DSpace at VNU: Residue profiles of organohalogen compounds in human serum from e-waste recycling sites in North Vietnam: Association with thyroid hormone levels

Environmental Research 137 (2015) 440–449 Contents lists available at ScienceDirect Environmental Research journal homepage: www.elsevier.com/locate/envres Residue profiles of organohalogen compounds in human serum from e-waste recycling sites in North Vietnam: Association with thyroid hormone levels Akifumi Eguchi a, Kei Nomiyama a,n, Nguyen Minh Tue a,b, Pham Thi Kim Trang b, Pham Hung Viet b, Shin Takahashi c, Shinsuke Tanabe a a b c Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577, Japan Centre for Environmental Technology and Sustainable Development, Hanoi University of Science, 334 Nguyen Trai, Hanoi, Vietnam Center of Advanced Technology for the Environment, Faculty of Agriculture, Ehime University, Tarumi 3-5-7, Matsuyama 790-8566, Japan art ic l e i nf o a b s t r a c t Article history: Received 11 August 2014 Received in revised form January 2015 Accepted January 2015 Available online February 2015 This study demonstrated the contamination levels of polychlorinated biphenyls (PCBs), hydroxylated PCBs (OH-PCBs), polybrominated diphenyl ethers (PBDEs), methoxylated PBDEs (MeO-PBDEs), hydroxylated PBDEs (OH-PBDEs), and bromophenols (BPhs), and their relationships with thyroid hormones (THs), in the serum of human donors from an e-waste recycling site and a rural site in Hung Yen province, Vietnam Occupationally related exposure was indicated by significantly higher residue levels of PCBs, OH-PCBs, PBDEs, and BPhs in the serum of donors from the e-waste recycling site (median: 420, 160, 290, and 300 pg g À wet wt, respectively) than those in the serum of donors from the rural site (median: 290, 82, 230, and 200 pg g À wet wt, respectively) On the other hand, levels of OH-/MeO-PBDEs were significantly higher in serum of donors from the reference site (median: 160 and 20 pg g À wet wt, respectively) than in those from the e-waste recycling site (median: 43 and 0.52 pg g À wet wt, respectively) In addition, we implemented stepwise generalized linear models to assess the association between the levels of TH and PCBs, PBDEs, and their related compounds In females, we found positive associations of PCBs and OH-PCB concentrations with total thyroxine, free thyroxine, total triiodothyronine, and free triiodothyronine, and a negative association with thyroid-stimulating hormone concentrations & 2015 Elsevier Inc All rights reserved Keywords: e-waste PCBs PBDEs Hydroxylated metabolites Thyroid hormones Introduction Electrical waste and electronic equipment, also known as e-waste, refers to end-of-life products encompassing information communication devices, consumer electronics, and household appliances (UNEP, 2005) These e-wastes contain many hazardous substances, such as heavy metals and persistent organohalogen compounds, which can be released into the environment (SVCT, 2002) In addition, recent recycling activities of e-waste in Vietnam are considered a problem Our research group has recently suggested that Vietnamese workers at an e-waste site are occupationally exposed to polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), dioxin-like compounds, and trace elements during recycling activities (Noguchi et al., 2014; Tue et al., 2010a, 2010b, 2013) Inappropriate methods of e-waste n Corresponding author Fax: þ81 89 927 8196 E-mail address: keinomi@agr.ehime-u.ac.jp (K Nomiyama) http://dx.doi.org/10.1016/j.envres.2015.01.007 0013-9351/& 2015 Elsevier Inc All rights reserved recycling or dismantling are related to increased environmental emissions of toxic chemicals that may affect human health The thyroid hormone (TH) system is an important endocrine target for many organohalogen contaminants It is well-known that TH plays a critical role in regulating biological processes, such as growth, metabolism, and neurodevelopment (Gelfand et al., 1987; Zoeller, 2003) The metabolism of PCBs and PBDEs result in the formation of a relatively large number of hydroxylated PCBs (OH-PCBs), hydroxylated PBDE congeners (OH-PBDE), and bromophenols (BPhs), which are associated with perturbed thyroid homeostasis and neurodevelopmental deficits (Cheek et al., 1999; Meerts et al., 2002) Some isomers of OH-PBDEs, BPhs and methoxylated PBDEs (MeO-PBDEs) have been found in humans and various animals (Eguchi et al., 2012; Malmberg et al., 2005; Malmvarn et al., 2008; Marsh et al., 2004; Mizukawa et al., 2013; Nomiyama et al., 2011a; Wan et al., 2009) Among MeO-PBDEs, two abundant isomers (6MeO-BDE47 and 2′MeO-BDE68) have been found to be natural A Eguchi et al / Environmental Research 137 (2015) 440–449 products (Teuten et al., 2005) Demethylation of MeO-PBDEs by cytochrome P450 (CYP) can result in the formation of more OHPBDEs than through the metabolism of parent PBDEs (Wan et al., 2009) On the other hand, an in vitro study has shown that exposure of human liver microsomes to BDE 99 led to the generation of OH-PBDEs and BPhs (Stapleton et al., 2009), and an in vivo study has shown that exposure of rats and mice to PBDEs led to the generation of OH-PBDEs (Malmberg et al., 2005; Morck et al., 2003; Qiu