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Biomonitoring in NHANES

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Biomonitoring in NHANES Powered By Docstoc
					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
                  Exposure Dose
                                                 Inhalation
                           Absorption following: Ingestion
                   Internal Dose                 Dermal Contact
  Metabolism                  Distribution
                       Target Organ            Elimination
   Elimination             Dose

                 Biologically Effective Dose

                          Effect
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                                                Blood
Metals (13)                                          Lead
PAH metabolites                                      Cadmium
Phthalate metabolites                                Mercury
Pesticides
  Organophosphorus                                   Serum
  Carbamates                                         Dioxins
  Herbicides                                         Furans
Repellants                                           PCBs
Phytoestrogens                                       Organochlorine
                                                       pesticides
                                                     Cotinine
                        Released: March 2003
                        www.cdc.gov/exposurereport
National Report on Human Exposure
to 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

In American population and subpopulations (age, sex,
race/ethnicity)
  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
Uses of National Report
   Source             Exposure              Effects


 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
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 studies
   Epidemiological studies (National
    Children’s Centers, NCS)
   Occupational studies
   Emergency investigations
      Pharmacokinetics of Environmental
    Chemicals in Body and Matrices Available
                  for Analyses
          Ingestion                     Inhalation                  Dermal

  Gastrointestinal                         Lung                      Primary Deposition Sites
       Tract

            Liver                  Portal Blood/                                Fat          Bone
                                   Blood Lymph
                                                                  Secretory             Soft
           Bile                                                   Structures          Tissues
                                                    Alveoli
                                    Kidney                                               Tears
                                                                   Secretions
   Feces
                                                  Expired         Saliva      Sweat           Milk
                   Urine          Bladder
                                                    Air
Needham et al. Neurotoxicology 2005 (online)
Rozman & Klaassen in Casarett & Doull’s Toxicology. The Basic Science of Poisons, 5th Edition 1996 p 91.
Post-Exposure Fate of a Persistent Chemical
           in Blood and Urine
           Blood
           Toxicant/Metabolite




            Hemoglobin Adduct



                                       Albumin Adduct
        DNA Adduct


   Urinary Adduct                                         Urinary Metabolite


                       1          10                100                 1000
                                 Time (Days)


   Needham and Sexton, JEAEE 10:611-629 (2000)
Post-Exposure Fate of a Nonpersistent
     Chemical in Blood and Urine
         Blood
         Toxicant/Metabolite


                     Urinary Metabolite


                               Albumin Adduct


                                  Hemoglobin Adduct

             DNA Adduct


Urinary Adduct


                       1                  10          100   1000
                                  Time (Days)

Needham and Sexton, JEAEE 10:611-629 (2000)
Persistent Chemicals
  Polychlorinated Biphenyls (PCBs)
  DDT → DDE
  Perfluorinated Chemicals
  Lead

Non Persistent Chemicals
  Chlorpyrifos → Trichloropyridinol (TCPy)
  Nicotine → Cotinine
Characteristics of Persistent Organic
             Pollutants
 Persist in environment
 Bioaccumulate through food chain
  (lipophilic)
 Pose risk of causing adverse effects
  humans/environment
 Long range transport
Stockholm Convention on POPs
Global treaty to protect human health and
the environment from POPs.

   Aldrin            DDT
   Dieldrin          Mirex
   Endrin            Hexachlorobenzene
   Chlordane         PCBs
   Heptachlor        Dioxins
   Toxaphene         Furans
Persistent Organic Pollutant: PCBs


  x and y = Cl
N ( x + y ) = 1-10
                     x                  y


   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
           300


           250


           200
  Ng/g




           150


           100


           50


MA 95th     0




                                                                                         Female
                           Female




                                               Female




MA 50th
                                                                   Female
                 Male




                                    Male




                                                        Male




                                                                            Male
NHB 95th
NHB 50th
NHW 95th
NHW 50th           12-19                   20-39               40-59               60+
Persistent Organic Pollutant: p,p’ - DDT

                H

 Cl            C          Cl     Cl             C         Cl

                C                               C
          Cl         Cl                   Cl         Cl
               Cl
               DDT                             DDE


       DDT use was banned in U.S. 1973
       Agriculture and malaria control
         50th & 95th Percentile of DDE by Age Group,
                          Race & Sex
         8000

