Chemosphere 87 (2012) 97–104

Contents lists available at SciVerse ScienceDirect

Chemosphere

journal homepage: www.elsevier .com/locate /chemosphere

Comparisons of polybrominated diphenyl ethers levels in paired South Koreancord blood, maternal blood, and breast milk samples

Tae Hyung Kim a,1, Du Yeon Bang b,1, Hyun Jung Lim a, A. Jin Won a, Mee Young Ahn a, Nabanita Patra a,Ki Kyung Chung c, Seung Jun Kwack c, Kui Lea Park c, Soon Young Han c, Wahn Soo Choi e, Jung Yeol Han d,Byung Mu Lee b, Jeong-Eun Oh f, Jeong-Hyun Yoon a, Jaewon Lee a, Hyung Sik Kim a,⇑a Laboratory of Molecular Toxicology, MRC Center and College of Pharmacy, Pusan National University, San 30, Jangjeon-dong, Geumjeung-gu, Busan 609-735, South Koreab Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Chunchun-dong 300, Changan-ku, Gyeonggi-do, Suwon 440-746, South Koreac National Institute of Food and Drug Safety Evaluation, Korea Food and Drug Administration, Seoul, South Koread The Korean Motherisk Program, Cheil Hospital & Women’s Health-care Center, Kwandong University, College of Medicine, Seoul, South Koreae Department of Immunology and Physiology, College of Medicine, Konkuk University, Chungju, South Koreaf Department of Civil and Environmental Engineering, Pusan National University, San 30, Jangjeon-dong, Geumjeong-gu, Busan 609-735, South Korea

a r t i c l e i n f o a b s t r a c t

Article history:Received 20 February 2011Received in revised form 24 November 2011Accepted 28 November 2011Available online 9 January 2012

Keywords:Polybrominated diphenyl ethersCord bloodMaternal bloodBreast milkThyroid hormones

0045-6535/$ - see front matter � 2011 Elsevier Ltd. Adoi:10.1016/j.chemosphere.2011.11.074

Abbreviations: BDE, brominated diphenyl ether; Pnyl ethers; SPE, solid phase extraction; T4, thyroxinhormone.⇑ Corresponding author. Tel.: +82 51 510 2816; fax

E-mail address: hkims@pusan.ac.kr (H.S. Kim).1 These authors contributed equally to this work.

Polybrominated diphenyl ethers (PBDEs), commonly used flame retardants, have been reported as poten-tial endocrine disruptor and neurodevelopmental toxicants, thus giving rise to the public health concern.The goal of this study was to investigate the relationship between umbilical cord blood, maternal blood,and breast milk concentrations of PBDEs in South Korean. We assessed PBDE levels in paired samples ofumbilical cord blood, maternal blood, and breast milk. The levels of seven PBDE congeners were mea-sured in 21 paired samples collected from the Cheil Woman’s Hospital (Seoul, Korea) in 2008. We alsomeasured thyroid hormones levels in maternal and cord blood to assess the association between PBDEsexposure and thyroid hormone levels. However, there was no correlation between serum thyroxin (T4)and total PBDEs concentrations. The total PBDEs concentrations in the umbilical cord blood, maternalblood, and breast milk were 10.7 ± 5.1 ng g�1 lipid, 7.7 ± 4.2 ng g�1 lipid, and 3.0 ± 1.8 ng g�1 lipid, respec-tively. The ranges of total PBDE concentrations observed were 2.28–30.94 ng g�1 lipid in umbilical cordblood, 1.8–17.66 ng g�1 lipid in maternal blood, and 1.08–8.66 ng g�1 lipid in breast milk. BDE-47 (45–73% of total PBDEs) was observed to be present dominantly in all samples, followed by BDE-153. A strongcorrelation was found for major BDE-congeners between breast milk and cord blood or maternal bloodand cord blood samples. The measurement of PBDEs concentrations in maternal blood or breast milkmay help to determine the concentration of PBDEs in infant.

� 2011 Elsevier Ltd. All rights reserved.

1. Introduction

Polybrominated diphenyl ethers (PBDEs) are widely used asflame retardants in electronic appliances, paints, textiles, and fur-nishings. PBDEs are now viewed as ubiquitous environmental pol-lutants due to their high levels of production and their persistenceand bioaccumulation in the environment (de Wit et al., 2010;Covaci et al., 2011). The presence of PBDEs has been extensivelyinvestigated in various foods and human tissues (Lorber, 2008;Frederiksen et al., 2009). In Asian countries, including South Korea,

ll rights reserved.

BDEs, polybrominated diphe-e; TSH, thyroid stimulating

: +82 51 513 6754.

large quantities of PBDEs are used; South Koreans rank second toNorth Americans with regard to PBDE levels. Recently, the manu-facture, distribution, and processing of products using penta- andocta-BDE congeners were prohibited in the European Union (EU),Canada, USA, and Asian countries. Deca-BDE is the only PBDE thatis still manufactured and used worldwide including South Korea,with the exception of Sweden and Maine, USA (KEI, 2001). How-ever, tetra-, penta-, and hexa-BDE mixtures are still detected inthe environment because deca-BDE (BDE-209) can be broken downinto the lower brominated congeners (Law et al., 2006; Chen et al.,2007). Deca-BDE is the only PBDE that is still manufactured andused in South Korea and other countries (KEI, 2001).

