&EPA
              United States
              Environmental Protection
              Agency
              Mobile Source Research
              Committee
              Washington DC 20460
              Technology Transfer
The Diesel Emissions
Research  Program

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Technology Transfer                          EPA-625/9-79-004
The Diesel Emissions
Research Program
Program Report—Mobile Source
Research Committee
Office of Research and Development

  Office of Health Research
     Washington, DC 20460

  Environmental Monitoring Systems Laboratory
     Research Triangle Park, NC 27711

  Environmental Sciences Research Laboratory
     Research Triangle Park, NC 27711

  Health Effects Research Laboratory
     Cincinnati, OH 45268

  Health Effects Research Laboratory
     Research Triangle Park, NC 27711

  Industrial Environmental Research Laboratory
     Research Triangle Park, NC 27711
Office of Air, Noise and Radiation

  Office of Mobile Source Air Pollution Control
     Washington, DC 20460
December 1979
Center for Environmental Research Information
Cincinnati, OH 45268

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                                                                                 Page
Table of Contents     Introduction 	  1
                        About Diesel Exhaust  	  3
                        Program Strategy 	  4
                        From Risk to Regulation 	  6


                        Collection and Characterization of Particulate Matter  	  7


                        Identification of The Potential Health Threats  	  9
                        Epidemiologica! Studies 	  9
                        Animal Studies  	10
                            Cancer and Related Effects  	10
                            Noncarcinogenic Effects 	19
                        In Vitro Studies 	22
                        Air Monitoring Studies  	26
                        Exposure  	28
                        Risk Assessment  	30
                        Control Technologies	32

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Introduction

                                                                ^l^^^^mm
                                                                Mobile Sources Res^p9^ eff orUhe
                                                                evaluate the public hMi*u P™9ra™, to
                                                        -OMSAPC
'"wo cancer and
mutation studies

Epidemiology


        Cincinnati,
                                                     'AnnArbor, Michigan
                                                      Washington, D.C.
                                                                             -OHEA
                                                                                     assessment
                                Research rr/ang,ePark
                           Worth Carolina^
                                                                    HERL-RTP
                                                                      • In vitro cancer and
                                                                       mutation studies
                                                                      • In vivo cancer and
                                                                      mutation studies
                                                                   ESRL-RTP
                                                                     * Exposure
                                                                   EMSL-RTP
                                                                                collection
                                                                    • Exposure

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           Parti culate
          collection and
          characterization
              (20%)
                                    Of control
                                   technologies
                                      (7%)
                                        Epidemiological
                                           studies
                                            (1*1
   Air
monitoring
  (13%)
Development of
   control
 technologies
     (6%)
      pidemiologica'
         studies
          (3%)
                               in vivo
                               studies
                                (32%)
                                                          Air
                                                       monitoring
                                                         (12%)
                                                                                      )n vivo
                                                                                      studies
                                                                                        (31%)
                                                                     In vitro
                                                                     studies
                                                                       (22%)
                                       TOTAL FUNDING
                                        1978 $4,7 million
                                        1979 $7-2 million
Funding allocates for
                                         includes:
                                          . Human P°Pu!ati™
                                                                                    plains how me m
                                                                          with i
                                                                          engine
                                                                                          use
                                             microorganism


                                            . Chemical characterization of
                                              diesel particles
                                                       •  « r,f dipsel poHutant
                                            . Monitoring of diesen
                                              levels in ambient air
                                        popula
                                                       tion ex
                                                emissions-

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About Diesel Exhaust
Diesel exhaust is a mixture of
particulate (sooty) matter and
various gases. The principal
gases present in diesel exhaust,
such as hydrocarbons, nitrogen
oxides, sulfur oxides, carbon
dioxide, and carbon  monoxide,
are similar to those already
emitted into the  atmosphere by
gasoline engines and other
combustion emission sources.
They are not expected to pose a
new regulatory problem to the
EPA because regulatory
mechanisms already exist for
controlling levels of these
pollutants.
                         The particles in diesel emissions,
                         however, differ significantly in
                         both quantity and composition
                         from the gasoline particles they
                         will replace. Even a well-tuned
                         diesel engine emits 30 to 100
                         times more particulate material
                         than a comparable gasoline
                         engine equipped  with a catalytic
                         converter.* While gasoline
                         particles are principally sulfur
                         compounds, diesel particles
                         consist of a carbonaceous
                         (carbon-containing) material
                         with primarily high molecular
                         weight organic chemicals
                         adsorbed (attached) to the
                         particle surface. These
                         chemicals, initially present  in
                         diesel emissions as trace
                         gaseous components, condense
                         onto the particles as the exhaust
                         coois. They may constitute  10 to
                         50 percent by weight of a diesel
                         particle, with  the actual
                         •Comparable figures are not available for
                         controlled diesel engines, since diesel
                         particulate control devices are still being
                         developed. However, it is likely that a
                         controlled diesel engine will still emit
                         substantially greater quantities of
                         particles than catalyst-controlled
                         gasoline engines.
percentage and composition
depending on such factors as
engine type, fuel type, driving
pattern, and engine efficiency.
Also of concern from a public
health standpoint is the fact that
many diesel particles are
respirable. That is, they are small
enough to penetrate deep into
the lung where either the
particles themselves or the
attached organics  may cause
adverse health effects.
Preliminary biological and
chemical tests have shown that
diesel particles may be
carcinogenic. What scientists do
not yet know is whether exposure
to environmental levels of diesel
emissions will increase the
incidence of cancer in exposed
populations. Studies to help
answer this question are an
important part of ORD's diesel
emissions research.

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            Program Strategy
The primary purpose of the
Diesel Emissions Research
Program is to assess the human
health risk associated with
conversion of passenger vehicles
from  gasoline to diesel fuel. The
basic program strategy for
accomplishing this goal is
illustrated in Figure 1.
                                  To determine the range and
                                  magnitude of potential health
                                  effects, ORD is examining whole
                                  diesel emissions, as well as
                                  gaseous (particle-free)
                                  emissions, diesel particles, and
                                  chemical extracts of diesel
                                  particles in a variety of
                                  experiments involving animals,
                                  plants, insects, mammalian cells,
                                  and microorganisms (Figure 2).
                                  These laboratory experiments
are being supplemented by
studies of disease patterns in
human population groups who
received occupational exposure
to diesel exhaust. Additional
studies are being conducted to
compare diesel exhaust to
substances, such as cigarette
smoke and coke oven emissions,
whose carcinogenic potential  is
already known from previous
epidemiological research. This
comparison will provide an idea
of the relative carcinogenic
potency of diesel emissions. By
combining the health effects data
with population exposure
projections, the EPA will assess
the human health risks posed by
diesel emissions for a variety of
diesel engine use and emissions
control scenarios.
             AMBIENT AIR
    Collection and Measurement of Samples
                                   DIESEL & OTHER PARTICULATE SOURCES
                                     Collection and Measurement of Samples
                                                                               GASOLINE
                                                                     Collection and Measurement of Samples
                                   Health Effects
                                   Assessment
                                     Particles
                                     Extracts
                   Exposure
                  Assessment
                  Levels emitted
                  Human exposure
                  projections
                 Levels emitted
                 Human exposure
                 projections
          Risk Assessment of
         Ambient Environment
'
'
Risk Assessment of
Diesel Emissions
'
<
Risk Assessment of
Gasoline Emissions
                                            J       I
                        Assessment of Relative
                         Contribution of D,esel
                         Risks to Existing Risks
                         from Ambient Particles

1
. r
Assessment of Relative
Risks of Diesel and
Gasoline Emissions
                                          Regulatory Decision
                                        Mak ng for Diesel Vehicles
Figure 1.
Diesel emissions research and risk assessment strategy.

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fl)
to
>.
«
"55
0}
Animals
Plants
Insects
Mammalian Cells
Microorganisms

Test Substance
Whole Diesel
Emissions
m
m
m
o
o
Gaseous
Emissions
Only
O
0
0
o
o
Diesel
Particles
e


m
m
Diesel
Parti cu late
Extract
m


m
m
KeY: © Study or studies completed or under way
O Proposed or planned studies

Figure 2.
Diesel Emissions Research Program health effects studies.
At the same time, ORD is
conducting two parallel health
effects and exposure
assessments to generate risk
estimates for gasoline emissions
and the ambient  air. By
comparing the risk assessment
for diesel emissions, gasoline
emissions, and ambient air, ORD
hopes to determine whether
diesel emissions  will pose a
significantly greater human
health threat than the gasoline
emissions they will replace or the
pollutants already occurring in
ambient air.*
'Ideally, whole diesel and gasoline
emissions would be compared in
long-term animal inhalation experiments.
Unfortunately, experimental and
programmatic restraints preclude this
line of investigation at present. In the
meantime, ORD scientists hope to
compare the carcinogenic and mutagenic
potential of gasoline particles.
However, technical difficulties associated
with collecting gasoline particles for
biological experiments (see Collection
and Characterization of Particutate
Matter) may limit the amount of
comparison that can be done between
gasoline and diesel emissions.

