United States
                    Environmental Protection
                    Agency
Health Effects
Research Laboratory
Research Triangle Park NC 27711
                    Research and Development
EPA/600/S9-86/030 May 1987
&EPA          Project  Summary
                    Environmental   Epidemiology:
                    The  Importance  of Exposure
                    Assessment
                     This project summary presents an
                    overview of a 1985 symposium on ex-
                    posure measurement and evaluation
                    methods for epidemiology cospon-
                    sored by the American Chemical Soci-
                    ety (ACS) and the United States Envi-
                    ronmental Protection Agency (EPA).
                     Entitled: "Environmental Epidemiol-
                    ogy:  The  Importance  of Exposure
                    Assessment," the symposium was or-
                    ganized by the ACS' Division of Envi-
                    ronmental Chemistry, and the EPA's
                    Health Effects Research Laboratory.
                    Held in Chicago on September 8-13,
                    1985, at the 190th ACS national meet-
                    ing, the symposium presented papers
                    by more than fifty distinguished scien-
                    tists representing academia, govern-
                    ment and industry in the U.S., Europe
                    and Africa.
                     After a brief assessment of the need
                    for such a symposium and a statement
                    of its intent, this project summary iden-
                    tifies the subject material and the affili-
                    ation of the authors.  The symposium
                    proceedings have been published and
                    their  availability is described in the
                    paragraph immediately below.
                     This Project Summary was devel-
                    oped by EPA's Health Effects Research
                    Labaoratory, Research Triangle Park,
                    NC, to announce key findings of the
                    research project that is fully docu-
                    mented in a separate report of the same
                    title (see  Project Report ordering
                    information at back).

                    Introduction
                     Epidemiology studies are a valuable
                    tool for assessing the  effects of chemi-
                    cal exposure in  humans. While they
                    cannot directly prove a cause-and-effect
relationship, they can demonstrate an
association between environmental ex-
posure to chemical(s) and observed
health effects in the exposed groups.
The strength of the association demon-
strated depends on how accurately ex-
posure of the groups can be assessed.
Unfortunately, most of the exposure
measurement and assessment work
currently being conducted is of limited
value for use in epidemiology studies;
rather, current exposure research is di-
rected towards developing methods for
detecting toxic chemicals in biological
samples (as opposed to living people)
or demonstrating that  specific source
results in exposure (but not quantifying
that exposure). The purpose of the sym-
posium is to bring together epidemiolo-
gists, chemists, and  mathematical
modelers so that they can gain insight
into each other's needs and capabilities,
thus resulting in  research projects  that
will allow the exposure of subjects in
epidemiologic studies to be more accu-
rately assessed.  This progress in  epi-
demiology is essential to enable scien-
tists to elucidate the risk of chemical
exposure incurred by  human beings
without the uncertainty of interspecies
extrapolation.

  Epidemiology studies are also impor-
tant in the regulatory process because
the results are necessary to  elucidate
the risk of human chemical exposure in-
curred by human  beings without the un-
certainty of interspecies extrapolation.
Because the EPA is required to develop
regulations under six separate legisla-
tive acts, these studies are usually con-
ducted to provide information for esti-