Recent studies have shown that PBDEs are detected in humanmaternal blood, breast milk, and adipose tissue samples (Fosteret al., 2011; Frederiksen et al., 2010; Petreas et al., 2011). The levelsof human exposure to PBDEs from in Asia–Pacific exhibit an

Table 1Physical characteristics of study subjects.

Subject characteristics (n = 21) Mean ± SD Median Range

MaternalAge in years 30.3 ± 3.87 29 25–41Pre-pregnancy body weight (kg) 51.7 ± 7.98 51 41–72Post-pregnancy body weight (kg) 68.6 ± 13.9 66 50–96Height (cm) 161 ± 6.24 160 150–171Pre-pregnancy BMI (kg m�2) 20.9 ± 2.17 20.1 19.4–25.7Gestation period (weeks) 36.9 ± 2.1 38.5 35.2–41.5

InfantsBody weight (g) 2990 ± 752 3041 1575–4550Length (cm) 46.9 ± 3.4 48.7 31.5–52.7BMI (kg m�2) 13.3 ± 2.84 14.5 11.4–14.9Head circumference (cm) 32.7 ± 3.98 33.8 30.3–37.5

98 T.H. Kim et al. / Chemosphere 87 (2012) 97–104

increasing trend for the past 30 years (Tanabe et al., 2008; Linder-holm et al., 2010); however, the total PBDE levels in Swedish breastmilk samples have recently been reported to be decreasing(Fängström et al., 2008). The total PBDEs concentrations in bloodand breast milk were higher in America when compared to thoseof European (Wilford et al., 2005; Roosens et al., 2010). A previousstudy reported that total PBDEs concentrations in breast milk,including BDE-209, ranged from 26.4 to 586 ng g�1 lipid in SouthKorea (Kang et al., 2010). Another study reported the total PBDEsconcentration calculated from the 13 most common congeners(BDE-15, BDE-28/33, BDE-47, BDE-49, BDE-66, BDE-85, BDE-99,BDE-100, BDE-140, BDE-153, BDE-154, and BDE-183) in both incin-erator workers and the general population was 16.8 ± 7.5 ng g�1 li-pid, indicating somewhat higher than those has been observed inother countries (Lee et al., 2007). Individual fetal blood PBDEs con-centrations are similar to the corresponding maternal concentra-tions, implying that measurement of maternal PBDE blood levelswould be useful in predicting fetal exposure (Mazdai et al.,2003). Recently, the assessment of fetal exposure to PBDEs hasbeen examined by measuring their concentrations from umbilicalcord blood (Herbstman et al., 2007; Antignac et al., 2009). How-ever, there have been no studies of PBDE concentrations in pairedsamples of maternal, cord blood, and breast milk samples. The aimof this study was to investigate the correlations of PBDE concentra-tions between cord blood, maternal blood, and breast milk usingpaired samples. In addition, the relationship between PBDE con-centrations and the level of thyroid hormones was examined aswell.

2. Materials and methods

2.1. Subjects

A total of 21 healthy pregnant women between the ages of 25and 41 years participated in this study. Study participation was vol-untary. Blood samples were donated from mothers following cesar-ean section at the Cheil Woman’s Hospital in Seoul, South Korea. Asyringe was used to obtain blood from the umbilical cord vein afterdelivery. Baseline physical characteristics (e.g., birth weight andsex) of infants were also recorded at the time of birth. Maternalblood samples were collected into a heparin-containing blood col-lection tube after delivery. Serum was separated from whole bloodby centrifugation and then transferred to glass bottles. The serumsamples were coded and stored at�20 �C until analysis. Breast milkwas collected using a breast milk pump at 7 d after delivery andstored in glass containers at �20 �C until analysis. Basic participantinformation, including smoking and drinking habits, age, gender,and present and previous occupations, was obtained from self-administered questionnaires at the time of enrollment. The samplecollection procedure was approved by the Maternal and Fetal Re-search Committee (CGH-IRB-2008-13) at the Cheil Woman’s Hospi-tal. Informed consent was obtained from all participants.

In this study, a total of 21 paired samples were analyzed forPBDEs concentration. Table 1 summarizes the physical characteris-tics of the study subjects. The mean infant body weight, height, andhead circumference were 2990 ± 752 g (range, 1575–4550 g),46.9 ± 3.4 cm (range, 31.5–52.7 cm), and 32.7 ± 4.0 cm (range,30.3–37.5 cm), respectively. No birth defects were documented.

2.2. Reagents and materials

The PBDE standards that contain 2,4,40-tribromodiphenyl ether(BDE-28), 2,20,4,40-tetrabromodiphenyl ether (BDE-47), 2,20,4,40,5-pentabromodiphenyl ether (BDE-99), 2,20,4,40,6-pentabromodiphe-nyl ether (BDE-100), 2,20,4,40,5,50-hexabromodiphenyl ether

