Older Adults’ Exposures: To What and Pathways
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Transcript of Older Adults’ Exposures: To What and Pathways
Older Adults’ Exposures: To What and Pathways
Larry L. Needham, Ph.D.Chief, Toxicology Branch
National Center for Environmental Health
Centers for Disease Control and Prevention
Atlanta, GA USA 30341
Exposure Pathway
Source
Water, Air, Food, Soil, Dust, Sediment, Personal Care Products
Internal Dose
InhalationIngestionDermal Contact
Target Organ Dose
Biologically Effective Dose
Absorption following:
DistributionMetabolism
Elimination
Elimination
Effect
Exposure Dose
Biomonitoring
Assessment of internal dose by measuring the parent chemical (or its metabolite or reaction product) in human blood, urine, milk, saliva, adipose, or other tissue.
CDC’s Second National Report on Human Exposure – data from NHANES 1999-2000
Urine
Metals (13)
PAH metabolites
Phthalate metabolites
Pesticides
Organophosphorus
Carbamates
Herbicides
Repellants
Phytoestrogens
Blood
Lead
Cadmium
Mercury
Serum
Dioxins
Furans
PCBs
Organochlorine pesticides
CotinineReleased: March 2003 www.cdc.gov/exposurereport
National Report on Human Exposureto Environmental Chemicals
What it is: An ongoing (every 2 years) biomonitoring
assessment of the exposure of the U.S. population to selected environmental chemicals
Matrices monitored: Urine; blood and its components
Major Findings: U.S. Population-based Reference Ranges
Geometric means
10th, 25th, 50th, 75th, 90th, and 95th percentiles
Age, sex, race/ethnicity breakout
Goals of National Report
Assess exposure to various chemicals (which?) Establish national “reference ranges” of these chemicals
(blood, urine) Track, over time, trends in these “reference ranges” Help set priorities on linking exposure to health outcomes
In American population and subpopulations (age, sex, race/ethnicity)
Uses of National Report
Assess effectiveness of efforts to reduce exposures (lead in gasoline; FQPA; POPs) in all Americans
In some cases, provide data for establishing source (pattern recognition, e.g., gasoline, dioxins/furans)
Provide data for risk assessment (dose-response and exposure assessment)
Provide data for linking environmental exposure data with interactions with genes, nutrition, and demographic data to eventually link with health outcome data
EffectsSource Exposure
Interpreting Data in the Report
The presence of a chemical in the body does not mean it causes disease
For many chemicals in the Report, more research is needed to interpret these levels
The Report provides new exposure data, but does not identify levels that cause disease Additional studies are needed
Other Uses of Biomonitoring Data
Clinical studiesEpidemiological studies (National
Children’s Centers, NCS)Occupational studiesEmergency investigations
Pharmacokinetics of Environmental Chemicals in Body and Matrices Available
for Analyses
Bile
Ingestion Inhalation Dermal
Gastrointestinal Tract
Lung
Blood/Lymph
PortalBlood
Kidney
Primary Deposition Sites
Soft Tissues
BoneFat
Secretory Structures
FecesBladderUrine
Liver
Secretions
Saliva Sweat Milk
TearsAlveoli
Expired Air
Needham et al. Neurotoxicology 2005 (online)Rozman & Klaassen in Casarett & Doull’s Toxicology. The Basic Science of Poisons, 5 th Edition 1996 p 91.
Post-Exposure Fate of a Persistent Chemical in Blood and Urine
BloodToxicant/Metabolite
DNA Adduct
Albumin Adduct
Hemoglobin Adduct
Urinary MetaboliteUrinary Adduct
1 10 100 1000
Time (Days)
Con
cent
ratio
n
Needham and Sexton, JEAEE 10:611-629 (2000)
Post-Exposure Fate of a Nonpersistent Chemical in Blood and Urine
Time (Days)
BloodToxicant/Metabolite
DNA Adduct
Albumin Adduct
Hemoglobin Adduct
Urinary Metabolite
Urinary Adduct
1 10 100 1000
Con
cent
ratio
n
Needham and Sexton, JEAEE 10:611-629 (2000)
Persistent ChemicalsPolychlorinated Biphenyls (PCBs)DDT → DDEPerfluorinated ChemicalsLead
Non Persistent ChemicalsChlorpyrifos → Trichloropyridinol (TCPy)Nicotine → Cotinine
Characteristics of Persistent Organic Pollutants
Persist in environmentBioaccumulate through food chain
(lipophilic)Pose risk of causing adverse effects
humans/environmentLong range transport
Stockholm Convention on POPs
Global treaty to protect human health and the environment from POPs.
