.081
MBP-TSHxT4
NoLog MBP-cTSHxT4Log TSHxT4
52.7573960335.15941.5460414552
72.624282178.37681.894187528
82.0718820134.7011.5403419903
92.9014583218.93121.2771781436
102.33845649125.5112.0986817898
112.6608654811.6761.0672940863
122.0718820175.9151.8803275964
132.4593924965.39721.8155591543
152.0791812521.59041.3342606885
172.4471580346.35431.6660900271
182.5118833678.56491.8952285621
212.3765769692.71.9670797341
222.4941545999.55661.9980700564
252.3384564967.50051.8293069898
262.434568930.36221.4823332367
282.30319606109.44362.0391903701
302.50242712106.4262.0270477396
312.1139433580.221.9042826576
322.9111576162.7591.7976760149
332.7874604777.81561.8910666704
342.66370093124.98072.0968429528
352.577491893.16341.9692453297
372.873320633.45941.5245181488
382.35410844154.46342.1888255902
402.568201726.78080.831280935
412.021189348.82021.6885995542
442.021189337.78951.5773711457
452.4899584872.93121.8629133594
462.829946718.1261.2583019757
472.117271366.93751.8256694882
492.4517864468.7281.837133706
511.9185545388.0851.9449019587
541.95279244134.91522.1300608815
552.5976951935.5631.5509983898
562.0492180259.6581.7756686898
572.4082399792.37481.9655535111
581.9590413940.50321.6074893365
602.16136840.24621.6047248811
612.5932860756.1181.7491021847
621.8142476149.37212.1742694867
632.8375884437.381.572639297
642.3364597336.88111.5668038657
652.14921911106.28172.0264584924
682.30749604137.18062.137292698
692.6424645249.4211.6939115288
702.3053513734.57121.5387144546
712.0791812573.70191.8674786839
722.5831987735.73061.5530403091
732.3138672248.8161.6885621903
772.65321251104.90242.0207854243
782.5105450158.031.7636525706
792.328379684.3151.9259048443
802.7168377244.7721.6510064951
812.3838153734.1171.5329708355
852.3673559262.00321.7924141041
861.98000337218.32982.3391130169
872.679427925.14251.4004084588
882.52113808149.82632.1755880546
902.557507231.41181.4970928236
921.9642596313.92931.143929292
292.075546961057.4053.0242413597
Data
NoLog MBP-CT4TSH-log
12.757396037.660.66181269
22.62428219.040.9380191
32.071882015.380.80955971
42.901458325.440.54157924
52.3384564911.731.02938378
62.660865485.560.32221929
72.071882017.231.0211893
82.459392496.680.99078269
92.079181256.240.5390761
102.447158035.890.89597473
112.5118833610.190.88705438
142.376576968.241.05115252
152.494154597.671.11327469
182.338456496.351.02653326
192.43456897.460.60959441
212.303196069.091.08062649
222.075546963.652.4619485
232.502427126.351.22427401
242.1139433571.05918462
252.911157619.70.8109042822
262.787460478.570.9580858527
272.663700937.571.2177470741
282.57749189.011.01452054
302.87332067.570.64542227
312.3541084410.661.16106839
332.568201724.160.2121876
342.02118938.580.75511227
372.02118938.850.63042788
382.489958488.560.93043959
392.82994675.30.53402611
402.117271310.710.79588002
422.4517864411.360.78175537
441.9185545311.150.89762709
471.9527924410.641.10311925
482.597695195.830.78532984
492.049218027.320.91115761
502.408239975.881.19617619
511.959041397.880.71096312
532.1613687.710.7176705
542.593286077.960.84818912
551.81424766.831.33984878
562.8375884460.79448805
572.336459739.530.58771097
582.1492191110.191.01828431
612.307496048.381.21404868
622.642464527.30.83058867
632.305351376.560.72181062
642.079181257.291.00475116
652.583198775.270.83122969
662.313867227.20.83122969
702.653212518.861.0733517
712.510545018.290.84509804
722.32837967.71.03941412
732.716837728.610.71600334
742.383815376.260.7363965
782.367355928.960.84010609
791.980003378.971.38632057
802.67942795.650.64836001
812.521138089.371.20384846
832.55750725.540.75358306
Sheet1 (2)
NoLog MBP-CT4TSH-log
12.757396037.660.66181269
22.62428219.040.9380191
32.071882015.380.80955971
42.901458325.440.54157924
52.3384564911.731.02938378
62.660865485.560.32221929
72.071882017.231.0211893
82.459392496.680.99078269
92.079181256.240.5390761
102.447158035.890.89597473
112.5118833610.190.88705438
12...
