Association between environmental chemical exposure and albumin-to-creatinine ratio is modified by hypertension status in women of reproductive age.

Chemicals have been identified as a potential risk factor of renal dysfunction. However, studies that consider both multiple chemicals and non-chemical risk factors, such as hypertension, are rare. In this study, we assessed the associations between exposure to several chemicals, including major metals, phthalates, and phenolic compounds, and the albumin-to-creatinine ratio (ACR). A group of Korean adult women in reproductive age (n = 438, aged between 20 and 49 years), who had previously been studied for association of several organic chemicals, was chosen for this purpose. We constructed multivariable linear regression models for individual chemicals and weighted-quantile sum (WQS) mixtures, by hypertension status. Among the study population, approximately 8.5% of the participants exhibited micro/macro-albuminuria (ACR ≥30 mg/g), and 18.5% and 3.9% exhibited prehypertension and hypertension, respectively. Blood cadmium and lead levels showed a stronger association with ACR only among women with prehypertension or hypertension. Among organic chemicals, depending on the statistial model, benzophenone-1 (BP-1) and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) showed a significant association regardless of hypertension status, but most associations disappeared in the (pre)hypertensive group. These findings clearly indicate that hypertension status can modify and may potentiate the association of environmental chemicals with ACR. Our observations suggest that low-level environmental pollutant exposure may have potential adverse effects on kidney function among general adult women. Considering the prevalence of prehypertension in the general population, efforts to reduce exposure to cadmium and lead are necessary among adult women to minimize the risk of adverse kidney function.

Variability of urinary creatinine, specific gravity, and osmolality over the course of pregnancy: Implications in exposure assessment among pregnant women.

Due to dilution status of the urine, chemical concentrations measured in spot urine are frequently adjusted using correction factors, such as creatinine, specific gravity (SG), or osmolarity of the urine. Urinary correction factors, however, can be influenced dramatically by physiological changes such as pregnancy. Details about the variation of urine dilution over the course of pregnancy are not well characterized. In the present study, we investigated the variation of urine correction factors over time among the pregnant women of Korea (n = 69) and Thailand (n = 102). Creatinine, SG, and osmolality were determined in the urine samples obtained in each trimester of the participating women, and were compared by sampling time and by nationality. Implication of the variation in these correction factors was studied using phthalate metabolites measured in the urine samples as model chemicals. Urinary correction factors significantly varied across the trimesters especially in Korean pregnant women: urinary creatinine and osmolality were significantly lower in the third trimester (T3) urine than the first trimester (T1) urine. Urinary creatinine and SG of the T3 urine of Korean pregnant women were also significantly lower than those reported from the non-pregnant women who participated in Korean National Environmental Health Survey (KoNEHS) 2015-2017. Among Thai women, however, these correction factors were rather stable across the pregnancy. Differences in ethnicity, or in behavior such as water consumption amount may partly explain the differences. Temporal changes in these urine correction factors influenced the urinary phthalate metabolite concentrations adjusted for dilution, in both Korean and Thai pregnant women. The present observations show that the variations of urinary correction factors should be considered in exposure assessment of urinary chemicals for pregnant women, in order to circumvent potential bias due to physiological changes occurring during pregnancy, and to reduce errors in exposure classification and association.

Exposure to organophosphate esters, phthalates, and alternative plasticizers in association with uterine fibroids.

Exposure to endocrine disrupting chemicals is suggested to be responsible for the development or progression of uterine fibroids. However, little is known about risks related to emerging chemicals, such as organophosphate esters (OPEs) and alternative plasticizers (APs). A case-control study was conducted to investigate whether exposures to OPEs, APs, and phthalates, were associated with uterine fibroids in women of reproductive age. For this purpose, the cases (n = 32) and the matching controls (n = 79) were chosen based on the results of gynecologic ultrasonography among premenopausal adult women in Korea and measured for metabolites of several OPEs, APs, and major phthalates. Logistic regression models were employed to assess the associations between chemical exposure and disease status. Factor analysis was conducted for multiple chemical exposure assessments as a secondary analysis. Among OPE metabolites, diphenyl phosphate (DPHP), 2-ethylhexyl phenyl phosphate (EHPHP), and 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP) were detected in >80% of the subjects. Among APs, metabolites of di-isononyl phthalate (DINP) and di(2-propylheptyl) phthalate (DPrHpP) were detected in >75% of the urine samples. The odds ratios (ORs) of uterine fibroids were significantly higher among the women with higher exposures to tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and tris(2-butoxyethyl) phosphate (TBOEP), di(2-ethylhexyl) terephthalate (DEHTP), DPrHpP, and di-(iso-nonyl)-cyclohexane-1,2-dicarboxylate (DINCH). In addition, urinary concentrations of mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), a sum of five di(2-ethylhexyl) phthalate metabolites (∑5DEHP), and mono(4-methyl-7-hydroxyoctyl) phthalate (OH-MINP) were significantly higher in the cases. In factor analysis, a factor heavily loaded with DPrHpP and DEHP was significantly associated with uterine fibroids, supporting the observation from the single chemical regression model. We found for the first time that several metabolites of OPEs and APs are associated with increased risks of uterine fibroids among pre-menopausal women. Further epidemiological and mechanistic studies are warranted to validate the associations observed in the present study.

