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Persistent Bioaccumulative Toxicants Workshop. Larry L. Needham, PhD National Center for Environmental Health Centers for Disease Control and Prevention April 22, 2002. Mission of Division of Laboratory Sciences. To develop and apply analytical methods for
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Persistent Bioaccumulative Toxicants Workshop Larry L. Needham, PhD National Center for Environmental Health Centers for Disease Control and Prevention April 22, 2002
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.
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.
National Report on HumanExposure to Environmental Chemicals Division of Laboratory Sciences, National Center for Environmental Health, CDC
Organization for NHANES DHHS FDA CDC NIH NCID NC CDPHP NCHS NC HIV,STD, &TB NIOSH NCIPC NCEH
NHANES MEC Division of Laboratory Sciences / NCEH NCID labs NCHSTP Medical Research Centers/ Academic labs Commercial labs 23 Participating Laboratories for NHANES
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
How did NHANES start? • The Health Examination Survey – the forerunner in the 1960’s • HANES I – 1971; Nutrition added as a major component
Six Principal Data Collection Methods • Household interview • Personal interviews • Physical examination • Anthropometry • Diagnostic screening • Laboratory analysis
The Mobile Examination Centers (MECs) • 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
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 MEC examination components
NHANES Laboratory in the MEC Laminar Flow Hood Coulter Counter for CBC
CDCNCHSMEC CDC NCEH DLS CDC CASPIR
What Purpose Does NHANES Serve? • Serves as a warning system for health problems
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
What Purpose Does NHANES Serve? • Helps identify who is at risk.
5 4 Nonsmokers Smokers Percent of the Population 3 2 1 0 0.1 1.0 10 100 1000 Serum cotinine (ng/mL) Distribution of serum cotinine in the U.S. Population (ages 4 and older), NHANES III (1988-1991)
5 4 No reported home or work ETS exposure 3 2 1 0 5 4 Reported home or work ETS exposure 3 2 1 0 5 4 Tobacco user 3 2 1 0 0.1 1.0 10 100 1000 Serum Cotinine, ng/mL Serum Cotinine Levels in the U.S. Population by Self-reported Exposure to Tobacco Smoke, NHANES III (1988-1991) Percentage of the Population
What Purpose Does NHANES Serve? • Shows if public health interventions have been successful through trend data.
Lead used in gasoline declined from 1976 through 1980 110 100 90 80 Gasoline lead Lead used in gasoline (thousands of tons) 70 60 50 40 30 1975 1976 1977 1978 1979 1980 1981 Year
Environmental Modeling Predicted Only a Slight Decline in Blood Lead Levels in People 110 17 Predicted blood lead 100 16 90 15 14 80 Gasoline lead Lead used in gasoline (thousands of tons) Mean blood lead levels (ug/dL) 13 70 12 60 11 50 10 40 9 30 1975 1976 1977 1978 1979 1980 1981 Year
NHANES II Blood Lead Measurements Found a Substantial Decline in Blood Lead Levels, 10 Times More Than Predicted From Environmental Modeling 110 17 Predicted blood lead 100 16 90 15 14 80 Gasoline lead Lead used in gasoline (thousands of tons) Mean blood lead levels (ug/dL) 13 70 12 60 11 50 Observed blood lead 10 40 9 30 1975 1976 1977 1978 1979 1980 1981 Year
NHANES III (1988-1991) Blood Lead Measurements Showed That After NHANES II (1976-1980), Blood Lead Levels Continued to Decrease As Gasoline Levels Declined 18 100 16 14 80 12 60 Lead used in gasoline (thousands of tons) Blood lead Mean blood lead levels (ug/dL) 10 Gasoline lead 40 8 6 20 4 0 2 1974 1976 1978 1980 1982 1984 1986 1988 1990 1992 Year
Blood lead levels in NHANES surveys: children 1- 5 years 100 88.2 80 Percent of children with blood lead levels <10 ug/dL 60 40 20 8.9 0 1976-80 NHANES II 1988-91 NHANES III
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
What purpose does NHANES serve? • In toxicology studies – helps prioritize.
OCH3 OCH3 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
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.
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.
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.
National Report on HumanExposure to Environmental Chemicals Division of Laboratory Sciences, National Center for Environmental Health, CDC
National Report on Human Exposure to Environmental Chemicals - 1999
National Report on Human Exposure to Environmental Chemicals –1999/2000
Primary Criteria for Consideration for Inclusion of Analytes in NHANES • 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?
Exposure Pathway (Partial) for Toxicant Source Environmental Fate and Transport Air, Water, Food, Soil, Surfaces Exposure GI tract wall Absorption Barriers Lung tissue Skin Internal Dose Biological Effective Dose
Life Cycle Death 2 y Young toddler Older toddler 1 y 3 y Infancy Birth Preschool Trimesters Embryonic (8d – 8w) 6 y Conception Pre High School 12 y 18-21 y Adolescence