(BDE-153), 2,20,4,40,5,60-hexabromodiphenyl ether (BDE-154) and2,20,3,4,40,50,6-heptabromodiphenyl ether (BDE-183) werepurchased from Wellington Laboratories (Guelph, ON, Canada). Amixture of 13C-labeled BDE-28, BDE-47, BDE-99, BDE-100, BDE-153, BDE-154 and BDE-183 was purchased from Wellington Labo-ratories and used as internal standards (MBDE-MXFS, WellingtonLaboratories). 13C-labeled BDE-138 (MBDE-138, Wellington Labo-ratories) was used as a recovery standard. Acetone, n-hexane,dichloromethane (DCM), methanol (MeOH), and nonane (residuepesticide grade) were purchased from J.T. Baker Co. (Phillipsburg,NY, USA). Anhydrous sodium sulfate (Na2SO4) was purchased fromWako Co. (Tokyo, Japan). High purity sulfuric acid (98%), formicacid (99%) and silica gel were purchased from Merck (Darmstadt,Germany). All other chemicals were purchased from Fluka Chemi-cal Corp. (Ronkonkoma, NY, USA). Silica gel was heated for at least19 h at 130 �C and the acidified silica gel (2 g of 44% sulfuric acidimpregnated, w/w) was prepared. All glassware was sonicatedwith detergent, rinsed with de-ionized water, and dried under ahood at room temperature. After dryness of glassware, all glass-ware was baked overnight at 400 �C. Before use, sonicated glass-ware was rinsed with acetone and hexane. A Visiprep™ SPEVacuum manifold (Supelco Inc., Bellefonte, PA, USA) was used forextraction and clean-up procedures.

2.3. Sample extraction and clean-up procedures

PBDE extraction from blood serum was performed according tothe modified method of Mazdai et al. (2003). All samples werethawed and homogenized. Internal standards (0.1 ng lL�1 mixtureof 13C-labeled BDE-99, BDE-100, BDE-153, BDE-154, and BDE-183)were added to a sample vial and the solvent was evaporated withthe cap off. The internal standards were re-dissolved in 100 lL ace-tone, and 2 mL cord blood sample was added. Then, the sampleswere vortexed and sonicated for 20 min at low intensity. Thespiked cord blood samples were equilibrated overnight at 4 �C.Next, 2 mL formic acid and 3 mL de-ionized water were added tothe samples, and the samples were equilibrated with ultrasonica-tion for 20 min. Before sample loading, the HLB cartridges wereactivated with MeOH and water. Samples were loaded at a positivepressure of 2–4 psi. The HLB cartridges were then rinsed with 1 mLdistilled water, and the pressure was adjusted to 6–8 psi to removewater from the cartridges. The sorbent bed was dried out thor-oughly at <20 psi positive pressure under nitrogen for 10 minand again by centrifugation (4000 rpm) for 20 min. The cartridgeswere eluted three times with 3 mL DCM using a Visiprep™ SPEVacuum manifold. The eluant was concentrated to �1 mL undera gentle nitrogen stream. An empty 6 mL cartridge was filled with2 g acidified silica, 200 mg activated silica, and 500 mg Na2SO4

(bottom to top) and was prewashed with 5 mL DCM. The concen-trated eluate was loaded onto the top of the clean-up cartridge

Table 2Concentration of PBDE congeners in fetal cord blood, maternal blood, and breast milk samples.

Congeners(ng g�1

lipid)

Cord blood (n = 21) Maternal blood (n = 21) Breast milk (n = 21)

Mean ± SD Median Range Positive(%)

Mean ± SD Median Range Positive(%)

Mean ± SD Median Range Positive(%)

Lipid (%) 0.12 ± 0.14 0.1 0.04–0.21 100 0.56 ± 0.28 0.52 0.27–1.24 100 3.42 ± 2.84 3.59 1.46–6.21 100BDE-28 0.33 ± 0.64 0.03 <LOQ–2.28 78.2 0.35 ± 0.31 0.26 <LOQ–

1.3756.2 0.31 ± 0.25 0.30 <LOQ–1.13 95.2

BDE-47 7.88 ± 3.90 7.65 2.06 ± 18.25 100 3.50 ± 2.25 3.21 0.97–6.52 100 1.23 ± 0.88 1.01 0.371�3.61 100BDE-99 0.42 ± 0.58 0.38 <LOQ–1.93 84.2 1.80 ± 0.91 1.65 <LOQ–

3.2774.5 0.40 ± 0.25 0.31 <LOQ–1.16 95.2

BDE-100 0.28 ± 0.41 0.15 <LOQ–1.26 45.3 0.42 ± 0.89 0.15 <LOQ–4.02

46.3 0.32 ± 0.24 0.25 <LOQ–1.05 85.7

BDE-153 1.63 ± 1.56 1.68 <LOQ–5.12 100 1.42 ± 0.79 1.66 0.52–3.96 100 0.71 ± 0.43 0.6 0.31–2.25 100BDE-154 0.21 ± 0.34 0.05 <LOQ–1.33 20.1 0.20 ± 0.38 0.05 <LOQ–

1.3215.8 <LOQ <LOQ 0

BDE-183 <LOQ <LOQ 0 <LOQ <LOQ <LOQ 0 <LOQ <LOQ 0RPBDEs 10.7 ± 5.13 12.04 2.28–30.94 100 7.7 ± 4.2 7.81 1.8–17.66 100 3.0 ± 1.8 2.51 1.08–8.66 100

The total concentration of PBDEs was calculated on the basis of the lipid percentage.Values below the limit of quantification (LOQ) were set to 1/2 LOQ.RPBDEs are sum of seven major BDE congeners.

Fig. 1. Distribution of polybrominated diphenyl ethers (PBDEs) congeners in paired umbilical cord blood, maternal blood, and breast milk samples (N = 21 samples). Congenerconcentrations are presented as the mean percentage of the RPBDEs concentrations.