Aldrin
Dieldrin
Endrin
Chlordane
Heptachlor
Toxaphene
DDT
Mirex
Hexachlorobenzene
PCBs
Dioxins
Furans
Persistent Organic Pollutant: PCBs
x y
x and y = Cl
N ( x + y ) = 1-10
209 congeners Production stopped 1977 Primary route of exposure; ingestion (certain foods) Indoor air (older electrical devices; fluorescent lights
contain PCB-filled capacitors; caulking materials)
50th & 95th Percentile of PCB 138 by Age Group, Race & Sex
Ng/
g
12-19 20-39 40-59 60+
MA 95th
MA 50th
NHB 95th
NHB 50th
NHW 95th
NHW 50th
Fem
ale
Fem
ale
Fem
ale
Fem
ale
Mal
e
Mal
e
Mal
e
Mal
e
0
50
100
150
200
250
300
Persistent Organic Pollutant: p,p’ - DDT
DDT use was banned in U.S. 1973 Agriculture and malaria control
Cl CCl ClC
C
H
Cl
Cl Cl
Cl
CCl Cl
DDT DDE
50th & 95th Percentile of DDE by Age Group, Race & Sex
Ng/
g
12-19 20-39 40-59 60+
MA 95th
MA 50th
NHB 95th
NHB 50th
NHW 95th
NHW 50th
Fem
ale
Fem
ale
Fem
ale
Fem
ale
Mal
e
Mal
e
Mal
e
Mal
e
0
1000
2000
3000
4000
5000
6000
7000
8000
Second Report Results
DDT banned in U.S. in 1973 Pesticide DDE is 3 times
higher in Mexican-Americans (3.9; 1.6; 1.3 ng/g)
Also measurable in 12-19 year olds (born after ban) (0.6 vs. 1.8 ng/g)
May be persisting in environment or from imported food
Perfluorochemicals (PFCs) in the EnvironmentProduced since 1950's for use in:
Surface treatments: soil and stain resistant coatings on textiles, carpet, leather
Paper protection: provides oil, grease and water resistance on paper products including those for food use
Performance chemicals including insecticide, fire fighting foams, industrial surfactants, acid mist suppression
3M phased out its fluorochemistry in May 2000
Perfluorinated Chemicals
S
O
O
NCF3(CF2)7
R
H
S
O
O
NCF3(CF2)7
R
CH2CH2OH
S
O
O
NCF3(CF2)7
R
CH2CH2COOH
S
O
O
OHCF3(CF2)n
CO
OHCF3(CF2)n
Sulfonamides Sulfonic acids (e.g., PFOS)
Carboxylic acids (e.g., PFOA)
Serum Pools: NHANES 2001/2002
34 People per pool (Total 1,734 people; 51 pools)
Unweighted; used for estimates of the “means”
0.75mL Serum per person
25.5 g Serum per pool 2 g BFRs/PCBs/Persistent Pesticides 22 g PCDDs/PCDFs/cPCBs 0.5 g Total Lipids 0.4 g Perfluorinated chemicals
NHANES 2001-2002 Pools
Race/Ethnicity Gender
Age Group (years)
Number of Pools12-19 20-39 40-59 60+
Non-Hispanic
White
M 2 (3) 3 3 3 (4)
F 2 (3) 4 3 4
Non-Hispanic
Black
M 3 1 1 1
F 3 1 1 1
Mexican-American
M 3 2 1 1
F 4 2 1 1( ) for perfluorinated chemicals
Mean and Range of PFOS by Age Group, Race and Sex
5.0
10.0
15.0
20.0
25.0
30.0
35.0
40.0
45.0
M(3)
F(4)
M(2)
F(2)
M(1)
F(1)
M(1)
F(1)
M(3)
F(3)
M(1)
F(1)
M(1)
F(1)
M(1)
F(1)
M(3)
F(3)
M(3)
F(4)
M(3)
F(3)
M(4)
F(4)
12-19 20-39 40-59 60+ 12-19 20-39 40-59 60+ 12-19 20-39 40-59 60+
Mexican-American Non-Hispanic Black Non-Hispanic White
Race/Ethnicity, Age, & Gender
ng/m
L
Mean and Range of PFOA by Age Group, Race and Sex
0.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
9.0
10.0
M(3)
F(4)
M(2)
F(2)
M(1)
F(1)
M(1)
F(1)
M(3)
F(3)
M(1)
F(1)
M(1)
F(1)
M(1)
F(1)
M(3)
F(3)
M(3)
F(4)
M(3)
F(3)
M(4)
F(4)
12-19 20-39 40-59 60+ 12-19 20-39 40-59 60+ 12-19 20-39 40-59 60+
Mexican-American Non-Hispanic Black Non-Hispanic White
Race/Ethnicity, Age, & Gender
ng/m
L
Mean and Range of TEQs by Age Group, Race and Sex
0
5
10
15
20
25
30
35
40
45
M(3)
F(3)
M(2)
F(2)
M(1)
F(1)
M(1)
F(1)
M(3)
F(3)
M(1)
F(1)
M(1)
F(1)
M(1)
F(1)
M(2)
F(2)
M(3)
F(4)
M(3)
F(3)
M(3)
F(4)
12-19 20-39 40-59 60+ 12-19 20-39 40-59 60+ 12-19 20-39 40-59 60+
Mexican-American Non-Hispanic Black Non-Hispanic White
Race/Ethnicity, Age, & Gender
To
tal T
EQ
Lead
Blood lead levels (BLLs)
1 year of age and greater
Year
1975 1976 1977 1978 1979 1980 1981
30
40
50
60
70
80
90
100
110
Gasoline lead
Lead
use
d In
gas