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       From Risk to Regulation
                The health risk assessment
                generated by ORD will be used by
                the EPA to determine whether
                and to what extent diesel
                emissions should be regulated.
                As a first step, the health risks
                will be balanced against any
                positive public health impacts
                that may result from conversion
                to diesel fuel. For instance, diesel
                fuel is less flammable than
                gasoline so that increased use of
                diesel-powered cars may result in
                fewer deaths or injuries from
                accidents involving  fire and
                explosions. Also, since diesel
                fuel is less volatile than gasoline,
                the diesel fuel cycle (including
                transportation and handling) will
                probably result in less loading of
                the atmosphere with precursors
                of hazardous  photochemical
                oxidants than does  the  handling
                of gasoline.
                                             In deciding how to regulate
                                             diesel emissions, the EPA will
                                             weigh the potential  health
                                             impacts, the cost and
                                             technological feasibility of
                                             controlling diesel emissions, and
                                             the general environmental  and
                                             economic impacts of any
                                             proposed regulations. While
                                             safeguarding public health will
                                             be the primary concern,
                                             economic and technological
                                             considerations may determine
                                             the optimum of a range of
                                             regulations that are acceptable
                                             from a public health standpoint.
               /
1977
  Particulate
  collection and
  characterization
  Epidemiology
  In vivo studies
  In vitro studies
  Ambient air
  monitoring and
  analysis
  Exposure
  Risk assessment
  Control
  technologies
  development
/  1978   /   1979    / 1980   /   1981    /    1962   /
                                                                           1983
                                               Critical review
                                                  Possible new study
                                      Carcinogen! city and mutagenicity studies     Noncarcinogenicity studies
                                                                  *
                                          Comparative study
                                                                                Intratracheal instillation study
                                                                  Long-term monitoring
                                                      „         _, ,.       In-vehicle monitoring and mobility
                                                      Computer modelmg     V,    pamrn determination
                                            cimy      >

                                            ^^
                      Preliminary risk assessment
                                                   Updated risk
                                                   ' assessment
                                                                                     Key
                                                                  Research
                                                                  commencement
                                                                  date

                                                                  Final report or
                                                                  research end date
Diesel Emissions Research Program schedule.

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      Collection and
Characterization of
  Participate Matter
 To determine the carcinogenic
 and mutagenic potential of diesel
 exhaust, ORD is conducting
 extensive chemical and
 biological testing of diesel
 particles and the organic
 chemicals associated with them.
 Diesel particles are being
 collected by the EPA's
 Environmental Sciences
 Research Laboratory in Research
 Triangle Park (ESRL-RTP) and by
 the Office of the Mobile Source
 Air Pollution Control (OMSAPC)
 in Ann Arbor, Michigan. These
 samples are being prepared,
 tested, and analyzed at the
 Environmental Monitoring
 Systems Laboratory in Research
Triangle Park (EMSL-RTP) to
determine which components of
diesel emissions  are biologically
active (i.e., carcinogenic or
mutagenic) and to characterize
the fuel type, engine type, and
driving patterns that generate the
active components.
                                                             The process involved in
                                                             collecting and preparing
                                                             particles for use in health effects
                                                             experiments is illustrated in
                                                             Figure 3.  Diesel exhaust is being
                                                             generated in the laboratory by
                          Figure. 3.
                          Preparation of particles and paniculate extract for experimental

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diesel engines attached to
dynamometers — devices that
"drive" the engines in a repetitive
series of idle, acceleration,
cruise, and deceleration modes
designed to approximate actual
driving patterns. Exhaust from
these engines is passed through
a dilution  tunnel to simulate the
mixing with ambient air that
occurs in an actual use situation.
 Jpon contact with the air, the
exhaust cools and the gaseous
organic chemicals present in the
exhaust condense and adsorb
onto the particles. After cooling
and mixing have occurred, the
particles are trapped  on a filter
and removed. They can then be
 used directly in biological (health
effects) tests or extracted with
 chemical  solvents which remove
 certain portions (or fractions)  of
 the organic chemicals.  Extracts
 containing specific organic
 fractions  are used in  both
 biological testing and chemical
 analysis.
 ESRL-RTP and OMSAPC are
 generating diesel particles and
 parti culate extracts from several
 different light-duty and
 heavy-duty engines using a
 variety of fuels and driving
 cycles. These extracts are being
 analyzed extensively at
 EMSL-RTP and ESRL-RTP to
 identify the chemical classes
 present in diesel particles and to
 investigate how the chemical
 composition varies with engine
 type, fuel type, and driving
 patterns. ESRL-RTP is studying
 theformation and aging of diesel
 exhaust pollutants under
 simulated atmospheric
  conditions. Samples of aged
  particles will be subjected to
  chemical analysis and to
  biological tests for carcinogenic
  and mutagenic potential. Such
  work will be useful in
  determining whether diesel
  exhaust becomes more or less
  hazardous as it is changed by
  such factors as dilution, sunlight,
  and  reactions with other
  pollutants.
EMSL-RTP is also preparing
samples of cigarette smoke
condensate and extracts of
gasoline exhaust, roofing tar
fumes, and coke oven emissions
for a series of comparative
biological studies. In the case of
gasoline exhaust from
catalyst-equipped cars, the
particles are so dilute that
substantial collection time is
required to obtain sufficient
material for biological tests.
Unfortunately, this may limit the
amount of comparison that can
be done between gasoline and
diesel emissions, since the more
definitive long-term experiments
require large amounts of extract.

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Identification  of the
              Potential
      Health Threats
   Epidemiologies! Studies
 Scientists have three basic
 biological tools to assess the
 human health risk posed by a
 substance: epidemiological
 studies, whole animal
 experiments, and in vitro (in
 glassware) tests using
 microorganisms and individual
 cells. As discussed in the
 following sections, ORD is
 utilizing all three methods in
 order to provide a broad range of
 information on the potential
 health effects associated with
 increasing  use of the diesel
 engine.
Epidemiological studies examine
the health and exposure histories
of specific population groups in
an attempt to correlate disease
patterns with exposure to a
chemical substance or other
disease-causing agent. The
populations  studied are often
groups of workers that have been
occupationally exposed to the
substance of interest. !n the case
of diesel exhaust, several groups
have been identified as possible
candidates for epidemiological
study. These include miners in
underground operations where
diesel-powered equipment is
used, mechanics in diesel bus
and truck garages, diesel truck
drivers, and  railroad workers
exposed to the diesel fumes of
locomotives.
                             Critical Literature Review.  A
                             few diesel epidemiological
                             studies were conducted prior to
                             the Diesel Emissions Research
                             Program. These studies were
                             primarily concerned with how
                             diesel exhaust affects the
                             respiratory system. Although
                             several  investigations found
                             associations between respiratory
                             disease and diesel exposure, the
                             majority of the studies did not
                             note adverse health effects i n the
                             study populations. However,
                             problems with the way in which
                             the studies were designed,
                             conducted, and reported make it
                             very difficult to draw firm
                             conclusions. The EPA's Health
                             Effects Research Laboratory in
                             Cincinnati,  Ohio (HERL-Ci) is
                             presently conducting a
comprehensive review of all the
diesel epidemiology literature.
This review will analyze the
strengths and weaknesses of the
published studies and then
synthesize their findings so that a
better judgment can be made of
the human health risks posed by
diesel emissions.
New Studies.  HERL-Ci also
plans to initiate its own
epidemiological study to
augment the existing data.
Feasibility studies are currently
under way to identify the most
appropriate populations for
study and to determine the most
useful study design. The two
possible studies that appear to
hold the most promise are a
historical cohort mortality study
and a case-control respiratory
cancer study.
                                In the historical cohort study, a
                                large group of individuals, such
                                as diesel mechanics, who had
                                received exposure to diesel
                                emissions at some time in the
                                past would be identified from
                                company or union records.
                                Mortality rates for the exposed
                                group would be computed and
                                the causes of death  would  be
                                compared with the general
                                population and other working
                                groups. Two key pieces  of data —
                                exposure levels and  smoking
                                habits — would have to be
                                projected from current
                                information. Exposure levels of
                                the study population would  be
                                estimated by measuring the

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              Animal Studies
10
                                current occupational exposure of
                                similar workers. The study
                                group's smoking habits would be
                                inferred from present day worker
                                trends. Information on smoking
                                histories would  be necessary to
                                ensure that smoking did not
                                account for the  health effects
                                observed in the study group.
                                Another epidemiological study
                                being considered is a
                                case-control study. In this type of
                                study, individuals are identified
                                who have had a specific disease
                                considered to be a possible
                                health effect from exposure to
                                the substance of interest. These
                                individuals are then matched
                                with an individual of the same
                                sex, age, and race  who did not
                                suffer the disease,  and the
                                histories of both individuals are
                                searched for evidence of
                                significant exposure to the
                                substance. The proposed diesel
                                exhaust case-control study
Health effects experiments in
which an organism is exposed to
a substance, such as diesel
particles, and then examined for
detrimental effects cannot be
performed on humans for
obvious ethical reasons. Animal
studies are therefore the closest
we can come to determining
experimentally how a substance
may affect the human organism.
They are an important
complement to epidemiological
studies which often provide only
limited information because of a
lack of available data.
                                would examine respiratory
                                cancer, since the potential of
                                diesel exhaust to cause this type
                                of cancer is a major concern.

