Report of the EPA
Program Planning Task Force
For Health Effects Research
Fiscal Year 1973
Submitted to the. Office of Research and Monitoring
January 19, 1972
FIRST DRAFT - COMPLETED
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TASK FORCE PARTICIPANTS
Membership Program /Affiliation
D. L. Coffin Cell Biology (Air) - RTP
R. D. Courter OPP Community Studies - Chamblee
M. F. Cranmer Pesticides Toxicology - Perrine
J. F. Finklea Division of Effects Research - RTP
D. E. Janes Electromagnetic Bioeffects - Twinbrook
J. H. Knelson Clinical Studies (Air) - RTP
Nicholas Lai las Program Officer - WSPD
L. J. McCabe Epidemiology (Water) - WSPD
Wellington Moore Toxicology (Air) - Cinn. - ETP
L. A. Plumlee Special Projects - ORM
J. A. Santolucito Pesticides Toxicology - Perrine
C. M. Shy - CHESS (AIR) - RTP
R. E. Stanley Radiation Bioeffects - WERL
J. F. Stara Toxicology - Cinn. - ETP
E. A. Tompkins Radiation Epidemiology - Twinbrook
M. T. Wagner Health Grants - RTP
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Table of Contents
Section Pages
I. Recommendations 1
II. Overview of Task Force Report 2
III. Optimal Blend in Health Research Activities 3
IV. EPA Needs for Health Intelligence 4
V. Output of Health Program at Three Levels of Funding 8
VI. Program Planning for Health Intelligence 10
Appendix A. Priority Ranking of Tasks Within EPA Al
Health Effects Research Program Elements
Appendix B. Proposed EPA Health Effects Program Structure Bl
Appendix C. Operational Problems Identified During EPA Cl
Health Effects Research Program Planning
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I. RECOMMENDATIONS
1. Critical Mass: The Health Planning Task Force recommends that
existing EPA health research personnel be geographically aggregated into
not more than four locations. This recommendation is based on the needs
of EPA for a considerably expanded output of health intelligence from
existing personnel resources. To achieve a desirable blend of 40%
intramural and 60% extramural expenditure of funds per operating
unit (i.e. Division) a certain critical mass must be reached at each
geographic location. The Health Planning Task Force agrees that 70
to 100 personnel (including professionals, technicians, clerks and
others) represents minimum mass size for operational units, that 150
to 250 personnel is a more desirable operational size, and that 250
to 300 personnel represents maximum manageable size. With the present
EPA health research personnel level of 388, adequate critical mass can
be achieved if personnel are geographically aggregated into operating
units at two to four locations.
2. Intramural and Extramural Research Support: Inadequacies of the
current EPA health research effort are discussed in a subsequent section
of this report. The Health Planning Task Force recognizes that increased
output of health intelligence will be required even at current personnel
levels. Therefore, a larger extramural program is required to meet
agency needs for health intelligence. The Health Planning Task Force
recommends that ^^^T^^on "be immediately added to the projected FY '73
budget of $19.2 million, and that these funds be committed to extramural
research even if present restricted staff levels of 388 personnel are
maintained.
3. Minimally Adequate Funding: The Health Planning Task Force strongly
recommends that the minimally adequate funding level (see Table I) of
$68. 7 million be allocated to health research in the immediate future.
This funding level provides EPA with a minimally adequate output of
health intelligence to support scheduled control actions, as discussed
in Section IV of this'report. The minimally adequate program will support
a much needed health research effort in Solid Wastes, Multimedia Toxic
Substances, Noise, and Water.
4. Priority Task Ranking: The Task Force recommends that existing and
added resources be optimally allocated by utilizing a priority task ranking
for each program element3 as given in Appendix A. This ranking should be
updated each year. *~'
5. Long-Term Studies: The Task Force recommends a special funding category
for well designed long-term studies to assure completion of long-term low-
level exposure studies.
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6. International Studies: The Task Force recommends block funding of
environmental health research institutes with available PL 480 and other
foreign currency programs. These institutes will require far less in-
house commitments of time and personnel per dollar spent than will project
by project support. At the same time, institute funding is likely to
develop environmental health resources overseas and achieve more visibility
for foreign currency commitments. Institute funding also will help foreign
countries to achieve critical mass sizes necessary for productive environ-
mental health research output.
7. Definition of Needs: The Task Force recommends better definition of
health needs by media, categorical, enforcement and regional offices and
by continued interaction between OEM headquarters management and operational
divisions.
8. Health Information System: An environmental health information system
is required to supplement intra-agency needs with current results of world-
wide scientific research.
9. Scientific Meetings: The Task Force recommends that up to date reports
from ongoing investigations be presented at semianual meetings held at EPA
laboratories. Such meetings would maximize cross^media contacts and help
offset, the disadvantages of geographic dispersion and program elements
limited by media and categorical considerations.
10. Operational Problems; The Task Force recommends that 0PM give prompt
consideration to the 12 operational problems cited in Appendix C.
II. OVERVIEW OF TASK FORCE REPORT
On November 18, 1971, the Chairman of the EPA Health Planning Task Force
was appointed. After consultation with laboratory directors, representatives
of media and categorical offices and the Health Effects Program Manager,
the Chairman selected individuals throughout EPA health programs to serve
on the Task Force. The document "Rationale for EPA Health Research: A
Guide for Program Management" served as the principal guideline to the
Task Force. Also considered were reports of previous Task Forces in this
area: EPA Health Task Force Report of June 4, 1971, and Task Force on
Health Research Program Planning - Phase I (August 26, 1971).
A meeting of the Task Force was held at NERC (RTP) for one week in mid
December and program elements were defined so as to assure maximum program
flexibility for the Office of Research and Monitoring. Research tasks to
achieve program objectives were outlined and Task Force members were asked
to detail the research needed and outputs with three levels of funding -
present, minimally adequate and optimal. Site visits were made to Twinbrook
and the Western Environmental Research Laboratories to obtain a clear picture
of the research involving radionuclides.
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A second meeting of the Task Force was held at the Perrine Primate
Laboratory, January 10 - 15, 1972, when members presented their detailed
research task plans. Priorities of tasks were set for each program
element, giving consideration to EPA's obligated control actions and
critical lack of knowledge in some areas.
