Bisphenol A (BPA) exposure during the perinatal and postnatal periods increases the susceptibility to disease over the life cycle. However, information on the BPA delivered to fetuses or infants via ...the placenta and breastfeeding is limited. We determined the BPA exposure levels in various bodily fluids and tissues of pregnant women and described fetus and infant exposures to BPA based on associations and BPA ratios in mother–neonate paired samples. Maternal serum, urine, placenta, breast milk, cord serum, and neonatal urine samples were collected from 318 mother–neonate pairs at six university hospitals in Korea. BPA levels were detected using liquid chromatography tandem mass spectrometry. The ratios of the BPA levels in the other sample types to the levels in maternal serum were calculated. BPA was detected in 79.5–100% of the maternal and fetal samples. The median BPA concentration in the samples decreased in the order of neonatal urine (4.75ng/mL), maternal urine (2.86ng/mL), cord serum (1.71ng/mL), maternal serum (1.56ng/mL), breast milk (0.74ng/mL), and the placenta (0.53ng/g). We estimated the ratios of BPA levels in the other sample types to those in maternal serum. The median (95th percentile) cord serum-to-maternal serum ratio was 1.12 (15.2) for 160 mother–fetal pairs, in which BPA was detected in both samples. The placenta-, maternal urine-, neonatal urine-, and breast milk-to-maternal serum ratios were 0.28 (5.31), 1.79 (29.9), 1.98 (28.2), and 0.51 (10.5), respectively. In addition, the median (95th percentile) cord serum-to-placenta ratio was 4.03 (45.8), and the neonatal urine-to-cord serum ratio was 1.95 (25.6). The 95th percentile values were 14–20-fold greater than the medians. Urine contained the highest BPA concentrations, followed by serum, breast milk, and the placenta. The variations of BPA ratio show individual differences in the amounts of BPA delivered from mother to fetus.
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•Not enough data on tissue distribution of BPA in mother‑neonate (or fetus) pair•The order of BPA concentrations in examined tissue or bio-samples are urine in mother and neonates>cord serum>maternal serum>breast milk>placenta.•BPA in cord serum, significantly associated with in maternal serum and urine but not in others.•The variations of BPA ratio show individual differences in the amounts of BPA delivered from mother to fetus.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
•Associations between urinary chemicals and obesity & DM were studied in KoNEHS Cycle 3.•Three different methods for adjusting urine dilution were compared.•Creatinine and SG appear to bias the ...associations with obesity and DM, respectively.•Following CAS, DEHP metabolites, MBzP, BPA, and EtP were associated with obesity.•Following CAS, urinary BPA, MeP, and EtP were associated with DM.
Phthalates and bisphenol A (BPA) have been suspected as risk factors for obesity and diabetes mellitus (DM) among humans. However, associations between phthalates and environmental phenols are often inconsistent across different populations. In this study, we recruited the adult population (n = 3782) of the Korean National Environmental Health Survey (KoNEHS) 2015–2017 (Cycle 3) and assessed the associations between urinary biomarkers of phthalate, BPA, and paraben exposure with obesity and DM. A potential collider issue with the use of urinary creatinine (Cr) or specific gravity (SG) exists when adjusting urinary dilution; therefore, a covariate-adjusted standardization (CAS) was employed for adjustment, and the results were compared. In the present population, the direction of the association often varied depending on the choices made to adjust urinary dilution. When using CAS, the direction of association resembled those of previously reported experimental observations. With Cr or SG adjustment, ORs for obesity decreased in the highest quartiles of monocarboxyoctyl phthalate (MCOP) OR (95% CI) = Cr: 0.71 (0.54, 0.93); SG: 0.68 (0.52, 0.90), monocarboxy-isononyl phthalate (MCNP) OR (95% CI) = Cr: 0.67 (0.52, 0.87); SG: 0.68 (0.52, 0.89), and mono(3-carboxylpropyl) phthalate (MCPP) in the urine OR (95% CI) = Cr: 0.60 (0.47, 0.76); SG: 0.61 (0.48, 0.77); however, with CAS, these negative associations disappeared. Instead, mono-benzyl phthalate (MBzP) OR (95% CI) = 1.31 (1.03, 1.66), BPA OR (95% CI) = 1.62 (1.27, 2.06), or ethyl paraben (EtP) OR (95% CI) = 1.51 (1.19, 1.91) concentrations in the highest quartile showed positive associations with a higher risk of obesity. On the other hand, for DM, an overall decrease in ORs was observed for phthalate metabolites and BPA following SG adjustment and disappeared with CAS adjustment. In addition, the highest quartiles of BPA, methyl paraben (MeP), and ethyl paraben (EtP) showed a significantly higher risk of DM than those in the lowest quartiles following CAS OR (95% CI) = BPA: 1.65 (1.06, 2.59); MeP: 1.68 (1.08, 2.60); and EtP: 2.74 (1.77, 4.24), respectively. The present observations outline the importance of using an appropriate adjustment method for urinary dilution in association studies on obesity and DM. In addition, several phthalates, BPA, and parabens were identified as potential chemical risk factors for these outcomes. Further studies are warranted in other populations to confirm these observations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•PFOS, PFOA, PFUnDA, and PFNA were the predominant compounds in breast milk.•Concentrations of PFASs were significantly correlated with maternal age, BMI, and parity.•Increased levels of PFASs were ...found in breast milk after the first month of nursing.•Snack consumption and frequency of eating-out were significantly associated with increased PFAS levels.•The infant exposure levels of PFOS and PFOA via breast milk were lower than the TDI.