                                Two approaches for the diesel
                                case-control study are being
                                examined. The first would make
                                use of the data that have been
                                collected  in large lung  cancer
                                case-control studies, such as
                                those currently underway in the
                                United States and Europe. The
                                fact that diesel engines are more
                                prevalent in Europe than in the
                                United States may increase the
                                probability of identifying
                                individuals who have had
                                significant exposure to diesel
                                exhaust. The second approach
                                would be to conduct the study
                                within an  industry where a variety
                                of exposures exists. The study
                                would attempt to discern
                                whether groups that received
                                higher exposures to diesel
                                exhaust have an increased risk of
                                lung  cancer.
Animal studies are particularly
useful for providing
dose-response data, that is,
information on how a
substance's effect varies with the
level of exposure. Often the
doses administered in animal
experiments are much higher
than environmental exposure
levels to  increase the likelihood
of observing an effect, if one
exists. The dose-response data
must then be extrapolated down
to lower  environmental levels of
exposure in order to determine
"safe" levels for human
exposure (See Risk Assessment
for a discussion of the extra-
polation  policy).
                                                                  Cancer and Related Effects.
                                                                  The carcinogenic and mutagenic
                                                                  potentials of diesel emissions,
                                                                  particles and particulate extracts
                                                                  are being examined in at least 18
                                                                  separate studies using mice, rats,
                                                                  rabbits and hamsters (Table 1).

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  Table 1
Mammalian Studies to Investigate the Carcinogenic, Mutagenic, and Teratogenic Potential of
Diesel Exhaust
11
Type of Study
Carcinogenicity


Carcinogenicity


Effects on
metabolism of
benzo(a) pyrene
[B(a)P], a known
carcinogen present in
diesel exhaust
Carcinogenicity


Carcinogenicity



Carcinogenicity
and mutagenicity

Carcinogenicity
and mutagenicity

Mutagenicity




Mutagenicity
(cytogenetic
study)
Mutagenicity


Mutagenicity


Mutagenicity
(dominant lethal
test in males)


Mutagenicity
(transport to
testes)

Mutagenicity
(dominant lethal
test in females)


Mutagenicity
(total reproductive
capacity in females)
Mutagenicity
(heritable
translocation
test)

Mutagenicity
(specific locus
test)

Teratogenicity
(birth defects)
1
i
Route of Test
Administration Animal
Inhalation Rats


Syrian
hamsters

" Mice





" Sen car
mice

Intratracheal Hamsters
instillation


Inhalation Strain A
mice

" Mice


"




" Syrian
hamsters

" Mice


" Syrian
hamsters

" Mice


" "





" "

"



" "


Rats and
rabbits


Biological
Endpoint
Transformed
liver cells

Cancer,
particularly
of the lungs
Distribution
and quantitation
of B(a)P
metabolites in
lung, liver and
testes
Skin tumor
formation

Respiratory
tract cancer


Lung cancer;
sperm
abnormalities
Chromosomal
abnormalities in
lymph cells
The ability of
urine of exposed
mice to cause
mutations in
bacteria
Chromosomal
damage

Heritable
defects and
egg abnormalities
Aberrations in
lung cells and
chromosomes
Dominant
lethal mutations
as shown by
increased fetal
death
Microscopically
observable
changes in
sperm structure
Dominant lethal
mutations as
shown by
increased
fetal death
Changes in
litter size

Partial and
complete
sterility;
chromosomal
abnormalities
Morphological
mutation (change
in skin color
and ear shape)
Skeletal and
soft tissue
abnormalities in
fetuses
Substances
Tested
Whole diesel
exhaust

"


..





••


Diesel particles,
diesel paniculate
extract

Whole diesel
exhaust

"


"




Diesel particles

Whole diesel
exhaust

Whole diesel
exhaust and
particles
Whole diesel
exhaust


"


"


"

-,



"


..


Laboratory
Perform-
ing Study
HERL- Ci


"


„





-


Illinois Institute
of Technology
Research Instiiute
for HERL-RTP
HERL-Ci

,,


"




"

"


• •


Oak Ridge
National
Laboratory
(ORNL) for
HERL-RTP
"


"


"

,,



"


HERL- Q


Study
Status/
Results
Results
available
9/79
Results
available
6/81
Results
available
9/80



Results
available
early 1981
Results
available


First results
available
12/79
Resu Its
available
12/79
First results
available
12/79


Results
available
12/79
Results
available
12/79
Results
available
12/79
Fetal death
not increased


No noticeable
effects


Increased
germ cell
killing and
fetal death

Results
available
11/79
Results
available
1/80


Results
available
2/80

No abnormalities
observed in
rats or rabbits


-------
12
                                   The studies vary in the route of
                                   exposure used (Figure 4), the
                                   dose levels administered, and the
                                   biological endpoints (effects)
                                   being investigated. Each study is
                                   designed to provide a different
                                   perspective on the ability of
                                   diesel emissions to cause cancer
                                   or mutations. Several
                                   comparative  studies are also
                                   being conducted to determine
                                   the carcinogenic potential of
                                   diesel particles relative to known
                                   human carcinogens.
  Cancer Studies.   In many of the
  cancer studies, the animals are
  being exposed to diesel exhaust
  through inhalation. This work is
  being done at the EPA's Health
  Effects Research  Laboratory in
  Cincinnati, Ohio, where a special
  exposure facility has been  built
  for the inhalation experiments
  (Figure 5). The animals are being
  exposed to diesel exhaust
  generated by a light-duty diesel
  engine attached to a
  dynamometer. As with the
  particulate collection, the
  dynamometer is programmed to
  drive the engine in a manner that
  simulates actual driving patterns.
  The resulting exhaust is diluted
  with purified air and shunted into
  the animal exposure chambers
  where it is monitored for
  concentrations of particles and
  gases.
                                             Diesel Exhaust
                                            Diesel Particles
                                            Diesel Particulate
                                               Extract
                                            Gasoline Exhaust
                                                 GPE
                                             RTV. CSC. COE
                                          KEY

                                          GPE = Gasoline particulate extract
                                          RTV = Roofing tar volatiles extract
                                          CSC = Cigarette smoke condensate
                                          COE = Coke oven emissions extract
                                                            Inhalation
 Skin    Intraperitoneal   Intratracheal
Painting     Injection     Instillation
       © Work in progress
       O Proposed study
       ^t Test organisms are insects
                                    Figure 4.
                                    Exposure methods and test substances for the Diesel Emissions Research Program
                                    whole animal studies.

-------
13
 Figure 5.
 Exposure chambers for inhalation experiments.

 Animals  in the carcinogenicity
 inhalation  experiments are being
 examined for a variety of
 biological effects indicative of
 carcinogenic potential, including
 lung and skin tumors and
 cancerous-like changes in
 individual cells of exposed
 animals. Inhalation studies are
 limited, however, in the size of
 the dose that can be given to the
 animals. High concentrations of
 the test substance may cause
 short-term toxic effects that
 adversely affect the animal
 before long-term effects such as
 cancer can appear. Because of
 this limitation, the cumulative
 dose received during the
 inhalation exposure period is
 often not sufficient to elicit
 cancer, even  when the substance
 administered is a known
 carcinogen. To counteract this
 problem, several of HERL-Ci's
 carcinogenicity inhalation
 studies are making use of
 innovative techniques that
 increase  the chance of detecting
 a carcinogen. For instance, some
studies are using special strains
 of animals that are highly
tumor-prone. Others are treating
the test animals with chemicals
to enhance the development of
an effect within the animals'
lifetime or the test period.

-------
                                    Intratracheal instillation
                                    Figure 6.
                                    Administration of diesel particles to hamsters by intratracheal instillation.
                                    (Photographs courtesy of Mr. Alan Sftefner. Illinois Institute for Technology Research Institute. Chicago. Illinois)
14
To examine the effects that may
occur at higher levels of
exposure than are possible in
inhalation experiments, a study is
being performed using the
intratracheal instillation route of
exposure in which concentrated
doses of diesel particles or
extract are directly applied to the
respiratory tract of the test
animals (Figure 6). The
intratracheal instillation study is
an important complement to the
inhalation experiments because
it increases the probability of
                                                                        observing an effect as well as
                                                                        reduces the amount of time
                                                                        necessary for the effect to
                                                                        appear. Using this technique,
                                                                        researchers may be able to
                                                                        obtain meaningful results  in a
                                                                        period of months rather than
                                                                        years.

