Fu-An Chen

Negative associations between PBDE levels and thyroid hormones in cord blood

Polybrominated diphenyl ethers (PBDEs) causing thyroidal effects have been demonstrated in in vivo and in vitro studies. PBDEs with structural similarities to thyroid hormones have increased recently, but the health effects for thyroid hormones have not been well studied. The study aimed to determine PBDE levels in cord blood and further to explore associations between prenatal PBDE exposures and thyroid hormones in cord blood. Fifty-four cord blood samples were collected after delivery. Cord-blood levels of BDE-15, 28, 47, 99, 100, 153, 154, and 183 were analyzed using a high resolution gas chromatograph with a high resolution mass spectrometer. Thyroid hormones were determined by an automated chemiluminescence analyzer. The mean, median, and standard deviation of ΣPBDEs were 4.72, 3.49, and 6.36 ng/g lipid, respectively. To adjust for confounding by maternal age, pre-pregnant BMI and gestational age, stepwise multiple linear regression was used after log(2) transformation of the exposure variables. A doubling of BDE-154 was associated with 0.043 ng/mL lower triiodothyronine (T3) values (adjusted r=-0.245, p=0.043). Likewise a doubling of BDE-153 was associated with 0.143 ng/mL lower free T3 (FT3) values and a doubling of BDE-183 with 0.084 ng/mL lower FT3 values (adjusted r=-0.487, p=0.023). In contrast, the T4 (thyroxine)/T3 ratio increased by 4.93 (adjusted r=0.277, p=0.017) when doubling BDE-100 exposure. No significant associations with BDE-47 or any other of the PBDEs was found. Our findings of an inverse relationship between BDE-153, BDE-154 or BDE-184 and thyroid hormones confirm the results of animal experiments but are in contrast to most epidemiological studies.

Concentrations of polybrominated diphenyl ethers in breast milk correlated to maternal age, education level, and occupational exposure

The aim of the present study is to determine whether levels of polybrominated diphenyl ethers in breast milk in the general population are associated with demographic parameters, socioeconomic status, lifestyle factors, and occupational exposure. Forty-six participants are randomly selected from healthy women recruited between April 2007 and April 2008 from local hospitals in southern Taiwan. Thirty PBDE isomers in breast milk are analyzed using a gas chromatograph with a high resolution mass spectrometer. The mean+/-standard deviation of Sigma PBDEs in breast milk is 3.59+/-1.07 ng/g lipid. Our current value of Sigma PBDEs in breast milk is 0.7-fold lower compared to the past value in our previous study between 2000 and 2001. Higher levels of Sigma PBDEs might be significantly associated with older maternal age and maternal age of the present study is between 22 and 42 years old. Levels of Sigma PBDEs and certain PBDEs in breast milk are not correlated with maternal pre-pregnant BMI (Body mass index), parity, and lipid contents of breast milk. The Sigma PBDEs level in breast milk is lower in more educated women after controlling for age and pre-pregnancy BMI in our subjects. The main factors associated with Sigma PBDEs in breast milk are age and education level among the binary variables of demographic, socioeconomic, and lifestyle characteristics in this report. The exploratory relationships are found between PBDEs in breast milk and age, education level, or occupational exposure due to small sampling size.

Impact of non-occupational exposure to polybrominated diphenyl ethers on menstruation characteristics of reproductive-age females