This report was written to present significant recommendations to the
Office of Research and Monitoring. The need for a critical mass of
investigators working at each laboratory was recognized as well as the
need for a blend of in-house and extramural research. Resource needs
are critical for all program elements and the extent of this need can
be seen from the comparison of the present and the minimally adequate
program.
The need for interactive program planning was demonstrated at Task Force
Meetings and much benefit was derived from this process. Continued input
to this process is needed from the media and category and enforcement
offices as well as from all EPA laboratories and regions. The best use
of EPA's resources can only be made if the capabilities of all laboratories
are efficiently applied to critical problems.
The report contains the following three appendices:
1. Appendix A - Priority Ranking of Tasks Within EPA Health
Effects Research Program Elements
2. Appendix B - Proposed EPA Health Effects Program Structure
3. Appendix C - Operational Problems Identified by the
Health Planning Task Force
III. ACHIEVING AN OPTIMAL BLEND IN HEALTH.RESEARCH ACTIVITIES
The Task Force recognized that geographic dispersion, media and categorical-
oriented program elements and significant variation in funding patterns are
challenges which must be met if EPA is to obtain the health intelligence
necessary for least cost environmental control. Health research is underway
in fourteen groups found in twelve different locations. The Task Force
believes that health research groups must attain a certain critical mass
if they are to achieve the dual capability of maintaining balanced, strong
intramural and extramural research programs. The size of such a critical
mass is determined by a number of factors including breadth of program
objectives, need for capable scientists to design and manage extramural
research grants and contract programs and the load of staff functions
requested from each operating unit. In general, a group that includes
laboratory studies, human studies and necessary exposure monitoring must
have a strength of 70 to 100 to reach a critical mass. Non-research staff
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4.
functions may easily require twelve man years of effort from such a group
annually. A more optimum operating group would contain 150 to 250 employees.
Groups over 300 are more difficult to manage if close scrutiny of research
progress is required without one or more intervening organizational echelons.
With the present EPA personnel ceiling of 388, critical masses can be achieved .
only if personnel are geographically aggregated into operating units at two
to four locations. This is not to say that activities may not be desirable,
for other reasons, in more than four locations, but rather to emphasize that
continued dispersion is an inefficient use of scarce resources.
Functionalization of health research is seriously hampered by media and
categorical-oriented program elements. This can only be overcome by systematic
cross media program planning program review and semiannual up to date reports
of ongoing investigations at various EPA laboratories.
The projected FY '73 resource allocations for each of the ten proposed
health effects research program elements, shown in Table 1, reveal important
contrasts. Viable programs exist for air and pesticides research. The
radiation program is marginal in scope and the water program is little more
than a skeleton. The Community Studies Program of the Office of Pesticides
is almost entirely a contract operation as is the Agency's participation
in the National Center for Toxicological Research. When dollars per
permanent position were computed, as shown in Table 2, additional con-
clusions were possible. At the current funding level, all of the program
elements except OPP pesticides and the National Center for Toxicological
Research have limited extramural funding capability. If one accepts that
each intramural permanent position requires $22,000 and that a reasonable
research balance would be 40% intramural effort and 60% extramural, then
a funding level of $55,000 per position in each program element would
require substantial increases for air, ORM pesticides, radiation and water.
All told, an infusion of $8.6 million for extramural activities is required
to optimize use of the presently assigned FY '73 personnel. This would
increase the FY'73 budget to $27.8 million. The minimally adequate and
optimal budgets show much better balance, although the water and radiation
programs could probably place greater emphasis on extramural activities.
IV. EPA NEEDS FOR HEALTH INTELLIGENCE
-i
The Council of Environmental Quality and the Environmental Protection Agency ;
must establish appropriate indices of environmental quality to assess the
magnitude of the problems we face and judge the progress of our protection
and restoration efforts. No meaningful environmental quality index can ^
be constructed without primary consideration of human healjh. Health
"inputs should include changes in human pollutant burden patterns, alterations
in the prevalence of pre-clinical sentinels of acute and chronic disease,
frequency of episodic disease outbreaks related to acute exposure, and
changes in selected morbidity and mortality trends attributable to pollutant
exposures.
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Table 1
FY 73 Resource Needs for Health Effects Research
($ Millions/Man Years)
Program Element
Biomedical (Air)
CHESS (Air)
Pesticides (ORM)
Pesticides (OPP)
Radiation
Solid Hastes
Water
Toxic Substances
Noi se
National Center
for Toxicoloqical
Research
TOTAL
Budget Level
Current
3.1/81
3.1/107
2.2/69
4.2/32
1.8/61
None
0.8/35
None
None
A. 0/3
19.2/388
Minimally Adequate
7.9/162
19.0/329
5.0/99
4.5/36
4.4/112
1.2/20
4.9/124
15.0/180
1.0/24
5.8/3
68.7/1089
Ootimal
15.7/234
27.6/442
8.2/169
4.9/38
6.5/140
1.8/30
9.5/156
22.3/270
1.5/37
8.0/3
106.0/1519
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Tattle 2
FY 73 Resource Needs for Health Effects Research
Program Element
t
Biomedical (air)
CHESS (air)
Pesticides (ORM)
Pesticides (OPP)
Radiation
Solid Wastes
Water
Toxic Substances
Noise
National Center for
lexicological
Research
Overall
Overall Excluding
NCTR
Budgeted Dollars
Current
Budget
38.2
28.9
31.9
131.2
29.5
None
22.5
None
None
(Not
Applicable)
49.5
39.6
per Permanent Position
Minimally
Adequate Budget
48.7
57.7
50.5
125.0
39.2
60.0
39.5
83.3
41.6
(Not
Applicable)
63.1
57.9
in Thousands
Optimal
1 Budget
67.0
62.4
48.5
128.9
46.4
60.0
60.8
82.5
40.5
(Not
Applicable)
69.8
64.6
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In the absence of an overall regulatory plan within EPA, the health
research program can be rationally based on (1) control actions mandated
by Iaw9 (2) identified toxic hazards of ubiquitous pollutants not as yet
subject to controls (3) reaction to newly identified hazards, and (4) the
need to supplement the scientific basis for existing standards. The present
level of funding for health research is inadequate to obtain needed health
support for the above objectives, particularly for short-term nitrogen
oxuie standards S; short-term carbon monoxide standards,, standards"for
hemical oxidants and fine particulates in airs drinking water
andrecreational water standards and standards for radipnucljdes emitted
by nuclear power plants. Furthermore., health intelligence programs to
support control programs in solid waste, multimedia toxic substances and
noise are totally absent. Control strategies for these ubiquitous
pollutants are becoming extremely costly9 since the sources of these
pollutants often provide goods and services critical to society's progress.