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mation of risk of exposure through a
given route or from a specific source.
  Case-control  and  cohort studies can
provide a  quantitative estimate of
health risk association with various en-
vironmental exposures, but it is often
difficult to  assess relevant exposures
for  individuals, because retrospective
epidemiologic studies require estimates
of past exposure which must be made
in light of current information. While it
is important to fully understand the
sources, routes, and extent of exposure
of individuals  to environmental toxi-
cants, obtaining such knowledge about
the  population included in an epidemi-
ology study may not be practical  and
may not  be achievable in all cases.
Prospective studies can be designed in
which exposure measurements are in-
cluded  as part of the study, but these
studies are generally not feasible be-
cause of the high costs of following a
cohort for a long period to determine
associations between exposure and an
observed health effect.
  It is important that the exposure data
collected for epidemiologic studies be
relevant and appropriate for both the
study design and regulatory needs. The
accurate measure or assessment of ex-
posure is paramount because random
misclassification of exposure for study
participants can only bias the outcome
of the study toward one or no associa-
tion between  exposure and disease.
Most epidemiologic studies have as-
sumed  that exposure to a contaminant
is an adequate surrogate of the dose. A
major limitation of past studies has
been lack of information on dose,  e.g.,
the amount of the contaminant of
metabolite in body tissue or the amount
that interacts with the target organ or
tissue.  Biologic markers of cumulative
dose would assist in improving the sen-
sitivity  of  epidemiologic studies,  and
should  be considered, whenever possi-
ble, to supplement the data collected on
exposure to environmental contami-
nants.

Symposium Papers and
Contributors

Chapter in Proceedings

Section I: Use of Biological
Monitoring  to Assess Exposure
  1. Detection of Aflatoxin BI Guanine
     Adducts in Human Urine Samples
     from  Kenya,  Lars O.  Dragsted,
     Johnston Wakhisi, and Herman
     Autrup
  2. Assessment of Human Exposure
    to Chemicals Through Biological
    Monitoring, Alfred M. Bernard and
    Robert R. Lauwerys
  3. The Monitoring  of  Exposure to
    Carcinogens by the GC-MS Deter-
    mination of Alkylated Amino Acids
    in Hemoglobin and of Alkylated
    Nucleic Acid Bases in Urine, Peter
    B. Farmer, David E. G. Shuker, Eric
    Bailey
  4. Determining DNA Adducts by Elec-
    trophore Labeling-GC, floger  W.
    Giese
  5. Quantification of  Tissue Doses of
    Carcinogenic Aromatic Amines,
    Paul L. Skipper, Matthew S.
    Bryant, and Steven R. Tannen-
    baum

Section II: Epidemiologic
Considerations for Assessing
Exposure
  6. The Feasibility of Conducting Epi-
    demiologic Studies of Populations
    Residing Near Hazardous  Waste
    Disposal Sites, Gary M. Marsh and
    Richard J. Cap/an
  7. Feasibility Study to Relate Arsenic
    in Drinking Water to Skin Cancer in
    the United States, Julian B. Andel-
    man and Margot  Barnett


Section III:  Health and
Exposure Data Bases
  8. Use and Misuse  of  Existing Data
    Bases  in Environmental Epidemi-
    ology:  The Case of Air Pollution,
    Peter Gann
  9. Opening and Controlling Access to
    Medicare Data, Glenn J. Martin
 10. Drinking Water Quality Data Bases,
    Nancy W. Wentworth, James W.
    Westrick, and Kaiwen K. Wang
 11. The FDA Total Diet Study Program,
    Pasquale Lombardo
 12. Overview  of EPA Major Air Data
    Bases,  David W. Armentrout
 13. National  Database on Body Bur-
    den of Toxic Chemicals, Philip E.
    Robinson, Cindy R.  Stroup, Anna
    S.  Hammons, M. Virginia Cone,
    C.  Donald Powers,  Maria/ice
    Ferguson, and Herman Kraybill
 14. Broad  Scan Analysis  of Human
    Adipose Tissue from the EPA FY 82
    NHATS Repository, John S. Stan-
    ley, Kathy E. Boggess, John E.
    Going, Gregory A. Mack, Janet C.
    Remmers, Joseph J. Breen, Fred-
    erick W. Kutz, Joseph Carra,  and
    Philip E. Robinson
Section IV: Assessment of
Exposure to Environmental
Contaminants For
Epidemiologic Studies

