1. Persistent Bioaccumulative Toxicants Workshop Larry L. Needham, PhD National Center for Environmental Health Centers for Disease Control and Prevention April 22, 2002

2. Mission of Division of Laboratory Sciences To develop and apply analytical methods for assessing human exposure to environmental chemicals (and ultimately to be a team member for preventing / reducing morbidity and/or mortality in the US population.

3. Mission statement (cont.) To address this mission, we collaborate with investigators within CDC, other federal agencies, state health departments, international agencies, academia, and industry. One of needs is to acquire background levels of environmental chemicals in human populations.

4. National Report on Human Exposure to Environmental Chemicals Division of Laboratory Sciences, National Center for Environmental Health, CDC

5. Organization for NHANES DHHS FDACDCNIH NCID NC CDPHP NCHS NC HIV,STD, &TB NIOSHNCIPCNCEH

7. 23 Participating Laboratories for NHANES NHANES MEC Division of Laboratory Sciences / NCEH NCID labs NCHSTP Medical Research Centers/ Academic labs Commercial labs

8. Eligible NHANES Population Civilian, non-institutionalized population of the United States Ages 2 months and older Residents of all 50 states and DC 5000 persons examined each year in 15 locations Survey design determines which populations are over-sampled

9. How did NHANES start? The Health Examination Survey – the forerunner in the 1960’s HANES I – 1971; Nutrition added as a major component

10. Six Principal Data Collection Methods Household interview Personal interviews Physical examination Anthropometry Diagnostic screening Laboratory analysis

11. The Mobile Examination Centers (MECs)

12. 4 Trailers attached to one another, each ~ 8’x45’ 3 Sets: 2 in operation at any given time 15 sites visited each year, 4-6 wk/location Survey design: Northern U.S. states in summer, Southern states in winter Average of 450 sample persons per survey location Provides standardized environment 20 Examinations per day in two sessions per day, (morning/afternoon or morning/evening), Wed-Sun

13. MEC examination components Dietary interviews/MEC interviews Phlebotomy Urine collection Blood pressure Physician’s exam Hearing Eye exam Dental exam DXA Muscle strength Balance Anthropometry Skin disease/Melanoma TB skin test Cognitive testing Cardiorespiratory fitness Peripheral vascular disease Peripheral neuropathy

14. NHANES Laboratory in the MEC Coulter Counter for CBC Laminar Flow Hood

15. CDC NCHS MEC CDC CASPIR CDC NCEH DLS

16. What Purpose Does NHANES Serve? Serves as a warning system for health problems

17. Urinary Iodine levels Monitoring of iodine levels through NHANES can provide a warning of thyroid deficiency trends Studies show that median iodine levels in the population are dropping due to decreased food iodization from salt Health problems could occur if trend continues

18. What Purpose Does NHANES Serve? Helps identify who is at risk.

19. Distribution of serum cotinine in the U.S. Population (ages 4 and older), NHANES III (1988-1991) 0.11.0101001000 5 4 3 2 1 0 Serum cotinine (ng/mL) Percent of the Population Smokers Nonsmokers

20. 0 1 2 3 4 5 No reported home or work ETS exposure 0 1 2 3 4 5 Reported home or work ETS exposure Percentage of the Population Serum Cotinine Levels in the U.S. Population by Self- reported Exposure to Tobacco Smoke, NHANES III (1988- 1991)

21. What Purpose Does NHANES Serve? Shows if public health interventions have been successful through trend data.

22. Year 1975197619771978197919801981 Lead used in gasoline (thousands of tons) 30 40 50 60 70 80 90 100 110 Gasoline lead Lead used in gasoline declined from 1976 through 1980

23. Year 1975197619771978197919801981 30 40 50 60 70 80 90 100 110 Mean blood lead levels (ug/dL) 9 10 11 12 13 14 15 16 17 Gasoline lead Predicted blood lead Lead used in gasoline (thousands of tons) Environmental Modeling Predicted Only a Slight Decline in Blood Lead Levels in People

24. Observed blood lead Year 1975197619771978197919801981 30 40 50 60 70 80 90 100 110 9 10 11 12 13 14 15 16 17 Gasoline lead Predicted blood lead Lead used in gasoline (thousands of tons) Mean blood lead levels (ug/dL) NHANES II Blood Lead Measurements Found a Substantial Decline in Blood Lead Levels, 10 Times More Than Predicted From Environmental Modeling