Lack of adequate scientific data for standards renders uncertain the true
social cost of exposure or the total benefit of control. The cost of
meeting emission standards tends to increase exponentially with the level
of control. Thus, if emission standards are more stringent than required"
to protect health, a large waste of society's resources occurs. Further-
more, because society places such a high value on health, the safety factor
imposed, when health intelligence is inadequate, must be proportionately
greater.
The Agency requires a considerably expanded health program to provide
reasonably credible and scientifically sound health data to support or
revise control strategies. Recent challenges to EPA regulatory plans,
both from within government and from affected industries, have been made
on the basis of inadequate health intelligence to support the selected
control action. An expanded, vigorous health research effort will give
EPA scientifically credible standards which can be defended in public
hearings and in court actions. A mosaic of health information will
enable EPA to reduce true social costs of pollutant exposure by providing
firm quantitative data on the contribution of environmental pollutants to
diseases of major public health importance. The high costs of environ-
mental controls may be minimized by establishing standards that are not
overly conservative for attaining the intended health benefit. On the
other hand, if the adverse health effects demand the expenditure, there
is more likelihood that the standard will be better accepted by the
public when the standards are well grounded in health intelligence.
Although expensive and requiring multi-year commitments, long-term low-
level health effects research is necessary for the acheivement of least
cost environmental control. Such epidemiological and toxicologic studies
must quantitate the portion of chronic disease attributable to environ-
mental pollutants now scheduled or considered for control. Even a limited
aggravation or acceleration in diseases of major public health significance
represents a heavy burden for society and our inadeuqate, overtaxed health
care system.
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In the following section, the output of a health research effort at
three levels of funding is evaluated in terms of the above cited needs.
The output from the various funding levels was critically judged by one
of two criteria: (1) does the health research output provide health ^
intelligence for regulatory action, or (2) does the research output
quantify health benefits of environmental control. .
V. OUTPUT OF HEALTH PROGRAM AT THREE LEVELS OF FUNDING
1. At Current Level of Funding: Because of the supplemental appropriation
last year a much desired growth was possible in CHESS and Bio-medical
Studies. A modest increase in appropriations in FY 72 allowed a start
in investigation of non-ionizing radiation's effects. Increases in
water pollution and water supply appropriations were not applied to
health effects research.
However, health effects research at current base levels of funding will
seriously curtail acquisition of needed health information. The CHESS
program will have to drop back from 37 communities to 17 or reduce the
number of health indicators under study in each community. Air monitor-
ing in CHESS will also be inadequate to support short-term air quality
standards and emergency episode actions.
Six positions at the inhalation toxicology laboratory in Cincinnati must
be eliminated to achieve a balanced budget at the projected FY 73 funding
level; this reduction would not allow start-up of the toxicological assess-
ment of stationary source pollution. Throughout the air-health effects
program, efforts to develop promising new health indicators crucial to
the definition of true social cost of air pollution will have to be
delayed or abandoned. Mobile physiologic laboratories could not be
aquired for the CLEVER program in Bio-medical Research.
The Radiation Program would not be able to award contracts for the
acquisition of data on the human health effects of ionizing radiation.
This data is essential for improving the information base required by
nuclear facility standards. Bioeffects research on tritium and krypton-85
would have to be stretched out and most likely would not provide the
needed output for standards. The uncertainty of long-term funding
makes rational planning of studies like that investigating cat leukemia
induced by radiostrontium difficult if not impossible.
Continuation of the inadequate funding level in water health effects
research will not provide health intelligence for the setting of
meaningful drinking water standards. Research on the effects of
chemical contaminants will be so stretched out that more problems will
arise than can be solved. Water quality standards will have to be enforced
without a scientific base to justify the health criteria on which they
are founded.
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There will be no programs in Noise, Solid Waste, or the most pressing
problem of multimedia toxic chemicals. The present inadequate intramural -
extramural blend of resources will continue and thus the existing manpower
of the Office of Research and Monitoring will not be optimally utilized
to provide needed health intelligence for environmental control actions.
2. At the Minimally Adequate Funding Level: The research effort at
this funding level will provide a minimally adequate but credible base
of health intelligence to support control actions presently mandated by
law. These actions include stationary source performance standards and
trace metals in air; fuels and fuel additives; recreational water quality
criteria; revised radiation protection guidance; standards for nuclear
fuel reprocessing plants; pesticides registration actions and guidelines
for pesticide use; municipal, residential and commerical solid waste
disposal guidelines. The research program will fill existing gaps in
health effects criteria for noise abatement.
The presently inadequate scientific criteria for existing air and drinking
water standards will be amply supplemented and made defensible through
health intelligence provided at this level. Although few aspects of new
technology hazards can be evaluated, minimally adequate funding will allow
ORM to build a substantial health information system rapidly responsive
to existing agency needs and world-wide scientific progress.
Significant steps will be completed within two to three years after fund-
ing toward development of the health portion of the environmental quality
index, especially in quantifying human pollutant burdens, pollutant induced
acute disease episodes, population profiles of pesticide residues, range
estimates for pollutant aggravations of acute and chronic respiratory
disorders, and precise estimates of excess mortality attributable to
environmental pollution in large urban centers.
As hazards of newly identified pollutants are manifested, the minimally
adequate resource level will allow the agency to assess the health impact
of substances whose toxic risk can be recognized through the Health
Information System. However, toxic assessment of substances for which
no information exists will require health resources available under the
optimal program.
Adequate estimates of the health costs of diseases clearly affected by
pollutant exposures can be derived with minimally adequate support.