et al., 2007) In recent years, scientists have paid considerable attention to potential risk to environmental and human health of both natural and anthropogenic halogenated phenolic compounds; however, few studies have reported exposure risk of PCBs, PBDEs and their hydroxylated/methoxylated derivatives in Asian developing countries, especially for donors of e-waste recycling sites In the present study, we aimed to determine serum concentrations of PCBs, OH-PCBs, PBDEs, MeO-PBDEs, OH-PBDEs, and BPhs in human donors at an e-waste recycling site and a rural site in northern Vietnam On the other hand, it was reported that iodide uptake is essential for the production of THs (Bianco et al., 2002), while perchlorate and thiocyanate can competitively inhibit iodide uptake by the thyroid gland via the sodium/iodide symporter, reducing the synthesis of TT3 and TT4 (Dohan et al., 2007; Tonacchera et al., 2004) However, a few studies focused on the associations among organohalogen contaminants, anions and THs (Alvarez-Pedrerol et al., 2009; Hisada et al., 2013; Lopez-Espinosa et al., 2009) Thus, we also examined the relationships between serum concentrations of THs and these organohalogen compounds and their metabolites to assess the effects on TH homeostasis in Vietnamese populations, considering various potential co-factors, such as donor characteristics and levels of perchlorate, thiocyanate and iodide analyzed in our previous research (Eguchi et al., 2014) 441 Table Characteristics of donors from e-waste recycling site and reference site in Vietnam n Age Height (cm) Weight (kg) BMI Gender Smoking Alcohol drinking Consumption of fish Consumption of meat and egg a Female Male Never Yes Never Yes o times/ week 1–3 times/ week 1–3 times/ week 4–6 times/ week e-waste recycling site (Bui Dau) Reference site (Doung Quang) 77 337 11a 160 78.1 51 78.6 207 2.4 45 32 55 22 53 24 73 34 377 11 1587 8.4 527 9.4 21 72.6 22 12 28 27 28 19 58 32 Arithmetic mean 7Standard deviation a previous study (Kunisue et al., 2011) Thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), total thyroxine (TT4), free T3 (FT3), and free T4 (FT4) were measured using Elecsyss kits (Roche Diagnostics, Mannheim, NY, USA) and Modular Analytics E170 systems (Hitachi Ltd., Tokyo, Japan) Analysis of THs in serum samples was commissioned to SRL Inc (Tokyo, Japan) The expected reference values in euthyroid humans are within 0.270–4.2 μU mL À for TSH, 0.80–2.0 ng mL À for TT3, 45– 117 ng mL À for TT4, 2.0–4.4 pg mL À for FT3, and 9.7–17 pg mL À for FT4 (Roche Diagnostics GmbH, 2008) Materials and methods 2.4 Measurements of organic contaminants in serum 2.1 Collection of serum samples Serum samples (1–2 g) were denatured with mL of M hydrochloric acid (HCl), and then spiked with the following surrogate internal standards: 13C12-labeled OH-PCBs (4′OH-CB29, 4′OHCB61, 4′OH-CB107, 4′OH-CB120, 4′OH-CB159, 4′OH-CB172, and 4OH-CB187), 13C12-labeled PCBs (CB28, 52, 95, 101, 105, 118, 138, 153, 156, 167, 170, 178, 180, 189, 194, 202, 206, 208, and 209), 13C12labeled PBDEs (BDE28, 47, 99, 153, 183, 197, 207, and 209), 13C12labeled OH-PBDEs (6OH-BDE47, 6′OH-BDE99, and 6′OH-BDE100), and 13C6-labeled BPhs (2,4,6-BPh; 2,3,4,6-BPh; and penta-BPh) The samples were then extracted according to QuEChERS method (Plossl et al., 2006), which entailed the following steps Each sample was poured into a 50 mL fluoroethylenepropylene centrifugation tube; added to this were aliquots of 2-propanol (2 mL), methyl tert-butyl ether (MTBE)/hexane (10 mL, 5:5 v/v, Wako, Osaka), and a mixture of MgSO4, NaCl, sodium citrate, and sodium hydrogen citrate sesquihydrate (4, 1, 1, 0.5 g, respectively, Agilent Tokyo), and the tube was shaken vigorously for by hand After centrifuging the tube at 3000 rpm for min, the supernatant was transferred to a mini-centrifuge tube (15 mL) containing a mixture of C18 and MgSO4 (150 mg each, Agilent, Tokyo), mixed for min, and centrifuged at 3000 rpm for After transferring the extract to a glass flask, M potassium hydroxide (KOH) in 50% ethanol/water was added and the mixture was shaken for 10 This organic–alkaline partition process was repeated twice, and the alkaline phases were combined The organic phase was concentrated and passed through an activated silica gel column (Wakogels DX, Wako, Osaka), where PCBs, PBDEs, and MeO-PBDEs were eluted with 80 mL of 5% dichloromethane (DCM)/hexane (DCM, Wako, Osaka) and were Human serum samples were collected from donors who were workers at an e-waste recycling site of Bui Dau (n ¼77) and donors who were residents from the rural area of Duong Quang (n ¼34) in Vietnam, during 2010 and 2011 (Fig S1) These 111 donors were informed beforehand about the purpose of the study at local government health stations where volunteers registered their consent to participate, and they consented to participation in our study All the participants were randomly selected without arbitrary criteria Informed consent was obtained from all donors, and this study was approved by the Ethical Committee of Ehime University, Japan Demographic, health, and diet information were collected through personal interviews (Table 1) All samples were shipped to Ehime University, Japan, on gel ice