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Donald G. Patterson Jr.*

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  1. THE USE OF FLUID MANAGEMENT SYSTEMS (FMS) PRODUCTS IN EPIDEMIOLOGICAL STUDIES AND IN EXPOSURE ASSESSMENT OF THE U.S. POPULATION TO PERSISTENT ORGANIC POLLUTANTS (POPs) Donald G. Patterson Jr.* *Exponent Inc., 4921 Bill Cheek Road, Auburn, GA 30011; e-mail: dpatterson@exponent.com *Axys Analytical Services Ltd, Sidney, BC, Canada; e-mail: dpatterson@axys.com RETIRED FROM: National Center for Environmental Health, Division of Laboratory Science, Organic Analytical Toxicology Branch, Centers for Disease Control and Prevention, Atlanta, GA

  2. OVERVIEW • What is biomonitoring? • External / internal dose measurement • U.S. reference ranges for chemical body burdens • Analytical considerations and FMS automated methods and Thermo Scientific HRMS contribution to the CDC National Report on Human Exposure to Environmental Chemicals

  3. Objectives of Exposure Assessment to Environmental Chemicals • Quantification of magnitude, duration, frequency and routes of exposure • Example: Air, water, food, soil, dust, etc. • Characterization and enumeration of the exposed population

  4. Human Biomonitoring • Two ways to do human exposure assessment • External dose measurement • Modeling to predict internal dose • Internal dose measurement • Direct measurement of the internal dose

  5. Predicting Levels of Toxicants in People Using Environmental Monitoring Is Very Difficult and Includes Many Assumptions Air levels Water levels Soil/dust levels Food levels Nutritional status Predicted levels of toxicants in people Mathematical modeling Lifestyle factors Personal habits Genetic factors Lung, intestine and skin absorption coefficients MANY OTHER FACTORS

  6. Inhalation Ingestion Dermal Contact Exposure Pathway Effect Source Water Air Food Soil Dust Sediment External Dose Absorption following: Exposure Assessment Internal Dose Metabolism Distribution Elimination Elimination Target Organ Dose • Specificity by: • Choice of matrix • Choice of analytes • Choice of analytical method • Sample preparation • Sample analysis Biologically Effective Dose

  7. Instead of predicting,Measure levels of toxicants in people

  8. Ingestion Inhalation Dermal Gastrointestinal Tract Primary Deposition Sites Lung Fat Bone Liver Portal Blood Blood Secretory Structures Soft Tissues Bile Alveoli Kidney Secretions Tears Feces Expired Air Saliva Sweat Milk Bladder Urine Absorption, Distribution, and Elimination of Toxicants in the Body

  9. Agent Orange Herbicide : Defoliant 2,4,5-Trichlorophenoxyacetic Acid * + 2,4-D in Diesel Oil * 2,3,7,8-TCDD contaminant

  10. The Agent Orange Vietnam Veteran Ranch Hand Dioxin Exposure Index was Not Correlated with Serum Dioxin Levels Theoretical linear relationship

  11. INTRODUCTION • PCDDs, PCDFs, PCBs are lipophilic compounds • Bioaccumulate up the food chain to humans • Can be measured in lipid stores of the human body • Exposure to humans primarily through food of animal origin (95%)

  12. Major Disadvantage in Adipose Tissue Studies • Surgical procedure required to obtain adipose tissue samples • LOW PARTICIPATION RATE

  13. Major Problem in Developing a Serum Method Percent Lipid TCDD Conc. Adipose Tissue ~ 95 ppt Serum ~ 0.6 ppq

  14. Before what is ‘abnormal’ can be determined, what is ‘normal’ must be defined

  15. National Report on Human Exposureto Environmental Chemicals • What it is: • An ongoing (every 2 years) biomonitoring assessment of the exposure of the U.S. population to selected environmental chemicals • Matrices monitored: Urine, blood and its components