However, the full impact of pollution on diseases of major public health
significance depends on optimal funding levels. The Agency can give
adequate support, under this level of effort, to a few selected, well
designed long-term low-level health effects studies of pollutant exposure.
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10
Limited research to identify toxic hazards of ubiquitous pollutants not
presently scheduled for control action can be supported at the minimally
adequate level. The Agency requires an expanded program at optimal fund-
ing to develop a predictive capability for new environmental hazards.
3. Output at Optimal Funding Level: The Health Planning Task Force has
devoted considerable time to present a complete health research program
(see Appendix B), achieved at an optimal funding level, to meet the
recognized health information needs of EPA. These endpoints are listed
in Table 3, in which the output at the three funding levels is compared
for each need category. Optimal funding will have the largest impact on
development of an environmental quality index, attainment of a predictive
posture for new environmental hazards, and firm estimation of the total
health costs of environmental pollution. Research at optimal funding
will enable identification of the more subtle pollutant induced health
effects, including pre-clinical sentinels of disease and pollutant
contributions to major public health disorders. This output will be
used to assess the true social cost of pollution as well as the total
health benefits of control, thus promoting public acceptance of the
necessary costs of regulatory actions.
VI. INTERACTIVE PROGRAM PLANNING
A successful health effects research program will both predict the unmet
needs of the Agency and be rapidly responsive to the regulatory and
enforcement problems encountered by the Agency. Program planning must,
therefore, be an interactive process involving inputs from the media,
categorical, regional and enforcement offices. Additional problems will
be recognized .by the Office of Research and Monitoring staff, laboratory
directors and investigators in the field. Environmental research needs
can be translated into a priority list of research tasks by an interactive
process involving each of these elements.
Interactive program planning requires systematic transmittal of comprehensive
resumes of agency needs and an assessment of the adequacy and the progress
of the research program designed to meet these needs. The Task Force
believes that such resumes should be presented by the ORM headquarters and
regional staff at the proposed semiannual effects research progress report
meetings. Another step in this Interactive Program Planning cycle is a
Task Force to determine tentative priority rankings of tasks in each of
the health effects research program elements. The Task Force provides a
sound basis for further discussion on the allocation of program resources.
Sufficient time should be allowed to permit each health effects program
representative to discuss and gather all pertinent information on tasks to
be performed in the subsequent fiscal year. The program planning effort
should be held on an annual basis and the one for FY 74 should be scheduled
now. Every effort should be made to minimize conflicting demands during
program planning activity. Task Force members believe that they have
attained a better understanding of the priorities of the Agency and the scope
of its required health effects research program. We hope the Agency benefits
from our efforts.
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Table 3. Expected Output of Health Research Program at 3 Funding Levels
EPA Health Needs
Output Funding Level
Current
Minimally Adequate
Optimum
1. Environmental Quality index (health portion)
2. Health information for control actions
mandated by law
3. Identify toxic hazards of ubiquitous
pollutants not as yet scheduled for
control
4. Reaction to newly identified pollutant
hazards
5. Supplement scientific base for existing
standards
6. Assess health cost of pollution exposure
7. Health information system
8. Long-term, low-level studies
o
o
o - Inadequate
+ - Minimal
++ - Significant
+++ - Substantial
++++ _ Optimum
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Appendix A
Priority Ranking of Tasks
Within EPA Health Effects
Research Program Elements
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Table of Contents
Program Element Pages
I. Biomedical Research (Air) A 1
Summary Statement
Priority Ranking
II. CHESS (Air) A 6
Summary Statement
Priority Ranking
III. Pesticides Health Effects Research (OR&M in FY '72) A 12
Summary Statement
Priority Ranking
IV. Pesticides Effects on Human Health (OR&M in FY '72) A 17
Summary Statement
Priority Ranking
V. Radiation Health Effects A 20
Summary Statement
Priority Ranking
VI. Health Effects of Solid Wastes A 24
Summary Statement
Priority Ranking
VII. Health Effects Research - Water A 26
Summary Statement
Priority Ranking
VIII. Health Effects of Multimedia Toxic Substances A 30
Summary Statement
Priority Ranking
IX. Noise Health Effects Research A 32
Summary Statement
Priority Ranking
X. National Center for Toxicologic Research A 35
Summary Statement
Priority Ranking
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A 1
A. PROGRAM ELEMENT NUMBER: 110203
B. TITLE: Biomedical Research
, PREPARED BY: j. F. Finklea . DATE: January 4, 1972
c- PROGRAM JUSTIFICATION: Assessment of the real or potential effects of
environmental pollutants on human health and welfare necessitates direct
studies of both human and animal systems to validate results of epidemiologic
studies; to develop new health indicators or techniques applicable to
epidemiologic studies; or to give indications of the potential toxicity
of new materials that might be introduced into the environment. Such studies
are essential to the establishment of defensible environmental standards not
excessively punitive to industry yet adequate for the protection of human
health and welfare.
D- OBJECTIVES: To develop health effects information that will facilitate the
development or revision of criteria and standards for environmental pollutants;
to test the adequacy of current primary standards in protecting human health;
to identify hazardous materials which may need control actions; and to define
the biologic effects of pollutants singly, in combination, or as they are
affected by other environmental factors and at various levels of exposure.
E. SCOPE: The Biomedical Research Program consists of laboratory and clinical
studies of the effects of pollutants on human health. Emphasis currently is
placed on studies of carbon monoxide, nitrogen oxides, photochemical oxidants
and the toxicity of automotive emissions. Some effort is expended to assess
the carcinogenic.ity of airborne polycyclic organic matter and the toxicity
of selected trace substances. Studies undertaken include development of
techniques or methods for assessing the effects of particular pollutants,
assessment of the direct effects at various levels of exposure, assessment
of the effects of exposure on susceptibility or potentiation of other
diseases, and the development of appropriate instrumentation or techniques
that will permit measurements of the effects in CHESS.
