Unrted States
Environmental Protection
Agency
              Office of Research and
              Development
              Research Triangle Park, NC 27711
ERA/600/R-00/079
August 2000
http://www.epa.gov/nheerl
v>EPA
           National Health and
           Environmental Effects
           Research Laboratory

           Human Studies Division
           Investigating the Environment's
           Impact on Human Health

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:PROTECTING
rHUMAN
  HEALTH
;• Epidemiologists study whether poten-
i dally susceptible subpopulattons, such
| as the elderly (right) and children
" (below), arc at a greater risk than the
I general population of experiencing
>: adverse health effects from environ-
 mental pollutants.
studies. However, the extrapolation of
in vitro and In vivo animal toxicology
data is complicated by factors unique
to humans, such as long life span, the
presence of pre-existing diseases, and
high inter-individual variability.
The mission of the U.S. Environmen-
tal Protection Agency (EPA) is to
protect human health and safe-
 guard the natural environment-
 air, water, and land - upon which
 life depends. ERA'S National
 Health and Environmental Effects
  Research Laboratory (NHEERL)
  supports the Agency's regulatory
  decision-making process by
  investigating potential risks that
  environmental contaminants
   may pose to humans and eco-
   systems.

   Much of this effort is achieved
   through controlled animal
                                                                      To provide directly applicable human
                                                                      data as well as to facilitate the
                                                                      extrapolation of nonhuman data, the
                                                                      multidisciplinary staff of NHEERL's
                                                                      Human  Studies Division (HSD)
                                                                      conducts a coordinated research
                                                                      program that integrates epidemio-
                                                                      logical, clinical, and laboratory-based
                                                                      studies.
                                            Using sophisticated equipment
                                            that concentrates outside air
                                            particles (right), scientists study
                                            the effects of exposures to these
                                            particles (left) at concentra-
                                            tions commonly encountered in
                                            large urban areas.

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"Through this integrated approach, HSD
continues to inform EPA's regulatory
standard-setting process for air and
water pollution, and pesticide control.
In addition, HSD often collaborates
with other EPA scientists as well as
researchers in other government agen-
cies, universities, and international
organizations to obtain needed data.
For example, collaborations between
HSD and the University of North
Carolina's Center for Environmental
Medicine and Lung Biology (CEMLB)
have generated human data that
directly influenced the setting of air
quality standards by demonstrating
that:
•   People with vascular heart
    disease have an increased
    sensitivity to carbon monoxide
•   Asthmatics have an increased
    sensitivity to ozone
•   Air pollutants may induce ad-
    verse health effects through a
    variety of subcellular (molecular)
    mechanisms
                                     The staff in the Subject Recruitment Office
                                     (below) enroll volunteers to study the acute
                                     effects of low-level exposures to common
                                     environmental pollutants.
 A field scientist (above) evaluates house-
 hold dust as a potential source of pesticide
 exposures.
                                                                            THROUGH
                                                                            HIGH
                                                                         |  QUALITY
                                                                         F  RESEARCH
                                                                         |L Geographic information systems allow
                                                                         jj  investigators to determine whether
                                                                         p  there is an association between the
                                                                         j*  spatial distributions of adverse health
                                                                         f" effects and environmental pollutants
                                                                         t  Oeft).

                                                                         B
                                                                         IP-
                                           AQ electron micrograph of the
                                           lining of a bronchus (above)
                                           reveals air pollution particles
                                           (dark granules) embedded
                                           between the hair-like cilia. The
                                           presence of a spherical mucoid
                                           droplet is typical.

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EPIPEMIOLOGICAL
STUDIES
              An Epidemiologist (right)
              analyzes blood parameters to
              determine whether the eld-
              erly are especially sensitive
              to the adverse health effects
              of air pollution particles.
                                                                            subpopulcrhons, including:
                                                                            •   The elderly
                                                                               People with pre-existing
                                                                               health conditions
                                                                               Infants and chi dren
                                                                            These studies involve analyses of
                                                                            existing health databases as well as
                                                                            new investigations using cohort,
                                                                            cross-sectional, and panel designs.
                                                                            Health effects of interest include:
        In a field study in Inner
        Mongolia (above), collabo-
        rating scientists use a global
        positioning system to deter-
        mine the distribution of ar-
        senic-contaminated wells.
The epidemiology program evaluates
the relationship between real-world
exposures to environmental contami-
nants and adverse health effects.
Environmental contamination may
result from:
•  Natural occurrence (e.g.,
   arsenic in drinking water)
•  Residential and industrial
   discharges into the air and water
•  Treatments intended to ensure
   food and water quality (e.g., by-
   products from water disinfection)
•  Agricultural practices (e.g.,
   pesticide contamination)
 HSD conducts national and interna-
 tional field studies, many of which
 focus  on particularly sensitive
                                                                            •  Cardiovascular disease
                                                                            •  Respiratory disease
                                                                            •  Reproductive & developmental
                                                                               abnormalities
                                                                            •  Neurological disease
                                                                            •  Cancer
                                                                            •  Infectious disease
                  HSD also conducts
                  epidemiological studies
                  to investigate the
                  incidence of drinking-
                  water contamination by
                  mioxDorganisms, such as
                  Cryptosporidium (left)
                  and Giardia (right),
                  which can cause severe
                  gastrointestinal illness.