Polybrominated diphenyl ethers (PBDEs) have documented effects on thyroid functions and rodent behavior in vivo. Epidemiological studies, however, have revealed only limited information about associations between PBDE exposure and menstruation characteristics. Our goal was to examine whether high breast milk PBDE levels in reproductive-age females lead to interference with menstruation characteristics. We analyzed 15 PBDE congeners in 46 breast milk samples. Fifteen PBDE congeners (BDE-15, 28, 47, 49, 99, 100, 153, 154, 183, 196, 197, 203, 207, 208, and 209) were analyzed using a gas chromatograph equipped with a high resolution mass spectrometer. The mean sum of PBDEs (SigmaPBDEs) in breast milk was 3.42 ng/g lipid. Womens age at menarche was not correlated with breast milk PBDE levels. Increased BDE-208 and 209 levels were significantly associated with the prolonged length of average and the longest menstrual cycle independent of age, pre-pregnant BMI, and parity. Higher concentrations of SigmaPBDEs and the higher brominated PBDEs from BDE-183 to 209, except 197, were significantly linked to women whose menstruation periods were still coming irregularly at the sampling time. Age-adjusted odds ratios (ORs) of BDE-153, 183, 207, 208, and SigmaPBDEs were significantly higher in women with length of average menstrual cycle >32 days, compared to the control. Women whose menstruation periods still came irregularly when they were 18 years old had higher age-adjusted ORs of BDE-207, 208, 209, and SigmaPBDEs than those whose periods came regularly at the same age. Although SigmaPBDEs and certain higher brominated PBDEs appear to have potential to prolong length of average menstrual cycle and delay the age when menstruation periods begin coming regularly, these findings are not conclusive because our sample size is small and more scientific evidence is needed.

Breast-milk levels of polybrominated diphenyl ether flame retardants in relation to women's age and pre-pregnant body mass index

The aim of the present study was to determine associations between the occurrence of PBDEs in breast milk of women and their demographic parameters. Participants were randomly recruited from the general population in southern Taiwan. Thirty two breast milk samples were collected and subsequently 30 congeners of PBDEs were analyzed using a high resolution gas chromatograph with a high resolution mass spectrometer. The mean and median of SigmaPBDEs were 3.54 and 3.31 ng/g lipid, respectively. SigmaPBDE levels in breast milk were not significantly correlated with age and pre-pregnant BMI of Taiwanese mothers. We did find, however, that the higher hexaBDE level was significantly related to older age (>29 years). Higher levels of SigmaPBDEs and higher brominated PBDEs, such as nonaBDEs and decaBDE, had slightly but not significantly negative correlations with lower pre-pregnant BMI (< or =21 kg/m(2)). There were no significant differences in PBDE levels among parity and ethnic groups. SigmaPBDE levels in Taiwanese breast milk were lower than those reported from the United States or Canada. SigmaPBDE levels of the present study (2007-2008) are significantly lower than those found in our previous report (2000-2001). Although our results were limited by the sampling size, preliminary results suggest the exploratory relations to show positive associations of PBDE homologues (e.g. triBDEs and hexaBDEs) with maternal age. PBDEs pattern of breast milk may have changed after pentaBDEs were stopped to use in Taiwan.

Associations of polybrominated diphenyl ethers (PBDEs) in breast milk and dietary habits and demographic factors in Taiwan.

The aim of this study was to examine levels of PBDEs in breast milk associated with seafood consumptions of Taiwanese mothers. Our participants were selected from healthy women recruited between December 2000 and November 2001 from a medical center in central Taiwan. The congeners of PBDEs in 20 milk samples were analyzed by a gas chromatograph with a high resolution mass detector. The mean level of BDE47 in breast milk from mothers with pre-pregnant BMI <22.0kg/m2 had a significantly higher magnitude compared to those with pre-pregnant BMI > or = 22.0kg/m2 (1.59 vs. 0.995ng/g lipid, p=0.041). We did not find significant correlations between PBDEs exposure levels and womens age, parity, blood pressure, annual household income, and education level. Women who ate more fish and meat did not show significantly higher PBDE levels than those who ate less, but a significant difference in PBDE levels was demonstrated between the higher (2.15ng/g lipid) and lower (3.98ng/g lipid) shellfish consuming subjects (p=0.002) after an adjustment for the confounders. The ratios of PCB153/BDE47, PCB153/BDE153, and PCB153/PBDEs were significantly correlated with frequent consumption of fish and shellfish. The PCB153/BDE153 ratio was not associated with the other dietary habits (i.e. meat). The ratios of PCB153/PBDEs may therefore be a new indicator for exposure as a result of seafood consumption.