and stored at À25 °C in the environmental specimen bank for global monitoring (es-BANK: http://esbank-ehime.com) (Tanabe, 2006) until chemical analysis 2.2 Chemicals The certified standards used for the identification and quantification of PCBs, OH-PCBs, PBDEs, OH-PBDEs, MeO-PBDEs, and BPhs are described in the Supplementary information 2.3 Thyroid hormone analysis THs in serum were analyzed by following the electrochemiluminescence immunoassay (ECLIA) procedures reported in 442 A Eguchi et al / Environmental Research 137 (2015) 440–449 concentrated for analysis by high-resolution gas chromatography (GC; Agilent 6890N) mass spectrometry (MS; JEOL JMS-800D) (HRGC/HRMS) The alkaline phase was acidified (pH 2) with sulfuric acid, then OH-PCBs, OH-PBDEs, and BPhs were extracted twice with 50% MTBE/hexane (60 mL, 5:5, v/v) The organic phases were passed through deactivated silica gel and then eluted with 50% DCM/hexane OH-PCBs, OH-PBDEs, and BPhs were methylated by using trimethylsilyldiazomethane (Tokyo Chemical Industry, Tokyo) Finally, the derivatized solution was passed through an activated silica gel packed column (Wakogels S1, Wako, Osaka), eluted with 140 mL of 10% DCM/hexane, and then concentrated identity-link function The concentrations of TSH, TT3, and FT3 were not normally distributed; hence, these data were analyzed by GLMs with a gamma distribution of the response variable and log link function For any model, the parameters that optimize the approximation of the likelihood can be found numerically The optimized likelihoods from different models can then be compared through Akaike’s information criterion (AIC) to maximize the model’s likelihood (Akaike, 1998) Selected models and their parameters are shown in Tables S5–S16 2.5 Quality assurance and quality control Results and discussion PCBs, OH-PCBs, PBDEs, MeO-PBDEs, OH-PBDEs, and BPhs were quantified using an isotope dilution method for the corresponding 13 C-labeled internal standards The recoveries for these internal standards in this analytical procedure were within 61–121%, 58– 120%, 43–108%, 79–112%, and 67–116% for OH-PCBs, OH-PBDEs, BPhs, PCBs, and PBDEs, respectively The signal to noise ratios (S/N) were higher than 10, and the deviation of ion intensity ratios was within 15% of those of the standard compounds Procedural blanks were analyzed simultaneously with every batch of four samples to check for interferences or contamination from solvent and glassware For each analysis, the mean procedural blank value was used for subtraction After the blank subtraction, the limit of quantification (LOQ) was defined as the amount of target compound that resulted in an S/N of 10:1 Only 2,4,6-BPh and BDE-209 were detected in the blank samples, with blank values of the average concentration values measured in the serum samples being around 10% and 1%, respectively For quality assurance and control, our laboratory participated in an inter-calibration exercise organized by the National Institute of Standards and Technology using the Standard Reference Material 1958 (NIST SRM 1958; PCBs, PBDEs, dioxin/furan, pesticides, and PFCs in human serum) 3.1 Residue profiles of PCBs and OH-PCBs in human serum 2.6 Statistical analysis The statistical analyses were performed with R program, Ver 3.0.1 (The R Foundation for Statistical Computing) and EZR (Saitama Medical Center, Jichi Medical University) (Kanda, 2013), which is a graphical user interface for R (version 2.13.0) The Wilcoxon rank-sum test was used to determine the difference in concentrations of organic compounds in samples collected from the reference site and from the e-waste recycling site The distributions of TH, PCBs, PBDEs, and their related compounds were assessed for normal distribution (Shapiro–Wilk test) FT4 and TT4 were normally distributed in Bui Dau, Duong Quang, and mixed locations (Bui Dau and Duong Quang) However, TSH, FT3, TT3, and all PCB, OH-PCB, PBDE, OH-PBDE, MeO-PBDE, and BPh congeners were not normally or log-normally distributed in all locations We implemented stepwise generalized linear models (GLMs) to assess the association between levels of TH and those of PCBs, PBDEs, and their related compounds This model was also used to examine the influence of other characteristics: perchlorate, iodide, thiocyanate (Eguchi et al., 2014), cholesterol, triglyceride, γ-GTP, BMI, age, gender (male ¼ 0, female ¼ 1), living site (reference¼0, e-waste¼1), meat and egg consumption (1–3 times/week ¼ 0, 4–6 times/week¼1), and fish consumption ( o1 times/week¼0, 1–3 times/week¼1) We also determined stepwise GLMs to assess the associations between PCBs, PBDEs, and their related compounds and characteristics The results obtained with p o0.05 were considered statistically significant The data for TT4 and FT4 were normally distributed in serum; hence, these data were analyzed by GLMs with a Gaussian distribution of the response variable and Concentrations of PCB and OH-PCB congeners in serum of donors from e-waste recycling and reference sites are shown in Table Total PCB levels were significantly higher (p o0.05) in donors from the e-waste recycling site (420 pg g À 1) than from the reference site (290 pg g À 1) (Table 2) Concentrations of PCBs