Elemental Speciation as an Essential Part of Formulating Exposure Assessments that Support Risk Estimates

Transcription

1 Elemental Speciation as an Essential Part of Formulating Exposure Assessments that Support Risk Estimates John T. Creed 1, Patricia A. Creed 1, Tatyana Pinyayev 1, Madhavi Mantha 2, John Trent 3, Edward Yeary 3, Jianping Xue 4, Michael Kohan 5, Karen Herbin-Davis 5, David Thomas 5, Kevin Kubachka 6, Traci Hanley 6, Nohora Shockey 6, Douglas Heitkemper 6, Joseph Caruso 7 1 U.S. EPA, NERL, MCEARD, Cincinnati, OH 2 Oak Ridge Institute for Science and Education Scholar, U.S. EPA, NERL, Cincinnati, OH 3 Student Services Contractor, NERL, MCEARD, Cincinnati, OH 4 U.S. EPA, NERL, HEASD, Research Triangle Park, NC 5 U.S. EPA, NHEERL, ISTD, Research Triangle Park, NC 6 Food and Drug Administration (FDA), Forensic Chemistry Center, Cincinnati, OH 7 University of Cincinnati, Department of Chemistry, Cincinnati, OH

2 ias Exposure Assessment for US Consumed Rice US Population Based Exposure Assessment for the Cooked Rice Monte Carlo Based Model Stochastic Human Exposure and Dose Simulation (SHEDS) Three Modeling Input Parameters Distribution of Bioaccessible US Consumed Rice US Rice Consumption Rates from WWEIA (2 day survey, 52,653 person/day) State Specific Arsenic Concentration from EPA Drinking Water Database

3 ias Exposure Assessment for US Consumed Rice US Population Based Exposure Assessment for the Cooked Rice US Rice Production and Import Statistics Monte Carlo Based Model Stochastic Human Exposure and Dose Simulation (SHEDS) Distribution of Bioaccessible US Consumed Rice

4 ias Exposure Assessment for US Consumed Rice US Population Based Exposure Assessment for the Cooked Rice State Specific Rice Production Missouri 6.5% Arkansas 45.6% US Rice Production and Import Statistics Monte Carlo Based Model Stochastic Human Exposure and Dose Simulation (SHEDS) Distribution of Bioaccessible US Consumed Rice California 21.1% Texas 5.8% Louisiana 13.3% 26 US Rice Mills 1 Sample/ GrainType/ Mill/Week 8 Weeks Mississippi 7.7% Domestic = 87% 4.05*10 9 pounds Types of Rice % of Total Production Long Grain Rice 55.6 Medium Grain Rice 19.2 Short Grain Rice 1.4 Brown 5.0 Parboiled 15.6 Instant composite samples were made based on Mill specific production

5 ias Exposure Assessment for US Consumed Rice US Population Based Exposure Assessment for the Cooked Rice Monte Carlo Based Model Stochastic Human Exposure and Dose Simulation (SHEDS) Distribution of Bioaccessible US Consumed Rice State Specific Rice Production California 21.1% Missouri 6.5% Arkansas 45.6% Texas 5.8% Louisiana 13.3% Mississippi 7.7% Imported Rice Sampling Cities Domestic = 87% 26 US Rice Mills 1 Sample/ GrainType/ Mill/Week 8 Weeks US Rice Production and Import Statistics 4.05*10 9 pounds Types of Rice % of Total Production Long Grain Rice 55.6 Medium Grain Rice 19.2 Short Grain Rice 1.4 Brown 5.0 Parboiled 15.6 Instant 3.2 Imported Rice Grain Specific Information Thailand 8.8% Two Thailand rice samples were collected and composited from 7 different cities in the US India 1.7% One sample of Indian rice was collected from 7 different cities in the US 40 composite samples were made based on Mill specific production