Research tasks are grouped into four projects. CLEANS (Clinical Laboratory
Evaluation and Assessments of Noxious Substances) utilizes controTled dosing
of human volunteers and includes ten tasks. CLEVER (CUnical Environmental
Epidemiology Research) using a sophisticated mobile laboratory includes six
tasks. ACTIONS (Assessment of Cellular Joxicity and .Interactions Of noxious
Substances) utilizes cells from animals and tissue culture and involves eight
tasks. Inhalation Toxicology utilizes controlled exposure of experimental
laboratory animals and involves six tasks.
F. RESULTS: The knowledge gained through Biomedical research will be made
available in a series of intramural and published reports relating
toxicological information to environmental quality. These reports will
provide health effects information for application toward epidemiological
studies as well as direct intelligence for the appraisal and setting of
environmental standards. The studies on carbon monoxide, oxidants and
nitrogen oxides will contribute to the revision of the respective criteria
and NAAQS. Other studies will assist in formulating decisions on the control
of fuel additives or other environmental pollutants.
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A 2
G. APPROACH: The Biomedical research program in an integrated series of
toxicological studies utilizing both animal and human inhalation exposure
facilities. Specific pollutant atmospheres are generated, monitored, and
provided to the experimental animals or subjects for specified periods of
time. Exposures may be of an acute short-term nature or of the chronic
long-term type. Effort is also directed toward defining the biologic fate
of environmental contaminants .as well as the development of improved
methodology (animal model systems and measurement techniques) which may be
applied for the detection of pre-clinical effects and subsequently utilized
in epidemiological studies.
Animal toxicology is conducted to identify, quantitatively and
qualitatively,the primary effects and target system; examine pollutants of
such character and/or concentration unsuitable for human studies due to
ethical as well as medical-legal limitations; provide in vitro manipulative
approaches to develop techniques for subsequent application to clinical and
epidemiological investigations; and provide chronic exposure conditions for
identifying potential carcinogenic, teratogenic and mutagenic effects.
Laboratory clinical investigations are used to develop improved methodology
for epidemiological studies; verify extrapolation of animal effects to man;
and test, in a cause and effect manner under controlled conditions,
correlative epidemiological results.
H. SUPPORTING CONTRACTS: (a) Experimental planning utilizes data available
through NADIS and Office of Fuels and Additives Registration; (b) Information
from BSSPC is needed for facility design for toxicity assessment of mobile
emissions; (c) Contracts: CRC-APRAC provides cooperative funds for effects
studies related to carbon monoxide. Contracts with non-government organizations
provide support to in-house programs in the areas of pollutant interaction and
carcinogenesis. The current contract effort utilizes $900,000 per year;
(d) Grants: support for research grants for the same type of work done under
this element total $785,000.
I. SPECIAL FACILITIES: The following special facilities are required:
TalAutomotive engines, dynamoneters, dilution systems, irradiation chambers,
animal exposure chambers; (b) Human environmental chambers. Beyond the
state-of-the-art, the following is required: (a) Equipment for telemetering
physiologic parameters; (b) Complex behavioral testing equipment for EEG,
time, object and pattern discrimination; and task performance with associated
program control computer.
J. INTERMEDIA RELATIONSHIPS: Anticipate relationships with other EPA Offices on
effects of pol1uti on research.
K. COORDINATION: Liaison with AEC, NIEHS, FDA, NCI.
L. UNRESOLVED POLICY ISSUES:
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PRIORITY LISTING OF BIOMEDICAL TASKS
Program
Task Structure
Priority Reference Suggested
Ranking (Anoendix fi) Title Location
1 Cl.
2 D6
3 C2
4 A3
5 A4
6 A7
7 Al
8 D5
9 Bl
10 C3
Effects of air pollutants on pulmonary
defense mechanisms
Biokinetic and toxicologic studies of
trace elements
Hazardous substances and cellular
physiology
Procurement of human environmental
exposure chambers
Instrumentation, of human environmental
exnosure chambers
Develooment of more sensitive neuro-
physiologic indicators
Effects of CO in persons with
coronary artery disease
Assessment of cardiopulmonary and
renal function after fuel and trace
metal emissions exposure
Acquisition of CLEVER mobile laboratory
Physiologic and pathologic studies of
RTP
Cinn.
RTP
RTP
RTP
RTP
RTP
Cinn.
RTP
RTP
FY 73
Present
145/4.5
305/15.3
130/4.5
100/2.0
110/0.4
105/1.5
150/2,5
75/3.6
166/3.0
98/4.0
Resource Needs ($000/MY)
Add-on MA Ontimum
250/7.0
357/16.0
225/6.6
100/2.0
200/0.6
190/2.5
238/3.5
104/5.0
237/4.0
200/6.0
550/9.0
390/22.5
400/7.0
100/2.0
200/0.6
190/2.5
238/3.5
172/7.0
237/5.0
348/7.0
1800/12.0
495/26.0
1750/12.0
115/5.0
290/3.0
265/7.0
390/8.0
292/7.0
320/15.0
920/8.0
11
Dl
hydorcarbon air pollutants
Comparative hazards of mobile and
stationary source emissions
Cinn.
300/15.0 405/20.0 500/25.0 660/31.0
t-O
-------
Page 2
PRIORITY LISTING OF BIGMEDICAL TASKS
Task
Priority
Ranking
12
14
15
16
17
18
19
20
21
22
23
Program
Structure
Reference
(Appendix B)
C4
A5
C6
C5
D4
B5
A2
A8
03
B2
B3
Title
Suggested
Location
Effect of NOx on erythrocyte function RTP
Auto exhaust effects on female beagles Cinn.