Part One:  Air Exposures
 15. Results from the First Three Sea-
    sons of the TEAM Study: Personal
    Exposures, Indoor-Outdoor Rela-
    tionships,  and  Breath  Levels ol
    Toxic Air Pollutants Measured for
    355 Persons in New Jersey, Lance
    A. Wallace, Edo D. Pellizzari, Ty D.
    Hartwell,  Charles M. Sparacino,
    Linda S.  Sheldon,  and Harvey
    Zelon
 16. Inhalation Exposures in  Indoor Air
    to Trichloroethylene from Shower
    Water, Julian B. Andelman, Amy
    Couch, and William W. Thurston

Part Two: Water and
Occupational Exposures
 17. Drinking Water'Characteristics and
    Cardiovascular Disease in a Cohort
    of Wisconsin  Farmers, Elaine
    Zeighami, Gunther F. Craun, and
    Charlotte A. Cottrill
 18. Empirical  Estimation  of Exposure
    in Retrospective  Epidemiologic
    Studies, Charles E. Lawrence and
    Philip R. Taylor
 19. Evaluation of Lead Exposures  in
    the Environment and Their Contri-
    bution to Blood  Levels in Children,
    Daniel Greathouse
 20. The Use of Industrial Hygiene Data
    in Occupational Epidemiology,
    Robert F. Herrickand. Larry J. Elliot

List of Contributors and
Affiliations
Julian B. Andelman, Graduate School of
  Public Health, University of Pitts-
  burgh, Pittsburgh,  PA  15261.
David W. Armentrout,  PEI Associates,
  Inc., 11499 Chester Road, Cincinnati,
  OH  45246.
Herman Autrup, Laboratory of Environ-
  mental Carcinogenesis, Fibiger Insti-
  tute, 70 Ndr. Frihavnsgade, DK-2100,
  Copenhagen, Denmark.
Eric Bailey, MRC Toxicology Unit, Medi-
  cal Research Council Laboratories,
  Woodmansterne Road, Carshalton,
  Surrey, SMS 4EF, England.
Margot Barnett, Graduate  School  of
  Public Health, University of Pitts-
  burgh, Pittsburgh,  PA  15261.
Alfred M. Bernard, Faculty of Medicine,
  Unit of Industrial and Medical Toxi-
  cology, Catholic University  of(

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  Louvain, Clos Chapelle-Aux-Champs,
  BP 30.54, B-1200, Brussels, Belgium.
Kathy E. Boggess, Midwest Research In-
  stitute, 425 Volker Boulevard, Kansas
  City, MO  64110.
Joseph J. Breen, Office of Toxic Sub-
  stances, U.S. Environmental Protec-
  tion Agency, 401  M Street,  S.W.,
  Washington, DC  20460.
Matthew S. Bryant, Department of Ap-
  plied Biological Sciences, Massachu-
  setts Institute of Technology, Cam-
  bridge, MA 02139.
Richard J. Caplan,  Department of Bio-
  statistics, Graduate School of  Public
  Health, University of Pittsburgh, Pitts-
  burgh,  PA 15261.
Joseph Carra, Office of Toxic  Sub-
  stances, U.S. Environmental Protec-
  tion  Agency, 401  M Street,  S.W.,
  Washington, DC  20460.
M. Virginia Cone, Science Applications
  International Corporation, 300  South
  Tulane Avenue, Oak Ridge, TN 37830.
Charlotte A. Cottrill, Epidemiology Sec-
  tion, Health Effects  Research Labora-
  tory, U.S. Environmental  Protection
  Agency, 26 West  St. Clair Street,
  Cincinnati, OH 45268.
Amy Couch, Graduate School of  Public
  Health, University of Pittsburgh, Pitts-
  burgh, PA 15261.
Gunther  F. Craun,  Epidemiology Sec-
  tion, Health Effects  Research Labora-
  tory, U.S. Environmental  Protection
  Agency, 26 West  St. Clair Street,
  Cincinnati, OH 45268.
Lars 0. Dragsted,  Laboratory of Envi-
  ronmental Carcinogenesis, Fibiger In-
  stitute, 70 Ndr.  Frihavnsgade, DK-
  2100, Copenhagen, Denmark.
Larry J. Elliott, Industrial Hygiene Sec-
  tion, Industrywide Studies Branch, Di-
  vision of Surveillance, Hazard Evalua-
  tions and Field Studies, National
  Institute for Occupational Safety and
  Health, 4676 Columbia  Parkway,
  Cincinnati, OH 45226.
Peter B. Farmer,.MRC Toxicology Unit,
  Medical Research Council Laborato-
  ries, Woodmansterne Road, Carshal-
  ton, Surrey, SM5 4EF, England.
Marialice Ferguson,  Science Applica-
  tions International  Corporation, 300
  South Tulane Avenue, Oak Ridge, TN
  37830.
Peter Gann, Department of Family and
  Community  Medicine, University of
  Massachusetts Medical School, 55
  Lake Avenue North, Worcester, MA
  01605.
Roger W. Giese, Department of Medici-
  nal Chemistry, College of Pharmacy
  and Allied Health Professions, North-
  eastern  University, 360 Huntington
  Avenue, Boston, MA 02115.
John E. Going, Midwest Research Insti-
  tute, 425 Volker  Boulevard, Kansas
  City, MO 64110.
Daniel Greathouse, Hazardous Waste
  Engineering Research Laboratory,
  U.S. Environmental Protection
  Agency, 26 West St. Clair Street,
  Cincinnati, OH  45268.
Anna  S. Hammons, Science Applica-
  tions International Corporation, 300
  South Tulane Avenue, Oak Ridge, TN
   37830.
Ty D.  Hartwell, Research Triangle Insti-
  tute, P.O. Box 12194, Research Trian-
  gle  Park, NC 27709.