and OH-PCBs in the present study were lower than those reported in Japan (PCBs: 2900 pg g À 1, OH-PCBs: 630 pg g À 1; Nomiyama et al., 2010), Romania (PCBs: 3100 pg g À 1, OH-PCBs: 175 pg g À 1; Dirtu et al 2010), Belgium (PCBs: 3380 pg g À 1, OH-PCBs: 310 pg g À 1; Dirtu et al 2010), and Sweden (PCBs: 3560 pg g À 1, OH-PCBs 2670 pg g À 1; Sjodin et al., 2000) but higher than those reported in India (PCBs: 110 pg g À 1, OH-PCBs: 54 pg g À 1; Eguchi et al., 2012) Concentrations of total OH-PCBs were significantly higher (p o0.05) in donors from the e-waste recycling site (160 vs 88 pg g À 1; Table 2) At both sites, congener profiles for OH-PCBs were dominated by 4′OH-CB107/4′OH-CB108 followed by 4OHCB146, 4OH-CB101/120, and 4OH-CB187 (46.5%, 9.5%, 10.5% and 9.0% for Bui Dau and 29.5%, 13.6%, 11.3% and 14.8% for Duong Quang, respectively) PCB congener profiles were different in each studied population Dominant PCB congeners in each population were CB153 (17.7% in Bui Dau; 29.3% in Duong Quang) and CB138 (29.3% in Bui Dau; 18.3% in Duong Quang) Levels of less-chlorinated PCB congeners, including CB28, CB74, CB105, and CB118, were higher at the e-waste recycling site than the reference site, consistent with our previous results on breast milk collected from Bui Dau (Tue et al., 2010a) Specific exposure to some of these more volatile congeners could be explained by release from old capacitors in e-waste (Tue et al., 2013) reported high levels of CB74 in serum (Freels et al., 2007), and relatively high levels of CB74 and lower levels of CB138 and CB180 were found in serum collected from capacitor manufacturing workers (Wolff et al., 1992) Among OH-PCBs, 4OH-CB107/4′OH-CB108 was the dominant metabolite at the reference site, followed by 4OH-CB146, 4OHCB187, and 4′OH-CB101/120 Several studies have reported that 4OH-CB107 was the dominant congener in human serum (Dirtu et al., 2010; Eguchi et al., 2012; Fangstrom et al., 2002; Nomiyama et al., 2010; Sandau et al., 2000; Sjodin et al., 2000); however, in Swedish and Slovakian populations, 4OH-CB187 was the dominant metabolite (Bergman et al., 1994; Park et al., 2009a) This metabolite is probably formed via the metabolism of CB183 and/or CB187, which represent 2% and 5% of the Aroclor 1254 mixture An entirely different profile was reported for wives of Swedish fishermen, with 4OH-CB146 being the main congener, followed by 4OH-CB107 and 4OH-CB187 (Weiss et al., 2006) Differences in OH-PCB profiles in human serum may reflect regional variations in using technical PCBs (Breivik et al., 2002a, 2002b; Ishikawa et al., 2007) We also assessed associations between PCB and OH-PCB concentrations and various characteristics using stepwise GLMs (Table S3) Table Concentrations of PCBs, OH-PCBs, PBDE, OH-PBDEs, MeO-PBDEs, and BPhs ands in serum of donors from the reference and e-waste recycling sites in Vietnam (pg g À wet wt) Reference area:Duong Quang (n¼34) SD 17 6.6 12 26 21 27 75 120 20 51 36 410 14 10 18 39 12 27 87 150 16 46 39 420 3.9 8.4 26 10 3.1 12 1.1 8.7 13 2.0 o 0.3 88 0.76 0.18 0.011 0.35 0.67 0.34 140 84 10 o 1.0 0.23 1.6 2.6 12 230 4.4 250 28 130 160 0.52 0.23 0.017 0.73 0.83 0.23 62 49 16 0.79 3.9 6.2 22 83 10 95 30 90 120 8.7 30 33 1st quartile Median 3rd quartile Max Mean SDg 57 43 81 220 63 140 480 830 88 270 230 2500 36 10 24 73 47 92 78 110 33 63 50 620 39 10 39 127 94 210 150 190 32 61 40 800 2.3 o 0.3 o 0.3 o 0.3 o 0.3 7.7 4.3 6.3 o 0.3 o 0.3 1.4 150 8.4 4.2 6.4 22 15 27 26 35 5.6 23 22 320 18n 7.0n 14n 36n 24n 45n 47 72 30 51 47n 420n 54 12 25 66 37 72 78 120 50 76 71 620 220 47 280 780 620 1400 1300 1500 150 300 210 6400 8.5 13 93 21 2.7 19 1.1 12 18 4.5 3.6 200 6.3 6.4 150 24 4.1 14 2.1 5.2 12 12 9.3 180 o 0.3 o 0.3 19 7.1 o 0.3 7.8 o 0.3 3.2 5.2 o 0.3 o 0.3 60 3.6 9.1 39 13 o 0.3 12 o 0.3 9.5 11 o 0.3 o 0.3 120 8.0n 12n 55n 16n 1.5 15n 0.46 12n 15n o 0.3 o 0.3n 160n 11 16 79 22 4.8 21 1.6 14 22 1.8 o0.3 210 27 32 1100 210 29 110 15 39 74 83 58 1300 o 0.3a o 0.3 o 0.3 o 0.3 6.8 5.2 3.4 6.1 o 0.3 6.7 4.5 52 7.0 o0.3 o0.3 8.5 14 9.8 21 35 10 24 18 180 17 4.2 6.9 17 19 17 48 77 18 40 25 290 22 7.4 11 29 29 36 116 143 29 63 42 540 o 0.3 o 0.3 2.5 o 0.3 o 0.3 6.5 o 0.3 o 0.3 4.2 o 0.3 o 0.3 19 o0.3 6.6 13 5.7 1.1 10 0.3 4.6 8.4 o0.3 o0.3 59 3.4 8.2 23 8.9 2.8 11 1.1 8.5 12 o0.3 o0.3 82 6.3 11 32 14 4.2 14 1.7 12 15 4.3 o 0.3 110 0.06 0.010 0.010 0.010 0.040 0.020 0.42 0.050 0.010 0.080 0.250 0.20 0.66 0.11 0.010 0.13 0.43 0.30 1.0 0.21 0.018 0.28 0.69 0.44 13 23 97 29 11 21 2.6 23 32 13 o 0.3 200 2.1 1.2 0.090 5.6 5.4 1.3 1.12 0.20 0.013 0.16 0.57 0.40 0.86 0.22 0.035 0.14 0.37 0.21 Min 0.34 0.010 0.010 0.010 0.060 0.11 1st quartile 0.68 0.090 0.010 0.048 0.34 0.27 Median 0.94n 0.14 0.010 0.14 0.54 0.35 3rd quartile 1.2 0.24 0.010 0.21 0.72 0.45 200 120 12 19 3.9 4.4 6.1 42 350 14 410 150 140 41 37 9.3 9.4 13 86 320 30 360 17 9.1 o 0.5 o 1.0 o 1.0 o 1.0 o 1.0 o 5.0 36 o 1.0 37 140 49 o 0.5 o 1.0 o 1.0 o 1.0 o 1.0 o 5.0 200 o 1.0 230 160n 78 o 0.5 o 1.0n o 1.0n o 1.0n o 1.0n 23n 260n o 1.0 290n 230 110 o 0.5 o1.0 o1.0 o1.0 o1.0 45 370 o1.0 450 120 350 440 6.5 37 43 9.4 21 27 o 0.3 7.4 7.7 o 0.3 19 25 o 0.3 32 37 12 46 49 39 160 160 o 0.3 0.52 0.52 4.4 4.4 o 0.3 o 0.3 o 0.3 o 0.3 o 0.3 o 0.3 o 0.3 o 0.3 