Occurrence and prenatal exposure to persistent organic pollutants using meconium in Korea: Feasibility of meconium as a non-invasive human matrix.

Prenatal exposure to persistent organic pollutants (POPs) is of great concern due to the vulnerability of fetus. Nineteen Polychlorinated biphenyls (PCBs), 18 organochlorine pesticides (OCPs) including DDTs, HCHs, chlordanes, and hexachlorobenzene, and 22 polybrominated diphenyl ethers (PBDEs) were measured in meconium samples from 72 newborn infants using high resolution gas chromatography/mass spectrometry. The median concentrations (on wet weight basis) of PCBs, OCPs, and PBDEs were 26.8pg/g, 66.7pg/g, and 2.32pg/g, respectively. Highly significant correlations were observed among the compounds of PCBs and OCPs, suggesting their similar sources and kinetic behaviors. BDE 47 had significant correlations with PCBs and OCPs, whereas BDE 209 was not correlated with any of the contaminants due to different exposure sources. The concentrations of p,p'-DDE, ß-HCH, and trans-nonaCHL between paired maternal blood-meconium and cord blood-meconium showed significant correlations, while PCBs and PBDEs were not significantly correlated in the paired samples. Maternal age and gestational age were demographic parameters affecting POP levels in meconium. Multiple regression analysis showed that the levels of several OCPs in cord and maternal serum were contributing factors governing the levels of these contaminants in meconium. Our results indicate that meconium can be utilized as a human matrix for prenatal exposure to several OCPs.

Association between Several Persistent Organic Pollutants in Serum and Adipokine Levels in Breast Milk among Lactating Women of Korea.

Exposure to several persistent organic pollutants (POPs) has been linked to alteration of lipid metabolism. Adipokines, such as leptin and adiponectin, are hormones that play roles in lipid metabolism, and have been suggested as markers of health effects that may lead to obesity. To date, only serum adipokines have been associated with POPs exposure. In the present study, for the first time, the associations between leptin and adiponectin in breast milk, and several POPs in serum were investigated among 82 lactating Korean women between 25 and 46 years of age. Breast milk adipokines are important because adipokine intake of infant through breastfeeding may influence the growth of infants. The median concentrations of leptin and adiponectin in skimmed milk of the Korean lactating women were 17.9 ng/L and 16.5 µg/L, respectively. Leptin concentrations in breast milk were negatively associated with ∑hexachlorohexane (HCH), oxychlordane, ∑chlordane, or 2,2',4,4',5,5'-hexachlorobiphenyl (CB 153) levels in maternal serum. Linear relationships between adiponectin and POPs concentrations were not observed, however, nonmonotonic relationship which showed generally positive associations was suggested for p,p'-dichlorodiphenyltrichloroethane (DDT) and ∑chlordane in quartile analysis. Our observations show that POPs at the current level of exposure may be associated with the alteration of lipid metabolism among lactating women. Implication of adipokine transfer to breastfed infants is of concern and deserves further investigation.

Synthetic musk compounds and benzotriazole ultraviolet stabilizers in breast milk: Occurrence, time-course variation and infant health risk.

Synthetic musk compounds (SMCs) and benzotriazole ultraviolet stabilizers (BUVSs) are used as additives in many consumer products. Limited data are available on the accumulation of SMCs in human fluids, and no data are available on BUVSs. In this study, 208 human breast milk samples were collected from 87 participants during the lactation period at <7, 15, 30, and 90 days after delivery in Korea. The total concentrations of SMCs and BUVSs ranged from

Infant exposure to polybrominated diphenyl ethers (PBDEs) via consumption of homemade baby food in Korea.