13...
142.376576968.241.05115252
152.494154597.671.11327469
16...
17...
182.338456496.351.02653326
192.43456897.460.60959441
20...
212.303196069.091.08062649
222.075546963.652.4619485
232.502427126.351.22427401
242.1139433571.05918462
252.911157619.70.81090428
262.787460478.570.95808585
272.663700937.571.21774707
282.57749189.011.01452054
29...
302.87332067.570.64542227
312.3541084410.661.16106839
32...
332.568201724.160.2121876
342.02118938.580.75511227
35...
36...
372.02118938.850.63042788
382.489958488.560.93043959
392.82994675.30.53402611
402.117271310.710.79588002
41.7.280.98227123
422.4517864411.360.78175537
43...
441.9185545311.150.89762709
45...
46...
471.9527924410.641.10311925
482.597695195.830.78532984
492.049218027.320.91115761
502.408239975.881.19617619
511.959041397.880.71096312
52...
532.1613687.710.7176705
542.593286077.960.84818912
551.81424766.831.33984878
562.8375884460.79448805
572.336459739.530.58771097
582.1492191110.191.01828431
59...
60...
612.307496048.381.21404868
622.642464527.30.83058867
632.305351376.560.72181062
642.079181257.291.00475116
652.583198775.270.83122969
662.313867227.20.83122969
67...
68...
69...
702.653212518.861.0733517
712.510545018.290.84509804
722.32837967.71.03941412
732.716837728.610.71600334
742.383815376.260.7363965
75...
76...
77...
782.367355928.960.84010609
791.980003378.971.38632057
802.67942795.650.64836001
812.521138089.371.20384846
82...
832.55750725.540.75358306
84...
851.964259637.370.2764618
86...
87...
Sheet2
Sheet3
-
Table III-4 Multivariate regression between TSH and T4 and their corresponding phthalate monoesters in cord blood (n=60)a
-
*Possible Hypotheses First, we postulated phthalate exposure may affect fetal thyroid function indirectly via decreased thyroid hormones from their mother. Animal studies have shown that in utero exposure to thyroid hormone affects the regulation of the hypothalamus-pituitary-thyroid axis in newborns (Alonso et al., 2007; Piosik et al., 1997). Our previous study showed decreased FT4 and T4 levels with increasing urinary MBP levels in pregnant women during the second trimester (Huang et al., 2007).Second, phthalate monoesters penetrate the human placenta and may have direct effects on fetal thyroid function.Some toxicological studies have shown that certain phthalates, such as DBP and DEHP, are possible thyroxine antagonists that affect the transportation, secretion, and action of thyroid hormones in adult animals (Hinton et al., 1986; Poon et al., 1997; Sugiyama et al., 2005).Although little information is available about phthalate exposure in utero and its effects on fetal thyroid function, some studies (Huang et al., 2007; Meeker et al., 2007) have shown possible negative effects in humans.
-
The study on relationship between urinary phthalate monoesters and house dust exposure in precocious puberty girls
-
Phthalate in house dust(Fromme et al., 2007)
-
*Exposure route of phthalatesINGESTIONSKIN ABSORPTIONINHALATIONnewlatesttips.info pureautismsolutions.com www.tedmiller.com/?cat=572blogs.babycenter.com Children prone to be higher exposedLower body weightHand to mouth behavior (sucking/ mouthing dust)[Schettler, 2006; Sathyanarayana, 2008; Wittassek, 2010]
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Fig 1 The framework of this study
Inclusion criteria:the appearance of secondary sexual characteristics < 8 years oldBreast / Pubic hair development : Tanner breast / pubic hair stage scores Menarche LHRH test: LH, FSH, E2 of plasma (Positive: LH>10mIU/ml)Bone age: advanceAbdominal Ultrasound / MRI Examination
Exclusion criteria:Precocious puberty caused by: Brain tumor/ ovary tumor/Hydrocephalus/ Congenital adrenal hyperplasia (CAH)