Robert F.  Herrick,  Industrial Hygiene
  Section,  Industrywide  Studies
  Branch, Division of Surveillance, Haz-
  ard Evaluations and Field Studies, Na-
  tional Institute  for  Occupational
  Safety and Health, 4676  Columbia
  Parkway, Cincinnati, OH 45226.
Frederick C. Kopfler, Health Effects Re-
  search Laboratory, U.S. Environmen-
  tal  Protection Agency, 26 West St.
  Clair Street, Cincinnati, OH  45268.
Herman Kraybill, National Cancer Insti-
  tute (retired), 17708  Lafayette Drive,
  Olney, MD  20832.
Frederick W. Kutz, Office of Toxic Sub-
  stances, U.S. Environmental  Protec-
  tion Agency, 401 M  Street, S.W.,
  Washington, DC  20460.
Robert R.  Lauwerys, Faculty  of
  Medicine, Unit of Industrial and Medi-
  cal Toxicology, Catholic University of
  Louvain, Clos Chapell-Aux-Champs,
  BP 30.54, B-1200, Brussels, Belgium.
Charles E. Lawrence,  Laboratory of
  Statistics and  Computer Sciences,
  Wadsworth Center for Laboratories
  and Research, New York State  De-
  partment of Health,  Room C-323,
  Albany,  NY 12201.
Pasquale Lombardo, Division of Chemi-
  cal  Technology, Center for Food
  Safety and Applied  Nutrition, Food
  and Drug Administration, 200  C
  Street, S.W., Washington, DC 20204.
Gregory A.  Mack,  Battelle  Columbus
  Laboratories, 505  King  Avenue,
  Columbus, OH  43201.
Gary M. Marsh, Center for Environmen-
  tal Epidemiology, A416 Crabtree Hall,
  Graduate School' of Public Health,
  University of Pittsburgh, Pittsburgh,
  PA  15261.
Glenn J. Martin, Health Care Financing
  Administration, Bureau of Data Man-
  agement and Strategy, Office of Infor-
  mation Resources Management,
  G-A-2 Meadows East Building, 6325
  Security Boulevard, Baltimore,  MD
  21207.
Edo D. Pellizzari, Research Triangle In-
  stitute, P.O. Box 12194, Research Tri-
  angle Park, NC 27709.
C. Donald Powers, Science Applications
  International Corporation, 300 South
  Tulane Avenue, Oak Ridge, TN 37830.
Janet C. Remmers, Office of Toxic Sub-
  stances, U.S. Environmental Protec-
  tion  Agency, 401  M Street, S.W.,
  Washington, DC 20460.
Philip E. Robinson, Office of Toxic Sub-
  stances, U.S. Environmental Protec-
  tion Agency (TS-798), 401 M Street,
  S.W., Washington, DC 20460.
Linda S. Sheldon, Research Triangle In-
  stitute, P.O. Box 12194, Research Tri-
  angle Park, NC 27709.
David  E.G. Shuker, MRC Toxicology
  Unit, Medical Research Council Labo-
  ratories, Woodmansterne Road, Car-
  shalton, Surrey, SM5 4EF, England.
Paul L. Skipper, Department of Applied
  Biological Sciences,  Room 56-313,
  Massachusetts Institute of  Technol-
  ogy, Cambridge, MA 02139.