Investigation of growth of lung RTP
function in children
Biological effects of trace elements,
tobacco smoke and NOx RTP
Interactions of air pollutants in RTP
etiology of nulmonary disease
Behavioral and neurological effects of Cinn.
trace metal and fuel emissions
Neurophysiologic effects of oollutant RTP
exposures
Effects of CO in myocardial infarction RTP
Effects of CO on humans performing RTP
driving tasks
Biochemical effects of fuel and trace Cinn.
metal emissions
Pollutant induced changes in chronic
lung disease cases
KTP
FY 73 Resource Needs
Present Add-on MA Optimum
75/4.0 134/6.0 337/8.0 840/7.0
52/0.1 S7/.2 HO/.5 HO/.5
120/1.5 175/2.5 175/2.5 250/7.0
198/0.1 198/0.1 485/0.9 1610/6.0
220/0.2 220/0.2 475/1.2 1725/6.0
50/2.5
80/3.0 145/5.0
60/1.0 170/2.0 180/5.0
311/8.0
250/7.0
47/0.2 47/0.2 47/0.2 55/0.5
90/1.0 122/2.5 122/2.5 215/2.0
97/4.8 237/7.0 274/8.0
90/2.0 170/3.0 180/5.0 250/7.0
Effects of N02 and CO on cardio- RTP
vascular function
90/2.0 170/3.0 180/5.0
250/7.0
-------
Page 3
PRIORITY LISTING OF BIOMEDICAL TASKS
Program
Task Structure
Priority Reference
Ranking (Appendix B)
24
25
26
27
28
29
30
A9
A6
B4
B6
C8
C7
A10
Title
Metabolic effects of long-term
voluntary exposure to metals
Isolated, perfused organ studies
Effects of pollutants on cancer
and mutation sentinels
Short-term pollutant exposures and
erythrocyte integrity
Suggested
Location
RTP
RTP
RTP
RTP
Pulmonary effect of chronic exposure Las Vegas
to oxidants and radiation
Procurement of air pollutants
for laboratory studies
RTP
Development of a health information ORM
sy s tern
TOTALS
Present
FY 73 Resource Needs ($000)/MY)
Add-on MA Optimum
50/0.2 135/0.2
45/0.1 45/0.1
150/3.0
73/0.1
175/1.0
118/1.5 153/2.0 173/3.0 250/6.0
70/1.0 170/2.0 180/5.0 250/7.0
60/1.0 170/2.0 180/5.0 250/7.0
80/0.0 130/6.5 130/6.5
85/0.5
1000/5.0 1100/6.0
3119/81 4890/111 7884/162 15677/234
-------
A 6
A. PROGRAM ELEMENT NUMBER; 110201
B. TITLE: Community Health and Environmental Surveillance Systems (CHESS)
PREPARED BY: J. F. Finklea DATE; January 5, 1972
C. PROGRAM JUSTIFICATION: The initial purpose of the CHESS program is to
define, in ambient situations, the effects of environmental pollution on
human health and welfare; and then subsequently to determine the benefits
derived from improving environmental quality. The information obtained
from the CHESS program is directly applicable to the standard setting
process and to the assessment of the adequacy of standards once they are
established.
D* OBJECTIVES: To develop and utilize in populations sensitive indicators of
human health, to determine dose-response relationships with environmental
pollutants singly or in combination. It is expected that the information
obtained from these studies will enable the development of defensible
environmental standards, the measurement of benefits derived from improving
environmental quality, and determination of the adequacy of standards
established.
E. SCOPE: CHESS currently covers only four (particulate, sulfur dioxide,
nitrogen oxides, and photochemical oxidants) of the pollutants covered by
the National Ambient Air Quality Standards. For carbon monoxide there is no
indication yet that it is possible to assess its effects in human populations
through epidemiologic studies; there are no health effects as such that can
be related to "hydrocarbons. Trace metals are being studied insofar as they
can be traced through all environmental pathways and their burdens determined
for one group of communities. Additional pollutants, such as PCB and
pesticides, are also included in the CHESS program.
CHESS includes four projects. Data Collection with 13 tasks, Information
Synthesis with 12 tasks, Bioenvironmental Measurements with 6 tasks, Develop-
ment of More Sensitive Health Indications with 12 tasks.
F- RESULTS: The knowledge gained through CHESS will be documented in a series
of intramural and published technical reports relating health .impact
indicators and important health covariates to environmental quality.
At least 8 reports per year are planned, one for each of the health indicators
currently utilized. The technical reports will also summarize the progress
in the research carried out as part of the health status evaluations and
body burden studies. The reports will provide health effects intelligence
for appraisal and setting of environmental standards.
G. APPROACH: CHESS is an integrated series of epidemiologic studies designed,
coordinated and largely funded by the Federal government. Under contract,
local health departments, universities or survey research organizations
operate special neighborhood environmental monitoring stations and collect
data from citizen volunteers living in communities with an exposure gradient
for specified pollutants. Bioenvironmental measurements are performed
in the field and in a Federal laboratory. A federal research group
synthesizes information from the data to produce intramural and published
technical reports. This Federal group is also responsible for research and
-------
A 7
development to find more sensitive impact indicators suitable for field
surveys, to improve bioenvironmental exposure monitoring and to refine
statistical procedures. As feasibility studies proceed, new health impact
indicators and pollutants will be integrated into the studies and indicators
no longer found useful will be eliminated.
H. SUPPORTING CONTRACTS; Under .contract, local health departments, universities
or survey research organizations operate special neighborhood environmental
monitoring stations and collect data from citizen volunteers living in com-
munities with an exposure gradient for specified pollutants.
The CRC-APRAC provides some support for carrying out studies that are the
same as the CHESS. The Health Research Council of New York provides approxi-
mately $20,000 a year for the New York area CHESS.
Interage.ncy Agreements: The Bureau of Occupational Safety and Health provides
trace metal analyses for one of the studies.
I. SPECIAL FACILITIES AND EQUIPMENT: Beyond the state-of-the-art, there are
requirements for developing procedures and instruments as follows: (a)
compact instrument package to measure indoor air quality; (b) automated
procedure for analysis of chromosomal aberration and exfoliative cytology;
(c) direct telemetry capability from continuous ambient air monitors to
the data bank; (d) better methods for trace elements analysis, i.e., alpha
scatter, ASV; (e) personal air quality monitors; (f) better methods for
particulate measurement, both as to the size and chemical composition;
(g) capability to measure metallo-enzyme kinetics.
J. INTERMEDIA RELATIONSHIPS: Human pollutant burden studies of metals and
synthetic organic materials involve the Water Quality, Solid Wastes, and
Pesticides elements of EPA. Data from the food and milk sampling program
of the Radiation element could be integrated into CHESS. Monitoring
exposure to ionizing and non-ionizing radiation and the effects of the
latter might be approached through CHESS.
