Estimating Methylmercury Intake for the General Population of South Korea Using Physiologically Based Pharmacokinetic Modeling

The Korean National Environmental Health Survey (KoNEHS 2009-2011) tracks levels of environmental pollutants in biological samples from the adult Korean population (age 19-88). Recent survey results for blood mercury (Hg) suggest some exceedance above existing blood Hg reference levels. Because total blood Hg represents both organic and inorganic forms, and methylmercury (MeHg) has been specifically linked to several adverse health outcomes, a need exists to quantify MeHg intake for this population. 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 used to estimate 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; 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 margin of exposure (MOE) estimates for specific KoNEHS subgroups. The derived MOEs across all subgroups, based on estimated geometric mean intake, ranged from 1.6 to 4.1. These results suggest MeHg exposures approaching the RfD for several subgroups of the Korean population, and not just for specific subgroups (eg, those who eat fish very frequently).

[1]  Y.F. Zhao,et al.  Estimation of methylmercury intake from the 2007 Chinese Total Diet Study , 2010, Food additives & contaminants. Part B, Surveillance.

[2]  Young-Seoub Hong,et al.  Methylmercury Exposure and Health Effects , 2012, Journal of preventive medicine and public health = Yebang Uihakhoe chi.

[3]  K. Yeum,et al.  Cut-off values of blood mercury concentration in relation to increased body mass index and waist circumference in Koreans , 2016, Journal of Investigative Medicine.

[4]  Panos G Georgopoulos,et al.  Reconstructing population exposures to environmental chemicals from biomarkers: Challenges and opportunities , 2009, Journal of Exposure Science and Environmental Epidemiology.

[5]  M. Feeley,et al.  Methylmercury blood guidance values for Canada. , 2010, Canadian journal of public health = Revue canadienne de sante publique.

[6]  G. Ginsberg,et al.  Development of a Single‐Meal Fish Consumption Advisory for Methyl Mercury , 2000, Risk analysis : an official publication of the Society for Risk Analysis.

[7]  Joachim D Pleil,et al.  Estimating Lifetime Risk from Spot Biomarker Data and Intraclass Correlation Coefficients (ICC) , 2013, Journal of toxicology and environmental health. Part A.

[8]  Harvey J Clewell,et al.  Use of Markov Chain Monte Carlo Analysis with a Physiologically‐Based Pharmacokinetic Model of Methylmercury to Estimate Exposures in U.S. Women of Childbearing Age , 2007, Risk analysis : an official publication of the Society for Risk Analysis.

[9]  Alan H. Stern,et al.  A Revised Probabilistic Estimate of the Maternal Methyl Mercury Intake Dose Corresponding to a Measured Cord Blood Mercury Concentration , 2004, Environmental health perspectives.

[10]  Jeongseon Kim,et al.  Reference levels of blood mercury and association with metabolic syndrome in Korean adults , 2014, International Archives of Occupational and Environmental Health.

[11]  Jeongae Lee,et al.  Correlation Between Total Mercury and Methyl Mercury-In Whole Blood of South Korean , 2013 .

[12]  Shi V Liu,et al.  Methyl mercury exposure from fish consumption in vulnerable racial/ethnic populations: probabilistic SHEDS-Dietary model analyses using 1999-2006 NHANES and 1990-2002 TDS data. , 2012, The Science of the total environment.

[13]  Yu-Mei Tan,et al.  Uses of NHANES Biomarker Data for Chemical Risk Assessment: Trends, Challenges, and Opportunities , 2015, Environmental health perspectives.

[14]  Harvey J. Clewell,et al.  Evaluation of the Uncertainty in an Oral Reference Dose for Methylmercury Due to Interindividual Variability in Pharmacokinetics , 1999, Risk analysis : an official publication of the Society for Risk Analysis.

[15]  G Drasch,et al.  Scientific comment on the German human biological monitoring values (HBM values) for mercury. , 2002, International journal of hygiene and environmental health.

[16]  J. Kern,et al.  Thimerosal-containing Hepatitis B Vaccine Exposure is Highly Associated with Childhood Obesity: A Case-control Study Using the Vaccine Safety Datalink , 2016, North American journal of medical sciences.

[17]  M. Berglund,et al.  Establishment of the cumulative margin of exposure for a group of polychlorinated biphenyl (PCB) congeners using an improved approach that accounts for both variability and uncertainty. , 2013, Regulatory toxicology and pharmacology : RTP.

[18]  D. Rice.  The US EPA reference dose for methylmercury: sources of uncertainty. , 2004, Environmental research.

[19]  H J Clewell,et al.  Evaluation of the uncertainty in an oral reference dose for methylmercury due to interindividual variability in pharmacokinetics. , 1999, Risk analysis : an official publication of the Society for Risk Analysis.