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                                   Mutation Studies.   A mutation is
                                   a permanent change in a cell's
                                   DMA, the genetic material that
                                   directs the reproduction and
                                   development of an organism.
                                   Mutation may occur in both
                                   nonreproductive (somatic) and
                                   reproductive (germ) cells. When
                                   a mutation occurs in the DMA of
                                   germ (i.e., sperm or egg) cells,
                                   nonviable or mutant offspring
                                   may result. To identify mutagenic
                                   substances, scientists can either
                                   examine the offspring of exposed
                                   animals for mutants, or they can
                                   look at the individual somatic or
                                   germ cells of exposed organisms
                                   for signs of DNA damage (Figure
                                   7). (This latter approach is the
                                   basis for the in vitro mutagenicity
                                   tests described under In Vitro
                                   Studies.) ORD is using both
                                   experimental approaches in a
                                   series of animal studies being
                                   conducted by HERL-Ci and by
                                   the Oak Ridge National
                                   Laboratory (ORNL) in Oak Ridge,
                                   Tennessee for HERL-RTP to
                                   investigate the mutagenic
                                   potential of diesel emissions.
                                   At HERL-Ci, individual somatic
                                   cells, eggs, and sperm of animals
                                   exposed to diesel exhaust
                                   through inhalation are being
                                   examined  for signs of genetic
                                   damage or abnormalities that
                                   could lead to the occurrence of
                                   mutations affecting future
                                   generations. At Oak Ridge,
                                   exposed animals are being bred
                                   to see whether they produce any
                                   mutant offspring. For instance, in
                                   the specific locus test, scientists
                                   expose a special strain of
                                               Exposure to chemical, radiation or
                                                 other mutation-causing agent
                                     Somatic (nonreproductive) cells
                                    Examine somatic cells for signs
                                        of genetic damage
                                                                             Examine offspring for mutation
                                                                               (e.g., patchy skin color)
                                                                      Examine germ cells for
                                                                      signs of genetic damage
15
Figure 7.
Approaches for detecting mutagenic substances.

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                                  Figure 8.
                                  Normal (dark) and mutant (dark and light) offspring of mice exposed to a mutagen in the
                                  specific locus test. Patchy skin is one of several specific types of mutation that may
                                  occur when this strain of mice is exposed to a mutagen.
                                  (Photograph courtesy of Or- Walderico Generoso. Oak Ridge National Laboratory. Oak Ridge. Tennessee}
16
                                  mutation-sensitive mice to diesel
                                  emissions and then examine
                                  their offspring for patchy skin
                                  color (Figure 8) and abnormally
                                  shaped ears. Other studies at
                                  ORNL will look for sterility of
                                  exposed animals, changes in
                                  litter size, and increased fetal
                                  death.
Teratogenicity Studies.
Teratogenic effects, more
commonly known as birth
defects, are any effects which
result from damage to the fetus.
Like mutation and cancer,
teratogenic  studies are believed
to result from damage to a
cell's genetic material. To
examine diesel exhaust's
teratogenic potential, HERL-Ci
scientists have been exposing
pregnant rats and rabbits to
diesel exhaust through inhalation
and then examining the exposed
animals  for impaired
reproductive performance and
their offspring for birth defects.
                                  So far, no abnormalities have
                                  been observed.
Comparative Studies.  One
method of evaluating the
cancer- or mutation-causing
ability of a substance is to
compare its performance  in a
series of tests with the
performance of other chemicals
whose potency is already known.
The Diesel Emissions Research
Program is pursuing this strategy,
by comparing diesel  emissions to
other substances — cigarette
smoke, roofing tar fumes, and
coke  oven emissions — whose
human  carcinogenic potential
has been determined from
previous epidemiological
studies. Three comparative

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Table 2  Comparative Studies for Carcinogenicity and Mutagenicity

Route of
Type of Study Administration
Carcinogenicity:
a) Initiation Skin
painting



b) Promotion


c) Cocarcinogenesis


d) Complete "

carcinogenesis
Carcinogenicity Intraperitoneal
injection
Carcinogenicity Intratracheal
instillation


Mutagenicity Inhalation
(whole-body
exposure)


'Key: DPE = Diesel particulate extract
CSC = Cigarette smoke condensate
RTV = Roofing tar volatiles extract
COE = Coke oven emissions extract
GPE = Gasoline particulate extract
B(a)P = Benzo(a)pyrene




























7
Laboratory Study
Test Biological Substances Perform- Status/
Animal Endpoint Tested' ing Study Results

Mice Skin tumors, DPE from three Oak Ridge Papilloma results
both malignant engines, CSC, National available 2/80-
(carcinoma) and RTV, COE, GPE, Laboratory for carcinoma results
nonmalignant B(a)P HERL-RTP available early
(papHloma) 1931
DPE from three " Carcinoma results
engines, CSC, available early
RTV, COE, B(a)P 1981
Carcinoma results
available early
1981
"
Results available
early 1981
Strain A Lung cancer DPE, CSC, RTV, HERL-Ci Results available
mice B(a)P 3/80
Hamsters Respiratory DP, DPE, CSC, Illinois Institute Results available
tract cancer RTV, B(a)P, and for Technology early 1980
possibly GPE Research Institute
for HERL-RTP
Fruit Mutation Whole diesel - Oak Ridge Results available
flies exhaust, National early 1980
gaseous diesel Laboratory
emissions, for HERL-RTP
gasoline exhaust






cancer studies are being Ideally, gasoline exhaust would
conducted (Table 2): one using also be evaluated in comparative
the intratracheal instillation experiments to determine
exposure technique, another in whether diesel exhaust is more
which the substances are or less carcinogenic than the
injected into the abdominal gasoline exhaust it will replace.
cavity (a technique known as Unfortunately, the problems
intraperitoneal injection), and a associated with obtaining
third study in which the extracts sufficient amounts of gasoline
are applied directly to the skin of particulateextractforafull range
mice (skin painting). of comparative whole animal
cancer experiments may
preclude this line of
The latter study, known as a skin investigation. Enough extract
tumorigenesis study, will look nas been obtained, however, to
for the formation of both benign conduct a skin initiation study in
and malignant (cancerous) mice- ln tnis study, extract is
tumors on the skin of exposed painted on the skin once,
mice (Figure 9). The followed by repeated application
study includes several
experiments to examine whether
diesel particulate extract can act
as a complete carcinogen,
whether it requires the presence
of another substance to exert a
carcinogenic effect (promoter or
initiator), or whether it can
augment the carcinogenic effect
of another (cocarcinogen)
chemical (Figure 10).

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                                           Figure  9.
                                           Skin tumors on mice treated with a known carcinogen. The smaller nodules on the
                                           righthand mouse are benign tumors. The larger nodules present on the center and
                                           left hand mouse are cancerous. HERL-RTP's skin painting studies will look for similar
                                           effects on mice treated with diesel particulate extract.
                                           (Photograph courtesy of Dr. Thomas Slags, Oak Ridge National Laboratory. Oak Ridge, Tennessee)
                                             COMPLETE CARCINOGEN
                                                Multiple application of
                                                a complete carcinogen
                                                                                   No added treatment
                                                                                                                 ->- Tumors
                                             INITIATOR and PROMOTER
                                                 Initiator
                                                                             Subsequent treatment with promoter
                                                                                                                     Tumors
                                                                    Note: An initiator or promoter acting alone will not produce tumors.
                                             COCARCINOGEN
                                               Simultaneous treatment
                                               with initiator & cocarcinogen
                                                                             Subsequent treatment with promoter
                                                                                                                  >• Greater or
                                                                                                          more rapid appearance
                                                                                                          of tumors than without
                                                                                                                  cocarcinogen
18
                                            Figure 10.
                                            Testing protocols for complete carcinogens, tumor initiators, tumor promoters and
                                            cocarcinogens.

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                                   of a chemical that is known to
                                   promote tumor formation. The
                                   study will compare the relative
                                   ability of gasoline and diesel
                                   extracts to act as tumor initiators
                                   — that is, to cause irreversible
                                   cellular damage capable of
                                   developing into tumors in the
                                   presence of a tumor promoter.
                                  A comparative study exposing
                                  fruit flies to whole diesel and
                                  gasoline exhaust will also  be
                                  conducted to compare the ability
                                  of diesel and gasoline emissions
                                  to cause mutations. This
                                  relatively rapid test will be used
                                  to provide a preliminary idea of
                                  whether diesel exhaust is more
                                  or less mutagenic than gasoline
                                  exhaust.
                                   Noncarcinogenic Effects.
                                   Noncarcinogenic effects of
                                   combustion emissions (such as
                                   chronic lung diseases) are
                                   generally caused by combustion
                                   gases, such as sulfur dioxide and
                                   nitrogen oxide, and by the
                                   particles with or without
                                   associated organic matter. These
                                   components are present in both
                                   gasoline and diesel exhaust. The
                                   replacement of gasoline by diesel
                                   emissions is therefore not
                                   expected to cause new or
                                   unusual noncarcinogenic human
                                   health effects.  To test this
                                   hypothesis, and to determine the
                                   range and magnitude of diesel's
                                   noncarcinogenic effects,
                                  scientists at the EPA's Health
                                   Effects Research Laboratory in
                                  Cincinnati, Ohio are conducting
                                  a series of noncarcinogenic
                                  health effects studies.
                                  study conducted prior to the
                                  Diesel Emissions Research
                                  Program had shown that diesel
                                  exhaust is capable of causing
                                  serious damage to respiratory
                                  tissue in hamsters. The questions
                                  that remain to be answered are:
                                  What sort of damage will diesel
                                  exhaust cause, and  under what
                                  exposure  conditions will diesel
                                  exhaust harm  human respiratory
                                  tissues?
                                  In 1977, HERL-Ci conducted a
                                  50-day pilot study to survey the
                                  potential noncarcinogenic health
                                  effects of diesel exhaust. These
                                  experiments exposed cats, rats,
                                  mice and guinea pigs to relatively
                                  high concentrations of exhaust
                                  through inhalation for a few days
                                  or weeks. Animals were then
                                  examined for a variety of
                                  short-term effects including lung
                                  damage, increased susceptibility
                                  to infection, biochemical
                                  changes in the lung and other
                                  tissues, signs of fibrosis and
                                  emphysema, changes in
                                  behavior, and the ability of the
                                  lungs to clear away particles. The
                                  only short-term effects observed
                                  were increased susceptibility to
                                  infection and some behavioral
                                  alterations in exposed rats.
19
The noncarcinogenic effect of
greatest concern is the ability of
diesel exhaust to cause chronic
lung diseases such as pulmonary
fibrosis and emphysema. Many
combustion products, including
gasoline emissions, are known to
cause lung damage, and there is
little question that diesel
exhaust, if inhaled in sufficient
concentration over a long
enough period of time, would
have a similar effect. In fact, one