olin
e(1
000
tons
)Lead Used in Gasoline Declined from 1976
Through 1980
Year
1975 1976 1977 1978 1979 1980 1981
Lead used ingasoline
(thousandsof tons)
30
40
50
60
70
80
90
100
110
Mean bloodlead levels
(g/dL)
9
10
11
12
13
14
15
16
17
Gasoline lead
Predicted blood lead
Predicted Blood Lead Changes with Decreasing Gasoline Lead
Observed blood lead
Year
1975 1976 1977 1978 1979 1980 1981
Lead used ingasoline
(thousandsof tons)
30
40
50
60
70
80
90
100
110
Mean bloodlead levels
(g/dL)
9
10
11
12
13
14
15
16
17
Gasoline lead
Predicted blood lead
NHANES II Blood Lead Measurements Found A Substantial Decline in Blood Lead Levels,
10 Times More Than Predicted from Environmental Modeling
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
Year
Lead
use
d In
gas
olin
e(1
000
tons
)
Blo
od le
ad le
vels
(g
/dL)
After NHANES II, EPA Further Restricted Leaded Gasoline and Gasoline Lead Levels Continued to Decline Through 1991
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
use
d In
gas
olin
e(1
000
tons
)
Blo
od le
ad le
vels
(g
/dL)
NHANES III (1988-1994) Showed Blood Lead Levels Continued to Decrease as Gasoline Levels Declined
1974 1976 1978 1980 1982 1984 1986 1988 1990 1992
2
4
6
8
10
12
14
16
18
Blo
od
lead
leve
ls (
g/dL
)
01994 1996 1998 2000
Year
Blood Lead Levels in the U.S. Population 1976 -2000
NHANES II, III, 1999-2000
For children 1 through 5 years old
Major Findings: Decline in Blood Lead Levels among Children
NHANES III (1991-94) Geometric mean BLL 2.7 g/dL 4.4% had BLLs 10 g/dL
NHANES 1999-2000 Geometric mean BLL 2.23 g/dL 2.2% had BLLs ≥ 10 g/dL Higher prevalence of BLLs in U.S. children occur in
urban settings, lower SES, immigrants and refugees
(Geltman et al., 2001)
Chlorpyrifos
Organophosphorus pesticideMany food usesTermiticideUse in and around homes and non-
residential settings - eliminated
Limitation: Specificity of Analysis
3,5,6-TCPy is “specific” metaboliteDialkyl phosphates are “nonspecific” metabolites
+ +
3,5,6-TCPyN OH
ClCl
Cl
N O
ClCl
Cl P
O
OR’
OR’N O
ClCl
Cl P
S
OR’
OR’
HO P
S
OR’
OR’ HO P
O
OR’
OR’
Chlorpyrifos (R’=ethyl) and Chlorpyrifos-methyl (R’=methyl) Metabolism and Env’l Degradation
50th & 95th Percentile of 3,5,6-TCPy by Age Group, Race & Sex
µg/
L
6-11 12-19 20-39 40-59
MA 95th
MA 50th
NHB 95th
NHB 50th
NHW 95th
NHW 50th
Fem
ale
Fem
ale
Fem
ale
Fem
ale
Mal
e
Mal
e
Mal
e
Mal
e
0
5
10
15
20
25
30
Cotinine
Nicotine metabolite that tracks exposure to tobacco smoke
For nonsmokers, tracks exposure to secondhand smoke
N
N
CH3
O
Serum cotinine (ng/mL)
Per
cent
age
of t
he p
opul
atio
n
0
1
2
3
4
5
0.1 1.0 10 100 1000
ETS exposure (nonsmokers)
Smokers
Exposure of the U.S. Population to Tobacco Smoke: Serum Cotinine Levels (NHANES III, 1988-1991)
Second Report Results
Decrease in ETS 1988-1991 to 1999-2000
Measured as serum cotinine Children: 58% decreased Adolescents: 55% decreased Adults: 75% decreased
50th & 95th Percentile of Cotinine by Age Group, Race & SexN
g/m
L
3-11 12-19 20-39 40-59 60+
MA 95th
MA 50th
NHB 95th
NHB 50th
NHW 95th
NHW 50th
0
1
2
3
4
5
6
7
8M
ale
Fem
ale
Mal
e
Fem
ale
Mal
e
Fem
ale
Mal
e
Fem
ale
Mal
e
Fem
ale
Third National Report on Human Exposure to Environmental Chemicals
Organochlorine pesticides: aldrin, dieldrin, endrinOP pesticides: additional metabolitesPyrethroids: 5 metabolitesHerbicides: mercapturate metabolites of acetochlor
and metolachlorPAHs: 1-, 2-, and 4-hydroxychrysene; 4- and 9-
hydroxyphenanthrene; 9-hydroxyfluorene; 3-hydroxybenzo(a)pyrene
Additional PCDDs and PCBsAdditional phthalate metabolites (e.g., oxidative
metabolites of DEHP and DnOP)
Includes chemicals from Second National Report (1999-2000) + the following in NHANES 2001-2002