Persistent Bioaccumulative Toxicants Workshop

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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

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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.

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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.

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National Report on Human Exposure to
Environmental Chemicals
Division of Laboratory Sciences, National Center
for Environmental Health, CDC
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Organization for NHANES
DHHS
FDA
CDC
NIH
NCID
NC CDPHP
NCHS
NC HIV,STD, TB
NIOSH
NCIPC
NCEH
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(No Transcript)
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23 Participating Laboratories for NHANES

• NHANES MEC
• Division of Laboratory Sciences / NCEH
• NCID labs
• NCHSTP

• Medical Research Centers/ Academic labs
• Commercial labs

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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

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How did NHANES start?

• The Health Examination Survey the forerunner in
  the 1960s
• HANES I 1971 Nutrition added as a major
  component

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Six Principal Data Collection Methods

• Household interview
• Personal interviews
• Physical examination
• Anthropometry
• Diagnostic screening
• Laboratory analysis

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The Mobile Examination Centers (MECs)
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The Mobile Examination Centers (MECs)

• 4 Trailers attached to one another, each 8x45
• 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

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MEC examination components

• Dietary interviews/MEC interviews
• Phlebotomy
• Urine collection
• Blood pressure
• Physicians 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

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NHANES Laboratory in the MEC
Laminar Flow Hood
Coulter Counter for CBC
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CDCNCHSMEC
CDC NCEH DLS
CDC CASPIR
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What Purpose Does NHANES Serve?

• Serves as a warning system for health problems

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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

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What Purpose Does NHANES Serve?

• Helps identify who is at risk.

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Distribution of serum cotinine in the U.S.
Population (ages 4 and older), NHANES III
(1988-1991)
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Serum Cotinine Levels in the U.S. Population by
Self-reported Exposure to Tobacco Smoke, NHANES
III (1988-1991)
Percentage of the Population
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What Purpose Does NHANES Serve?

• Shows if public health interventions have been
  successful through trend data.

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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
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Environmental Modeling Predicted Only a Slight
Decline in Blood Lead Levels in People
110
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Predicted blood lead
100
16
90
15
14
80
Gasoline lead
Lead used in gasoline (thousands of tons)
Mean blood lead levels (ug/dL)
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70
12
60
11
50
10
40
9
30
1975
1976
1977
1978
1979
1980
1981
Year
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NHANES II Blood Lead Measurements Found a
Substantial Decline in Blood Lead Levels, 10
Times More Than Predicted From Environmental
Modeling
110
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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
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NHANES III (1988-1991) Blood Lead Measurements
Showed That After NHANES II (1976-1980), Blood
Lead Levels Continued to Decrease As Gasoline
Levels Declined
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100
16
14
80
12
60
Blood lead
Lead used in gasoline (thousands of tons)
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
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Blood lead levels in NHANES surveys children 1-
5 years
100
88.2
80
Percent of children with blood lead levels lt?10
ug/dL
60
40
20
8.9
0
1976-80 NHANES II
1988-91 NHANES III
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• 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

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What purpose does NHANES serve?

• In toxicology studies helps prioritize.

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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

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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.

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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.

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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 gt700 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.

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National Report on Human Exposure to
Environmental Chemicals
Division of Laboratory Sciences, National Center
for Environmental Health, CDC
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National Report on Human Exposure to
Environmental Chemicals - 1999
Matrix Age Range N Assessment
Blood ? 1 year 3,189 Pb, Cd
Blood 1-5 years 248 Hg
Blood 16-49 years (F) 679 Hg
Urine ? 6 years 1000 Sb, BA, Be, Cd, Ce, Co, Pb, Mb, Pt, Th, W, U
Urine ? 6 years 1000 OPs (6), Phthalates (7)
Serum ? 3 years 2263 cotinine
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National Report on Human Exposure to
Environmental Chemicals 1999/2000
Matrix Age Range N Assessment
Blood ? 1 year Pb, Cd
Blood 1-5 years Hg
Blood 16-49 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
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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?

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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
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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