S-Space Graduate School of Public Health (보건대학원) Dept. of Public Health (보건학과) Theses (Ph.D. / Sc.D._보건학과)
Mercury exposure and associated health effects among the general populations of Korea : 한국의 일반 인구집단 대상 수은 노출 및 건강영향
- 보건대학원 환경보건학과
- Issue Date
- 서울대학교 보건대학원
- Mercury ; Methylmercury ; Biomonitoring ; Dose reconstruction ; Physiologically based pharmacokinetic model ; Harzard quotient ; Obesogen ; Body burden
- 학위논문 (박사)-- 서울대학교 보건대학원 환경보건학과, 2017. 8. 김성균.
- ratios of MeHg intake to model-predicted blood MeHg were then combined with KoNEHS-based blood MeHg values to produce MeHg intake estimates. These intake estimates were ultimately compared with the Reference Dose (RfD) for MeHg (0.1 μg/kg/day) and reported as hazard quotient (HQ) for specific KoNEHS subgroups. The GM of blood Hg was 3.08 μg/L and about 25 % of total population exceeded the HBM-I. Though the exceedances were derived from single measurement per individual, however those were decreasing with the lower ICC and the more repeated data. The predicted exposure dose was 35.8 ng/kg/day for total population. And the corresponding HQ value was 0.36 for total (range: 0.24 ~ 0.63). The GM was only used for deriving the HQ because using the tail of simulation data requires careful interpretation. Considering the results were derived using only the GM, the potential at-risk population could be existed for each population.
In Chapter III, the perturbation of clinical chemistry markers including ALT, γ-GTP, total cholesterol, triglyceride, total lipid, and IgE were investigated as the effects associated with exposure to Hg. GMs of blood Hg and clinical chemistry markers were determined and odds ratios of out-of-reference range for each marker were estimated by gender and quantile of blood Hg adjusted for age, BMI, smoking and alcohol consumption. The blood Hg level was categorized into quantile groups - low: < 25th (2.05 μg/L), medium: 25th ~ 75th (4.75 μg/L), high: > 75th – to diagnose the effect of Hg on the reference ranges. The levels of ALT, γ-GTP and total lipid were increased with blood Hg
group for both sexes, and the GMs for total cholesterol and TG were significantly increased in men across the blood Hg. Regarding to γ-GTP, the high blood Hg group was associated with a 2.8-fold increase for being out-of reference range in the male group (OR=2.77
95% CI: 1.72-4.46), while 2.1-fold increase in the female group (OR=2.11
95% CI: 1.35-3.30). High Hg group in men was associated with about 1.5-fold risk for total cholesterol. Especially, the significant contribution of blood Hg to high γ-GTP were retained after adjustment for other co-exposing chemicals in the multivariate linear model. Our results suggest that Hg exposure even as low as environmental levels among general population could perturbate lipid metabolism although further mechanistic researches needs to be confirmed.
In Chapter IV, the association between environmental exposures and health outcomes in children were investigated using the Childrens Health and Environmental Chemicals in Korea (CHECK). The fetal body burden for Hg was derived by using PBPK model, and the growth effects from Hg exposure at the developmental period were analyzed using several statistical approaches. Among 106 paired data out of total 334 pairs, the GM for Hg in maternal blood and cord blood was 4.47, 7.35 μg/L, and that of placenta and meconium was 9.0, 36.9 ng/g, respectively. Though the sample size of infants hair was too small (n=25) for the following analysis, however, the GM was as high as 443 ng/g. The derived fetal body burden was ranged between 26.3 and 86.9 mg based on the 106 cord blood. Cord blood Hg was positively associated with length at birth (p-value: 0.0132), while weight at birth (p-value: 0.1764) and head circumference (p-value: 0.4579) were not associated with cord blood Hg. According to the logistic regression model, the cord blood Hg were not significant for the standardized height (OR: 1.30 (0.55, 3.07)), weight (OR: 0.76 (0.36, 1.62)), and PI (OR: 0.817 (0.377, 1.77)). However, the LS mean estimates for the follow up weights represent the more rapid increasing slopes in the high cord blood Hg group compared to the low Hg group for both sexes. These results indicated that fetus would have high body burden, and exposure to Hg associated with the taller height at birth and the rapid weight increasing.
This study revealed the highly exposed population for Hg and conducted exposure assessment across the population based on the estimated MeHg. All HQs were below 1, but the upper 5 percentiles of HQ were above 1 except for those who consumed fish rarely. These results indicate that the potential at-risk population could be existed for each population, not only for those in consuming fish frequently. Also, Hg exposure even as low as environmental levels among general population could perturbate lipid metabolism although further mechanistic researches confirm. Furthermore, fetus would be exposed to certain amount of Hg (26.3 ~ 86.9 μg/kg/day), and that could be influenced on the growth at birth and weight inceasing in later life. Therefore, more researches for fetal body burden are required, and growth effects should be
investigated adjusting for other confounders including Hg level in diet and coexposure from other chemicals.
Mercury (Hg) is a naturally occurring heavy metal compound and a ubiquitous contaminant of soil, air, foods, and other media. There are several forms of Hg in the environment
inorganic Hg such as amalgam, and organic Hg, especially methylmercury (MeHg), which is known for the most toxic form of Hg. According to two Korean national surveys, the geometric mean (GM) for Hg in blood was higher than that in similar national surveys done in Canada and the USA, and a substantial people in South Korea have the high level of blood Hg. Regarding to the biomonitoring level, the German Federal Environmental Agency set the guideline values for 5 μg/L (The HBM-I) as a control value for which no action is needed, and 15 μg/L (The HBM-II) as an action level for which medical care or advice is recommended. Meanwhile, the main exposure source for the general population is diet, especially fish consumption. It is absorbed and condensed in the human body via fish intake. In fact, about 80 % of blood Hg consists of MeHg. In order to regulate the exposure amount, the United States Environmental Protection Agency (US.EPA) recommended 0.1 μg/Kg/day for MeHg as the reference dose (RfD).
There have been several studies conducted investigating Hg exposure, however, there has been no study for the exposure amount of Hg based on the individual internal dose among the South Korean population. And the extent of Hg exposure should be investigated, especially for the related health effects as a suspected obesogen. In addition, Hg can be transferred from mother to fetus via placenta. Though women in South Korea have the high blood Hg compared to those in other countries, there has been no study for fetal body burden during pregnancy. Thus, exposure assessment for sensitive population is required. Therefore, this study was conducted for investigating the exceedances above the guidance values among South Korean. And the corresponding exposure dose for MeHg was calculated, which can be compared to the RfD. Next, the associations between Hg and health outcomes were investigated using clinical chemistry markers. Lastly, fetal body burden was derived by using the PBPK model and investigated the growth effects of exposure to Hg among infants.
In Chapter II, the Korean National Environmental Health Survey (KoNEHS 2009-2011) were used to derive the exposure amount for Hg. Gender, age, and frequency of fish consumption were first identified as important predictors of KoNEHS blood Hg levels using generalized linear models. Stratified distributions of total blood Hg were then converted into distributions of blood MeHg using fractions of MeHg to total Hg from the literature. Next, a published physiologically-based pharmacokinetic (PBPK) model was used to predict distributions of blood MeHg as a function of MeHg intake