Estrogenic effects in the influents and effluents of the drinking water treatment plants

Estrogen-like endocrine disrupting compounds (EEDC) such as bisphenol A, nonylphenol, and phthalic acid esters are toxic compounds that may occur in both raw- and drinking water. The aim of this study was to combine chemical- and bioassay to evaluate the risk of EEDCs in the drinking water treatment plants (DWTPs). Fifty-six samples were collected from seven DWTPs located in northern-, central-, and southern Taiwan from 2011 to 2012 and subjected to chemical analyses and two bioassay methods for total estrogenic activity (E-Screen and T47D-KBluc assay). Among of the considered EEDCs, only dibutyl phthalate (DBP) and di (2-ethylhexyl) phthalate (DEHP) were detected in both drinking and raw water samples. DBP levels in drinking water ranged from <MDL to 0.840xa0μg/L and from <MDL to 0.760xa0μg/L in raw water. DEHP had higher detection rate (82.1xa0%) than other compounds and was present in both drinking water and raw water from all the DWTPs. The highest daily drinking water intake calculated for male and female were 0.0823 and 0.115xa0μg/kg per day. The two selected bioassays were conducted for the first batch of 56 samples and a detection rate of 23xa0% for estradiol equivalent (EEQ) lower than the LOQ to 1.3 and 15xa0% for EEQ lower than LOQ to 0.757 for the second 53 samples. Our results showed a good correlation between E-screen and chemical assay which indicates that a combination of both can be used in detecting EEDCs in environmental samples.

The inhibition effect of 2,3,7,8-tetrachlorinated dibenzo-p-dioxin-induced aryl hydrocarbon receptor activation in human hepatoma cells with the treatment of cadmium chloride.

Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), considered as endocrine disruptors, tend to accumulate in fatty tissues. Dioxin-responsive element chemical activated luciferase gene expression assay (DRE-luciferase assay) has been recognized as a semi-quantitative method for screening dioxins for its fast and low-cost as compared with HRGC/HRMS. However, some problems with the bioassay, including specificity, detection variation resulted from different cleanup strategies, and uncertainty of false-negative or false-positive results, remain to be overcome. Cadmium is a prevalent environmental contaminant around the world. This study was aimed to examine the effects of cadmium on the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced activation of aryl hydrocarbon receptor (AhR)-mediated gene expression in human hepatoma cells (Huh7-DRE-Luc cells and Huh7 cells). Ethoxyresorufin-O-deethylase (EROD) and DRE-luciferase assay were employed to determine the enzyme activity of cytochrome P450 1A1 (CYP1A1) and activation of AhR, respectively. The results showed that Cd(2+) levels significantly inhibited the induction of TCDD-induced CYP1A1 and DRE luciferase activation in hepatoma cells. The 50% inhibited concentrations (IC(50)) of CdCl(2) were 0.414 microM (95% confidence interval (C.I.): 0.230-0.602 microM) in Huh7-DRE-Luc cells and 23.2 microM (95% C.I.: 21.7-25.4 microM) in Huh7 cells. Accordingly, prevention of interference with non-dioxin-like compounds in a DRE-luciferase assay is of great importance in an extensive cleanup procedure.

Use of a highly sensitive recombinant hepatoma cell method to determine dioxin concentrations in samples of fish and crab from a hotspot area