o 0.3 o0.3 o0.3 o0.3 50 o 0.5 o 0.5 o 1.0 o 1.0 o 1.0 o 5.0 80 o 1.0 100 82 48 o1.0 o1.0 o1.0 o1.0 o5.0 170 o1.0 170 120 84 o1.0 o1.0 o1.0 o1.0 o5.0 220 o1.0 230 190 130 23 o 1.0 o 1.0 o 1.0 o 1.0 o 5.0 290 o 1.0 300 290 180 55 o 1.0 4.7 15 22 68 380 34 450 o 0.3 9.5 9.5 o0.3 55 62 25 130 140 50 190 240 o 0.3 o 0.3 o 0.3 o0.3 o 0.3 o 0.3 o0.3 o 0.3 o 0.3 o 0.3 29 29 Max 6.7 1.8 0.23 0.50 1.8 1.3 920 1100 290 170 43 41 52 520 2300 130 2300 39 110 140 o 0.3 39 39 443 2.2 17 20 4.1 4.4 19 6.4 2.8 4.1 0.81 6.1 6.4 3.4 0.00 44 Min A Eguchi et al / Environmental Research 137 (2015) 440–449 PCBs CB28 CB70 CB74 CB99 CB105 CB118 CB138 CB153 CB170 CB180 CB187 Total PCBsb OH-PCBs 4-OH-CB61 4’-OH-CB79 4-OH-CB107/108 4-OH-CB101/120 3’-OH-CB138 4-OH-CB146 3-OH-CB153 4’-OH-CB172 4-OH-CB187 4-OH-CB199 4-OH-CB202 Total OH-PCBsc OH-PCBs/PCBs ratio 4-OH-CB107/CB105ỵ 118 4-OH-CB146/CB138ỵ 153 3-OH-CB153/CB138ỵ 153 4-OH-CB172/CB170ỵ 180 4-OH-CB187/CB187 Total OH-PCBs/Total PCBs PBDEs BDE47 BDE99 BDE100 BDE153 BDE183 BDE197 BDE207 BDE209 ∑tetra-hexaBDEs ∑hepta-nonaBDEs Total PBDEs OH-PBDEs 2’OH-BDE68 6OH-BDE47 Total OH-PBDEs MeO-PBDEs 2’MeO-BDE68 6MeO-BDE47 Total MeO-PBDEs Mean e-waste recycling area: Bui Dau (n¼77) A Eguchi et al / Environmental Research 137 (2015) 440–449 11 300 15 6.2 7.8 41 410 o 0.5n 220 8.0n 2.5 o 0.5n 20n 300n o 0.5 120 4.3 o 0.5 o 0.5 12 180 76 1400 85 57 140 180 1400 3rd quartile Median 1st quartile o 0.5 68 o 0.5 o 0.5 o 0.5 o 0.5 90 14 230 18 12 18 42 230 8.8 270 14 7.2 6.7 36 310 o 0.5 400 7.9 o 0.5 o 0.5 8.0 400 o 0.5 280 o 0.5 o 0.5 o 0.5 o 0.5 280 a n 1.4 81 Significantly higher than in the other group (p o 0.05: Wilcoxon rank sum test) Concentrations were lower than the limit of quantification (LOQ) b Including congeners not listed in the table c Including congeners not listed in the table d Sum of congeners of 2,4,5-BPh, 2,3,4,6-BPh, 2,3,5,6-BPh and pentaBPh o0.5 200 o0.5 o0.5 o0.5 o0.5 200 o0.5 150 o0.5 o0.5 o0.5 o0.5 150 o 0.5 100 o 0.5 o 0.5 o 0.5 o 0.5 100 80 1.4 o 0.5 220 0.24 o 0.5 o 0.5 0.27 220 BPhs 2,4,5-BPh 2,4,6-BPh 2,3,4,6-BPh 2,3,5,6-BPh PentaBPh ∑metaboliteBPhsd Total BPhs Min SDg Mean 3rd quartile Median 1st quartile Min SD Mean Reference area:Duong Quang (n¼34) Table (continued ) The Concentrations of PCBs and OH-PCBs positively correlated with age and negatively correlated with fish consumption (o1 times/week ¼ 0, 1–3 times/week¼1) Fish consumption has been positively correlated with PCB concentration (Sjodin et al., 2000) However, we observed an opposite trend, unclear reasons; however, there may be some bias related to less people eating more fish (herein, DQ ¼6 and BD¼ 4) Other characteristics were not significantly associated with PCB or OH-PCB concentrations When concentration ratios of OH-PCBs to their possible parent PCB congeners were calculated, ratio of 4OH-CB107ỵ 108/ CB105ỵ 118 was markedly higher in donors from the e-waste recycling site than in those from the reference site (Table 2), suggesting that CYP1A1 upregulation was because of exposure to indoor dust containing “high levels of dioxin-related compounds released from e-waste recycling (Tue et al., 2010b) 3.2 Residue profiles of PBDEs, MeO-PBDEs, OH-PBDEs, and BPhs in human serum Max e-waste recycling area: Bui Dau (n¼77) Max 444 PBDE, MeO-PBDE, OH-PBDE, and BPh concentrations are shown in Table PBDE and BPh concentrations were significantly higher in e-waste recycling workers than in residents at the reference site, according to GLM results (reference¼0, e-waste¼1) (Table S4) Other characteristics did not markedly associate with PBDE or BPh concentrations Significantly higher levels (p o0.05) of PBDEs were found in serum samples from the e-waste recycling site (290 pg g À 1) than from the reference site (230 pg g À 1) PBDE concentrations at the e-waste recycling (290 pg g À 1) and reference sites (230 pg g À 1) were similar to or higher than in Indian e-waste recycling workers (150 pg g À 1; Eguchi et al., 2012), Swedish rubber workers (400 pg g À 1; Thuresson et al., 2005), and electronics dismantlers (210 pg g À 1; Sjodin et al., 1999), indicating that PBDE levels in Vietnamese subjects were comparable with these occupational workers but lower than e-waste recycling workers in China (930– 4800 pg g À 1; Jin et al., 2009; Zhao et al., 2010) (Fig 1B) BDE47 was the dominant congener in all PBDE samples, followed by BDE99 and BDE209 (55%, 30%, and, 7.2%, respectively) BDE153 concentrations at each location were relatively lower than other reports These profiles may reflect higher consumption of deca-BDE technical mixtures in Asia (Watanabe and Sakai, 2003) Significantly higher (p o0.05) OH-PBDE and MeO-PBDE concentrations were detected at the reference (160 and 20 pg g À 1, respectively) than at e-waste recycling sites (43 and 0.52 pg g À 1, respectively), with unclear reasons; however, numbers of children and detailed information on food intake may be important OHPBDE concentrations found in the present study were generally lower than those found in fetal and maternal serum samples from the United States (290 pg g À 1; Qiu et al., 2009), serum samples from children living near a waste disposal site in Nicaragua (260 pg g À 1; Athanasiadou et al., 2008), and