Limited data are available on the residue levels of polybrominated diphenyl ethers (PBDEs) in baby food. In this study, 24 PBDE congeners were determined in 147 homemade baby food samples collected from 97 households for 6-, 9-, 12-, 15-, and from 24 to 27-month-old infant groups during the period of 2012-2013. The concentrations of total PBDEs (ΣPBDE) ranged from 24.5 to 6000 (mean: 263) pg/g fresh weight, higher than those found in commercial formulae from the United States. The predominant congeners were BDEs 209 and 47, accounting for 92% of the ΣPBDE concentrations, reflected by high deca-BDE consumption in Korea. The residue levels and detection rates of BDE 47 in the baby food samples showed a gradual increasing trend with an increase in infant ages, due to changes in the food ingredients from hypoallergenic to greasy. The daily intakes of BDEs 47 and 209 via baby food consumption ranged from 0.04 to 0.58, 0.80 to 20.3, and 1.06 to 22.3 ng/kg body weight/day for 6-, 9-, 12-, 15-, and 24-27-month-old infant groups, respectively; these intakes were lower than the oral reference doses proposed by the US EPA. Together with three exposure sources, baby food, breast milk and dust ingestion for 6-month-old infants, the daily intake of ΣPBDE was 25.5 ng/kg body weight/day, which was similar to the intake via baby food consumption only for over 24-month-old infants in our study. This indicates that baby food is an important exposure pathway of PBDEs for over 24-month-old infants. This is the first study regarding the occurrence and exposure assessment of PBDEs via homemade baby food.

Homemade weaning foods as a source of lead and mercury exposure in Korean infants - A dietary risk assessment study.

Lead (Pb) and mercury (Hg) are neurodevelopmental toxicants that pose risks to cognitive and behavioral health. Given early childhood's vulnerability to these metals, understanding their sources and pathways of exposure during infancy is crucial for public health. During the weaning process, infants may be exposed to metals through the baby food they consume. We aimed to assess metal exposure through homemade weaning foods by analyzing 288 samples consumed by 157 Korean infants aged 6-, 9-, 12-, 15-, and 24-27 months. Pb was detected in 65 % of samples, with levels reaching up to 169 ng/g. Notably, 58 % exceeded the Maximum Level (ML) of 10 ng/g, with a median concentration of 14.7 ng/g fresh weight. Total Hg was found in 88 % of samples, with a median concentration of 4.56 ng/g fresh weight. Estimated median daily intakes of Pb and Hg were 0.29 and 0.09 µg/kg/d, respectively. Considering a benchmark dose for Pb (0.5 µg/kg/d by EFSA), 94 % (the margin of exposure <10) of all age groups was estimated to have a potential health concern associated with homemade baby food consumption. For Hg, only 6 % exceeded a hazard quotients of 1 compared to a provisional tolerable weekly intake for Hg (4 µg/kg/week by WHO). This study marks the first direct assessment of daily Pb and Hg intake through homemade baby food among Korean infants. Our findings underscore the urgent need for heightened awareness regarding metal exposure through homemade baby food.

Polybrominated diphenyl ethers (PBDEs) in breast milk of Korea in 2011: current contamination, time course variation, influencing factors and health risks.

Breast milk is a valuable biological specimen to assess maternal and infant exposure to polybrominated diphenyl ethers (PBDEs). In this study, 208 breast milk samples were collected from 89 participants during lactation period, at <7, 15, 30, and 90 days postpartum, in four cities in Korea, and were determined for 19 PBDE congeners. The total PBDE concentrations (ΣPBDE) ranged from 0.23 to 68.4 (mean: 2.73) ng/g lipid weight, and were within the ranges reported for European and Asian countries. Within a month of lactation after delivery, no significant changes were found in the PBDE concentrations. The predominance of BDE 153 rather than BDE 47 was found in the most samples that BDE 153 was detected, and was likely to be associated with stepwise debromination of BDE 209. No associations were found between PBDE concentrations in breast milk and demographic parameters, except for ΣPBDE with maternal age and delivery mode. Certain types of diet such as corn, seafood and nut correlated significantly with PBDE levels in breast milk. The estimated daily intakes of ΣPBDE for breast-feeding infants were lower than the guidelines proposed by the US EPA, indicating limited health risk from PBDEs through breast feeding.