Charles M. Sparacino, Research Trian-
  gle Institute, P.O. Box 12194,  Re-
  search  Triangle Park, NC  27709.
John S. Stanley, Midwest Research In-
  stitute, 425 Volker Boulevard, Kansas
  City,  MO  64110.
Cindy R.  Stroup, Office of Toxic Sub-
  stances, U.S. Environmental Protec-
  tion Agency (TS-798), 401 M Street,
  S.W., Washington, DC 20460.
Steven R. Tannebaum,  Department of
  Applied Biological Sciences. Massa-
  chusetts Institute of Technology,
  Cambridge, MA 02139.
Philip  R. Taylor, Cancer Prevention
  Studies Branch, Division of Cancer
  Prevention and Control, National Can-
  cer Institute, Blair Building, Bethesda,
  MD  20892.
William W. Thurston, Graduate School
  of Public Health, University of Pitts-
  burgh,  Pittsburgh,  PA 15261.
Johnston Wakhisi, Department of
  Surgery,  University of  Nairobi,
  Nairobi, Kenya.
Lance Wallace, U.S. Environmental Pro-
  tection Agency (RD-680), 401 M
  Street,  S.W., Washington, DC 20460.
Kaiwen K. Wang, Office of  Drinking
  Water (WH-550), U.S. Environmental
  Protection Agency, 401 M Street,
  S.W., Washington, DC 20460.
Nancy W. Wentworth, Office of  Re-
  search  and  Development (RD-680),

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     U.S.  Environmental Protection
     Agency, 401 M Street, S.W., Washing-
     ton, DC 20460.
   James J. Westrick, Technical Support
     Division (ODW), U.S. Environmental
     Protection Agency, 26 West St. Clair
     Street, Cincinnati, OH  45268.
   Elaine A. Zeighami, Health Effects and
     Epidemiology Group, Oak Ridge Na-
     tional  Laboratory, Building 4500-S,
     F-256, Oak Ridge, TN 37831.
   Harvey Zelon,  Research Triangle Insti-
     tute, P.O. Box 12194, Research Trian-
     gle Park, NC 27709.
      The EPA authors Frederick C. Kopfler and Gunther F. Craun are with the
       Health Effects Research Laboratory, Research Triangle Park, NC 27711.
      The complete report, entitled "Environmental Epidemiology: The Importance
       of Exposure Assessment," (Order No. PB 87-132 866/AS; Cost: $24.95,
       subject to change) will be available only from:
             National Technical Information Service
             5285 Port Royal Road
             Springfield. VA 22161
             Telephone: 703-487-4650
      The EPA authors can be contacted at:
              Health Effects Research Laboratory
              U.S. Environmental Protection Agency
              Research Triangle Park, NC 27711
United States
Environmental Protection
Agency
Center for Environmental Research
Information
Cincinnati OH 45268
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