A new and easy fast-screening test (the Ad-DR (adenoviral vector-dioxin response) bioassay) for dioxins in biological samples from highly dioxin-contaminated areas was developed. The aryl-hydrocarbon-receptor (AhR) reporter system was utilized to transport a dioxin-responsive-element (DRE) via an adenovirus vector into rat hepatoma (H4IIE) cells before each experiment; these DRE-H4IIE cells were utilized in the Ad-DR bioassay. Biological extracts were simultaneously analyzed by the Ad-DR bioassay and high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS). A good correlation was found between the results of the HRGC/HRMS assay and those of the Ad-DR bioassay (R(2) = 0.920, p < 0.001). The bio-analytical equivalent (BEQ) value found in fish or crab caught in the abandoned pentachlorophenol plant (AP) was extremely high compared with the BEQ in fish or crab caught in two rivers nearby this abandoned plant. Dioxins were more heavily bioaccumulated in fish viscera than in fish muscles or in the whole fish. Two-way analysis of variance tests identified the significant effects of fish collection site, fish or crab tissue sample and the interaction between them on dioxin levels in the tissues of these aquatic animals. In conclusion, the Ad-DR bioassay is a useful tool to determine dioxin levels in samples of fish and crab. Compared with fish tissues, where a sample is taken (in the PCP plant or nearby rivers) is the most important factor to determine bioaccumulation of dioxins in fish.

Association between Organochlorine Pesticide Levels in Breast Milk and Their Effects on Female Reproduction in a Taiwanese Population

Only few studies have focused on organochlorine pesticides (OCPs) in breast milk and the related health risks for women in Taiwan. Our goal is to examine breast milk OCPs and their associations with female reproductive function (infertility, gynecological diseases, and menstruation characteristics) as well as their correlation with sociodemographic parameters (age, pre-pregnant body mass index (BMI), annual incomes, population, birth year, and parity) and dietary habit. The breast milk samples were collected in southern Taiwan (n = 68) from 2013 to 2016 and the OCP residues were analyzed using high resolution gas chromatography with low resolution mass spectrometry (HRGC/LRMS). The results show that the most abundant OCP residues in the breast milk was ΣDDT with the geometric mean ± standard deviation of 9.81 ± 7.52 ng−1 lipid−1 followed by ΣHCH (0.539 ± 0.557 ng−1·lipid−1). In the principal component analysis, cis-chlordane (cis-CHL) and γ-HCH were found to be related to participants who received medical treatment for infertility, and 4,4′-DDT was associated with those who received gynecological surgery. The logistic regression showed that the odds ratio (OR) of log γ-hexachlorocyclohexane (γ-HCH) was higher for mothers who had received medical treatment for infertility than for the normal group (OR = 25.6, p = 0.035) after adjustments for age, pre-pregnant BMI, annual income, population (i.e., native-born Taiwanese), birth year, and parity. Cow milk and beef consumption as well as menstruation characteristics such as average menstrual period (>5 days), shortest menstrual period (<3 days), and women who had taken hormonal drugs were significantly associated to several OCP residues in the breast milk. In addition, ΣHCH including β-HCH and γ-HCH was correlated with annual family income and gravidity as well as cow milk and beef consumptions. Overall, γ-HCH exhibited a probable association with the infertility diseases of Taiwanese women, and dietary habit might play an important role in the female Taiwanese exposure to OCPs.

Levels of PCDD/Fs, PBDEs, and PBDD/Fs in Breast Milk from Southern Taiwan

This study investigates the congener-specific concentrations of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), polybrominated dibenzo-p-dioxins/furans (PBDD/Fs), and polybrominated diphenyl ethers (PBDEs) in 25 breast milk samples from southern Taiwan. Most investigated congeners in Taiwanese breast milk are detectable except for PBDD/Fs. The geometric means of PCDD/Fs and PBDEs in the breast milk are 2.44xa0pg WHO2005-TEQ/g lipid and 2810xa0pg/g lipid. Several PCDD/F and PBDE congeners were highly correlated to each other like 1,2,3,7,8-PeCDD and 2,3,4,7,8-PeCDF (ru2009=u20090.919, pu2009<u20090.001). The longest duration of menstruation could be predicted by BDE-153 (βu2009=u20090.252) and 1,2,3,4,6,7,8-HpCDF (βu2009=u20090.345) with adjustment of confounders using a multiple stepwise linear regression model (ru2009=u20090.963, pu2009<u20090.001).