6 ias Exposure Assessment for US Consumed Rice US Population Based Exposure Assessment for the Cooked Rice Monte Carlo Based Model Stochastic Human Exposure and Dose Simulation (SHEDS) Distribution of Bioaccessible US Consumed Rice Non-Speciation Based Analysis Speciation Based Analysis Types of Arsenic Analysis Chemical Extraction Total Digest Market Basket Study Most toxic = Least toxic 1. Dilute Nitric Acid Extraction 1. Acid / Base 2. MeOH / Water 3. Water 2. IC-ICP-MS Bioaccessibility 1. In-vitro studies that mimic human GI system Bioavailability 1. Tedious Add Cross-species saline solution, 5M HCl and pepsin 2. Place correlation? in 37 o C water bath with platform agitator 3. for Ethical 1hr issues Synthetic Stomach Extraction Synthetic Intestine Extraction 1. Adjust ph to 6 with 1 M NaHCO 3 2. Add pancreatin solution & 1M NaOH 3. Place in 37 o C water bath with platform agitator for 2hrs Rice Gastrointestinal Extract IC-ICP-MS Improved Risk Characterization/Increase Cost

7 ias DNAS (ng/g) Exposure Model Parameters US Population Based Exposure Assessment for the Cooked Rice Monte Carlo Based Model Stochastic Human Exposure and Dose Simulation (SHEDS) Distribution of Bioaccessible US Consumed Rice ias Chemical Extraction vs Bioaccessibility (DNAS vs Gastrointestinal) ias DNAS 86.2 ng/g ± 58 y = x ias Gastrointestinal 60.9 ng/g ± ias Gastrointestinal (ng/g) TLG-Imp Basmati-Imp Ins Par WSG Brn WMG WLG

8 As Exposure As Exposure (mg/day) (µg) Rice Consumption (g/day) ias Exposure (mg/day) Population in millions US Population Based Exposure Assessment for the Cooked Rice Monte Carlo Based Model Stochastic Human Exposure and Dose Simulation (SHEDS) 86.2 ng/g ± ng/g ± 49 Distribution of Bioaccessible US Consumed Rice Exposure Model Parameters Drinking Water Concentration (ng/g) Second Six Year review data set 24 Cumulative 325 Exposure Source Density Estimate for: Rice Consumption Estimate Function for: (mg/day) of (g/day) (mg/day) ias (g/day) exposure from Rice US Population states, US 49,474 Population utilities, 224,035 records Population served ~230 million Samples 12 from Population Non-Hispanic The 95% ias Black from Population Cooked Rice Tribal, ias Asian Enzyme & Pacific = Populations 4.9 mg/day ias DNAS = 7.2 mg/day ias Water = 0.9 mg/day Censoring: No detects > 10 ppb were replaced with 10 ppb No 20 detects 40 < 0.5 Population ppb 60 were Percentile replaced 80 with ppb Drinking Water Percentile Population Concentration Percentile (ng/g) US Rice Consumption Rates from WWEIA (2 day survey, 52,653 person/day) No detects are treated as ½ MDL in best estimate of As 6 concentration Mexican American Population Mexican American Population Other Hispanic Population Other Hispanic Population Non-Hispanic White Population Non-Hispanic White Population Non-Hispanic Black Population Tribal, Asian & Pacific Populations Mean 95 th % Mean 95 th % Enzyme Rice DNAS Rice Water State Specific Arsenic Concentration from EPA Drinking Water Database

9 Drinking Water vs. Rice as an Exposure Source

10 Drinking Water vs. Rice as an Exposure Source

11 Drinking Water vs. Rice as an Exposure Source

12 Presystemic Biotransformation of Arsenic Oxides Key: RedOx methylation thiolation 11

13 Biotransformation of MMA in the Cecum of a Mouse (MMA) Homogenized mouse cecum anaerobic incubation at 37 o C - 70 o C ship Analyze supernatant by IC-ICP-MS

14 Biotransformation of Arsenicals by the Microbes present in a Mouse Cecum Arsenicals DMA: Kubachka, et. al, J. Anal. At. Spectrom., 2009, 24, ias: Pinyayev, et. al, Chem. Res. Toxicol., 2011, 24, Homogenized mouse cecum anaerobic incubation at 37 o C -70 o C ship Analyze supernatant by IC-ICP-MS

15 Arsenicals present in food undergo changes prior to absorption in your intestine Dietary Arsenicals Drinking Water Arsenicals Presystemic Biotransformation Presystemic biotransformation may alter cellular uptake and metabolism relative to the parent arsenic oxide 14

16 Acknowledgement We would like to thank Steve Hensley and the Rice Federation for providing samples. 15