T.H. Kim et al. / Chemosphere 87 (2012) 97–104 99

and eluted with 8 mL DCM. The final elute was concentrated undera gentle nitrogen stream at room temperature until dryness, re-sol-ubilized in 30 lL of nonane and transferred to an amber vial. Thefinal sample volume was adjusted for analysis to 50 lL with recov-ery standard. Breast milk samples (2 mL) were processed by usingsame procedure of cord blood samples.

2.4. Quality assurance and quality control

Multi-level calibration curves that included the total concentra-tion range found in samples were created for quantification. Ana-lytic identification was based on relative retention times and themass detector. The limit of quantification (LOQ) was set to a sig-nal-to-noise ratio of 3. The LOQs method was used to determineaverage analyte recoveries for PBDEs in the umbilical cord blood,maternal blood and breast milk samples. Procedure blanks (dis-tilled water) were analyzed concurrently with samples to checkblank contamination during sample preparation. None of the targetPBDEs was detected in the procedure blanks. To check instrumen-tal stability, a quality control standard was analyzed after every tensamples.

2.5. PBDE analysis

The concentration of each PBDE congener was determined by agas chromatograph interfaced with a high-resolution mass spec-trometer (GC, Agilent 6890 series, Agilent Technologies, CA, USA

and HRMS, JMS-800D, Tokyo, Japan). Gas chromatographic separa-tion was carried out using a fused silica column (DB-5HT; 15 m by0.25 mm i.d.; film thickness, 0.10 lm; J&W Scientific, CA, USA).Injection was performed in the splitless mode at 280 �C with a con-stant gas (helium) flow of 1.0 mL min�1. The GC oven temperatureprogram was set as follows: 140 �C for 1 min, increase to 320 �C at10 �C min�1, and hold at 320 �C for 1 min. The LOQs for each con-gener varied from 0.1 to 0.5 ng g�1 lipid. The average internal stan-dard recovery was >75%. Procedural blanks were included in eachsample batch. The values obtained from the procedural blankswere subtracted from the sample values.

2.6. Thyroid hormone and lipid measurements

Serum thyroxine (T4) and thyroid stimulating hormone (TSH)were measured in the Cheil Woman’s Hospital (Seoul, Korea) usingradioimmunoassay kits (Diagnostic Products Corp., Los Angeles,CA). Total cholesterol and triglycerides were enzymatically quanti-fied in the Cheil Woman’s Hospital using separate serum aliquots.Total lipids in blood samples were calculated as the sum of totalcholesterol and triglycerides but did not include phospholipids(Schecter et al., 2010).

2.7. Statistical analysis

The PBDEs concentrations in human samples are presented asthe thematic means, medians, and range. Values below the limit

Fig. 2. Total polybrominated diphenyl ethers (PBDEs) concentrations in paired umbilical cord blood, maternal blood, and breast milk samples. Individual PBDE concentrationis indicated as the mean percentage of the RPBDE concentration.

100 T.H. Kim et al. / Chemosphere 87 (2012) 97–104

of quantification (LOQ) were set to 1/2 LOQ for statistical analysis.All statistical analyses were completed using SPSS version 13.0 J(SPSS Inc., Chicago, IL, USA). The Spearman’s rank correlation coef-ficient was used to assess the correlation between serum thyroidhormone levels and PBDE concentrations.

3. Results and discussion

3.1. PBDE concentrations in umbilical cord blood, maternal blood, andbreast milk

The mean congener concentrations of BDE-28, BDE-47, BDE-99,BDE-100, BDE-153, BDE-154, BDE-183, and the total PBDEs(sumPBDEs) are presented in Table 2. The total PBDE concentra-tions of seven congeners were 10.7 ± 5.13 ng g�1 lipid in cordblood, 7.7 ± 4.2 ng g�1 lipid in maternal blood, and 3.0 ± 1.8 ng g�1

lipid in breast milk. The only six main BDE congeners (BDE-28, -47,-99, -100, -153, and -154) were detected in both cord and maternalblood samples. The total PBDE concentrations in cord blood rangedfrom 2.28 to 30.94 ng g�1 lipid. The total PBDE concentrations inmaternal blood ranged from 1.8 to 17.66 ng g�1 lipid. The totalconcentration of PBDEs in cord and maternal blood were compara-ble to those measured in blood samples from South Korean incin-erator workers (Lee et al., 2007). Based on these results, the totalPBDEs concentration in cord blood samples (median value = 12.0ng g�1 lipid) is lower in South Korea than in the USA (39 ng g�1

lipid; Mazdai et al., 2003) but higher than in Sweden (1.7 ng g�1 li-pid; Guvenius et al., 2003), Spain (4.3 ng g�1 lipid; Gómara et al.,2007), and Belgium (1.6–6.5 ng g�1 lipid; Roosens et al., 2010).

In general, BDE-47, BDE-99, and BDE-153 are globally detectedmajor PBDE congeners in the human blood. The above data showthat human exposure to PBDEs in South Korea is similar to or

greater than that in other countries. However, previous study indi-cated that the PBDEs levels (16.8 ± 7.5 ng g�1 lipid) in the blood ofworkers at municipal waste incinerators in South Korea were muchhigher than those reported in European countries. BDE-183 con-centrations, in particular, were significantly higher in the bloodof workers than those in the general population (Lee et al., 2007).Although the use of penta- and octa-BDE has been banned in allconsumer products from South Korean since 2006, the level ofenvironmental contamination of these congeners is higher thanin Europe, where the prohibition of penta-, octa-, and deca-BDEuse has consequently led to the decrease in both environmentaland biological levels of PBDEs (Hong et al., 2009).