K. COORDINATION: Research personnel from each media office have been briefed
in CHESS.Very close working liaison is maintained with the Biomedical
Research element. The studies utilize the data available through NADIS.
Meteorologists required for analysis of the data are provided-by the
Meteorological Support Element. The Biomedical Research element consists
of work closely related to CHESS; effects and pollutants identified and
studied under Biomedical Research are utilized to guide epidemiological
studies and vice-versa.
L. UNRESOLVED POLICY ISSUES: None
-------
PRIORITY LISTING OF CHESS TASKS
Program
Task
Priority
Ranking
1
2
3
4
5
6
7
8
9
10
11
12
Structure
Reference Suggested
(Appendix B) Titlfi Location
A3
A5
Al
C2
5C
C4
Bll
Bl
B2
P3
B4
B5
CHESS Chattanooga studies data
collection
CHESS Los Angeles Basin studies data
collection
CHESS New York Metropolitan studies
data collection
CHESS environmental exposure
surveillance
CHESS analysis of routine aerometric
samnles
CHESS surveillance of metallic and
organic exposures
CHESS quantitation of population at
risk and health costs
CHESS chronic respiratory disease
reports
CHESS reports on retrospective studies
of lower resniratory disorder
CHESS reports on prospective studies
of acute resoiratory disorders
CHESS reports on pulmonary function
CHESS reports on effects of acute
RTP
RTP
RTP
RTP
RTP
RTP
RTP
RTP
RTP
RTP
RTP
RTP
FY 73
Present
245/1.5
420/2.0
420/2.0
475/23.5
100/5.0
120/6.0
80/4.0
120/6.0
120/6.0
120/6.0
120/6.0
120/6.0
Resource Needs ($000/MY)
Add-on MA Optimum
250/1.5
425/2.0
425/2.0
2075/29.5
100/5.0
120/6.0
100/5.0
140/7.0
140/7.0
140/7.0
140/7.0
140/7.0
350/1.5
425/2.0
425/2.0
4740/60.0
100/5.0
240/12.0
500/16.0
240/12.0
240/12.0
240/12.0
240/12.0
240/12.0
350/1.5
425/2.0
425/2.0
6700/76.0
100/5.0
500/25.0
600/16.0
240/12.0
240/12.0
240/12.0
340/12.0
240/12.0
air pollution episodes
5=
CO
-------
Page 2
PRIORITY LISTING OF CHESS TASKS
Program
Task
Priority
Ranking
13
14
15
16
17
18
19
20
21
22
23
Structure
Reference
(Appendix
P.fi
B7
B8
B9
BIO
D3
D4
D5
A2
A4
A6
R) Title
CHESS reports on aggravati
symptoms in the elderly
CHESS reports on aggravati
asthma
CHESS reports on human pol
burdens
Location
on of RTP
on of RTP
lutant RTP
CHESS reports on daily mortality RTP
CHESS efforts to imnrove statistical RTD
techniques
Erythrocyte indicators for
studies
Erythrocyte metabolism and
pollutants
Mettalloenz.yme response to
pollutants
CHESS Southeastern studies
collection
CHESS Utah studies - data
St. Louis Regional Air Pol
field RTP
air RTP
ai r RTP
- data RTP
collection RTP
lution RTP
FY 73 Resource Needs ($000/MY)
Present Add-on MA Optimum
120/6.0 140/7
120/6.0 140/7
100/5.0 120/6
100/5.0 100/5
120/6.0 140/7
20/1.0 40/1
20/1.0 20/1
20/1.0 40/1
370/2
250/1
370/2
.0
.0
.0
.0
.0
.0
.0
.0
.0
.5
.0
240/12.0
240/1
320/1
160/8
450/1
220/3
220/3
500/4
370/2
250/1
370/2
2.0
5.0
.0
5.0
.0
.0
.5
.0
.5
.0
240/12
240/12
320/15
160/8.
450/15
220/3.
220/3.
800/21
370/2.
250/1.
800/4.
.0
.0
.0
0
.0
0
0
.0
0
5
0
24
A7
studies - data collection
CHESS Chicago stationary source
studies - data collection
RTP
250/1.5 475/2.0 875/4.0
-------
Page 3
PRIORITY LISTING OF CHESS TASKS
Program
Task
Priority
Ranking
25
26
27
28
29
30
31
32
33
34
35
Structure
Reference
Suggested FY 73 Resource
(Appendix P) Title Location Present
C3
D7
D8
Dl
D2
D6
Cl
D9
D10
C6
A8
CHESS surveillance of special
pollutant exoosures
Exfoliative cytology and air
pollutant exnosure
Immunologic effects of air
pollutants
Damage to erythrocytes caused
by air pollutants
Shifts in hemoglobin dissociation
curves caused by air pollutants
Cytological location of metallic
pollutants
Adaptation of personal monitors
for field use
Leucocyte metabolism and air
pollutant exposure
Plasma enzymes, hormones and
seminal metabolic profiles
as indicators of pollutant
exposure
Indoor air pollution studies Las
CHESS Southwest studies -data
RTP
RTP
RTP
RTP
RTP
RTP
PIP 40/2.0
RTP
RTP
Vegas
RTP
Add-on
20/1.0
50/1.0
50/1.0
20/1.0
30/1.0
20/1.0
40/2.0
15/0.5
15/0.5
-
.