serum samples from Japanese volunteers (450 pg g À 6OH-BDE47; Fujii et al., 2014) but higher than those in donors from India (30 pg g À 1; Eguchi et al., 2012) Our results differ compared with previous reports, possibly because of differences in exposure levels caused by dietary habits Of the 28 OH-PBDE (tri- to octa-) isomers monitored in this study, 6OH-BDE47 and 2′OH-BDE68 were dominant at each location These congeners have been predominantly detected in several marine and terrestrial animals (Malmberg et al., 2005; Mizukawa et al., 2013; Nomiyama et al., 2011a; Wan et al., 2009), suggesting that dietary intake was an primary exposure route for these congeners (Eguchi et al., 2012; Valters et al., 2005; Wan et al., 2010) Congener profiles for BPhs were dominated by 2,4,6-BPh (99% and 87% for Duong Quang and Bui Dau, respectively) Total BPh A Eguchi et al / Environmental Research 137 (2015) 440–449 445 Fig Comparison of serum concentrations of (A) PCBs and (B) PBDEs in Vietnamese donors analyzed in this study with previous data References: (1) Eguchi et al (2012); (2) Zhao et al (2010); (3) Nomiyama et al (2010); (4) Dirtu et al (2010); (5) Sjodin et al (2000); (6) Sjodin et al (1999); (7) Thuresson et al (2005); and (8) Jin et al (2009) n Note: (1), (2), (3), (4), (5), (6), (7) ¼Median value, (8)¼ Mean value (SD was not shown in reference) nnPCB and PBDE concentrations were converted to wet basis using serum lipid levels of 7.9 g L À as applied by Longnecker et al (2003) concentrations were significantly (po 0.05) higher at the e-waste recycling (300 pg g À 1) than in donors from reference sites (200 pg g À 1) The predominance of 2,4,6-tri-BPh, even in donors living at the reference site (Table 2), may reflect potential for exposure from both dietary and non-dietary indoor sources This congener has been regarded as a natural product in several marine organisms (Malmberg et al., 2005; Marsh et al., 2004; Nomiyama et al., 2011a, 2011b; Wan et al., 2009) and is also manufactured at high volumes (9500 t/year in 2001) for use as flame retardants and wood preservatives/fungicides (Watanabe and Sakai, 2003) Contrastingly, 2,3,4,6-tetra-BPh, 2,4,5-tri-BPh, 2,3,5,6-tetraBPh, and penta-BPh were more prominent at the e-waste recycling site (4.5%, 2.8%, 2.3%, and 2.2%, respectively) (Table 2) Total levels of non-2,4,6-BPhs in donors from the e-waste recycling site (36 pg g À 1) were significantly higher (p o0.05) than at the reference site (median: 0.27 pg g À 1), indicating that accumulation of these BPhs is related to exposure to e-waste contaminants 2,4,5tri-BPh has been detected as a metabolite of BDE99 in human hepatocytes in vitro (Stapleton et al., 2009), possibly resulting from simple cleavage at the ether bond Further, three types of BPh metabolites have been identified in mice blood after exposure to PBDEs (Qiu et al., 2007) In this study, 2,3,4,6-tetra-BPh and BDE209 showed a weak (but significant) positive correlation (p o0.05) Increased exposure to PBDEs from e-waste recycling and/or inhalation from house dust containing these contaminants may have contributed to higher levels of these BPh metabolites (Suzuki et al., 2008) 3.3 Association between thyroid hormone concentrations and PCBs, PBDEs, and related compounds TH concentrations in most samples were within normal limits However, FT3, TT3, and TT4 concentrations were significantly lower in serum samples from the e-waste recycling site (3.3 pg g À 1, 1.2 ng g À 1, and 78 ng g À 1, respectively) than from the reference site (3.5 pg g À 1, 1.3 ng g À 1, and 85 ng g À 1, respectively; Table 3) Serum TT4 and TT3 concentrations in females were significantly higher (p o0.05) than in males (Table 3) Sex differences may be related to hormone balance Soldin et al (2004) reported that estrogen induced serum thyroxine-binding globulin (TBG), the main transport protein for THs in humans, followed by increased serum TT4 concentration, whereas androgen therapy reduced Table Concentrations of thyroid hormones (pg g À wet wt), γ-GTP (IU L À 1) and lipids (mg dL À 1) in serum of donors from reference and e-waste sites, Vietnam Reference area: Duong Quang (n ¼34) Mean TT3 TT4 FT3 FT4 TSH γ-GTP Phospholipid Total cholesterol Triglyceride a n 1.5 85 3.8 1.3 1.8 35 210 180 140 a SD 0.65 12 1.3 0.18 1.5 45 34 36 130 Min 1.0 51 2.9 1.0 0.040 9.0 160 120 36 1st quartile 1.2 80 3.3 1.2 0.91 13 180 150 64 e-waste recycling area: Bui Dau (n¼ 77) Median * 1.3 85* 3.5* 1.2 1.5 19 200 170 99 3rd quartile 1.5 90 3.8 1.3 2.2 28 230 210 150 SD standard deviation Significantly higher than in the other group (p o 0.05: Wilcoxon rank sum test) Max 4.8 130 11 1.7 8.2 220 330 260 740 Mean 1.2 81 3.4 1.3 1.6 180 240 200 220 SDa 0.29 17 0.72 0.20 0.90 740 47 39 190 Min 0.80 46 2.3 0.85 0.020 8.0 120 110 50 1st quartile 1.1 68 3.1 1.2 1.0 15 210 170 110 Median 1.2 78 3.3 1.3 1.4 20 230* 190* 170* 3rd quartile 1.4 93 3.5 1.4 2.1 43 260 220 240 Max 2.7 140 8.2 1.9 4.6 4800 370 380 1100 446 Table Coefficients of multiple linear regression of thyroid hormone levels with contaminant levels as controlling factors.n TT3 Estimate 0.0023 0.00097 Standard Error 0.00094 0.00073 p-Value FT3 Estimate Standard Error p-Value 0.014 0.017 0.011 