Precocious puberty girls (case)
Inclusion criteria:Age from 2 to 8 years non-precocious puberty No secondary sex characteristicsNo breast development No appearance of breast tissue No appearance of pubic hair No menarche
Exclusion criteria:the child who dose not meet any one of the inclusion criteria
Normal girls (control)
Informed consents
Questionnaires
Demographic dataFamily circumstance Medical historyDietary habit
Examination by pediatrician
Collect spot urine sample
LC-MS/MS
MMP, MEP, MBP, MBzP, MEHP, MEOHP, MEHHP
Radioimmunoassay
Kisspeptin 54LH, FSH, E2
Collect blood sample
GC/MS
DMP, DEP, DBP, BBP, DEHP
Collect dust sample (Childs bed, bedroom floor, sofa, living room floor, areas above floor)
Intervention
-
*Sampling strategy for dust- 5 samplesKitchenbathroomParents roomLiving roomPlayroom
Bed (or sofa)FloorUpper floorMajor activity area(Sleeping room)Sample 1Sample 2Sample 5Minor activity area(Parents room, living room, playroom et al.)Sample 3Sample 4
-
Dust collection equipmentUsing aluminum-made collector & cellulose filterCovering with aluminum foil and then sealing by parafilm after collecting enough dust sample
-
*
-
Distributions of phthalate levels in settled dust (n=965) (g/g dust)*N.D.: non-detection
No. of above detection limit (%)No. of missing data (%)Mean (sd)PercentileMin5th25th50th75th95thMaxDMP47 (4.9)90 (9.3)0.8 (4.4)N.D.N.D.N.D.N.D.N.D.2.1119.6DEP67 (6.9)90 (9.3)2.1 (10.7)N.D.N.D.N.D.N.D.N.D.3.1196.0DBP825 (85.5)137 (14.2)46.0 (93.8)N.D.7.114.123.141.8139.31173.2BBzP575 (59.6)98 (10.2)6.8 (17.2)N.D.N.D.N.D.2.86.223.3312.5DEHP865 (89.6)100 (10.4)1761.0 (2346.5)79.0337.5665.41128.91932.54428.724209.7
-
*Worldwide comparison of phthalates concentrationND, no data. a 50th and 95th percentiles. b Mean concentration. c 90th percentile.[Adapted from Kolarik, 2008]
StudyCountryNo.DEHP (mg/g dust)BBzP (mg/g dust)DBP (mg/g dust)50th95th50th95th50th95thPresent studyTAIWAN9651.234.430.0030.020.020.14Kolarik et al. 2008Bulgaria1840.997.980.331.569.8530.8Bornehag et al. 2004Sweden3460.774.070.130.600.150.57Pohner et al. 1997Germany2720.452.00NDNDNDNDOie et al. 1997Norway380.64b0.11b0.10bButte et al. 2001Germany2860.742.600.050.320.050.24Becker et al. 2002Germany1990.421.190.010.210.040.16Clausen et al. 2003Denmark230.862.59NDNDNDNDRudel et al. 2003USA1200.340.85c0.040.28c0.020.04cKersten and Reich 2003Germany650.601.600.020.230.050.18Fromme et al. 2004Germany300.701.540.030.220.060.13Becker et al. 2004Germany2520.511.84NDNDNDND
-
nmean (sd)medianrangeAveragelevels of allsampling siteSampling site at MAJOR roomSampling site at MINOR roombedfloorupper floor levelsbed/sofafloorDMP8750.8 (4.4)0.10.1-119.61900.6 (1.6)0.10.1-18.91830.7 (2.5)0.10.1-32.51291.3 (8.8)0.10.1-119.61860.7 (1.6)0.10.1-12.81870.6 (1.5)0.10.1-14.3DEP8752.1 (10.7)1.00.1-196.01902.3 (8.7)1.00.1-86.61831.7 (7.2)1.00.1-88.21871.2 (3.5)1.00.1-45.41291.0 (1.2)1.00.1-10.61863.8 (19.8)1.00.1-196.0DBP82846.0 (93.8)23.10.1-1173.217825.0 (25.3)17.84.5-212.618367.9 (121.5)33.64.1-984.716845.4 (91.2)20.93.4-834.312838.4 (100.9)17.10.1-956.617150.6 (97.6)30.50.1-1173.2BBzP8676.8 (17.2)2.80.1-312.51865.4 (8.4)2.80.1-82.91839.0 (20.2)4.20.1-185.01833.3 (4.4)2.00.1-40.21295.2 (12.5)2.10.1-120.818610.4 (27.3)3.50.1-312.5DEHP8651761.0 (2346.5)1128.979.0-24209.7187895.4 (509.3)799.579.0-3416.91831757.6 (2339.8)1235.8235.4-23292.31841203.7 (1218.2)807.9119.5-9681.11293196.4 (4360.3)1477.3302.6-24209.71822199.6 (1677.8)1798.2292.1-17218.3
-
*
-
DBP level and wooden floor*Significantly higher DBP concentration was found at major activity room and above floor level when using wooden materials for flooring in the room.