In the case of breast milk, the five major BDE congeners (BDE-28, -47, -99, -100, and -153) were identified, with total cumulatedconcentrations ranging from 1.08 to 8.66 ng g�1 lipid. Similar tomaternal blood, BDE-47 and BDE-153 were abundant in breastmilk, whereas BDE-154 and BDE-183 were less than limit of quan-tification (LOQ) (Table 2). One previous study reported that PBDEsconcentrations (six congeners including BDE-28, -47, -99, -100, -153, and -154) detected in the breast milk of Korean, Japan, andChina were 3.7 ng g�1 lipid, 1.7 ng g�1 lipid, and 1.9 ng g�1 lipid,respectively (Haraguchi et al., 2009). The observed concentrationof total PBDEs (five major BDE congeners) in our study was3.0 ± 1.8 ng g�1 lipid (median = 2.5) and the levels in PBDEs de-tected from breast milk were lower than previously reported data(Haraguchi et al., 2009).

3.2. Congener profiles of PBDEs

We compared the distribution of each BDE congener in pairedsamples. As shown in Fig. 1, BDE-47 and BDE-153 were found tobe the most abundant congeners in the majority of the paired

Fig. 3. The relationships between maternal blood and cord blood for concentrations of polybrominated diphenyl ethers (PBDEs) congeners. The Spearman’s rank correlationcoefficient was used to assess correlation between maternal blood and cord blood for concentrations of various matrices.

Fig. 4. The relationships between breast milk and cord blood for concentrations of polybrominated diphenyl ethers (PBDEs) congeners. The Spearman’s rank correlationcoefficient was used to assess correlation between maternal blood and cord blood for concentrations of various matrices.

T.H. Kim et al. / Chemosphere 87 (2012) 97–104 101

Table 3Thyroid hormone and lipid concentrations in maternal and cord blood samples.

Subject characteristics (n = 21) Mean ± SD Median Range

MaternalTSH (lU mL�1) 1.7 ± 1.15 2 0.1–4.9Free T4 (pmol L�1) 12.7 ± 3.48 10 8.7–21T3 (pmol L�1) 154.5 ± 28.5 151 126–26Total cholesterol (mg dL�1) 269.5 ± 49.1 265 173–429Triglyceride (mg dL�1) 289.7 ± 129.2 270 117–394

InfantsTSH (lU mL�1) 11.4 ± 9.8 8.6 3.2–30.1Free T4 (pmol L�1) 16.7 ± 4.1 16 1.7–22T3 (pmol L�1) 64.7 ± 8.3 62 54–86Total cholesterol (mg dL�1) 69 ± 16 68 42–132Triglyceride (mg dL�1) 23.3 ± 12 42 7–79

102 T.H. Kim et al. / Chemosphere 87 (2012) 97–104

human samples, and these congeners were also detected in allindividual samples. As a percentage of the total PBDE concentra-tion in the cord blood, they accounted for 74% and 18% of thePBDEs (seven congeners), respectively. In the maternal blood,BDE-47 and BDE-99 accounted for 46% and 26% of PBDEs, respec-tively. In the breast milk, the PBDE concentrations were as follows:BDE-47 (42%) > BDE-153 (23%) > BDE-99 (13%) > BDE-100(12%) > BDE-28 (11%). These results are very similar to previouslyreported data that found the most common congeners detectedin Japanese human blood (Takasuga et al., 2004) and breast milk(Inoue et al., 2006) were BDE-47 and BDE-153. The reason thatBDE-47 were detected abundantly in human samples seems tobe due to its long half-life compared to those of other congeners,making it remain in the food chain for a long time.

Several studies have examined the internal PBDEs exposure onpaired maternal and umbilical cord blood samples and the levels oftotal PBDEs detected in maternal and cord blood samples show asimilar pattern (Foster et al., 2011). However, a few studies havereported a shift in congener composition from maternal blood toumbilical cord blood (Guvenius et al., 2003; Bi et al., 2006). Mater-nal blood primarily contains BDE-47 and BDE-153, while theumbilical cord blood contains a highly increased amount of BDE-47. Although the levels observed in fetal and maternal plasma werehighly correlated, the placental transport of PBDE congeners seemsto be decreased as the degree of bromination. We also analyzed thedistribution patterns of total PBDEs in cord-maternal blood pairedindividual samples (Fig. 2). The PBDE congener profiles in thematernal blood and breast milk were correlated, whereas no signif-icant correlations were found between the cord blood and breastmilk samples. In contrast to previous data, BDE-183 was not de-tected in our paired samples. BDE-183 was highly detected inoccupationally exposed workers (Sjödin et al., 1999; Kim et al.,2005). BDE-183 has a rather short apparent half-life in humans

Fig. 5. The correlation coefficient of the polybrominated diphenyl ethers (PBDEs) conconcentrations were determined and plotted against the corresponding levels of total PBsamples and plotted against the corresponding levels of total PPBDEs in each sample. N

(Thuresson et al., 2006) and the subjects in this study were fromthe general population, suggesting they were not directly exposedto PBDEs. This finding is in agreement with other studies indicatingthat the most pronounced biomagnification is for tetra- to hexa-BDEs, with lower levels of bioaccumulation of the higher bromi-nated (hepta- to deca-BDEs) congeners (Yogui and Sericano, 2009).