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                                To follow up this study, HERL-Ci
                                is conducting a series of
                                inhalation experiments (Table 3)
                                to examine various types of
                                noncarcinogenic damage that
                                may occur in animals exposed to
                                diesel exhaust for  extended
                                periods of time.  These studies
                                include:
                                 • Long-term studies in cats and
                                   mice to look for various types
                                   of structural, chemical, and
                                   functional lung  damage

                                 • Neurobehavioral studies to
                                   investigate effects on the
                                   nervous system  and behavioral
                                   developments
                                 • A series of experiments to
                                   determine the degree to which
                                   diesel exhaust impairs an
                                   animal's resistance to
                                   infection.
                                 Some of these studies have been
                                 completed. The neurobehavioral
                                 studies have shown that rats
                                 exposed to diesel emissions are
                                 less active than normal and that
                                 diesel emissions may delay
                                 development in young animals.
In the infectivity study, resistance
to infection was found to be
impaired in exposed mice,
confirming the preliminary
results obtained in the pilot
study. Unfortunately, it is not
easy to extrapolate
dose-response data for
noncarcinogenic effects down
from the relatively high doses
used in these studies to the much
lower environmental exposure
levels. Nevertheless, the studies
are valuable for identifying
possible health effects of
concern.
Table 3  Mammalian Studies to Investigate the Noncarcinogenic Effects of Diesel Exhaust
Type of Study
Neuro-
behavioral
Infectivity

Reproduction
(multigeneration)
Lung damage
Lung function
Lung deposition,
retention, and
Hoaranrp
Laboratory
Route of Test Biological Substances Perform-
Ad ministration Animal Endpoint Tested ing Study
Inhalation Newborn Neurobehavioral Whole diesel HERL-Ci
and adult abnormalities exhaust
rats
Mice Impaired
resistance to
infection

Effects on
fertility and
other aspects of
reproduction and
development
Effects on
lung cells
Cats Noncarcinogenic
lung disease;
sperm
abnormalities
Hamsters Body and Carbonaceous HERL-RTP
organ burdens particles
of diesel exhaust (diesel surrogate)
Study
Status/
Results
Reduced activity
and possibly
delayed
development in
exposed animals
Impaired
resistance to
infection
observed in
exposed animals
Results
available
10/80
Results
available
9/79
Results
available
11/80
Study
proposed
for funding
20

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                                                                          60 days post-exposure
                                     One-hour post-exposure
                                     Figure 11.
                                     Clearance of diesel particles from lung tissue. Hamsters were treated with a single dose
                                     of diesel particles by intratracheal instillation and then sacrificed either one hour or
                                     60 days after treatment. The proposed deposition, retention, and clearance study would
                                     investigate similar phenomena in animais exposed to particles through inhalation.
                                     (Photographs courtesy of Mr. A/an Shefner, Illinois Institute for Technology Research Institute. Chicago, Illinois)
21
One other noncarcinogenicity
study, proposed by HERL-RTP, is
being considered for funding.
This study would investigate the
deposition, retention, and
clearance (Figure 11) of particles
in the lungs of animals exposed
through inhalation. Specifically,
the study would  attempt to
answer such questions as:
•  What concentration of
   particles will overload an
   animal's natural defense and
   clearance mechanisms thus
  making the animal  more
   susceptible to disease ?

• What happens to the organics
  associated with the inhaled
  particles? For instance, how
  fast do they enter the blood
  stream? At what site(s) in the
  body do they tend to
  accumulate? How fast can
  they be cleared away after
  termination of exposure?

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               In Vitro Studies
22
In vitro tests (Figure 12) detect
the ability of a chemical to alter
the genetic material (DNA) of
simple organisms (bacteria,
yeast) or mammalian cells
(human or animal). In humans,
genetic alterations may cause
mutation, birth defects, and
possibly cancer. Since simple
organisms or single cells do not
have the biological complexity
of the human body, positive
in vitro tests are currently
considered to be suggestive but
not definitive evidence that a
chemical is carcinogenic or
mutagenic to humans.
                                  In vitro tests are rapid and
                                  inexpensive compared to animal
                                  tests and epidemiological
                                  studies. They are most commonly
                                  used as rapid screening devices
                                  to provide a preliminary idea of a
                                  chemical's mutagenic or
                                  carcinogenic potential until more
                                  conclusive animal or
                                  epidemiological studies can be
                                  conducted. In vitro tests are also
                                  valuable in cases where animal
                                  tests simply cannot be
conducted; for instance, when
the number of substances to be
tested is so large that animal
tests would be prohibitively
expensive, or when not enough
of the test substance is available
to conduct a whole animal test.
                                                                    Testing for Carcinogenic and
                                                                    Mutagenic Potential.  At the
                                                                    beginning of the Diesel
                                                                    Emissions Research Program,
                                                                    diesel particulate extract was
                                                                    tested in the Ames test (Figure
                                                                    13), a well known in vitro test for
                                                                    mutagenicity. The Ames test uses
                                          TEST SYSTEM
                                                                     CONTROL
                                                 Apply substance of
                                                 interest to microorganism
                                                 or cell system
                                                                               Use same microorganism
                                                                               or cells as test system but
                                                                               do not add chemical
 Figure 12.
 Basic in vitro test procedure.

-------
                                                                          a special strain of bacteria that
                                                                          will not grow unless they have
                                                                          been mutated. Bacteria exposed
                                                                          to diesel extract in the Ames test
                                                                          did grow, indicating that diesel
                                                                          exhaust was potentially
                                                                          mutagenic and possibly
                                                                          carcinogenic* to humans. To
                                                                          support this finding, scientists at
                                                                          the EPA's Health Effects
                                                                          Research Laboratory in Research
                                                                          Triangle Park (HERL-RTP) are
                                                                          examining diesel particles and
                                                                          particulate extract in a battery of
                                                                          in vitro tests (or assays) using
                                                                          human and mammalian cells
                                                                          {Table 4). Whole and gaseous
                                                                          (particle-free) emissions are also
                                     Figure 13.
                                     Counting bacterial colonies in the Ames
                                     test.
'Mutation involves damage to a cell's
DNA. Cancer is also believed to result
1rorn damage to a cell's DNA, so
chemicals that are mutagenic are
generally suspected of being
carcinogenic.
Table 4  In Vitro Tests to Determine the Carcinogenic and  Mutagenic Potential of Diesel Emissions*
Type of Study
Carcinogenesis
Carcinogenesis
Mutagenesis
Mutagenesis
(Ames test)
Mutagenesis
Mutagenesis
Mutagenesis
Test
Organism
or Cells
Embryonic Syrian
hamster cells
Mouse cells
(BALBc3T3
fibroblasts) and
embryonic Syrian
hamster cells
Chinese hamster
ovary cells
Bacteria
(Salmonella
typhimurium)
Mouse cells
(L5178Y lymphoma
cells and BALBc3T3
fibroblasts)
Yeast
(Saccharomyces
cerevisiae D3)
Humal cells
(lymphocytes)
Biological
Endpoint
Viral enhancement
of oncogenic
transformation
Oncogenic
transformation
Chromosomal damage
(sister chromatid
exchange)
Gene mutation
Gene mutation
DNA damage
(mitotic
recombination)
Chromosomal damage
Laboratory
Performing
Study
Northrop Services,
Inc. for HERL-RTP
Microbiological
Associates and
Northrop Services,
Inc. for HERL-RTP
Northrop Services,
Inc. for HERL-RTP
HERL-RTP
SRI, International
and Microbiological
Associates for
HERL-RTP

North Carolina
State University
for HERL-RTP
Study
Status/
Results
Results available
late 1979
Results available
early 1980
Results available
late 1979
Results available
late 1979
Results available
late 1979
Results available
late 1979
Results available
1980
* The following substances are being tested in the in vitro tests: diesel particles and diesel particulate extract from five diesel engines; coke oven
 emissions extract; cigarette smoke condensate; roofing tar volatiles extract and gasoline particulate extract.
23

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                                      A.
                                      Figure 14.
                                      Oncogenic transformation assay. A. Positive response. Following exposure to a test
                                      substance, three cells on the petri plate became transformed and spread in a cancerous-
                                      (ike growth, indicating that the test substance may be carcinogenic. B. Negative
                                      response. Exposure to a second test substance had no effect on the cells on the petri
                                      plate, suggesting that the second test substance may not have carcinogenic properties.
                                      C, Scanning electron micrograph of transformed cells (2000x). D. Scanning electron
                                      micrograph of normal cells (3000x).

