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 Human Exposureto Environmental

Chemicals

Division of Laboratory Sciences,National Center for Environmental

Health,CDC

Organization for NHANES

DHHS

FDA CDC NIH

NCIDNC

CDPHPNCHS

NCHIV,STD,

&TBNIOSH NCIPC NCEH

23 Participating Laboratories for NHANES

• NHANES MEC• Division of Laboratory

Sciences / NCEH• NCID labs• NCHSTP

• Medical Research Centers/ Academic labs

• Commercial labs

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)

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

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

NHANES Laboratory in the MEC

CoulterCounter for CBC

LaminarFlow Hood

CDCNCHSMEC

CDC CASPIR

CDC NCEH DLS

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

Comparison of Median Urinary Iodine Concentration by Gender and Survey, NHANES I and III (Using Same Analytical Method)

0

50

100

150

200

250

300

350

400

NHANES I (1971-1974) NHANES III (1988-1994)Med

ian U

rinar

y Iod

ine C

once

ntra

tion

(ug/

L)

Total Male Female

What Purpose Does NHANES Serve?

• Helps identify who is at risk.

Distribution of serum cotinine in the U.S. Population(ages 4 and older), NHANES III (1988-1991)

0.1 1.0 10 100 1000

5

4

3

2

1

0

Serum cotinine (ng/mL)

Per

cen

t o

f th

e P

op

ula

tio

n

Smokers

Nonsmokers

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

0

1

2

3

4

5

Tobacco user

0.1 1.0 10 100 1000

Serum Cotinine, ng/mL

Per

cen

tag

e o

f th

e P

op

ula

tio

nSerum Cotinine Levels in the U.S. Population by Self-

reported Exposure to Tobacco Smoke, NHANES III (1988-1991)

What Purpose Does NHANES Serve?

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

Year

1975 1976 1977 1978 1979 1980 1981

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

Year

1975 1976 1977 1978 1979 1980 1981

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

Observed blood lead

Year

1975 1976 1977 1978 1979 1980 1981

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

Year

1974 1976 1978 1980 1982 1984 1986 1988 1990 1992

0

20

40

60

80

100

2

4

6

8

10

12

14

16

18

Blood leadGasoline 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

0

20

40

60

80

100

Percent of childrenwith blood lead levels <10 ug/dL

1976-80NHANES II

1988-91NHANES III

88.2

8.9

Blood lead levels in NHANES surveys: children 1- 5 years

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.

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

OCH3

OCH3

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 Human Exposureto Environmental

Chemicals

Division of Laboratory Sciences,National Center for Environmental

Health,CDC

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

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

• 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

Exposure Pathway (Partial) for Toxicant

SourceSource

Environmental Fateand Transport

Exposure

Absorption Barriers

Air, Water, Food, Soil,

SurfacesGI tract wall

Lung tissue

Skin

Internal Dose

Biological Effective Dose

Life Cycle

Conception

Birth

Death

1 y

2 y

3 y

6 y

12 y18-21 y

InfancyYoung to

ddler

Older toddler

Preschool

Pre High School

Adolescence

TrimestersEmbryonic (8d – 8w)