[20]  Yu-Mei Tan,et al.  Reconstructing exposures from biomarkers using exposure-pharmacokinetic modeling--A case study with carbaryl. , 2015, Regulatory toxicology and pharmacology : RTP.

[21]  H J Clewell,et al.  Sensitivity of physiologically based pharmacokinetic models to variation in model parameters: methylene chloride. , 1994, Risk analysis : an official publication of the Society for Risk Analysis.

[22]  S. Masunaga,et al.  An Exposure Assessment of Methyl Mercury via Fish Consumption for the Japanese Population , 2009, Risk analysis : an official publication of the Society for Risk Analysis.

[23]  G. Rice,et al.  DERIVATION OF U.S. EPA'S ORAL REFERENCE DOSE (RFD) FOR METHYLMERCURY , 2000, Drug and chemical toxicology.

[24]  J. Angerer,et al.  The German Human Biomonitoring Commission. , 2007, International journal of hygiene and environmental health.

[25]  Marike Kolossa-Gehring,et al.  Update of the reference and HBM values derived by the German Human Biomonitoring Commission. , 2011, International journal of hygiene and environmental health.

[26]  R. Kelishadi,et al.  Association of serum lead and mercury level with cardiometabolic risk factors and liver enzymes in a nationally representative sample of adolescents: the CASPIAN-III study , 2014, Environmental Science and Pollution Research.

[27]  Ji Myung Kim,et al.  The association of heavy metals in blood, fish consumption frequency, and risk of cardiovascular diseases among Korean adults: The Korean National Health and Nutrition Examination Survey (2008-2010) , 2012 .

[28]  Yun-Chul Hong,et al.  Temporal variability of blood lead, mercury, and cadmium levels in elderly panel study (2008-2014). , 2017, International journal of hygiene and environmental health.

[29]  K. Mahaffey,et al.  Blood organic mercury and dietary mercury intake: National Health and Nutrition Examination Survey, 1999 and 2000. , 2004, Environmental health perspectives.

[30]  H. Kwon,et al.  International Symposia on Integrated Exposure Assessment for Hazardous Materials , 2012, Environmental Health and Toxicology.

[31]  Sean M Hays,et al.  Interpreting human biomonitoring data in a public health risk context using Biomonitoring Equivalents. , 2012, International journal of hygiene and environmental health.

[32]  J. Shim,et al.  Sex differences in the relationship between blood mercury concentration and metabolic syndrome risk , 2014, Journal of Endocrinological Investigation.

[33]  K. Sucher,et al.  Dietary habits and health beliefs of Korean-Americans in the San Francisco Bay Area. , 2000, Journal of the American Dietetic Association.

[34]  G. Ginsberg,et al.  Development of a single-meal fish consumption advisory for methyl mercury. , 2000 .

[35]  A. Paris,et al.  Integrating variability in half-lives and dietary intakes to predict mercury concentration in hair. , 2010, Regulatory toxicology and pharmacology : RTP.

[36]  Kerstin Becker,et al.  German Environmental Survey 1998 (GerES III): environmental pollutants in blood of the German population. , 2002, International journal of hygiene and environmental health.

[37]  H. Satoh,et al.  Hair-to-blood ratio and biological half-life of mercury: experimental study of methylmercury exposure through fish consumption in humans. , 2012, The Journal of toxicological sciences.

[38]  Harvey J Clewell,et al.  Use of a Physiologically Based Pharmacokinetic Model to Identify Exposures Consistent With Human Biomonitoring Data for Chloroform , 2006, Journal of toxicology and environmental health. Part A.

[39]  Jae-Hong Park,et al.  Total mercury concentrations in the general Korean population, 2008-2011. , 2014, Regulatory toxicology and pharmacology : RTP.

[40]  Jerry L. Campbell,et al.  Quantitative interpretation of human biomonitoring data. , 2008, Toxicology and applied pharmacology.

[41]  Dae-seon Kim,et al.  The relationship between the fish consumption and blood total/methyl-mercury concentration of costal area in Korea. , 2012, Neurotoxicology.

[42]  D. Jacobs,et al.  Population correlates of circulating mercury levels in Korean adults: the Korea National Health and Nutrition Examination Survey IV , 2014, BMC Public Health.

[43]  Harvey J Clewell,et al.  Development of Pbpk Models for Pfoa and Pfos for Human Pregnancy and Lactation Life Stages , 2013, Journal of toxicology and environmental health. Part A.

[44]  Byung-Kook Lee,et al.  Blood total mercury and fish consumption in the Korean general population in KNHANES III, 2005. , 2010, The Science of the total environment.

[45]  H J Clewell,et al.  Determination of a site-specific reference dose for methylmercury for fish-eating populations. , 2000, Toxicology and industrial health.