         7000

         6000

         5000
  Ng/g




         4000

         3000

         2000

         1000

MA 95th    0




                                                                                        Female
                          Female




                                              Female




MA 50th
                                                                  Female
                Male




                                   Male




                                                       Male




                                                                           Male
NHB 95th
NHB 50th
NHW 95th
NHW 50th          12-19                   20-39               40-59               60+
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
Environment
 Produced 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
 Sulfonamides                  Sulfonic acids
                               (e.g., PFOS)
         O
                 CH2CH2COOH             O
 CF3(CF2)7 S N
                               CF3(CF2)n S OH
          O      R
                                         O
          O
                 CH2CH2OH
 CF3(CF2)7 S N                Carboxylic acids
          O      R             (e.g., PFOA)
          O                                  O
                 H             CF3(CF2)n C
 CF3(CF2)7 S N                               OH
          O      R
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
                                         Age Group (years)
 Race/Ethnicity           Gender         Number of Pools
                                    12-19   20-39   40-59   60+
 Non-Hispanic                 M     2 (3)    3       3      3 (4)
    White                     F     2 (3)    4       3       4
 Non-Hispanic                 M       3      1       1       1
    Black                     F      3       1       1       1
   Mexican-                   M      3       2       1       1
   American                   F      4       2       1       1

 ( ) for perfluorinated chemicals
           Mean and Range of PFOS by Age
           Group, Race and Sex
        45.0

        40.0

        35.0

        30.0
ng/mL




        25.0

        20.0

        15.0

        10.0

         5.0
                M F M         F M F         M F M         F M F         M F M         F M F         M F M          F M F
               (3) (4) (2)   (2) (1) (1)   (1) (1) (3)   (3) (1) (1)   (1) (1) (1)   (1) (3) (3)   (3) (4) (3)    (3) (4) (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
           Mean and Range of PFOA by Age
           Group, Race and Sex
        10.0
         9.0
         8.0
         7.0
         6.0
ng/mL




         5.0
         4.0
         3.0
         2.0
         1.0
         0.0
                M F M F M F M F M F M F M F M F M F M F M F M F
               (3) (4) (2) (2) (1) (1) (1) (1) (3) (3) (1) (1) (1) (1) (1) (1) (3) (3) (3) (4) (3) (3) (4) (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
                 Mean and Range of TEQs by Age
                 Group, Race and Sex
            45

            40

            35

            30
Total TEQ




            25

            20

            15

            10

             5

             0
                  M     F     M        F     M         F     M           F     M      F     M        F      M          F     M           F     M     F     M         F      M         F     M           F
                 (3)   (3)   (2)      (2)   (1)       (1)   (1)         (1)   (3)    (3)   (1)      (1)    (1)        (1)   (1)         (1)   (2)   (2)   (3)       (4)    (3)       (3)   (3)         (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
          Lead


Blood lead levels (BLLs)
1 year of age and greater
      Lead Used in Gasoline Declined from 1976
                   Through 1980
                        110

                        100
Lead used In gasoline




                        90
    (1000 tons)




                        80
                                                      Gasoline lead
                        70

                        60

                        50

                        40

                        30
                          1975   1976   1977   1978   1979   1980     1981

                                               Year
       Predicted Blood Lead Changes with
           Decreasing Gasoline Lead
             110
                                                                     17

             100                           Predicted blood lead      16

             90                                                      15

             80                                                      14
Lead used in                                  Gasoline lead
 gasoline                                                            13   Mean blood
             70                                                           lead levels
(thousands                                                                 (g/dL)
  of tons)                                                           12
             60
                                                                     11
             50
                                                                     10
             40
                                                                     9
             30
               1975   1976   1977   1978      1979     1980       1981
                                    Year
     NHANES II Blood Lead Measurements Found A
        Substantial Decline in Blood Lead Levels,
   10 Times More Than Predicted from Environmental
                        Modeling
             110
                                                                      17

             100                            Predicted blood lead      16

             90                                                       15

             80                                                       14
Lead used in                                   Gasoline lead
 gasoline                                                             13   Mean blood
             70                                                            lead levels
(thousands                                                                  (g/dL)
  of tons)                                                            12
             60
                                                                      11
             50
                                Observed blood lead                   10
             40
                                                                      9
             30
               1975   1976   1977    1978      1979     1980       1981
                                     Year
After NHANES II, EPA Further Restricted Leaded
Gasoline and Gasoline Lead Levels Continued to
Decline Through 1991
                                                                            18