0.0082 0.093 0.11 0.018 0.039 0.16 0.070 Estimate 0.00033 0.00027 0.00021 0.00017 0.11 0.13 0.0010 0.0020 0.000059 0.00062 0.00097 0.000044 0.11 0.041 0.19 0.0039 0.50 0.16 0.23 0.48 0.0025 0.010 0.011 0.0088 0.0022 0.30 0.067 0.12 0.29 Standard Error p-Value 0.0013 0.00067 0.049 0.00077 À 0.00126 0.00048 0.049 0.11 0.11 0.026 0.011 0.039 0.019 0.020 0.019 FT4 0.118 0.067 0.073 0.036 0.083 0.099 0.023 0.060 0.11 0.0051 0.033 0.00026 0.00016 0.11 0.0015 0.00091 0.0019 0.00089 0.00049 0.00076 0.099 0.069 0.014 À 0.011 0.0044 0.020 À 0.0064 0.0045 0.16 TSH Estimate Standard Error p-Value 0.00014 0.00010 0.155 0.0018 0.0043 0.00017 0.00085 0.0017 0.00011 0.037 0.011 0.146 0.00060 0.00035 0.083 À 0.00067 À 0.00051 0.0099 　 　 À 0.00048 0.0016 0.00043 0.00025 0.0060 0.00030 0.00083 0.124 0.044 0.109 　 　 0.11 0.063 0.0015 0.00042 0.00063 0.00030 0.00028 0.00024 0.0013 0.00081 0.0016 0.000064 0.0050 0.0021 0.0029 0.0073 0.0046 0.00029 0.00072 0.00017 0.00025 0.00010 0.00011 0.000091 0.00060 0.00032 0.00058 0.000022 0.0031 0.00067 0.0012 0.0030 0.0015 0.00013 0.038 0.018 0.016 0.0066 0.011 0.0093 0.034 0.014 0.0065 0.0057 0.116 0.0032 0.022 0.019 0.0027 0.030 0.00020 0.00011 0.076 0.00017 0.000099 0.094 Estimate Standard Error p-Value À 0.00084 0.00043 0.054 0.0014 0.00079 0.081 À 0.0040 0.0015 0.0080 À 0.0070 0.0032 0.029 À 0.0023 À 0.0010 À 0.00092 0.0012 0.00049 0.00051 0.052 0.037 0.074 À 0.0061 0.0033 0.069 0.0015 　 À 0.0043 0.0011 0.174 　 0.039 0.0021 Total concentrations: refer to Table for further details n These models report the contaminants–thyroid hormone association after adjusting for perchlorate, iodide, thiocyanate, cholesterol, triglyceride, γ-GTP, BMI, age, gender, living site, consumption of meat and egg and consumption of marine fish Blank cells indicate factors eliminated by stepwise procedures A Eguchi et al / Environmental Research 137 (2015) 440–449 All donors CB118 CB138 CB153 CB170 CB180 CB187 4OH-CB79 4OH-CB101/120 4OH-CB187 Total OH-PCBsa BDE209 6OH-BDE47 ∑metaboliteBPhsb Male CB138 CB153 4OH-CB61 4OH-CB187 　 BDE47 6OH-BDE47 Female CB74 CB99 CB105 CB118 CB138 CB153 CB170 CB180 CB187 Total PCBsc 4OH-CB79 4OH-CB101/120 4OH-CB146 4OH-CB172 4OH-CB187 Total OH-PCBs 6OH-BDE47 2,4,6-BPh ∑metaboliteBPhs Total BPhsd TT4 A Eguchi et al / Environmental Research 137 (2015) 440–449 serum TBG and TT4 levels Our results revealed that females had a significant positive correlation between FT4 and most PCB and OHPCB congeners (r ¼0.23–0.56, p o0.05), but only CB138 and CB153 (r ¼ 0.21–0.27, p o0.05), positively correlated with FT4 in males (Table 4) TT3, FT3, and TT4 had a significant positive association with hepta-chlorinated PCBs and some OH-PCB congeners in female serum samples: TT3 with CB187, FT3 with 4OH-CB79 and 4OH-CB172, and TT4 with 4OH-CB101/120 TSH demonstrated significant negative correlation with CB74, CB118, and the sum of the non-2,4,6-BPhs in female serum samples One possible mechanism involved in TH homeostasis disruption is the competitive binding of OH-PCBs and BPhs to TH transport protein transthyretin (TTR) found in blood (Cheek et al., 1999; Londono et al., 2010; Park et al., 2009a, 2009b) Furthermore, binding affinity of OH-PCBs, OH-PBDEs, and BPhs with TTR has been comparable to that of THs (Marchesini et al., 2008; Ucan-Marin et al., 2010) However, serum TH concentrations did not significantly correlate with PBDEs, OHPBDEs, 2,4,6-BPh, or total BPhs We observed significant positive correlations between PCB and OH-PCB concentrations and FT4 and negative correlations between lower-chlorinated PCB concentrations and TSH in females; however, few compounds significantly correlated with THs in males (Tables 4, S5–S16) Our results also suggest that gender differences exist regarding the effects of organochlorines on THs Previous studies also found associations between POPs and THs in women Chlorinated POPs, including PCBs and levels of T3 and T4, negatively correlated in females, particularly pregnant women (Chevrier et al., 2008; Koopmanesseboom et al., 1994; Takser et al., 2005) In vivo studies with rats have reported that TT4 and TT3 levels significantly decreased in Aroclor 1254- and 4OH-CB107-exposed groups, whereas FT4 levels did not significantly change (Meerts et al., 2002) Many epidemiological studies examining associations between PCBs and thyroid function have reported no association with FT4 (Hagmar et al., 2001; Hallgren et al., 2001; Meeker et al., 2007; Sala et al., 2001) However, some studies reported positive and negative associations with FT4 It has also been reported that DLCs have altered thyroid hormone homeostasis (Chevrier et al., 2008; Koopmanesseboom et al., 1994; Takser et al., 2005) e-waste recycling workers from Bui Dau are occupationally exposed to dioxin-like compounds and trace elements during recycling activities (Noguchi et al., 2014; Tue et al., 2010a, 2010b, 2013) Exposure to dioxin-like compounds positively associated with FT4 (Calvert et al., 1999), indicating that exposure to dioxin-like compounds was reflected by decreasing FT4 levels Workers exposed to PCBs and chlorinated napthalenes at an electrical capacitor manufacturing facility in Illinois (Persky et al., 2001) and fish consumers with