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Breastfeeding is an important exposure pathway to perfluoroalkyl substances (PFASs) for newborn infants. Nevertheless, reports are limited on the occurrence and time-course of PFASs in breast milk, and most studies have focused on the analysis of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). In this study, 16 PFASs were analyzed in breast milk samples (n=293) collected from 128 mothers in Korea during various lactation periods to assess maternal exposure levels, contamination profiles, time-course variations, and infant health risks. The total concentrations of PFASs (ΣPFAS) ranged from 31.7 to 1004 (median: 188) ng/L, which was within the ranges recently reported for Asian and European populations. After a month of nursing, the concentrations of PFOS, PFOA, perfluorononanoic acid (PFNA), and ΣPFAS significantly increased. This could be due to changes in the dietary and behavior patterns of the mothers after the first month of lactation. The concentrations of PFOS and PFOA were significantly correlated with maternal age, body mass index, and parity. Certain types of diet (e.g. consuming snacks and milk) and eating-out frequency were significantly associated with increasing levels of PFAS. Significant correlations and similar time-course trends were found between PFASs and PCBs/DDTs, implying similar exposure sources and biokinetics for these contaminants. The estimated daily intakes of PFOS and PFOA via the consumption of breast milk were below the tolerable daily intakes for infants suggested by the European Food Safety Authority (EFSA).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Exposure to persistent organic pollutants (POPs) during pregnancy is associated with a disruption in thyroid hormone balance. The placenta serves as an important environment for fetal development and ...also regulates thyroid hormone supply to the fetus. However, epigenetic changes of thyroid regulating genes in placenta have rarely been studied. This study was conducted to evaluate the association between several POP concentrations in maternal serum and DNA methylation of thyroid hormone-related genes in the placenta. The placenta samples were collected from 106 Korean mother at delivery, and the promoter methylation of the placental genes was measured by a bisulfite pyrosequencing. The deiodinase type 3 (DIO3), monocarboxylate transporter 8 (MCT8), and transthyretin (TTR) genes were selected as the target genes as they play an important role in the regulation of fetal thyroid balance. Because people are exposed to multiple chemicals at the same time, a multiple-POP model using principal component analysis (PCA) was applied to evaluate the association between the multiple POPs exposure and the epigenetic change in placenta. In addition, a single-POP model which includes one chemical each in the statistical model for association was conducted.
Based on the single-POP models, serum concentrations of p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) and brominated diphenyl ether-47 (BDE-47) were significantly associated with an increase in placental DIO3 methylation, but only among female infants. Among male infants, a positive association between serum p,p′-DDT and MCT8 methylation level was found. According to the multiple-POP models, serum DDTs were positively associated with DIO3 methylation in the placenta of female infants, while a positive association with MCT8 methylation was observed in those of the male infants. Our observation showed that in utero exposure to DDTs may influence the DNA methylation of DIO3 and MCT8 genes in the placenta, in a sexually dimorphic manner. These alterations in placental epigenetic regulation may in part explain the thyroid hormone disruption observed among the newborns or infants followed by in utero exposure to POPs.