                          100                                               16




                                                                                 Blood lead levels (g/dL)
  Lead used In gasoline




                          80                                                14
      (1000 tons)




                                                                            12
                          60
                                  Blood lead
                                               Gasoline lead                10
                          40
                                                                            8

                          20                                                6

                                                                            4
                           0
                                                                            2
                            1974 1976 1978 1980 1982 1984 1986 1988 1990 1992

                                                 Year
NHANES III (1988-1994) Showed Blood Lead Levels
Continued to Decrease as Gasoline Levels Declined
                                                                            18

                          100                                               16




                                                                                 Blood lead levels (g/dL)
  Lead used In gasoline




                          80                                                14
      (1000 tons)




                                                                            12
                          60    Blood lead
                                               Gasoline lead                10
                          40
                                                                            8

                          20                                                6

                                                                            4
                           0
                                                                            2
                            1974 1976 1978 1980 1982 1984 1986 1988 1990 1992
                                                  Year
Blood Lead Levels in the U.S. Population
              1976 -2000
       NHANES II, III, 1999-2000
                            18

                            16
Blood lead levels (g/dL)




                            14

                            12

                            10

                             8

                             6

                             4

                             2

                             0
                                 1974 1976 1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000
                                                              Year
Major Findings: Decline in Blood Lead
Levels among Children
 For children 1 through 5 years old
   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 pesticide
  Many food uses
  Termiticide
  Use in and around homes and non-
   residential settings - eliminated
Limitation: Specificity of Analysis
     Chlorpyrifos (R’=ethyl) and Chlorpyrifos-methyl (R’=methyl)
     Metabolism and Env’l Degradation

Cl             Cl                                Cl
                     S                                             Cl
                                                                         O
Cl       N     O     P     OR’                  Cl                 O     P     OR’
                                                          N
                     OR’                                                 OR’



              S                                                         O
                                 Cl            Cl
                    OR’                               +       HO        P     OR’
      HO      P             +
             OR’                 Cl        N     OH                     OR’
                                      3,5,6-TCPy

     3,5,6-TCPy is “specific” metabolite
     Dialkyl phosphates are “nonspecific” metabolites
           50th & 95th Percentile of 3,5,6-TCPy by Age
                        Group, Race & Sex
           30


           25


           20
  µg/L




           15


           10


            5


MA 95th     0




                                                                                      Female
                          Female




                                              Female




MA 50th
                                                                  Female
                Male




                                   Male




                                                       Male




                                                                           Male
NHB 95th
NHB 50th
NHW 95th
NHW 50th           6-11                   12-19               20-39               40-59
Cotinine
  Nicotine metabolite
   that tracks exposure
   to tobacco smoke                 O
                               N

  For nonsmokers,            CH3
   tracks exposure to     N
   secondhand smoke
Exposure of the U.S. Population to Tobacco
Smoke: Serum Cotinine Levels (NHANES III,
1988-1991)
                               5

                                         ETS exposure
Percentage of the population




                               4                                       Smokers
                                         (nonsmokers)

                               3


                               2


                               1


                               0
                                   0.1    1.0           10       100    1000
                                            Serum cotinine (ng/mL)
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 & Sex
           8

           7

           6

           5
  Ng/mL




           4

           3

           2

           1

           0
               Male




                                  Male




                                                     Male




                                                                        Male




                                                                                        Male
                         Female




                                            Female




                                                               Female




                                                                               Female




                                                                                                     Female
MA 95th
MA 50th
NHB 95th
NHB 50th
NHW 95th
NHW 50th          3-11              12-19              20-39              40-59                60+
Third National Report on Human
Exposure to Environmental Chemicals
Includes chemicals from Second National Report (1999-
2000) + the following in NHANES 2001-2002
 Organochlorine pesticides: aldrin, dieldrin, endrin
 OP pesticides: additional metabolites
 Pyrethroids: 5 metabolites
 Herbicides: mercapturate metabolites of acetochlor
  and metolachlor
 PAHs: 1-, 2-, and 4-hydroxychrysene; 4- and 9-
  hydroxyphenanthrene; 9-hydroxyfluorene; 3-
  hydroxybenzo(a)pyrene
 Additional PCDDs and PCBs
 Additional phthalate metabolites (e.g., oxidative
  metabolites of DEHP and DnOP)

				
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