exposure to organochlorines living near the Great Lakes (Turyk et al., 2006) had decreased TSH levels TH production is controlled by a complex mechanism of positive and negative regulation Although TSH stimulates TH secretion, TH suppresses TSH Feedback between these two hormones allows TH levels to be maintained within a narrow dose range (Vandenberg et al., 2012) Although sample size was limited in this study, negative feedback effect may have been detected following low-dose exposure to PCBs and their metabolites using applicable statistical analyses Some PCBs, OH-PCBs, and BPhs significantly correlated with FT3, TT3, TT4, and TSH, respectively, in the present study Associations between organohalines and TT4 and/or TT3 were reported to be significantly negative in half of the studies cited in a review (Abdelouahab et al., 2008); however, remaining studies found no association with these hormones An in vivo study showed that PCBs reduced serum FT4 and TT4 in a dose-dependent manner (Martin and Klaassen, 2010) In this study, residual levels of PCBs and OH-PCBs in serum were one order lower than those of epidemiological studies (1700–6700 pg (Hagmar et al., 2001; Hallgren 447 et al., 2001; Meeker et al., 2007; Sala et al., 2001)), and three to four orders lower than with in vitro TTR inhibition assays (IC50: OH-PCBs 7.3–32.7 nM; Marchesini et al., 2008) Previous studies have demonstrated that OH-PBDEs compete with THs for binding sites on human plasma proteins Based on in vitro studies using human cells, IC50 range for OH-PBDEs was from 22–110 nM for TTR and 100–870 nM for TBG, depending on the congener (Marchesini et al., 2008) OH-PBDE concentrations in serum from Vietnamese populations were two to three orders of magnitude lower than the IC50 value for TT4–TTR binding activity There were no marked associations between THs and PBDEs or OH-PBDEs in this study Several researches have also reported that associations between PBDEs and TT3, TT4, FT3, FT4, and TSH were not clear (Mazdai et al., 2003; Roze et al., 2009) A recent study showed negative associations between PBDE levels and TT3 and FT3 in cord blood (Lin et al., 2011) and positive associations between PBDEs and TSH levels in pregnant women (Zota et al., 2011) Another study reported positive associations between PBDE and OH-PBDE concentrations and TSH (Zota et al., 2011) PCBs, PBDEs, and their metabolites may disrupt TH homeostasis in pregnant women and negatively affect neurological development of fetuses (Roze et al., 2009; Herbstman et al., 2010) Thus, detailed investigations on their exposure effects for pregnant women and the health effects for neonates are required In this study, we used a generalized linear model to examine associations between TH and other compounds, including perchlorate, iodide, and thiocyanate (Eguchi et al., 2014; Tables 4, S5– S16) Consequently, iodide and thiocyanate levels were found to contribute to TH variations (Tables S5–S16) Iodide is essential for TH production (Bianco et al., 2002) Thiocyanate can competitively inhibit iodide uptake by the thyroid gland via the sodium/iodide symporter, reducing TT3 and TT4 synthesis (Dohan et al., 2007; Tonacchera et al., 2004) It has been suggested that iodide and thiocyanate were covariates in the association between PCBs and OH-PCBs with THs, indicating that analysis of these anions is necessary to elucidate effects of TH disruption In summary, we determined serum concentrations of organohalogen compounds and their metabolites and examined associations with THs in Vietnamese populations PCB, OH-PCB, PBDE, and BPh concentrations in serum samples from the e-waste recycling site were significantly higher than in those from the rural site, indicating occupationally related exposure to these compounds Concentrations of these contaminants were lower in Vietnam than in the US and European countries; however, PCB and OH-PCB levels correlated with serum TH concentrations in Vietnamese females Therefore, detailed investigations on exposure effects in females are required; particularly those focused on pregnant women and health effects in developing newborns Acknowledgment This study was supported by Grants-in-Aid for Young Scientists (A) (No 25701014), Grants-in-Aid for Scientific Research (A) (No 25257403) and Grant-in-Aid for Research Activity start-up (No 26881003) from the Japan Society for the Promotion of Science (JSPS), Japan, the Global Center of Excellence (COE) Program of the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan, and the Environment Research and Technology Development Fund (K2311 and 3K133001) from the Japanese Ministry of the Environment We also acknowledge the JSPS Research Fellowships for Young Scientists (DC1 and PD) in Japan that were provided to Dr A Eguchi (Nos 22-6331 and 25-6617) 448 A Eguchi et al / Environmental Research 137 (2015) 440–449 Appendix A Suplementary information Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/j.envres.2015.01.007 References Abdelouahab, N., Mergler, D., Takser, L., Vanier, C., St-Jean, M., Baldwin, M., Spear, P A., Chan, H.M., 2008 Gender differences in the effects of organochlorines, mercury, and lead on 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