Free Cortisol Mediates Associations of Maternal Urinary Heavy Metals with Neonatal Anthropometric Measures: A Cross-Sectional Study.

Prenatal exposure to heavy metals is known to be associated with adverse birth outcomes and oxidative stress biomarkers. In this study, we examined whether maternal free cortisol or 8-Hydroxy-2-Deoxyguanosine (8-OHdG) could mediate associations between maternal heavy metal exposure and birth outcomes. A total of 182 healthy pregnant women were recruited. Heavy metals (including Pb, Hg, and Cd), free-cortisol, and 8-OHdG were analyzed in urine at delivery. Birth outcomes including birth weight, length, Ponderal index, and head circumference were measured. To examine associations of maternal urinary heavy metals with biomarkers and birth outcomes, generalized linear models were employed. Birth length was positively associated with Pb (ß = 0.78, 95% CI: 0.09−1.46) and Hg (ß = 0.84, 95% CI: 0.23−1.45) (both p < 0.05). The Ponderal index, a measure of a newborn's leanness, was negatively associated with maternal urinary Pb (ß = −0.23, 95% CI: −0.46−−0.07) and Hg (ß = −0.26, 95% CI: −0.44−−0.08) (both p < 0.05). No association between maternal Cd and birth outcomes was observed. Most heavy metals showed positive associations with free cortisol and 8-OHdG. Free cortisol was identified as a mediator underlying the observed relationship between Hg and birth length or Ponderal index. This study observed adverse birth outcomes from maternal exposures to Pb and Hg. Increased free cortisol related to Hg exposure was suggested as a possible causal pathway from Hg exposure to birth outcomes such as the Ponderal index.

Urinary paraben concentrations of adult women by fasting status: Comparison between Korea and the United States.

Personal care products (PCPs) are considered as a major source of paraben exposure; however, the dietary contribution is not well known. We compared the urinary levels of methyl-, ethyl-, and propyl-paraben (MeP, EtP, and PrP), and investigated their associations with fasting status and contacts with other potential exposure sources among Korea and the US adult women. A group of fasting, non-pregnant adult women (n = 469) was recruited from Seoul, Ansan/Incheon, and Jeju, Korea in 2015-2016, and their urine was measured for parabens. Non-fasting Korean women of matching age (25-45 years) were chosen from the Korean National Environmental Health Survey (KoNEHS) Cycle 3 (n = 579). For the US women, both fasting (n = 154) and non-fasting (n = 201) females were chosen from the NHANES 2015-2016 participants. In fasting Korean women, the urinary MeP, EtP, and PrP concentrations (median) were measured at 47.30, 17.90, and 2.30 ng/mL, respectively. Urinary EtP and PrP levels in fasting Korean women were significantly lower than those in non-fasting women (EtP and PrP median of 26.40 and 3.57 ng/mL). On average, the difference in urinary EtP levels by fasting status was greater among the highly exposed groups. In the US population, EtP levels were significantly lower (median ranged 1.55-1.80 ng/mL depending on fasting status), but MeP levels were higher (67.90-84.35 ng/mL) than those of the Korean population. When only fasting women were considered, the median EtP levels of Korean women were 11.5-fold greater than those of US women, suggesting that the non-dietary contributions of EtP exposure could not be ignored among Korean women. Regardless of fasting status, MeP and PrP were significantly correlated, and their urinary levels in fasting Korean women were correlated with the use of several personal care products. The major dietary and non-dietary sources that may explain EtP exposure in Korean women warrant further investigation.

Associations of exposure to phthalates and environmental phenols with gynecological disorders.

Phthalates and environmental phenols might be associated with some benign diseases that have been found to be hormone-sensitive. Current knowledge on adverse effects of these chemicals among reproductive women is limited and often controversial. Therefore, the purpose of this study was to investigate the association between the urinary concentration of phthalates and environmental phenols and gynecological disorders from 512 women of reproductive age. The association between chemical concentration and disease in the control and case groups was statistically determined with the questionnaire survey data and measurements using the LC-MS/MS. The results have shown that DEHP metabolites, ethyl paraben and 3,4-DHB showed significant direct associations with leiomyoma and benign ovarian tumors (p < 0.05). We found statistically significant positive relationships between exposure to chemicals (some DEHP metabolites, DHB) and prevalence of gynecologic disorders (p < 0.05). Furthermore, the ORs for leiomyoma associated with these compounds in always user for personal care products (PCPs) was higher than those of sometimes user. High levels of urinary concentrations of these compounds such as DEHP metabolites and parabens and their metabolites showed significant associations with leiomyoma and benign ovarian tumors.