Sampling site*50th (25th-75th)p-valueUsing wooden floorNo wooden floorMajor bed19.1 (12.0-26.6)17.3 (11.6-29.4)0.74Major floor38.1 (25.3-92.5)30.6 (17.9-52.5)0.02Upper floor33.3 (18.6-62.9)18.8 (12.1-31.5)
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Wax using and phthalates concentration*Regular waxing was associated with higher BBzP and DEHP levels in dusts collected from the floor.
Using waxNo using waxpn50th (25th-75th)n50th (25th-75th)BBzP89.0 (6.7-11.3)1233.9 (1.0-8.1)0.04DEHP82209.2 (1575.1-2809.4)1231105.0 (640.5-1743.4)0.01
-
Parental occupations and DEHP levels*DEHP
Sampling site*With parental occupantNo parental occupantpn50th (25th-75th)n50th (25th-75th)Major bed14707.4 (611.9-1233.9)173805.1 (543.8-1131.0)0.64Major floor151379.8 (670.2-1811.2)1681232.3 (736.1-1857.2)0.90Minor bed153030.9 (1409.0-7054.5)1141450.8 (813.5-3019.9)0.02Minor floor151801.3 (1156.0-2582.5)1671795.1 (1183.0-2894.8)0.82Upper floor151058.9 (654.1-2632.1)169798.3 (486.2-1351.2)0.09Average level of five sites152107.6 (1643.4-2456.9)1781446.9 (1054.7-1985.3)0.03
-
*
-
Worldwide comparison of phthalate metabolites concentration*
MMPMEPMBPMBzPMEHPMEHHPMEOHP1932-125.615.558.65.2 8.848.945.23286-11-91.341.439.45.12--CDC, 20053936-111.4585.131.133.44.4123.333.6CDC, 20051632-28163-64.519.214.92.911.4Sathyanarayana et al., 20086Premature newborns----10029623419Calafat et al., 2004906.4-9.2
- Correlation of concentrations between dust-borne phthalates in different place and their corresponding metabolites of childs urine *p
- Correlation of concentrations between dust-borne phthalates and their corresponding metabolites of childs urine *p
- Dietary pattern and phthalates metabolites*p
-
*
-
SubjectsThe present case-control study was carried out from 2006 to 2009.
71 central precocious puberty (CPP) girls were recruited from the policlinic of Pediatric Endocrinology in National Cheng Kung University Hospital and 29 normal similar age-range girls were recruited as control group from elementary school or kindergarten.
-
Table The levels of seven PAEs metabolite in case and control (g/g-creatinine)Wilcoxon rank sum test; Geometric mean (Range) The analytical results of urine samples
Case
(N=71)
Control
(N=29)
P-value
MMP
7.74 (0.83-64.3)
5.66 (0.94-31.3)
0.168
MEP
26.9 (1.21-379)
12.0 (1.06-337)
0.001
MBP
93.6 (22.3-451)
77.9 (20.5-275)
0.230
MBzP
7.72 (1.14-84.3)
4.44 (0.95-50.4)
0.007
MEHP
12.8 (4.03-69.3)
9.02 (3.07-29.6)
0.048
Case
(N=39)
Control
(N=9)
MEHHP
65.5 (24.5-291)
31.1 (12.3-202)
0.002
MEOHP
60.8 (21.9-244)
29.1 (13.8-177)
0.001
-
(g/L)
MMP
MEP
MBP
MBzP
MEHP
MEHHP
MEOHP
70
2.6-11.5
5.57
18.54
67.00
5.60
8.77
64.05
59.98
29
2.1-8.4
3.26
6.90
44.78
2.55
5.33
27.53
25.73
99
2.1-11.5
4.76
13.88
59.54
4.45
7.58
55.05
51.01
328
6-11
-
91.3
41.4
39.4
5.12
-
-
CDC, 2005
393
6-11
1.45
85.1
31.1
33.4
4.41
23.3
33.6
CDC, 2005
163
2-28
163
-
64.5
19.2
14.9
2.9
11.4
Sathyanarayana et al., 2008
6
Premature newborns
-
-
-
-
100
2962
3419
Calafat et al., 2004
90
6.4-9.2
-
(mg/kg)
DMP
DEP
DBP
BBP
DEHP
100
0.12
(0.12-12.1)
1.00 (0.08-124)
30.2 (6.13-1173)
3.81
(1.00-313)
1521 (374-7436)
101
0.12 (0.12-32.5)
1.00 (0.08-88.2)
34.2 (4.67-985)
3.50
(1.00-185)
1229 (294-23292)
100
0.12 (0.12-2.12)