In this study, a linear regression was used to evaluate the rela-tionships between maternal blood and cord blood or breast milkand cord blood for the concentrations of specific BDE-congener.We found strong positive correlations between maternal bloodand cord blood samples for total PBDE (r2 = 0.3317, p < 0.05),BDE-28 (r2 = 0.805, p < 0.05), BDE-100 (r2 = 0.525, p < 0.05)(Fig. 3), indicating increasing concentrations in umbilical cordblood with increasing concentrations in maternal blood. Statisti-cally significant correlations were found for BDE-28 (r2 = 0.778,p < 0.05) and BDE-100 (r2 = 0.815, p < 0.05) between breast milkand umbilical cord blood samples. However, no statistically signif-icant correlations were observed between breast milk and umbili-cal cord blood for BDE-47 and BDE-99 (Fig. 4).

3.3. Correlation of PBDEs concentration with thyroid hormone

In this study, thyroid hormones were measured in both mater-nal and cord blood samples. As shown in Table 3, the serum TSHconcentrations (1.7 ± 1.15 lU mL�1) in the maternal blood weresignificantly lower than in the infant blood samples(11.4 ± 9.8 lU mL�1). However, the maternal T3 concentrations(154.5 ± 28.5 pmol mL�1) were significantly higher than those ininfants (64.7 ± 8.3 pmol mL�1). Total cholesterol and triglyceridesare often used to normalize to lipid content. As expected, the lipidcontent of the two types of plasma were very different, showingconsiderably lower levels in the umbilical cord blood when com-pared to the maternal blood. The absolute total lipid levels in thecord blood were approximately 20% that of maternal blood(Table 3).

PBDEs are structurally similar to thyroid hormones, and thus itwas postulated that PBDEs could be associated with the abnormalthyroid hormone levels. In animal studies, a significant correlationbetween high PBDE concentrations in fetal blood and the levels ofthyroid hormones has been observed (Lema et al., 2008; Tsenget al., 2008). In addition, since thyroid hormone play critical rolesin regulating neurogenesis in the brain during developmentalstages of fetus, PBDEs could induce neurotoxicity by altering thy-roid hormone levels. Previous study showed that neonatal and fetalPBDE exposure in mice exerted a permanent effect on spontaneousbehavior, learning, and memory (Eriksson et al., 2002). By contrast,in humans, there is inconclusive data regarding the association be-tween PBDEs exposure and thyroid hormone levels. Some studiesshowed that thyroid hormone concentrations were clearly

gener levels and thyroid hormone concentrations in the cord blood. (A) Free T4DEs in each sample. (B) The TSH concentrations were determined in the cord blood= 21.

T.H. Kim et al. / Chemosphere 87 (2012) 97–104 103

associated with total PBDEs levels in human blood (Hagmar et al.,2001; Zhou et al., 2002; Julander et al., 2005), whereas other studyreported no correlation between serum PBDEs and thyroid hor-mone concentrations (Herbstman et al., 2008). In this study, a lin-ear regression was used to evaluate the relationship between PBDEconcentrations and thyroid hormone levels (TSH and free T4) in thecord blood and maternal blood samples. Neither of these relation-ships was statistically significant, and this could be attributed tothat sample size was too small to determine a significant finding(Fig. 5).

4. Conclusions

In conclusion, PBDE concentrations were determined in umbil-ical cord blood, breast milk, and maternal blood samples obtainedfrom South Korean participants. The results suggest that PBDE con-centrations are higher or similar to ranges reported in the EU. It isunclear whether the current PBDE concentrations in human bio-logical samples have an adverse effect on human health. Becausenearly all individuals have been exposed to at least low PBDE lev-els, health impact studies should include an assessment at the pop-ulation level. Further studies measuring various PBDEconcentrations in dairy products, meat, seafood, fruits, vegetables,air or drinking water are necessary to assess pathways of humanexposure to PBDEs.

Acknowledgments

This work was supported by the National Toxicology Program(08162NTP559) fund from the Korea Food & Drug Administrationand National Research Foundation of Korea (NRF) grants fundedby the Korea government (No.20090083538). The authors wouldlike to thank the Aging Tissue Bank for providing researchresources.

References

Antignac, J.P., Cariou, R., Zalko, D., Berrebi, A., Cravedi, J.P., Maume, D., Marchand, P.,Monteau, F., Riu, A., Andre, F., Le Bizec, B., 2009. Exposure assessment of Frenchwomen and their newborn to brominated flame retardants: determination oftri- to deca- polybromodiphenylethers (PBDE) in maternal adipose tissue,serum, breast milk and cord serum. Environmental Pollution 157, 164–173.

Bi, X., Qu, W., Sheng, G., Zhang, W., Mai, B., Chen, D., Yu, L., Fu, J., 2006.Polybrominated diphenyl ethers in South China maternal and fetal blood andbreast milk. Environmental Pollution 144, 1024–1030.

Chen, S.J., Luo, X.J., Lin, Z., Luo, Y., Li, K.C., Peng, X.Z., Mai, B.X., Ran, Y., Zeng, E.Y.,2007. Time trends of polybrominated diphenyl ethers in sediment cores fromthe Pearl River Estuary, South China. Environmental Science and Technology 41,5595–5600.

