Grantee Research Project Results
Final Report: Modeling Dietary Contributions to Arsenic Dose and Methylation: Elucidating Predictive Linkages
EPA Grant Number: R833992Title: Modeling Dietary Contributions to Arsenic Dose and Methylation: Elucidating Predictive Linkages
Investigators: Burgess, Jefferey L. , Harris, Robin B. , Martinez, M. Elena , O’Rourke, Mary Kay , Hsu, Paul
Institution: Mel and Enid Zuckerman College of Public Health
EPA Project Officer: Hahn, Intaek
Project Period: October 1, 2008 through September 30, 2010 (Extended to September 30, 2011)
Project Amount: $499,999
RFA: Development of Environmental Health Outcome Indicators (2007) RFA Text | Recipients Lists
Research Category: Human Health
Objective:
Despite the recent decrease in the U.S. Maximum Contaminant Level (MCL) for arsenic in drinking water from 50 to 10 ppb (U.S. EPA), excessive exposure continues to occur in the United States through non-regulated sources. Food is a major source of arsenic (As) exposure (Schoof et al., 1999), and variations in diet may help explain the high variability in urine arsenic concentration in populations with low arsenic levels in their drinking water and no apparent exposure to arsenic in dust. Dietary contributions are important not just to arsenic exposure but also may influence the extent of arsenic methylation and toxicity. Thus, it is essential to develop a set of indicators evaluating the contribution of dietary sources to arsenic dose and methylation. There is currently inadequate information on whether regulatory change in the arsenic drinking water MCL will be sufficient for decreasing the public’s overall exposure to arsenic and arsenic methylation products, and inadequate information on the effect of Hispanic ethnicity on arsenic dose and extent of methylation.
Summary/Accomplishments (Outputs/Outcomes):
The focus of this study was to determine the role of dietary arsenic intake and the effect of nutrient intake on total and speciated urinary arsenic biomarkers. The local/regional study populations that were used in these analyses were the National Health and Exposure Survey (NHEXAS)-Arizona, the Arizona Border Survey (ABS), and the Arizona subgroup of the Binational Arsenic Exposure Survey (BAsES). National data came from the 2003-2004 National Health and Nutrition Examination Survey (NHANES).
Aim 1 assessed the validity of modeling dietary intake of total arsenic by comparing estimated As intake to measured intake in the NHEXAS-Arizona and Arizona Border Survey populations, and by evaluating the goodness of fit of models of urinary total As excretion based on measured vs. modeled dietary As adjusted for As intake from drinking and cooking water and other potential confounders.
We found that modeled dietary total arsenic intake provides a correlative approach to estimating exposure that, as hypothesized, can be used to predict urinary total As exposure. In Aim 1, modeled dietary As based on Total Diet Study (TDS) mean arsenic results resulted in a gross underestimate of measured As intake from duplicate diet samples. Modeled dietary As based on TDS maximum As residue data or on mean total As residue data published by Schoof et al. (1999) yielded better approximations of measured dietary As. In subjects with measurable urinary As, both measured and modeled dietary As exposure were predictive of urinary total As. In Aims 2 and 3, as well, dietary As exposure estimates based on Schoof As residue data (1999) were predictive of urinary As outcomes. Furthermore, dietary As was more closely associated with urinary total As than drinking and cooking water As in all three local/regional study populations.
We took this a step further by using modeled estimates of dietary total and inorganic As intake to model urinary total As, As sum of species (defined as the sum of inorganic As, and its metabolites, MMA and DMA), and indicators of arsenic methylation efficiency (%MMA and DMA:MMA) in the Arizona subpopulation of a binational arsenic exposure survey (BAsES) and in the 2003-2004 NHANES population. In both the BAsES and NHANES models, the modeled dietary total and inorganic arsenic intake were significantly associated with urinary As sum of species, but the relation of dietary As to As methylation patterns was less clear. Neither dietary or water As intake were related to % MMA or DMA:MMA in the BAsES population, and other factors, such as sex and BMI, explained the bulk of the variance in these models. In the NHANES population, dietary total but not inorganic As was predictive of %MMA and DMA:MMA, and smoking and ethnicity were additional predictors. There were inconsistencies in the models of As methylation patterns between BAsES and NHANES, and we were not able to validate the BAsES methylation models with the NHANES models. However, certain factors that were predictive in some of our models, such as sex and cigarette smoking, were also related to methylation patterns in the population in northern Chile (Hopenhayn-Rich et al., 1996c).