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CLINICAL
STUDIES
   Clinical physiology equipment,
   which looks similar to exercise
   equipment (right), is used to
   measure the effects of air pol-
   lutants on lung function.
   Prior to conducting any human
   exposures, volunteers are care-
   fully screened by trained health
   professionals (below).
The Human Studies Division complies with
the requirements of the "Common Rule"
to ensure that its clinical studies in-
volve short-term, real-world expo-
sures conducted in a safe and ethi-
cal manner.  Using state-of-the-art
          technology, human volun-
          teers are exposed under
          controlled conditions to
          ambient concentrations of
          common environmental
          pollutants, such as:

           •   Air particles

           •   Ozone
           •   Hazardous air pollutants
           •   By-products from water
               disinfection
           •   Fuel additives
              Using sophisticated non-invasive instruments like gamma cameras
              (above), scientists can study how microscopic air pollutants deposit
              in the lungs (insetX:
The health effects of these pollutants
are then measured along a wide range
of physiological parameters, including:

    •  Respiratory function

    •  Respiratory tract dosimetry
    •  Cardiovascular function

    •  Neurobehavioral effects
    •  Pharmacokinetics
    •  Cellular/molecular processes

    •  Immune status, including
       allergic response
                                                                                         y.._—s
                                                                         A specially designed pharmacokinetic chamber
                                                                         (above) allows investigators to periodically
                                                                         sample a volunteer's blood during a one-hour
                                                                         controlled exposure to determine how the body
                                                                         absorbs and eliminates environmental pollut-
                                                                         ants.


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STUDIES
  Electron microscopy (right) is used
  to obtain high resolution images,
  such as an epithelial cell dividing
  In culture (below). Such images
  permit detection of subtle struc-
  tural changes in cells following
  exposure to environmental toxi-
  cants.
To understand how environmental
contaminants induce adverse health
effects at the tissue, cellular, and
subcellular levels, HSD scientists also
expose human cell cultures to pollut-
ants and look for:

         Evidence of cellular injury,
         inflammation, and repair
         Integrity of host defense
         mechanisms
         Altered gene expression
         Changes in cellular com-
         munication pathways
 HSD scientists also develop and vali-
 date biomarkers of exposure, effect
 and susceptibility. Such efforts facilitate
 extrapolation of nonhuman data and
 improve epidemiological assessments
 of exposure and health effects.
 Currently, HSD is developing biomarkers
 to assess:

•   DMA damage from ambient air
    particles
•   Exposure to arsenic found in
    drinking water
•   Pesticide exposure in children
•   DNAadductformation
•   Exposure to microbial pathogens
                                          Computer-assisted image
                                          analysis is used to measure
                                          subtle changes in human
                                          tissues, such as lung
                                          sections (right), that may
                                          result from exposure to air
                                          pollutants.
    A visiting scientist (above) uses molecular
    biology techniques to investigate how
    pollutants niay disrupt cell function.

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FOSTERING
INTERACTIONS
HSD and the unique research
facilities depicted in this brochure
are located in the Human Studies
Facility on the medical campus
of the University of North Carolina
(UNC) at Chapel Hill. Comple-
menting its research capabilities,
the Facility's offices and varied
meeting places- including a main
seminar room, library, and four
conference rooms - encourage
collaboration and the free ex-
change of ideas with scientists at
. local universities as well as other
research institutions throughout
Research Triangle Park.
l!

 CONTACT
 INFORMATION
                             For more information about research programs in the Human Studies Division and
                             the availability of facilities for use by non-EPA scientists conducting research in the
                             public interest, please contact:

                                            Ipfficeofthebirector
                                            ilHuman Studies Division
                                            'J&, , : : -  ' " -'"- ' ;•-•;-•-•-•-• '  -•••   ...:••
                                            IIPA/NHEERL
                                                  ...... .......... "
                                            ^Research Triangle Park, NC 2771 1
                                            ^Telephone: (9 19) 966^5200
                                            [Fax: (919;) 966-621 2 ,  _;
                                            f|mafl: Hs^.rrp-hsd@epa.gov

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1 FACILITY
  LOCATION
i	-
The Human Studies Facility (HSR) is located at 104 Mason Farm Road in Chapel
Hill, North Carolina. Also located in the facility is UNC's Centerfor Environmental
Medicine and Lung Biology (CEMLB), with whom HSD conducts some of its
collaborative studies. In total, the HSF is occupied by almost 100 scientific and
administrative staff.
Some of the photographs In this brochure"
depict non-EPA employees performing work
under contract or through a cooperative i
agreement with the EPA.
                                           Printed on Recycled Paper

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