25. Year 1974197619781980198219841986198819901992 0 20 40 60 80 100 2 4 6 8 10 12 14 16 18 Blood lead Gasoline lead Lead used in gasoline (thousands of tons) Mean blood lead levels (ug/dL) NHANES III (1988-1991) Blood Lead Measurements Showed That After NHANES II (1976-1980), Blood Lead Levels Continued to Decrease As Gasoline Levels Declined

26. 0 20 40 60 80 100 Percent of children with blood lead levels <10 ug/dL 1976-80 NHANES II 1988-91 NHANES III 88.2 8.9 Blood lead levels in NHANES surveys: children 1- 5 years

27. How was it proven that the declining blood lead levels were due to changes in the environment, and not due to analytical errors? MEASUREMENT OF LONG-TERM, STABLE QUALITY CONTROL MATERIALS CALIBRATED AGAINST NIST SRMs

28. What purpose does NHANES serve? In toxicology studies – helps prioritize.

29. Methyl Eugenol Occurs naturally in clove oil, nutmeg, allspice, walnuts Uses: Flavoring agent, insect attractant, fragrance (30,000 kg/yr) Consumption Rate: 6 g/day OCH 3

30. DLS’ Commitment to Analyses for NHANES Has Increased With Each Successive Survey 1971-1975 HANES I - 20,000 subjects NHANES Central Laboratory established Strictly nutrition-oriented survey 22 Analytes measured, all at CDC Hematology a primary component; CBC done in MEC Abell-Kendall reference cholesterol method used 1976-1980 HANES II - 20,000 subjects Six outside labs are added 21 analytes measured; blind QC added Trace metals added (Pb, Zn, Cu) Hepatitis and STD prevalence first assessed EPA assessed human exposure to OC and OP pesticides and phenols.

31. DLS’ commitment to analyses for NHANES has increased with each successive survey 1982-1984 Hispanic HANES - 12,000 subjects Mexican-American, Cuban, Puerto-Rican subjects Four outside labs 37 Analytes measured, HPLC debuts Hair collection for trace metals added EPA assessed human exposure to OC and OP pesticides and phenols.

32. DLS’ commitment to analyses for NHANES has increased with each successive survey 1988-1994 NHANES III - 30,000 subjects 12 contract labs First survey to use bar codes 85+ Analytes; cotinine is major component Lab manual is >700 pages and is published on CD-ROM) RBase used for survey database; still using mainframe LN2 storage introduced for reserve serum aliquots Selenium, Genetics component added Subset for VOCs and pesticide metabolites.

33. National Report on Human Exposure to Environmental Chemicals Division of Laboratory Sciences, National Center for Environmental Health, CDC

34. National Report on Human Exposure to Environmental Chemicals - 1999 MatrixAge RangeNAssessment Blood  1 year 3,189Pb, Cd Blood1-5 years248Hg Blood16-49 years (F)679Hg Urine  6 years ~1000Sb, BA, Be, Cd, Ce, Co, Pb, Mb, Pt, Th, W, U Urine  6 years ~1000OPs (6), Phthalates (7) Serum  3 years 2263cotinine

35. National Report on Human Exposure to Environmental Chemicals –1999/2000 MatrixAge RangeNAssessment Blood  1 year Pb, Cd Blood1-5 yearsHg Blood16-49 years (F)Hg Blood  12 years VOCs Serum  3 years cotinine Serum  12 years PCBs (38), PCDDs (7), PCDFs (10), coplanar PCBs (4), OC insecticides (10) Serum  12 years Se Urine  6 years Sb, Ba, Be, Cd, Ce, Co, Pb, Mb, Pt, Th, W, U, Hg Urine  6 years OPs (6), Phthalates (7), PAHs (18), Phytoestrogens (8), additional NPPs

36. Does the test have biological relevance? Is there a correlation between the biomarker and dietary intake or exposure data? Does the condition occur frequently enough in the population? Is there a validated method available? Can we afford the cost of the assay? Is there financial support for the assay? Primary Criteria for Consideration for Inclusion of Analytes in NHANES

37. Exposure Pathway (Partial) for Toxicant Source Environmental Fate and Transport Exposure Absorption Barriers Air, Water, Food, Soil, Surfaces GI tract wall Lung tissue Skin Internal Dose Biological Effective Dose

38. Life Cycle Conception Birth Death 1 y 2 y 3 y 6 y 12 y 18-21 y Infancy Young toddler Older toddler Preschool Pre High School Adolescence Trimesters Embryonic (8d – 8w)