Exposure assessment of polybrominated diphenyl ethers (PBDE) in early life stage using biomonitoring data

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Mi-Yeon Shin

보건대학원 보건학과
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서울대학교 대학원
Polybrominated diphenyl ethers (PBDEs)BDE 209BDE 47maternal transferreverse dosimetryphysiologically based pharmacokinetic (PBPK) model
학위논문 (박사)-- 서울대학교 대학원 : 보건학과, 2017. 2. 김성균.
Polybrominated diphenyl ethers (PBDEs), a group of synthetic organic chemicals with 209 congeners, have been widely used as chemical flame retardants for several decades. Owing to the stable chemical structure and strong tendency for bio-accumulation of PBDEs, they have been found in many biota specimens as persistent pollutants, and are regarded as endocrine disruptors. Endocrine disruption during critical developmental periods may result in irreversible effects on differentiating tissue, including the brain. It imply that exposure to PBDEs in early life stage should be focused on.
Many researches have reported the exposure distribution of PBDEs in early life stage as analyzed umbilical cord serum, and the levels were considerable compared to the levels in maternal serum. It support that the fetus is exposed to PBDEs through the mother. The exposure amounts from placenta transfer would be retained in young children after birth, which could be supported that the estimated half-lives of PBDEs in human body are long enough. However, this part has not been considered to estimate exposure amounts in young children. If the ignored amounts can be estimated, knowledge gaps will be filled to better understand the total exposure to PBDEs in young children.
The prenatal exposure of PBDEs influence on fetus through placental transfer and young children through lactational transfer. In other words, prenatal exposure closely related to the exposure levels across early life stage. Through the previous studies, positive associations between prenatal exposure from predominant exposure sources and fetus exposure were reported. Among the predominant sources, food intake was closely associated with the fetus exposure but dust ingestion was different by countries. However, the observed associations were drawn from the studies with small sample size or were not approved through experimentally. Therefore, the relationships between environmental sources and the levels in human tissues should be assessed through epidemiology study and verified to generalize for the results.
In order to address these issues, we analyzed PBDEs in multiple media, estimated total body burden of neonates using biomonitoring data, established the association among PBDEs detected in multiple media and approved the results that revealed in the present study. For this purpose, pregnant women –neonate pairs were recruited before delivery from five university hospitals, located in Ansa, Jeju, Pyungchon, and Seoul in South Korea, from February 2011 to December 2011. We only included healthy subjects without histories of thyroid disease. Maternal and umbilical cord serum were collected at delivery, and breast milk samples were collected three times within a month postpartum. House dust (domestic vacuum cleaner bags) were collected during gestation. Meanwhile, sixteen pregnant Sprague-Dawley rats on gestation day (GD) 0 were purchased and were randomly assigned to one control and three exposed groups. Rats in the exposed groups were gavaged every day with a mixture of BDE 209 and radiolabeled BDE 47. The rats were serially sacrificed at prenatal day 14, birth, and postnatal day 4, respectively. Four control rats were sacrificed at the end of the exposure period. Rat dam blood and their offspring were collected at each sacrifice day. PBDE congeners were measured in maternal serum, cord serum breast milk, house dust, rat dam serum, offspring whole body.
In Chapter II, the total body burden in neonates was estimated using body burden model (BBM) with human biomonitoring data (umbilical cord serum). And then physiologically based pharmacokinetic (PBPK) model was applied to reflect the elimination of the initial body burden in young children. The initial body burden was 1.15 μg and the amount was decreased to 0.22 μg in the 12-month-old infants. The body burden was conversed to estimated daily intake (EDI
ng/kg bw/day) for comparison to the EDI from conventional exposure assessment. Because each EDI represents prenatal and postnatal exposure, respectively, the EDIs had to be summed to investigate total daily intake in young children. The contribution of prenatal and postnatal exposure to the total exposure in 24 month children were 26% and 74%, respectively. Our results imply that prenatal exposure amounts should be involved when assess total exposure in young children. The approach of our study could be applied to the other congeners that have long half-lives and helpful to understand the entire exposure on early life stages.
In Chapter III, the relationships between exposure to house dust (as predominant source) and predominant PBDE congeners in mother-neonate tissues were investigated using various statistical analysis. The predominant congener were BDE 209 and 47 for house dust and human tissues, respectively. While house dust exposure was not associated with the levels in maternal serum, significantly associated with cord serum. That is, house dust would be transferred into the fetus and metabolized from BDE 209 to BDE 47.
However, there was unexplained part, considering the exposure continuum (exposure source-pregnant women-fetus). In other words, the association was not observed in the first link. It could be explained that the source of BDE 47 detected in maternal serum was not house dust or dilution effect from food which has abundant BDE 47. Although the results have meaningful information that prenatal exposure to house dust may contribute to fetus, the results should be approved experimentally.
In Chapter IV, to verify the results from our epidemiology study, animal model was used. BDE 209 and BDE 47 was mixed and daily administered to pregnant rats. BDE 209 and BDE 47 represent exposure of house dust and food, respectively. While placental transfer was driven by house dust exposure compared to food exposure, lactational transfer was led mainly by food exposure. That is, BDE 209 tends to more transferred into fetus compare to BDE 47. The results can support to the result of association between house dust and pregnant women-fetus. Meanwhile two congeners were both transferred to breast milk with considerable levels. Breast feeding of pups in high exposure group should be reconsider.
Overall, the relationship between prenatal exposure and levels in fetus was approved through human epidemiology study with experimental study. And the knowledge gaps were filled to better understand the total exposure to PBDEs in young children as estimate total body burden in neonates. Although the total exposure amounts was lower than the threshold values proposed by the U.S EPA, continuous surveillance of PBDEs exposure and finding additional exposure sources deserves further investigation considering vulnerable characteristics of infants.
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Graduate School of Public Health (보건대학원)Dept. of Public Health (보건학과)Theses (Ph.D. / Sc.D._보건학과)
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