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