Covaci, A., Harrad, S., Abdallah, M.A., Ali, N., Law, R.J., Herzke, D., de Wit, C.A., 2011.Novel brominated flame retardants: a review of their analysis, environmentalfate and behaviour. Environment international 37, 532–556.

de Wit, C.A., Herzke, D., Vorkamp, K., 2010. Brominated flame retardants in theArctic environment – trends and new candidates. The Science of the TotalEnvironment 408, 2885–2918.

Eriksson, P., Viberg, H., Jakobsson, E., Orn, U., Fredriksson, A., 2002. A brominatedflame retardant, 2,20 ,4,40 ,5-pentabromodiphenyl ether: uptake, retention, andinduction of neurobehavioral alterations in mice during a critical phase ofneonatal brain development. Toxicological Sciences 67, 98–103.

Fängström, B., Athanassiadis, I., Odsjö, T., Norén, K., Bergman, A., 2008. Temporaltrends of polybrominated diphenyl ethers and hexabromocyclododecane inmilk from Stockholm mothers, 1980–2004. Molecular Nutrition & FoodResearch 52, 187–193.

Foster, W.G., Gregorovich, S., Morrison, K.M., Atkinson, S.A., Kubwabo, C., Stewart,B., Teo, K., 2011. Human maternal and umbilical cord blood concentrations ofpolybrominated diphenyl ethers. Chemosphere 84, 1301–1309.

Frederiksen, M., Vorkamp, K., Thomsen, M., Knudsen, L.E., 2009. Human internal andexternal exposure to PBDEs – a review of levels and sources. InternationalJournal of Hygiene and Environmental Health 212, 109–134.

Frederiksen, M., Thomsen, C., Frøshaug, M., Vorkamp, K., Thomsen, M., Becher, G.,Knudsen, L.E., 2010. Polybrominated diphenyl ethers in paired samples ofmaternal and umbilical cord blood plasma and associations with house dust in aDanish cohort. International Journal of Hygiene and Environmental Health 213,233–242.

Gómara, B., Herrero, L., Ramos, J.J., Mateo, J.R., Fernández, M.A., García, J.F., González,M.J., 2007. Distribution of polybrominated diphenyl ethers in human umbilicalcord serum, paternal serum, maternal serum, placentas, and breast milk fromMadrid population, Spain. Environmental Science and Technology 41, 6961–6968.

Guvenius, D.M., Aronsson, A., Ekman-Ordeberg, G., Bergman, A., Norén, K., 2003.Human prenatal and postnatal exposure to polybrominated diphenyl ethers,polychlorinated biphenyls, polychlorobiphenylols, and pentachlorophenol.Environmental Health and Perspective 111, 1235–1241.

Hagmar, L., Björk, J., Sjödin, A., Bergman, A., Erfurth, E.M., 2001. Plasma levels ofpersistent organohalogens and hormone levels in adult male humans. Archivesof Environmental Health 56, 138–143.

Haraguchi, K., Koizumi, A., Inoue, K., Harada, K.H., Hitomi, T., Minata, M., Tanabe, M.,Kato, Y., Nishimura, E., Yamamoto, Y., Watanabe, T., Takenaka, K., Uehara, S.,Yang, H.R., Kim, M.Y., Moon, C.S., Kim, H.S., Wang, P., Liu, A., Hung, N.N., 2009.Levels and regional trends of persistent organochlorines and polybrominateddiphenyl ethers in Asian breast milk demonstrate POPs signatures unique toindividual countries. Environment International 35, 1072–1079.

Herbstman, J.B., Sjödin, A., Apelberg, B.J., Witter, F.R., Patterson, D.G., Halden, R.U.,Jones, R.S., Park, A., Zhang, Y., Heidler, J., Needham, L.L., Goldman, L.R., 2007.Determinants of prenatal exposure to polychlorinated biphenyls (PCBs) andpolybrominated diphenyl ethers (PBDEs) in an urban population.Environmental Health and Perspectives 115, 1794–1800.

Herbstman, J.B., Sjödin, A., Apelberg, B.J., Witter, F.R., Halden, R.U., Patterson, D.G.,Panny, S.R., Needham, L.L., Goldman, L.R., 2008. Birth delivery mode modifiesthe associations between prenatal polychlorinated biphenyl (PCB) andpolybrominated diphenyl ether (PBDE) and neonatal thyroid hormone levels.Environmental Health and Perspectives 116, 1376–1382.

Hong, S.H., Munschy, C., Kannan, N., Tixier, C., Tronczynski, J., Héas-Moisan, K., Shim,W.J., 2009. PCDD/F, PBDE, and nonylphenol contamination in a semi-enclosedbay (Masan Bay, South Korea) and a Mediterranean lagoon. Chemosphere 77,854–862.

Inoue, K., Harada, K., Takenaka, K., Uehara, S., Kono, M., Shimizu, T., Takasuga, T.,Senthilkumar, K., Yamashita, F., Koizumi, A., 2006. Levels and concentrationratios of polychlorinated biphenyls and polybrominated diphenyl ethers inserum and breast milk in Japanese mothers. Environmental Health andPerspectives 114, 1179–1185.

Julander, A., Karlsson, M., Hagström, K., Ohlson, C.G., Engwall, M., Bryngelsson, I.L.,Westberg, H., van Bavel, B., 2005. Polybrominated diphenyl ethers-plasmalevels and thyroid status of workers at an electronic recycling facility.International Archives of Occupational and Environmental Health 78,584–592.