                                      (Scanning Electron Micrographs courtesy of Dr. K. Muse, Department of Zoology, North Caroline State University
                                      Rtteigk, NCI
                                      scheduled for testing. The test
                                      battery will look for the potential
                                      of diesel emissions to cause
                                      several different types of genetic
                                      alterations, including:

                                      • Gene mutation

                                      • DMA damage

                                      • Chromosomal alterations

                                      • Oncogenic transformation, or
                                        cancerous-like changes
                                        (Figure 14).
Resu Its of these tests will provide
a preliminary idea of diesel's
mutagenicand carcinogenic
potential until results of the
long-term animal studies become
available. In vitro tests will also
enable HERL-RTP scientists to
characterize the type(s) of
genetic effects that diesel
exhaust is capable of causing at
the cellular level.
24

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                                    Preparations are underway to
                                    examine whole, gaseous, and
                                    participate emissions from
                                    gasoline engines in the same
                                    battery of tests to compare the
                                    carcinogenic and mutagenic
                                    potential of diesel and  gasoline
                                    emissions.
                                    Relative Potency Ranking. In
                                    another line of research,
                                    HERL-RTP scientists are
                                    investigating the use of in vitro
                                    tests for ranking various
                                    substances with  respect to
                                    carcinogenic potency.* Extracts
                                    from five different diesel engines
                                    and three  known carcinogens
                                    (cigarette  smoke, roofing tar
                                    fumes, and coke oven emissions)
                                    are being tested in the battery of
                                    in vitro tests and in the whole
                                    animal skin painting tests
                                    described  earlier (see Cancer
                                    and Related Effects). HERL-RTP
                                    scientists will attempt to
                                    determine whether there is a
                                    consistent pattern of activity in
                                    the in vitro and the more
                                    definitive skin painting tests. For
                                    instance: Does the substance
                                    that shows least activity in  the/'/7
                                    vitro tests  also cause the fewest
                                    skin tumors?
                                    If an in vitro test appears to be a
                                    fairly accurate potency indicator,
                                    it may be used in the Diesel
                                    Emissions Research Program to
                                    provide a rapid estimate of
                                    relative potency when time or
                                    cost constraints do not permit
                                    more extensive testing. For
                                    instance, by examining particles
                                    trapped by the various control
                                    devices being developed (see
                                    Control Technologies), the test
                                    could provide rapid assessment
                                    as to which technologies are
                                    most successful in reducing
                                    hazardous emissions.
25
*At present, in vitro tests are only used as
yes/no indicators of mutagenic and
carcinogenic potential. Although the level
of biological activity observed (for
instance, the number  of bacteria that
mutate) varies with the substance being
tested, scientists do not yet know whether
the level of activity correlates with
mutagenic or carcinogenic potency.
                                   Streamlining Chemical Analysis.
                                   In another innovative line of
                                   research, the Ames test is being
                                   used to help identify specific
                                   hazardous chemicals in diesel
                                   particulate extract. Normally, the
                                   chemical analysis of a complex
                                   mixture containing thousands of
                                   chemicals is an expensive and
                                   time-consuming procedure. The
                                   substance must first be divided
                                   into a large number of distinct
                                   fractions, each  of which must
                                   then be analyzed separately for
                                   its individual chemical
                                   components. To simplify this
                                   process, HERL-RTP is using  the
                                   Ames test as a rapid screening
                                   tool to indicate which  of the
                                   fractions should receive highest
                                   priority for chemical analysis.
                                   As a first step in this research,
                                   diesel extract was divided into
                                   seven fractions  by scientists at
                                   the EPA's Environmental
                                   Sciences Research Laboratory in
                                   Research Triangle Park. Each
                                   fraction was then tested in the
                                   Ames test for mutagenic
                                   potential. Mutagenic fractions
                                   were further divided and the
                                   resulting subfractions were
                                   tested in the Ames test. By
                                   repeating this process, ORD
                                   scientists hope to isolate the
                                   most hazardous elements of
                                   diesel  extract. Once the
                                   subfractions reach a manageable
                                   size, they will  be chemically
                                   analyzed for specific toxic
                                   chemicals.
Hazardous subfractions are
important since they may be the
subject of specific regulatory
action. For instance, in
establishing regulations for
controlling diesel emissions, the
EPA may set forth standard
procedures for fractionating
diesel particulate extract, and
then require that the
carcinogenic potential  and
toxicity of specific subfractions
generated by these procedures
be reduced or eliminated  in
controlled emissions.

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Air Monitoring Studies
 26
The Diesel Emissions Research
Program is funding two studies
to monitor and analyze diesel
emissions in the ambient air. This
research is being performed by
the EPA's Environmental
Monitoring Systems Laboratory
in Research Triangle Park
(EMSL-RTP). One short-term
study will compare the risk from
diesel emissions to health risks
posed by pollutants already
present in ambient air. The other,
a long-term monitoring  study,
will determine how air quality is
affected by an increasing use of
the diesel engine.
                                               SAMPLING
                                   J
                                                   42nd St
                                    Outside bus
                                    terminal
                                    (Ambient diesel jevels)
                                                   41st St
                                                         New York Port
                                                         Authority Bus
                                                         Terminal (High
                                                         diesel levels)
                                               ANALYSIS
                                                   Biological Tests

                                                    In vitro test
                                                    • Particulate extract
                                                    Tradescantia test
                                                    • Whole and gaseous
                                                      (particle-free)
                                                      emissions
                                                    Skin painting
                                                    • Particulate extract
                                                   Chemical Analysis
                                                      Particulate extract
                                                      Whole and gaseous
                                                      emissions
                                    Figure 15.
                                    Comparing air from areas of high and
                                    ambient diesel emission levels.
Comparative Study.  In the
short-term study, whole air,
gaseous (particle-free), and
particulate samples were taken
from areas with expected high
and ambient concentrations of
diesel emissions. The high level
samples were collected over a
15-day period from inside the
New York Port Authority Bus
Terminal. This site has high
diesel levels due to the constant
flow of  buses, but is relatively
free of gasoline and other
exhausts. Ambient concentration
samples were taken from a site
near the terminal. The particulate
samples were collected using
massive-volume air samplers.
Only recently  developed, these
samplers are unique in their
ability to separate the collected
particles into various size ranges.


Particulate extracts from both
sites are being compared in a
series of chemical and biological
tests (Figure 15). Chemical
analysis will identify known
carcinogens and mutagens,
while in vitro tests will examine
the carcinogenic and mutagenic
potential of the extracts. Animal
(skin) painting tests may be
conducted if a sufficient sample
is available, pf particular interest
will be  the biological and
chemical  characteristics of  the
smaller-sized (respirable)
particles.
                                   Whole and gaseous samples
                                   from the two sites are also being
                                   subjected to chemical analysis to
                                   identify organic chemicals and
                                   other gaseous components
                                   present in diesel emissions. In
                                   addition, the biological activity of
                                   these samples is being examined
                                   in a recently developed
                                   mutagenicity test for gaseous
                                   substances. This unusual test
                                   utilizes the  plant Tradescantia
                                   (commonly known as
                                   spiderwort), whose flower petals
                                   and stamen hair cells turn from
                                   blue to pink following contact
                                   with gaseous mutagens. To
                                   conduct this test, a mobile
                                   laboratory (Figure 16} was used so

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                                    Mobile laboratory for on-site testing of
                                    ambient air
                                    Exposure chamber inside the mobile
                                    laboratory.
                                    Tradescantia flower
                                                                       Normal (darker) and mutant (lighter)
                                                                       stamen hair cells
                                    Figure 16.
                                    Tradescantia mutagenicity test.
                                    (Photographs courtesy of Mr. Lloyd Schairer. Brookhaven National Laboratory. Brookhaven. New York)
27
                                    plants could be directly exposed to
                                    ambient air at both sampling sites.
                                    By counting the number of stamen
                                    hair cells that change color
                                    following exposure, scientists will
                                    be able to rapidly determine the
                                    mutagenic potential  of the test
                                    substances.
                                   Results of this short-term study
                                   will be used in assessing whether
                                   high ambient concentrations of
                                   diesel pollutants pose a greater
                                   human health hazard than
                                   pollutants present in ambient air
                                   in a major metropolitan area.
                                   Also,  data on the air samples
                                   taken within the Port Authority
                                   Terminal will aid in determining
                                   potential health effects of
                                   "worse-case" ambient exposure.
Long-Term Monitoring.
EMSL-RTP's long-term air
monitoring study is designed to
monitor the change in air quality
that will take place during the
next few years as large numbers
of New York City taxicabs convert
from gasoline to diesel engines.
Diesel conversion of taxicabs is
expected to  have a measurable
impact on local diesel pollutant
levels  because taxicabs account
for approximately one-third of
the passenger  miles driven in
Manhattan. In this study, air
samples from a site in New York
City's Central Park will be
collected at 3-month intervals for
3 years and tested in In vitro and
possibly skin painting tests for
mutagenic and carcinogenic
potential. Like the short-term
study, this project will be used in
estimating whether the change
from gasoline to  diesel fuel will
pose a greater  human health
threat than ambient air now
present in New York City. It will
also provide  baseline data
against which to  compare any
future changes in air pollutant
levels.