•Promoter DNA methylation of placental genes related to thyroid hormone was measured.•Some maternal serum POPs were associated with methylation of these placental genes.•DNA methylation of DIO3 and MCT8 genes by maternal POP was differed by infant sex.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Chronic kidney disease (CKD) is a global health threat of growing concern. Recently, exposure to endocrine disrupting compounds (EDCs) such as phthalates and bisphenol A has been suggested as a risk ...factor for CKD. However, most epidemiological studies have focused on a limited number of urinary chemicals. This study aimed to identify chemical determinants of the urinary albumin-to-creatinine ratio (ACR), which is a kidney function marker, among multiple major EDCs including phthalate metabolites, bisphenols, and benzophenones in a Korean female population (20–45 years old, n = 441). First, the creatinine-adjusted urinary concentration of each urinary chemical was associated with ACR in a linear regression model (single-pollutant model). Then, compounds with a significant association with ACR in the single-pollutant model were added in a multi-pollutant model and evaluated for their association with ACR. Moreover, to prevent potential reverse causality due to impaired kidney function, quartile analyses were performed for the subjects with healthy renal function (ACR < 9.71 mg/g). In addition to creatinine adjustment, the statistical analysis was also conducted with specific gravity-adjusted concentrations of urinary chemicals, and the results were compared. Several compounds measured in the urine showed a significant association with ACR in the single-pollutant model. In the multi-pollutant model, however, only monobutyl phthalate and benzophenone-1, which are metabolites of dibutyl phthalate and benzophenone-3, respectively, showed significant positive associations. The association of these chemicals remained significant in a couple of the sensitivity analyses with a different adjustment of urine dilution and in a subpopulation with normal ACR. In conclusion, among dozens of urinary chemicals, monobutyl phthalate and benzophenone-1 consistently showed a strong association with urinary ACR. Confirmation of our observation in other human populations and experimental studies is warranted.
•Multiple urinary compounds were associated with ACR among healthy adult female.•For the first time, association of benzophenones with kidney function was observed.•MBP, a metabolite of DBP, also consistently showed strong association with ACR.•Association of bisphenol A and DEHP with ACR was not obvious.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Associations of phthalates and bisphenol A with thyroid hormones were assessed.•Phthalates were associated with decreased free T3 and increased TBG.•BPA was associated with decreased total T3 and ...increased total T4.•Associations with free T3 and TBG were stronger in adults without thyroid antibodies.
Exposure to consumer chemicals such as phthalates and phenolic compounds has been associated with thyroid hormone disruption in humans. However, information related to factors that may influence such associations, e.g., transport and activation of the hormones, and autoimmunity status, is limited. In the present study, we employed a subpopulation of adults (n = 1,254) who participated in the Korean National Environmental Health Survey (KoNEHS) 2015–2017, and associated urinary concentrations of major phthalate metabolites, bisphenol A (BPA), and parabens, with thyroid hormone-related measures, including free and total T3 and T4, TSH, thyroxine-binding globulin (TBG), calculated peripheral deiodinase (DIO) activity, and thyroid autoantibodies of thyroperoxidase (TPO) and thyroglobulin (Tg). Phthalate metabolites were negatively associated with total T4 and free T3, and positively associated with total T3. These observations could be explained by TBG levels and calculated peripheral DIO activity that were positively associated with phthalates exposure. In contrast, BPA was positively associated with total T4 and negatively associated with total T3, without any changes in TBG concentration. Serum TPO and Tg antibodies were not associated with urinary phthalate metabolites and BPA. However, thyroid autoantibody status appeared to modulate the association of some phthalates with thyroid hormones. For parabens, little to negligible association was observed. The results of our observation show potential underlying mechanisms of phthalates-induced thyroid hormone disruption, and suggests the importance of consideration of thyroid autoimmunity status in association studies for thyroid disrupting chemicals.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Current knowledge on adverse endocrine disruption effects of persistent organic pollutants (POPs) among newborn infants is limited and often controversial. To investigate the associations between ...prenatal exposure to major POPs and thyroid hormone levels among newborn infants, both cord serum or maternal serum concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (OCPs) were compared with five thyroid hormones in cord serum of newborn infants as well as TSH in bloodspot collected at 2 day after birth (n=104). Since cord serum thyroid hormones could be affected by those of mothers, thyroid hormone concentrations of the matching mothers at delivery were adjusted. In cord serum, BDE-47, -99, and Σchlordane (CHD) showed significant positive associations with cord or bloodspot TSH. At the same time, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and hexachlorbenzene (HCB) showed negative associations with total T3 and total T4 in cord serum, respectively. Maternal exposure to β-hexachlorhexane (β-HCH), ΣCHD, ΣDDT, or p,p'-DDE were also associated with neonatal thyroid hormones. Although the sample size is small and the thyroid hormone levels of the subjects were within the reference range, our observation supports thyroid disrupting potential of several POPs among newborn infants, at the levels occurring in the general population. Considering the importance of thyroid hormones during gestation and early life stages, health implication of thyroid hormone effects by low level POPs exposure deserves further follow up investigations.