  16. Chemicals in 4th Report ~265 Chemicals • Metals • Polychlorinated biphenyls, dioxins, and furans • Organochlorine pesticides • Carbamate pesticides • Organophosphorous pesticides • Pyrethroid pesticides • Herbicides • Polycyclic aromatic hydrocarbons • Phthalates • Phytoestrogens • Pest repellants • Cotinine • Perfluorinated chemicals • Brominated flame retardants • VOCs • Perchlorate • Bisphenol A and alkylated phenols • Triclosan, parabens, acrylamide • Sunscreen agent • Speciated arsenic www.cdc.gov/exposurereport

  17. NHANES 2001/2002 U.S. Reference Range90th Percentile for Gender and Age Group Total TEQ (2005 TEFs) (95% Confidence Intervals)

  18. *********AUTOMATION IS ABSOLUTELY ESSENTIAL TO CONDUCT LARGE SCALE EXPOSURE ASSESSMENTS OR EPIDEMIOLOGICAL STUDIES

  19. MATERIALS AND METHODS • Integrated, automated sample extraction (SPE), clean-up (Power-Prep), and automated evaporation systems manufactured by Fluid Management Systems (FMS) in Waltham, MA • Extracts measured by isotope-dilution GC-high resolution mass spectrometry on a Thermo Scientific DFS HRMS

  20. Sensitivity: TCDD Specification20 fg SN ≥ 200:1(4 s) S/N 239:1 (4s) • Highestsensitivityfor: • Quantifyingatlowestlevels • High precision • Reducing sample amounts GC-HRMS

  21. Thermo MAT95XL Mass Spectrometer

  22. COWS MILK HUMAN MILK

  23. 5g Whole Milk (n=2) FMS Automated [SPE-Power Prep-Evaporation] Percent Recovery

  24. 5g Whole Milk (n=2) FMS Automated [SPE-Power Prep-Evaporation] Percent Recovery

  25. FMS (5g, n=2) AUTOMATED SPE (HLB)-POWER-PREP CLEANUP OF NIST HUMAN MILK SRM-1954 COMPARED TO CDC (5g, n=12) BY HRGC-IDHRMS IN PPQ

  26. FMS (5g, n=2) AUTOMATED SPE (HLB)-POWER-PREP CLEANUP OF NIST HUMAN MILK SRM-1954 COMPARED TO CDC (5g, n=12) BY HRGC-IDHRMS IN PPQ

  27. FMS (5g, n=2) AUTOMATED SPE (HLB)-POWER-PREP CLEANUP OF NIST HUMAN MILK SRM-1954 COMPARED TO CDC (5g, n=12) BY HRGC-IDHRMS IN PPQ

  28. HUMAN SERUM

  29. FMS (11g, n=3) AUTOMATED SPE (HLB)-POWER-PREP CLEANUP OF NIST SERUM SRM-1958 COMPARED TO CDC (25g, n=12) BY HRGC-IDHRMS IN PPQ

  30. FMS (11g, n=3) AUTOMATED SPE (HLB)-POWER-PREP CLEANUP OF NIST SERUM SRM-1958 COMPARED TO CDC (25g, n=12) BY HRGC-IDHRMS IN PPQ

  31. FMS (11g, n=3) AUTOMATED SPE (HLB)-POWER-PREP CLEANUP OF NIST SERUM SRM-1958 COMPARED TO CDC (25g, n=12) BY HRGC-IDHRMS IN PPQ

  32. CONCLUSIONS • The recoveries for the PCDDs, PCDFs, and cPCBs are very good and the CVs for the quantification of these analytes are excellent, particularly at the low levels • The PCDDs, PCDFs, cPCBs in human serum have been validated against CDC results

  33. CONCLUSIONS • The FMS integrated automated- extraction-cleanup-evaporation system performs remarkably well and ‘Cookbook Methods’ have been developed for: • cows milk, human milk, fish oil, fish meal, human serum, infant formula and water using the Thermo-DFS-HRMS system for quantification • Methods for other analytes and matrices are under development

  34. NEW METHOD DEVELOPMENT ACTIVITIES ON-GOING • PCB Congeners • Persistent Pesticides • Polychlorinated Naphthalenes • PolybrominatedDiphenyl Ethers • Polybrominated Dioxins and Furans • PolyhalogenatedAlkanes • Perfluorinated Compounds • Other Food Matrices • Urine for Metabolites