Urinary levels of phthalates and DINCH metabolites in Korean and Thai pregnant women across three trimesters.

Phthalates are anti-androgenic chemicals and may cause long-lasting adverse effects on growing fetuses. Understanding their exposure profile during pregnancy, therefore, is of public health importance. Because both behavioral and physiological changes of pregnant women are expected to be substantial, the amount of phthalate exposure is expected to vary significantly over the course of pregnancy. Temporal trend of phthalate exposure during pregnancy, however, is largely unknown, especially in Asian women. The purpose of this study is to investigate the urinary concentrations of metabolites for major phthalates and alternative plasticizers over the course of pregnancy among Korean (n = 81) and Thai women (n = 102). Twenty-four metabolites from 15 plasticizers, such as dimethyl phthalate (DMP), diethyl phthalate (DEP), di-isobutyl phthalate (DiBP), di-n-butyl phthalate (DnBP), benzyl butyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP), dioctyl phthalate (DnOP), diisononyl phthalate (DiNP), diisodecyl phthalate (DiDP), di(2-ethylhexyl) terephthalate (DEHTP), and di-(iso-nonyl)-cyclohexane-1,2-dicarboxylate (DINCH), were measured in urine samples collected in each trimester from pregnant women. While the levels of several phthalate metabolites were significantly different by trimester among Korean women, those of Thai women were relatively consistent. Urinary metabolites of DEP and DnOP were higher in Thai pregnant women compared to Korean pregnant women. The detection frequencies of the DINCH metabolite were 67.4% and 44.9% among Korean and Thai pregnant women, respectively. However, the ratio of DINCH to DEHP metabolites was significantly higher in Thai women. According to risk assessment, 11.9% of Korean and 5.3% of Thai women were considered at risk due to phthalate exposure, and DEHP, DnBP and DiBP were identified as major risk drivers. Considering the vulnerability of growing fetuses, further studies are warranted to identify major sources of exposure to these plasticizers during pregnancy.

Urinary metabolites of dibutyl phthalate and benzophenone-3 are potential chemical risk factors of chronic kidney function markers among healthy women.

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.

Maternal exposures to persistent organic pollutants are associated with DNA methylation of thyroid hormone-related genes in placenta differently by infant sex.

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.

Association of urinary phthalate metabolites and phenolics with adipokines and insulin resistance related markers among women of reproductive age.

Chemicals such as phthalates and phenolics have been associated with metabolic markers in humans. However, most studies have only looked at a limited number of chemicals, and little is known about their potential effects on adipokines in humans. In the present study, the associations between dozens of urinary chemicals, including phthalate metabolites and phenolics, and markers related to insulin resistance as well as major adipokines, were assessed among the women of reproductive age (n = 459, between 20 and 48 years of age) recruited from major cities in Korea between 2015 and 2016. Adipokines such as adiponectin and leptin, and insulin resistance related markers such as glucose and insulin, were analyzed in serum. Associations between urinary chemicals and the adipokines or insulin resistance related markers were assessed in two steps. First, ordinary least squares (OLS) regression was used to assess the association of each urinary chemical with the adipokines or insulin resistance related markers (single-pollutant model). Second, several chemicals were selected using elastic net regression and were subsequently analyzed with OLS regression model (multi-pollutant model), considering simultaneous exposure to multiple chemicals. In both single- and multi-pollutant models, several urinary chemicals consistently showed significant associations with adipokines or the insulin resistance related markers. The sum of di-(2-ethylhexyl) phthalate metabolites (ΣDEHPm) and ethyl paraben (EtP) were associated with increased serum adiponectin levels. Urinary ΣDEHPm levels also showed positive associations with fasting glucose. Moreover, urinary mono-methyl phthalate (MMP), mono-isobutyl phthalate (MiBP), and bisphenol S (BPS) levels showed positive associations with the homeostasis model assessment for insulin resistance (HOMA-IR). Interestingly, urinary propyl paraben (PrP) levels showed a negative association with HOMA-IR, in both models. Our observations show that among many consumer chemicals, phthalates may affect serum adipokines, and thus glucose, and insulin resistance in adult females. Further confirmation is warranted in other populations.