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                Exposure
Exposure information is essential
for assessing the overall public
health impact of widespread
introduction of diesel cars.
Human population exposure to
air pollutants can  either be
directly measured using portable
sampling devices  or estimated
using complex computer models
(Figure 17). Computer models
combine information on such
factors as vehicle types, number
of miles travelled, emissions
characteristics, roadway
configurations, and directly
measured pollutant
concentrations to predict
pollutant levels as a function of
distance from the pollution
sources. Ideally, data on the
average proximity of the U.S.
population with respect to the
pollution sources would then be
worked into the computer model
to project the number of
individuals that will  be exposed
to various levels of pollutants.
                                  Computer Modeling of Pollutant
                                  Levels.  As part of the Diesel
                                  Emissions Research Program,
                                  scientists at the EPA's
                                  Environmental Sciences
                                  Research Laboratory in Research
Triangle Park are using existing
computer models to project how
diesel conversion of motor
vehicles will affect the levels of
various pollutants in five U.S.
cities— New York, St. Louis,
Kansas City, Phoenix, and Los
Angeles. Future pollutant levels
are being predicted for a range of
diesel particulate control
scenarios. Where possible,
projections will be tested against
ambient air quality
measurements in order to verify
the accuracy of the various
models. The program's ambient
air monitoring studies will
contribute to this work by
establishing a baseline against
which future particle levels can
be compared as diesel cars are
introduced.
   Emissions characteristics
   Roadway configurations
   Number of vehicles
   Types of vehicles
   Average number of miles travelled
   Weather data
     Population activity patterns
                      Pollutant levels with respect to
                      distance from traffic arteries and
                      other diesel emissions sources
                                                                                Exposure projections
                                                                            Diesel Pollutant Levels
Figure 17.
Computer modeling of human population exposure to diesel emissions.
28

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                                      Meter showing
                                      instantaneous
                                      carbon monoxide
                                      level
                                                          ' Digital display of cumulative exposure

                                                       'Strip chart with permanent record of pollutant concentration
                                    Figure 18.
                                    Portable monitor to measure individual exposure to carbon monoxide.
                                    Research to Help Estimate
                                    Population Exposure.  At the
                                    EPA's Environmental Monitoring
                                    Systems Laboratory in Research
                                    Triangle Park, scientists are
                                    working to define patterns in
                                    population activities (e.g., work,
                                    recreation, commuting) so that
                                    they can generate more  precise
                                    population exposure data. In
                                    order to broaden our knowledge
                                    about pollutant exposure,
                                    EMSL-RTP scientists are also
                                    conducting a study to measure
                                    individual exposure to carbon
                                    monoxide, one of the gases
                                    present in  diesel and other
                                    vehicular emissions. This study is
                                    utilizing personal monitors
                                    attached to passengers in buses
                                    and cars, and portable monitors
                                    placed inside the vehicles (Figure
                                    18). Passengers are generally
subjected to higher pollutant
levels than pedestrians, so the
data generated will provide an
idea of worst-case general
exposure to carbon monoxide.
Portable carbon monoxide
monitors may also prove useful
for estimating individual
exposure to diesel particles if
research indicates that ambient
diesel particle levels correlate
with ambient carbon monoxide
levels. Commercial  companies
are currently developing portable
monitors for directly measuring
individual exposure to diesel
particles. If suitable, these
instruments may be used by
EMSL-RTP in future exposure
studies.
29

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     Risk Assessment
Ultimately, the human health
effects and exposure data
generated by the Diesel
Emissions Research Program
will be combined to assess the
public health risk associated with
diesel exhaust—a process known
as risk assessment (Figure 19).
The estimated risk will then be
used by the EPA along with other
important factors in deciding
how stringently to regulate diesel
emissions. Risk assessment will
be performed by the EPA's Office
of Health and Environmental
Assessment (OHEA) in
Washington, D.C.
                                 In assessing diesel's
                                 noncarcinogenic health risk,
                                 OHEA will draw heavily upon
                                 previous experience with other
                                 atmospheric pollutants. The
                                 noncarcinogenic effects of
                                 combustion gases have been
                                 well studied, and there is good
                                 reason to  believe that diesel
                                 exhaust will have similar effects.
                                 To establish the carcinogenic
                                 risk of diesel exhaust, diesel
                                 particles and paniculate extract
                                 are being examined in animal
                                 studies (see Identification of
                                 Potential Health Threats). These
studies will generate information
on how the likelihood of
developing cancer varies with
dose. However, because the
doses used in animal
experiments are generally much
higher than actually occur in the
ambient environment, the
dose-response data from these
experiments must be
extrapolated downward in order
to predict the increased
incidence of cancer that could
occur in human populations
exposed to lower environmental
levels of diesel pollutants.
30
                                        QUANTIFICATION OF
                                         HEALTH EFFECTS
                                          QUANTIFICATION OF
                                             EXPOSURE
                                         Identify health effect
                                           of concern
                                            I
                                      Define the nature and degree
                                        of the effect at different
                                        doses (dose-response)
                                        Determine who is exposed
                                          Determine the level(s)
                                             of exposure
                                                          Estimate the level of
                                                         occurrence of effects on
                                                            the population
                                  Figure 19.
                                  The risk assessment process.

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i
LINEAR THRESHOLD LINEAR NONTHRERHOI n
^
ence of Cancer
T3
c
D)
1


(1






C

t
0)
o
c
The lowest dose at Q
which no effect occurs -g
is greater than zero 
x -c


- u>
' j» °


Effect may occur
at any dose greater
than zero
/X








fc'


                                  Figure 20.
                                  The threshold concept.

                                  In extrapolating the
                                  dose-response data to
                                  low-exposure levels, the EPA's
                                  current policy is to use a linear
                                  nonthreshold dose-response
                                  relationship. This relationship
                                  assumes that exposure to even
                                  extremely low doses of a
                                  substance can potentially result
                                  in cancer (Figure 20). Such a
                                  relationship is considered to be
                                  conservative because it probably
                                  overestimates cancer incidence
                                  at low exposures. It is the EPA's
                                  cancer assessment policy to use
                                  such an extrapolation in the
                                  absence of better information
                                  because of its conservative
                                  nature.
                                  To assist the linear nonthreshold
                                  extrapolation of risk, the relative
                                  carcinogenic risk of diesel
                                  exhaust will be determined as
                                  discussed in the Program
                                  Strategy section by comparing
                                  them vitro and in vivo activity of
                                  diesel exhaust to carcinogenic
                                  agents — coke oven emissions,
                                  roofing tar fumes, and cigarette
                                  smoke — whose relative potency
                                  is already known from previous
                                  epidemiological studies. These
                                  substances will be used as a
                                  yardstick against which to
                                  estimate the carcinogenic
                                  potency of diesel exhaust in
                                  animal and in vitro experiments.
                                  Such a comparison will provide
                                  an idea of the degree of human
                                  health risk associated with diesel
                                  exhaust.
 While the above risk assessments
 will be very valuable, even more
 informative for regulatory
 decision-making would be an
 estimate of the risk of diesel
 exhaust relative to gasoline and
 other combustion emissions
 already present in ambient air.
 Unfortunately, technical
 problems associated with
 collecting sufficient samples for
 definitive health effects
 experiments may limit the extent
 of risk comparison that can be
 made between  diesel emissions
 and gasoline exhaust, and
 between diesel emissions and
 ambient air. It  is possible,
 however, to collect enough
 particles from gasoline
 emissions and ambient air to
 perform the in vitro and, in some
 cases, whole animal skin
 painting tests for rough potency
 assessments. At present,  this
 work is being done on a limited
scale. If early results of the
 comparison suggest that  this
 information will be important for
 regulatory action, these studies
will be expanded.
31

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Control Technologies
32
The primary responsibility for
developing control technologies
lies with automobile
manufacturers, who must ensure
that every new vehicle meets
emissions standards set by the
EPA. To keep abreast of the
control technology development
situation, the  Diesel Emissions
Research Program is funding  a
small effort to investigate and
develop technologies for
controlling diesel emissions.
Results of this research will
assist regulators in determining
what level of control is
technologically and
economically feasible.
Paniculate Control.   The main
thrust of the control technologies
research, currently under way at
the EPA's Industrial
Environmental Research
Laboratory in Research Triangle
Park (IERL-RTP) is to develop
and evaluate particulate control
devices. IERL-RTP is currently
investigating five particulate
control concepts — three filters,
an electrostatic device, and a
cyclonic agglomerator (Table 5).
Prototypes of these devices will
be built and tested by IERL-RTP
and its contractors.
                                                                     An important factor that must be
                                                                     considered in designing these
                                                                     devices is how to handle the
                                                                     large amount of toxic particles
                                                                     that accumulate as light flaky
                                                                     material on the after-treatment
                                                                     device at the rate of about 1
                                                                     kilogram every 1,000 to 2,000
                                                                     miles (Figure 21). These particles
                                   Figure 21.
                                   Particulate control filter and collected particles. A. Clean filter prior to diesel exhaust
                                   exposure. B. Outer casing (silver) and exposed filter (black). Filter contains particles that
                                   accumulated after exposure to emissions from a light-duty diesel engine run for
                                   approximately 2,000 kilometers. Jar contains additional loose particles that
                                   accumulated within the device during the same exposure period. C. Photomicrograph
                                   of diesel particles removed from a control device.
                                   fPhotograph courtesy of Eikosha Company, Tokyo. Japan)

