exposure assessment using biomonitoring · biomonitoring assessment of internal dose exposure by...
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Exposure Assessment
using
Biomonitoring
June 29, 2004
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Biomonitoring
assessment of internal dose exposure by
measuring a toxicant (or its metabolite) in human
specimens such as blood, urine, saliva, or adipose
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External dose: air, water, food, soil, dust
Internal dose: blood, serum, urine, tissue
Health effect
Exposure and health effects pathway
inhalationingestionskin absorption
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• Parent chemical in serum, urine, saliva
• Metabolite in serum, urine, saliva
• Protein adduct (albumin or hemoglobin) in serum or whole blood
Note the different exposure time frames represented by each of these measurements
Choice of matrix and form of chemical
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Blood/serum level
1 10 100 1000
Time (Days)
Con
cent
ratio
n
Albumin adductHemoglobin adduct
Urinary metabolite
Persistent toxicant in blood and urine
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Blood/serum level
1 10 100 1000
Time (Days)
Con
cent
ratio
n
Urinary metabolite
Albumin adduct
Hemoglobin adduct
Non-persistent toxicant in blood and urine
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Biomonitoring measurements can
CALIBRATE and VALIDATE
an exposure index based on other information
The exposure index can then be applied to many
people including persons who have died
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Case control studies
Nested case control studies
Assessment of 20-30 potentially highly exposed
Multiple specimens collected over time to characterize time changes of an exposure
Cross sectional sample of population
Broad profile of measurements investigating a health effect of unknown cause (e.g., cancer cluster)
Couple the right epidemiologic design to the appropriate biomonitoring measurement to answer the public health question of interest
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• Best if have health threshold level (e.g., lead ≥ 10 µg/dL)
• In absence of health threshold level, 95th percentile can be used to define‘unusually high’ exposures
(see data from Second National Report on Human Exposure toEnvironmental Chemicals, 2003 at www.cdc.gov/exposurereport)
Identifying ‘unusually high’ exposures
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CDC’s Second National
Report on Human Exposure
to Environmental Chemicals
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• U.S. population and major U.S. demographic subgroups(today’s presentation)
• Special population groups with known or suspected elevated exposures
• Special populations with disease known or suspected to result from chemical exposures
Priority population groups forbiomonitoring exposure assessment
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Report Data
116 chemicals
Selected participants in NHANES 1999-2000
Blood and urine levels of chemicals and metabolites
Sample size: 2000-2500 (more for cotinine, lead, cadmium)
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Chemicals in the Second Report
• Lead, mercury, cadmium, uranium, thallium,
other heavy metals
• Cotinine (tobacco smoke exposure)
• Dioxins, furans, and coplanar PCBs
• Non-coplanar polychlorinated biphenyls (PCBs)
• Polyaromatic hydrocarbons (PAHs)
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Chemicals in the Second Report (cont’d)
• Organochlorine pesticides
• Organophosphate and carbamate insecticides
• Herbicides
• Phytoestrogens
• Phthalates
• Pest repellants and disinfectants
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Public Health Uses of the Report
• what chemicals get into Americans
• how many people have elevated levels
• effectiveness of exposure reduction efforts
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Public Health Uses (continued)
• reference ranges – identifying unusual exposure
• levels in susceptible groups, like women of childbearing age or children
• priorities for health research
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For chemicals with limited health risk information:
Just because we can measure it,does not mean it is harmful
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Table 58. 1-hydroxy pyrene
Total, age 6 and older 79.8 14.9 34.8 78.0 187 434 730 2312(69.0-92.2) (11.8-18.4) (28.3-41.7) (68.1-92.6) (161-229) (372-505) (568-934)
Age group 6-11 years 90.8 18.6 55.7 91.9 170 299 413 310
(72.2-114) (14.8-36.3) (39.8-69.9) (77.9-124) (124-210) (206-399) (279-652)
12-19 years 105 24.1 48.0 108 226 473 642 693(85.0-129) (19.2-33.5) (39.5-61.4) (78.1-133) (172-290) (317-618) (406-1170)
20+ years 74.8 13.6 30.7 70.1 187 446 795 1309(64.0-87.4) (10.0-16.3) (24.7-36.7) (63.0-84.9) (157-232) (372-570) (570-940)
Gender Males 90.1 18.0 37.1 86.1 227 496 751 1106
(76.0-107) (14.1-23.5) (30.0-48.6) (73.2-99.8) (178-282) (401-577) (577-1020)
Females 71.2 13.7 32.1 70.9 163 361 669 1206(61.6-82.3) (9.90-15.8) (26.6-36.9) (63.7-86.1) (149-197) (284-451) (387-940)
Race/ethnicity Mexican-Americans 74.2 16.1 34.0 68.3 161 344 545 766
(64.5-85.4) (14.3-19.6) (29.9-39.6) (59.5-82.8) (119-213) (268-463) (405-638)
Non-Hispanic blacks 108 20.8 46.6 100 245 586 812 528(87.0-135) (17.9-24.0) (34.8-58.0) (76.2-148) (199-350) (420-778) (541-1360)
Non-Hispanic whites 73.7 13.8 32.3 72.9 178 399 748 831(61.1-88.9) (9.40-17.7) (24.3-39.7) (63.3-86.3) (153-222) (324-506) (451-977)
Geometric mean and selected percentiles of urine concentrations (in µg/L) for the U.S. populationaged 6 years and older, National Health and Nutrition Examination Survey, 1999-2000.