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We collected influent and effluent samples from four sewage treatment plants (STPs) as well as surface water samples in Han River of Seoul, Korea, in three sampling events representing different flow ...conditions, i.e., April, June, and August, 2005, and analyzed for eleven pharmaceuticals including acetaminophen, caffeine, carbamazepine, cimetidine, diltiazem, trimethoprim, and five sulfonamide antibiotics, using LC-MS-ESI. Pharmaceuticals of high annual production amount were detected in higher level in STP influents. Levels of pharmaceutical residues in the influents were the highest for acetaminophen (average 27,089 ng/L), followed by caffeine (23,664 ng/L), cimetidine (8045 ng/L), and sulfamethoxazole (523 ng/L). Levels of acetaminophen and caffeine in STP effluents were very low compared to the influent concentrations. However cimetidine was detected in relatively high levels even in STP effluent samples. In effluent samples, cimetidine showed the highest level (5380 ng/L), followed by caffeine (278 ng/L), sulfamethoxazole (193 ng/L), and carbamazepine (111 ng/L). The concentration of cimetidine was also the highest in surface water samples (average 281 ng/L), which is the highest level reported from surface water worldwide to our knowledge. Caffeine (268.7 ng/L), acetaminophen (34.8 ng/L), and sulfamethoxazole (26.9 ng/L) were also detected in relatively high levels. Levels of pharmaceuticals detected in surface water samples upstream STPs were generally very low compared to the downstream samples, suggesting that the STPs potentially be a major source of the test pharmaceuticals into Han River. The hazard quotients (HQs) were calculated for the test pharmaceuticals based on their occurrences in surface water, and no pharmaceutical resulted in HQ greater than one, suggesting that their potential environmental impact may be low.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
To understand potential risks of major pharmaceutical residues in waters, we evaluated ecotoxicities of five major veterinary pharmaceuticals, i.e., chlortetracycline, oxytetracycline, ...sulfamethazine, sulfathiazole, and erythromycin, which have been frequently detected in freshwater environment worldwide. We conducted acute and chronic toxicity tests using two freshwater invertebrates (
Daphnia magna
and
Moina macrocopa
) and a fish (
Oryzias latipes
). In general,
D. magna
exhibited greater sensitivity than
M. macrocopa
, and chronic reproduction was the most sensitive endpoints for both organisms. The population growth rate was adversely influenced by exposure to chlortetracycline, sulfamethazine, or sulfathiazole in water fleas, but reduction in population size was not expected. In
O. latipes
, the tested pharmaceuticals affected several reproduction related endpoints including time to hatch and growth. Based on the toxicity values from the present study and literature, algae appeared to be the most sensitive organism, followed by
Daphnia
and fish. Hazard quotients derived from measured environmental concentrations (MECs) and predicted no effect concentrations (PNECs) for erythromycin and oxytetracycline exceeded unity, suggesting that potential ecological effects at highly contaminated sites cannot be ruled out. Long-term consequences of veterinary pharmaceutical contamination in the environment deserve further investigation.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Persistent organic pollutants such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (OCPs) are of global concern because of their widespread ...contamination and adverse health effects. Potential endocrine disruption, especially of thyroid status by PCBs has been repeatedly suggested in both experimental and epidemiological studies. However the associations with PBDEs or OCPs have been arguable especially in human populations. We investigated the associations between major groups of POPs and thyroid hormone balances among pregnant women. One hundred five pregnant women at delivery were recruited from four cities of Korea in 2011 and were investigated. Blood samples were collected within a day before delivery. Serum was then analyzed for 19 PCBs, 19 PBDEs, and 19 OCPs, along with five thyroid hormones (free and total T3 and T4, and TSH). Several PCBs such as PCB28, 52, and 118 showed negative associations with T3 or T4. BDE47 and total PBDEs showed significant associations with T3 or T4. For OCPs, dichlorodiphenyltrichloroethanes (DDTs) and hexachlorobenzene (HCB) were generally associated with reduction of T3 or T4. The thyroid hormone levels of all subjects were within the reference range, however exposure to several target POPs were clearly related with potential for disrupting thyroid hormone balance among pregnant women, at the current level of exposure. Although subtle, the changes in thyroid hormones should be seen with caution because even minor changes within pregnant women may have significant consequences especially on sensitive population like fetus.
•Associations between POPs and thyroid hormone levels were examined in pregnant women.•Several PCBs and OCPs are significantly associated with T3 or T4 levels.•PBDEs showed thyroid disrupting potential, but the directions were inconsistent.•Implications of POPs exposure on fetus during gestation deserve further investigation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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