Kang, C.S., Lee, J.H., Kim, S.K., Lee, K.T., Lee, J.S., Park, P.S., Yun, S.H., Kannan, K., Yoo,Y.W., Ha, J.Y., Lee, S.W., 2010. Polybrominated diphenyl ethers and syntheticmusks in umbilical cord serum, maternal serum, and breast milk from Seoul,South Korea. Chemosphere 80, 116–122.

Kim, B.H., Ikonomou, M.G., Lee, S.J., Kim, H.S., Chang, Y.S., 2005. Concentrations ofpolybrominated diphenyl ethers, polychlorinated dibenzo-p-dioxins anddibenzofurans, and polychlorinated biphenyls in human blood samples fromKorea. The Science of the Total Environment 336, 45–56.

Korea Environment Institute (KEI). Environmental Risk Assessment and Regulationon Flame Retardants. Korea Environment Institute, Seoul, Korea, 2001 (inKorean).

Law, R.J., Allchin, C.R., de Boer, J., Covaci, A., Herzke, D., Lepom, P., Morris, S.,Tronczynski, J., de Wit, C.A., 2006. Levels and trends of brominated flameretardants in the European environment. Chemosphere 64, 187–208.

Lee, S.J., Ikonomou, M.G., Park, H., Baek, S.Y., Chang, Y.S., 2007. Polybrominateddiphenyl ethers in blood from Korean incinerator workers and generalpopulation. Chemosphere 67, 489–497.

Lema, S.C., Dickey, J.T., Schultz, I.R., Swanson, P., 2008. Dietary exposure to 2,20 ,4,40-tetrabromodiphenyl ether (PBDE-47) alters thyroid status and thyroidhormone-regulated gene transcription in the pituitary and brain.Environmental Health and Perspectives 116, 1694–1699.

Linderholm, L., Biague, A., Månsson, F., Norrgren, H., Bergman, A., Jakobsson, K.,2010. Human exposure to persistent organic pollutants in West Africa – atemporal trend study from Guinea-Bissau. Environment International 36, 675–682.

Lorber, M., 2008. Exposure of Americans to polybrominated diphenyl ethers. Journalof Exposure Science and Environmental Epidemiology 18, 2–19.

Mazdai, A., Dodder, N.G., Abernathy, M.P., Hites, R.A., Bigsby, R.M., 2003.Polybrominated diphenyl ethers in maternal and fetal blood samples.Environmental Health and Perspectives 111, 1249–1252.

Petreas, M., Nelson, D., Brown, F.R., Goldberg, D., Hurley, S., Reynolds, P., 2011. Highconcentrations of polybrominated diphenylethers (PBDEs) in breast adiposetissue of California women. Environment International 37, 190–197.

Roosens, L., D’Hollander, W., Bervoets, L., Reynders, H., Van Campenhout, K.,Cornelis, C., Van Den Heuvel, R., Koppen, G., Covaci, A., 2010. Brominated flameretardants and perfluorinated chemicals, two groups of persistent contaminantsin Belgian human blood and milk. Environmental Pollution 158, 2546–2552.

Schecter, A., Colacino, J., Sjödin, A., Needham, L., Birnbaum, L., 2010. Partitioning ofpolybrominated diphenyl ethers (PBDEs) in serum and milk from the samemothers. Chemosphere 78, 1279–1284.

Sjödin, A., Hagmar, L., Klasson-Wehler, E., Kronholm-Diab, K., Jakobsson, E.,Bergman, A., 1999. Flame retardant exposure: polybrominated diphenylethers in blood from Swedish workers. Environmental Health andPerspectives 107, 643–648.

104 T.H. Kim et al. / Chemosphere 87 (2012) 97–104

Takasuga, T., Senthilkumar, K., Takemori, H., Ohi, E., Tsuji, H., Nagayama, J., 2004.Impact of fermented brown rice with Aspergillus oryzae (FEBRA) intake andconcentrations of polybrominated diphenylethers (PBDEs) in blood of humansfrom Japan. Chemosphere 57, 795–811.

Tanabe, S., Ramu, K., Isobe, T., Takahashi, S., 2008. Brominated flame retardants inthe environment of Asia-Pacific: an overview of spatial and temporal trends.Journal of Environmental Monitoring 10, 188–197.

Tseng, L.H., Li, M.H., Tsai, S.S., Lee, C.W., Pan, M.H., Yao, W.J., Hsu, P.C., 2008.Developmental exposure to decabromodiphenyl ether (PBDE 209): effects onthyroid hormone and hepatic enzyme activity in male mouse offspring.Chemosphere 70, 640–647.

Thuresson, K., Höglund, P., Hagmar, L., Sjödin, A., Bergman, A., Jakobsson, K., 2006.Polybrominated diphenyl ether exposure to electronics recycling workers-afollow up study. Chemosphere 64, 1855–1861.

Wilford, B.H., Shoeib, M., Harner, T., Zhu, J., Jones, K.C., 2005. Polybrominateddiphenyl ethers in indoor dust in Ottawa, Canada: implications for sources andexposure. Environmental Science and Technology 39, 7027–7035.

Yogui, G.T., Sericano, J.L., 2009. Polybrominated diphenyl ether flame retardants inthe US marine environment: a review. Environment International 35, 655–666.

Zhou, T., Taylor, M.M., DeVito, M.J., Crofton, K.M., 2002. Developmental exposure tobrominated diphenyl ethers results in thyroid hormone disruption.Toxicological Sciences 66, 105–116.