Geometric mean
(95% conf. interval)
Sample size
Selected percentiles(95% confidence interval)
10th 25th 50th 75th 90th 95th
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Percent of children 1-5 years of age in the United Stateswith blood lead levels ≥ 10 µg/dL
0
20
40
60
80
100
1976-1980 1988-1991 1991-1994 1999-2000
Per
cent
88.2
8.64.4 2.2
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Exposure of the U.S. population to tobacco smoke:serum cotinine levels, 1988-1991
Serum cotinine (ng/mL)
Per
cent
of t
he p
opul
atio
n
0
1
2
3
4
5
0.1 1.0 10 100 1000
Non-smokers(ETS exposure) Smokers
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0.0
0.1
0.2
0.3
0.4
0.5
0.6
Geo
met
ric m
ean
seru
m c
otin
ine
(ng/
mL)
≥ 4Number of hours exposed at work
Serum cotinine levels for non-tobacco users in the U.S. population, ages 17 and older, NHANES III, 1988-1991
1−30
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0.00
0.10
0.20
Ser
um c
otin
ine
(50th
perc
entil
e in
ng/
mL)
1988 - 1991 1999-2000
0.20
0.05
Decline in exposure of U.S. populationto environmental tobacco smoke
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Decline in cotinine levels by age group (1988-1991 to 1999-2000)
Children 58%
Adolescents 55%
Adults 75%
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Cotinine levels, 1999-2000
Children – levels more than 2X adults
Non-Hispanic blacks - levels more than 2X whitesor Mexican-Americans
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ExposureExposure to environmental tobacco smokeamong casino workers
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0.0
0.5
1.0
1.5
2.0
Ser
um c
otin
ine
(geo
m. m
ean
in n
g/m
L)
NHANES NIOSH study
No homeor work
exposure
Casinoworkers
Homeand workexposure
Homeexposure
only
Workexposure
only
Exposure of casino workers to environmental tobacco smoke
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World Trade Center – detecting unusual levels of exposure
• 370 firefighters studied
• blood and urine samplescollected while fires still burning
• 110 fire related chemicals tested
PAHsMetalsCyanideDioxins/furans/PCBsVolatile organic compounds
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0
20
40
60
80
100
120
140
160
180
SpecialOperationsFirefighters
OtherFirefighters
ControlFirefighters
Adults –2nd Exposure Report
1-hy
drox
y py
rene
1-hydroxy pyrene levels in WTC firefighters(geometric means in ng/L)
7.0% of exposed firefighters above 95th percentile of 2nd Report
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SpecialOperationsFirefighters
OtherFirefighters
ControlFirefighters
Adults –2nd Exposure Report
antim
ony
Antimony levels in WTC firefighters(geometric means in µg/L)
16.5% of exposed firefighters above 95th percentile of 2nd Report
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
0.40
0.45
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U.S. troop exposure to depleted uranium in Iraq
• exposure from shrapnel
• exposure from battle explosions
• .045 µg/L is adult 95th percentile for urine uranium from 2nd Report
• to date, all soldier levels we havemeasured have been below this95th percentile
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Blood mercury levels in women of childbearing age (16-49 years), 1999-2000
• EPA reference dose for blood mercury is 5.8 µg/L
• In 2nd Report, the 95th percentile for women 16-49 years is 7.1 µg/L
• 7.8% of women of childbearing age exceed the EPA RfD
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Future Directions for the Report
• More chemicalsVOCs (benzene, MTBE, toluene, styrene, others)perfluorinated compoundspolybrominated diphenyl ethers (PBDEs)speciated arsenicseparate measurements for methyl mercury and ethyl mercuryperchlorateacrylamidePAHs with 5 and 6 rings, the more carcinogenic PAHsmore ….
• New Report every two years (2001-2002, 2003-2004, 2005-2006, etc)
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www.cdc.gov/exposurereport