Bisphenol A in infant urine and baby-food samples among 9- to 15-month-olds.

Diet is the predominant source of bisphenol A (BPA) intake, but limited data are available on BPA levels in the diet of younger infants. This study investigated BPA levels in baby-food and urine samples collected from young infants (under 2 years old). Samples of homemade baby food (n = 210) and urine (n = 187) were collected at 9, 12, and 15 months after birth from a panel of Korean infants (n = 173). BPA levels in urine and food were measured using HPLC-MS/MS and GC-MS, respectively. BPA was above the limit of detection (LOD) in 85.5-85.7% of the urine samples and 32.5-76.3% of the baby-food samples. The median levels of BPA were 0.45 ng/g wet weight (IQR: not detectable to 5.16 ng/g wet weight) in homemade baby food, 0.93 µg/L (IQR:

Perfluoroalkyl substances (PFASs) in breast milk from Korea: Time-course trends, influencing factors, and infant exposure.

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).

Placental transfer of persistent organic pollutants and feasibility using the placenta as a non-invasive biomonitoring matrix.

The placenta is a crucial organ for the supply of oxygen and nutritional elements from mother to fetus. Several studies have reported evidence of the placental transfer of persistent organic pollutants (POPs). Despite the importance of prenatal exposure to POPs, the transport process of POPs via the human placenta is not well understood. To investigate the transport processes of these contaminants and to assess the feasibility of the placenta as a non-invasive biological matrix, we measured 19 polychlorinated biphenyls (PCBs), 18 organochlorine pesticides (OCPs), and 24 polybrominated diphenyl ethers (PBDEs) in placenta tissues. The total concentrations of PCBs, OCPs, and PBDEs in placental tissues ranged from 0.36 to 75.2 (median: 5.85) ng/g lipid wt, 1.37 to 250 (63.5) ng/g lipid wt, and 1.21 to 427 (11.7) ng/g lipid wt, respectively. The BDE 209 concentrations were higher than those reported in previous studies presumably because of the high consumption of deca-BDE technical mixtures in Korea. The concentrations of all of the POPs in placental tissues correlated significantly with each other, but BDE 209 concentration did not correlate with that of any other contaminants possibly because of different exposure sources and kinetics. Maternal age, body mass index, and parity were contributors to the accumulation of several POPs in the placenta. Partitioning ratios between maternal blood-placenta-cord blood showed that lower molecular-weight and hydrophobic POPs were preferentially transported from maternal blood to the placenta and that higher molecular-weight and hydrophobic contaminants tended to remain in placental tissues. Regression analysis showed significant relationships between the POP concentrations in multiple biological matrices such as maternal blood, placenta, cord blood, and meconium. These relationships suggest that the placenta can be used as a non-invasive matrix for biomonitoring prenatal exposure to several POPs.

Prenatal exposure to persistent organic pollutants and methylation of LINE-1 and imprinted genes in placenta: A CHECK cohort study.

Prenatal exposure to persistent organic pollutants (POPs) has been linked to numerous adverse birth outcomes among newborn infants in many epidemiological studies. Although epigenetic modifications have been suggested as possible explanations for those associations, studies have rarely reported a relationship between POP exposure during pregnancy and DNA methylation in the placenta. In the present study, we investigated the association between prenatal exposure to several POPs, including organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs), and methylation levels of long interspersed element 1 (LINE-1), as well as imprinted genes in placental DNAs among Korean mother-child pairs (N = 109). We assessed the association of DNA methylation not only with each target POP (single-POP models) but also with multiple POPs applying principal component analysis (multiple-POP models). Potential associations between placental DNA methylation and birth outcomes of newborn infants were also estimated. In single-POP models, significant associations were detected between OCP measurements and placental DNA methylation. Elevated concentrations of ß-hexachlorhexane (ß-HCH) in maternal serum collected during delivery were significantly associated with a decrease in methylation of LINE-1 in the placenta. Higher levels of p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) in maternal serum were associated with hypermethylation of insulin-like growth factor 2 (IGF2). In multiple-POP models, a significant and positive association between DDTs and IGF2 methylation was also observed. Placental LINE-1 methylation was inversely associated with birth length. Our observations indicate that prenatal exposure to several POPs including DDTs is associated with the changes in methylation of genes, including major imprinted genes in the placenta. The consequences of these epigenetic alterations in placenta during development deserve further investigation.