In the NHEXAS-AZ, Arizona Border Survey and BAsES populations, we also stratified by tap water As concentration above vs. below the MCL and modeled the effects of dietary As on urinary As excretion in each strata. This analysis was intended to provide insight into the potential impact and efficacy of the current regulations in reducing exposure to arsenic and its metabolites. Differences in dietary As intake were expected to account for the majority of the variability in urinary arsenic biomarkers in populations with drinking water arsenic less than 10 ppb. However, in all three study populations, dietary As contributed the majority of exposure regardless of stratification by tap water As. Drinking water As, in addition to dietary As, was associated with urinary total As and sum of species in subjects with tap water As > 10 ppb, but had no relation to urinary total As in subjects living in households with water As concentrations below the MCL.
It was hypothesized that Hispanics in our Arizona study populations and Hispanic-Americans and Asian-Americans in the NHANES population would show higher levels of dietary As intake and urinary total and sum of species As than non-Hispanics, potentially due to cultural dietary differences and increased consumption of rice. In this study, differences by ethnic group were inconsistent across populations. The expectation was that NHEXAS/ABS and BAsES would show similar effects of ethnicity because of presumed similarities in the study populations. However, in NHEXAS/ABS, Hispanics had higher mean dietary As exposure than non-Hispanics and lower mean exposure from drinking and cooking water, but showed no difference in mean concentration of total As in the urine. In contrast, Hispanics in BAsES, showed no differences in As exposure from ingestion of either food or water, but mean urinary total As and MMA were significantly lower among Hispanics as compared with non-Hispanics. In NHANES, dietary total As exposure was significantly higher in "other races," "other Hispanics," and non-Hispanic blacks as compared with non-Hispanic whites. Dietary inorganic As was significantly higher in "other races," "other Hispanics," and Mexican-Americans (listed in order from highest to lowest) as compared with non-Hispanic whites.
Part of aims 2 and 3 of this study was to assess the role of specific nutrients on As methylation efficiency. We postulated that increased dietary intake of folate, protein, methionine, Vitamin B-12, and Vitamin B-6—nutrients involved in one-carbon metabolism—might modulate the effects of dietary As and its methylation. Models of the relation between dietary intake of these nutrients, individually and in multivariable models, and urinary As biomarkers showed significant effects. In BAsES, increased dietary protein was associated with deceased % MMA and increased DMA:MMA in univariate analysis, and decreased sum of species As in multivariable models—i.e., protein intake appeared to be associated with a decrease in absorbed dose. In a multivariable model of sum of species As in NHANES, increased intake of protein was also associated with a significant decrease in absorbed dose.
Conclusions:
Dietary arsenic, alone and in combination with arsenic ingested from drinking water and water used in food preparation, contributes significantly to total arsenic exposure. An estimated 3-15% of the population is exposed to arsenic above the Provisional Tolerable Daily Intake of 2.1 μg/kg body weight/day, and median exposure from food alone is 4-35 times higher than from drinking and cooking water combined, yet there are currently few standards in the United States regarding arsenic in food, and these apply only to the products of animals (e.g., eggs, poultry) treated with arsenical veterinary drugs.
Modeled dietary arsenic estimates based on residue databases correlate well with measured arsenic in composite food samples but may not yield accurate estimates of intake. However, modeled estimates of dietary exposure are better predictors of urinary arsenic than estimates of exposure to arsenic from drinking and/or cooking water, at least in the United States, where water arsenic concentrations are generally low.
The importance of food and beverages to total exposure to arsenic should instigate efforts to improve monitoring of arsenic and establish standards for arsenic in foods.
Journal Articles on this Report : 3 Displayed | Download in RIS Format
Other project views: | All 8 publications | 3 publications in selected types | All 3 journal articles |
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Kurzius-Spencer M, O'Rourke MK, Hsu CH, Hartz V, Harris R, Burgess JL. Measured versus modeled dietary arsenic and relation to urinary arsenic excretion and total exposure. Journal of Exposure Science and Environmental Epidemiology 2013;23(4):442-449. |
R833992 (Final) |
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Kurzius-Spencer, M, Burgess, JL, Harris, RB, Hartz, V, Roberge, J, Huang, S, Hsu, CH, O'Rourke. Contribution of diet to aggregate arsenic exposures-An analysis across populations. Journal of Exposure Science and Environmental Epidemiology 2014;24(2):156-162. |
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Kurzius-Spencer, M, Harris, RB, Hartz, V, Roberge, J, Hsu, CH, O'Rourke, MK, Burgess, J. Relation of dietary inorganic arsenic to serum matrix metalloproteinase-9 (MMP-9) at different threshold concentrations of tap water arsenic. Journal of Exposure Science and Environmental Epidemiology 2016;26(5):445-451. |
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Supplemental Keywords:
Arsenic, metalloid, modeling, exposure and risk assessment, 1-carbon metabolism, methylation, health effects, carcinogen, sensitive populations, Hispanics, public policyProgress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.