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  Table 5   Control Devices Under Development by IERL-RTP
          Type of Device
                                        Collection
                                                                Storage
                                                                                            Disposal
     Cyclonic agglomerator
     Deep-bed filter
     Catalytic filter
     Electrostatic filter
     Two-stage electrostatic collector
Particles are agglomerated
on a fine mesh and then
transported to a secondary
collector by a cyclonic device
which directs the particle flow

Particles are collected on a
deep-bed filter with suitable
capacity for particle storage

Particles are collected on a
relatively shallow filter which
has a suitable surface (substrate)
for catalytic oxidation

Particles are charged and then
collected on an electrostatically
charged filter

Particles are electrostatically
charged and then collected in
electrostatic fields between
concentric rings
                                                         Particles are compacted and
                                                         stored in the secondary
                                                         collector
                                                         Particles are compacted and
                                                         stored in the filter
                                                         Particles are not stored
                                                         Particles are stored on the
                                                         filter
                                                         Particles are automatically
                                                         washed off the rings with oil;
                                                         oil is stored in a sump
Secondary collector must be
emptied at approximately
5,000-mile intervals
Filter must be replaced at
approximately 5,000-mile intervals
                                                                                   Particles are continuously burned
                                                                                   off by catalytic oxidation
Disposal method to be developed
Particle-laden oil must be
drained from the sump at
approximately 5,000-mile intervals
33
                                        must be either burned off or
                                        stored and periodically removed.
                                        If the latter approach is used,
                                        sufficient storage capacity must
                                        be available so that car owners
                                        are not unduly inconvenienced
                                        by a frequent need to attend to
                                        particle removal and disposal.
                                        Provisions  must also be made for
                                        ultimate disposal of the toxic
                                        particles. IERL-RTP is
                                        investigating a variety of particle
                                        storage and removal methods
                                        (Table 5) as potential solutions
                                        for the particle handling
                                        problem. In some cases,
                                        conventional particle removal
                                        technologies for stationary
                                        sources are being modified for
                                        application to moving vehicles.
                                               Testing of the particulate control
                                               technologies will involve a
                                               determination of how successful
                                               each device is in reducing the
                                               amount of particles contained in
                                               the exhaust. Each device will be
                                               tested on a variety of diesel
                                               engines to determine how engine
                                               parameters affect control
                                               effectiveness.  Particles emitted
                                               by controlled and uncontrolled
                                               engines will also be compared in
                                               the Ames mutagenicity test to
                                               provide an idea  of whether the
                                               control technologies reduce  the
                                               levels of mutagenic and possibly
                                               carcinogenic chemicals in diesel
                                               exhaust.

                                               Organic Emissions Control.
                                               Since specific  organic fractions
                                               of diesel  emissions may be
                                               regulated in the  future,
                                               IERL-RTP is investigating
                                               methods of reducing the level of
                                              toxic organics  in diesel
                                              emissions. One approach  for
                                              organics  control  is to reduce

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                                  ENGINE MODIFICATION
                                   Fuel injection systems
                                   Variable geometry turbo charging
                                   Fumigation
                                   Insulated engines
         FUEL MODIFICATION
         • Additives
         • Emulsions
         • Fuel properties

                                                                   AFTERTREATMENT-
                                                                   • Filters
                                                                   • Scrubbers
                                                                   • Electrostatic precipitators
                                                                   • Catalytic converters
                                              Approaches for diesel emissions control.
                                 participate emissions since
                                 diesel particles contain
                                 substantial amounts (10 to 50
                                 percent by weight) of organics.
                                 As described above, participate
                                 control devices are being tested
                                 to determine their effectiveness
                                 for reducing organic emissions.
                                  In another line of research,
                                  IERL-RTP engineers are
                                  exploring the possibility of using
                                  oxidation catalysts to burn the
                                  organics, thereby reducing them
                                  to relatively innocuous gases.
                                  Since catalysts generally work
                                  best on molecules in the gas
                                  phase, tests are being done to
                                  determine how soon the diesel
                                  organics condense onto the
                                  particles after leaving the engine.
                                  Preliminary results indicate that
                                  diesel organics may remain
                                  gaseous in the tail pipe long
                                  enough to  be acted upon by a
                                  catalytic device. If these results
                                  are confirmed by further tests,
                                  IERL-RTP may try to develop
                                  suitable catalyses) for oxidizing
                                  the high molecular weight
                                  organics that characterize diesel
                                  emissions.
Fuel and Engine Modification.
Other possible means of
reducing hazardous emissions
include modifying the fuel or
the engine. These approaches
are being pursued under other
EPA programs and,  if they prove
fruitful, may be utilized or
expanded upon by the Diesel
Emissions Research Program.
34

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     Other Federal Agency
      Diesel Health Effects
                    Research
 This document describes
 EPA's Diesel Emission
 Research Program. In addition
 to this effort, the Department
 of Energy is conducting a
 research program which will
 provide additional data to
 permit the Federal Govern-
 ment to develop and
 implement a regulatory
 program which will protect
 human health while minimiz-
 ing restrictions on the
 utilization of thediesel engine.
 The two prog rams are
 coordinated and comple-
 mentary.

 Both Programs:

   • augmentthesmall eptdemi-
     ological data base presently
     available concerning the
     health effects of actual
     human exposures to diesel
     emissions.

   • improve our knowledge of
     the chemical characteriza-
     tion of mutagenic and
     carcinogenic agents that are
     associated with diesel
     paniculate emissions.

   • improve knowledge of the
     potential human exposures
     to diesel paniculate
     emissions.

   • provide risk assessments of
     increased diesel use.

Budgets for diesel health
effects research:
                                              DOE
                        EPA
FY79
FY80
FY81*
2.2
2.8
2.4
5.7
6.3
6.5
                                   'Presidential Budget Submission
Distinctive features of the
programs:

             DOE

•  Uses primarily animal inhala-
   tion experiments.

•  Uses multiple exposure/dose
   levels to determine dose-
   response relationships.

•  Focuses on carcinogenic end
   point.

             EPA
•  Uses inhalation, other in vivo
   models such as  skin painting
   and  intraperitoneal  injection
   and in vitro bioassays.

•  Determines relative carcino-
  genic potency of diesel
  paniculate extract as compared
  to other known carcinogens.
• Uses pulmonary, behavioral,
  mutagenic effects, and  enzyme
  induction end points in  addition
  tocarcinogenicity.

• Performs bioassays in particles
  found in ambient air samples
  where diesels are and are not
  expected to be significant
  contributors.
35

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This project was coordinated by the Center for Environmental Resear? Information
under the direction of Clarence A. demons. This report was prepared for the EPA Mobile Source
Research Committee under the guidance of Roger S. Cortesi, Matrix Manager Mobile Source Research
Program. All material was written by Jan Connery of Energy Resources Co.  Inc. Cambridge,
Massachusetts from material provided by the Research Comm.ttee; Virginia Hathaway of JACA Corp.
Philadelphia, Pennsylvania was coordinator for production.


Acknowledgement is made to the many persons who were involved in reviewing draft material and
especially to those who provided technical assistance. Major contributors were:

        Enviromental  Monitoring Systems Laboratory— RTF
           Thomas R. Mauser and Robert H. Jungers

        Environmental Sciences Research Laboratory— RTP
           Ronald L.  Bradow

        Health Effects  Research Laboratory— Ci
           Norman A. Clarke, R. John Garner, Robert K. Miday, and William E. Pepelko

        Health Effects  Research Laboratory — RTP
           Larry Claxton, Judith A. Graham, Joellen Huisingh,
           Stephen Nesnow, James R. Smith, and Orin W. Stopinski

        Industrial Environmental Research Laboratory— RTP
           James H. Abbot, Dennis Drehmel, and John W. Wasser

        Office of Health and  Environmental Assessment — DC
            Roy Albert and Todd  Thorslund

        Office of Mobile Source Air Pollution Control — Ann Arbor
            Allan Ader, Charles Gray, Karl Hellman, and Joseph H. Somers

        Office of Monitoring and Technical Support— DC
            Lance Wallace
        Office of  Research Program Management— DC
            Mitchell Luxenberg
  Comments or questions regarding this report should be addressed to:

         Roger S. Cortesi
         Office of Health Research (MD-683)
         U. S. Environmental Protection Agency
         Washington, DC 20460

         Area Code (202) 426-2382
 This report has been reviewed and approved for publication. Mention of trade names or commercial
 products does not constitute endorsement or recommendation for use.

 Single copies of this report are available from:
         Center for Environmental Research Information
         U. S. Environmental Protection Agency
         Cincinnati, OH 45268
36

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