1.00
(0.08-86.6)
16.2 (4.49-153)
2.50
(1.00-82.9)
658 (253-3417)
101
0.12 (0.12-12.6)
1.00 (0.08-45.4)
21.9 (3.39-834)
2.13
(1.00-14.7)
905 (162-9681)
46
0.12 (0.12-5.34)
1.00 (0.08-10.6)
18.3 (4.99-320)
2.59
(1.00-24.0)
1411 (303-23829)
38
-
10
100
110
640
ie et al., 1997
23
-
-
-
-
858
Clausen et al.,2003
30
1.5
29.7
47.0
29.7
(5-816)
703
(231-1763)
Fromme et al., 2004
120
-
4.98 (ND-111)
20.1 (ND-352)
45.5 (3.87-1310)
340 (16.7-7700)
Rudel et al., 2003
65
-
-
47
19
600
Kersten and Reich, 2003
346
-
0
(0-2425)
150
(0-5446)
135 (0-45549)
770
(0-40459)
Bornehag et. al., 2005
()
-
ResultsTable The kisspeptin-54 levels, basal hormones and physical characteristics from part of precocious puberty and normal girls in this study.
Normal girls
(N=11)
Precocious puberty girls (N=26)
P-value
LHRH test positive (N=11)
Treatment with Leuplin; Menarche (N=15)
Kisspeptin-54* (pmol/l)
1.95 (1.69-2.18)
2.14 (1.71-2.61)
2.29 (1.98-2.86)
0.02
-
Fig The association between Kisspeptin-54 and ln MBP-Cr (g/g-Cr).R2= 0.288;p= 0.001Results
-
Results (Intervention strategies):
PVC
()
-
creatinine()(ng/mL)
P&
Pre-post MEP
19.2
(2.04-622)
71.5
(10.3-282)
-
-
-
-
0.08#
Pre-post MBP
-
-
130
(16.6-846)
16.8
(1.70-150)
114
(16.5-846)
19.2
(1.7-163)
0.01*,1 0.018*,2
Pre-post MEHHP
-
-
-
-
73.6
(5.98-895)
20.3
(7.05-108)
0.042*
Pre-post MEOHP
-
-
-
-
27.1
(0.71-483)
8.21
(1.51-53.4)
0.079#
Pre-post MECCP
-
-
-
-
93.7
(21.6-722)
21.1
(5.93-27.8)
0.013*
&: Wilcoxon Rank Sum Test#: p
-
creatinine() (ug/g-creatinine)
P&
Pre-post MMP
-
-
3.44
(0.02-12.4)
1.81
(0.22-5.38)
-
-
0.079#
Pre-post MEP
-
-
-
-
38.5
(0.51-450)
5.71
(1.14-61.0)
0.072#
Pre-post MBP
53.5
(7.15-247)
16.6
(3.21-158)
-
-
-
-
0.066#
&: Wilcoxon Rank Sum Test
#: p
-
DEHPDBPBBzPDEHPMBPMEHHPMEOHPDBPDEHP/MEP MEHPMEHHPMEOHPDEPDEHPDEPDEHP()MBPkisspeptinDBPkisspeptin
-
?
-
AcknowledgementsWe are grateful for the financial support of Taiwan National Science Council and deeply appreciative of the subjects participated in this study.Livestock Research Institute, Council of AgricultureMain-Lian Lee, Ming-Chih TengDepartment of PediatricsYen-Yin Chou, Shio-Jean Lin Department of Obstetrics and GynecologyPao-Lin Kao, and other gynecologistsResearch Center of Environmental Trace Toxic SubstancesAll stuffs
***Phthalates are widely used as plasticizer to increase the polymers flexibility , elongation or ease of processing.The mostly commercial used phthalates including these five types.Due to their lipophilic property, they are easily to bioaccumulate in human being.They will become metabolites in our body including these types, and DEHP will have second metabolites.**This slide show the application of phthalates.They are widely used in childrens toys, personal care products, medical devices, building materials, and food packaging.Almost everything in our daily life. **This slide show the application of phthalates.They are widely used in childrens toys, personal care products, medical devices, building materials, and food packaging.Almost everything in our daily life. *General population may exposed to phthalates via food intake, inhalation, dermal contact with cosmetics and personal care products.
*************************** phthalate **Logstics*********