Needs ($000/MY)
MA
80/4.0
480/8.0
450/12.5
220/3.0
220/3.0
220/6.0
200/5.0
220/6.0
450/8.0
65/4.0
500/2.5
Optimum
160/8.0
730/21.0
i
750/21.5
220/3.0
220/3.0
400/11.0
300/10.0
300/7.0
600/8.0
65/4.0
500/2.5
collection
-------
Paqe 4
PRIORITY LISTING OF CHESS TASKS
Propram
Task
Priority
Ranking
36
37
33
39
40
41
Structure
Reference
(Appendix R)
A9
A10
All
A12
Dll
D12
42
A13
Title
CHESS Mountain studies -
data collection
CHESS Northwest studies -
data collection
CHFSS Coastal studies -
data collection
CHESS Lakes studies -
data collection
Cytoqenetic alnormalities
caused by air pollutants
CHESS Research grants oroqram
to elucidate air pollution
effects on significant acute
and chronic diseases
CHESS selected pollutant
exposure studies - data
collection
Sugnested
Location
RTP
RTP
RTP
RTP
RTP
RTP
FY
Present
-
-
-
-
-
RTP
FY 73 Resource Needs ($000/MY)
Add-on
MA
500/2.5
475/2.0
500/2.5
500/2.5
720/6.0
Optimum
500/2.5
475/2.5
500/2.5
500/2.5
1510/15.0
1520/13.0 3690/26.0
700/4.0
TOTALS
3130/107 6435/127 19025/329 27565/442
-------
A 12
A. PROGRAM ELEMENT NUMBER: 510101
B. TITLE: Pesticides Health Effects
PREPARED BY: Morris Cranmer DATE: January 14, 1972
C. PROGRAM JUSTIFICATION: Section 4 of the Federal Insecticide, Fungicide
and Rodenticide Act (FIFRA) requires that every economic poison (pesticide)
shipped or marketed in interstate commerce shall be registered with EPA to
insure that such products shall be safe and effective. Also, Section 403(d)
of the Federal Food, Drug and Cosmetic Act provides that any person who has
registered or applied for registration of an economic poison under FIFRA
may submit a petition to establish a tolerance for this product on a raw
agricultural commodity. This responsibility covers both the occupationally
exposed and general population. Effects data from laboratory animals must be
generated and crosswalked with human situations if EPA is to be responsive
to these legislative mandates.
D. OBJECTIVES: To assure that safety in use patterns and human exposures to
pesticides are below that which will detrimentally affect the health and well
being of humans. The estimate of tolerable exposures will be developed from
relevant animal toxicology studies to assure that sensitive indicators of
subtle but hazardous effects are available for human safety evaluation.
E. SCOPE: Pesticidal chemicals are one group of toxic agents which contribute
to environmental pollution and pose an unanswered challenge to man's health
either through the stress of one chemical agent or the potentiation by other
toxicants. The health effects from repeated acute exposures or long-term, low-
level and massive exposures are not known. The scope of this program is to
provide necessary toxicology information on health effects to support the
administrative decision with respect to cancelation or restriction procedures.
This effort at current funding supports 29 tasks describing acute and subacute
toxicity in rorlenti, teratology in rodents and primates, development
and reproduction, pathology, biochemistry and metabolism, neurophysiology and
behavior, clinical studies, animal care and maintanence and review and
evaluation.
F. RESULTS: With adequate funding a predictive toxicology program would
provide the necessary toxicological information to support administrative
review of registrations, to provide sentinels of disease for human epidemiology
studies and to substantiate and provide mechanistic understandings of the effects
of pesticides on the general population and occupationally exposed. At the
current level of funding, a minimum predictive program is operable with the
major effort allocated to the resolution of problems already identified as of
concern to the agency.
-------
A 1.3
G. APPROACH: Through the use of relevant animal models including primates
controlled experiments will be implemented to describe the developmental,
birth defect, metabolic and biochemical, neurophysiological and pathological
effects of pesticides. These studies will be designed to provide dose-
response and population at risk data as well as to elucidate mechanisms of
effects and to develop better sentinels of effects which can be used in
interpreting human population exposure to pesticides. These studies will be
of both short term and lifetime durations.
H. SUPPORTING CONTRACTS: Support for the maintenance of the primate breeding
colony will be contracted if implemented because of position ceilings.
I. SPECIAL FACILITIES: Additional cage washing capability will be constructed
to supplement the currently inadequate equipment and a close circuit T.V.
monitoring system will be installed in the primate breeding facility. More
adequate laboratory and animal facilities would enhance the efficiency of the
output of the Perrine, Chamblee and Wenatchee sites. A permanent central
facility would optimize output.
J. INTERMEDIA RELATIONSHIPS: Pesticides in air standards must be established
by FY 75. An air criteria document is required in FY 74. Hater standards are
currently being revised. The disposal of pesticide in solid waste and air is
a pollutant problem.
K. COORDINATION: Coordination is required with media offices and the Office of
Pesticides Programs and with Community Pesticide Studies and CHESS. Interaqenc.v
coordination with DOC, DOT, DOD, NSF and DHEW is also necessary.
L. UNRESOLVED POLICY ISSUES: New pesticide legislation. Transfer of
Community Studies Branch from Office of Pesticides Programs to OR&M.
-------
PEP.RIME PESTICIDES
Task
Priority
Ranking
1
Program
Structure
Reference
(Appendix B)
1
6
7
8
9
10
6
7
8
9
10
Maintain experimental
animal facility
Establish primate breed-
ing colony.
Effects of long term
pesticide exposure on
EEC and EKG in primates.
Effects of pesticides on
drug metabolizing en-
zymes .
General analytical sup-
port of intralaboratory
toxicology.
Primate teratology.
General pathology sup-
port of intralabora-
tory toxicology studies.
F2 alpha reproduction
studies in rodents.
Acute LD,.-, oral and
dermal.
Effect of pesticides on
neuromuscular function
and peripheral synaptic
performance.
FY 73 Resources Needs ($000/MY)
Suggested PresentMinimallyOptimal
Location Adequate
Perrine, Chamblee 220.U/ll.b 1080,0/18.0 1360.0/45.0
Perrine
Perrine
27.0/1.3 108.0/2.0 216.0/4.0
40.5/2.0 122.0/2.0 806.0/3.0
Perrine, Chamblee ?41 R/-|2 0 594.0/12.0 925.8/23.0
Perrine, Chamblee
Perrine
30.5/2.0 81.0/2.0 121.5/3.0
27.0/1.3 81.0/3.0 108.0/4.0
Perrine, Chamblee 18.5/0.6 37,0/1.0
Chamblee
Chamblee
Perrine
51.6/1.5
27.0/1.3 37.8/1.0 43.2/1.5
27.0/1.3 37.8/1.0 43.2/1.5
27.0/1.3 35.4/1.5 45.6/1.5
-------
'age
PERRINE PESTICIDES
Task
Priority
Ranking
n
17
18
19
20
Program
Structure
Reference
(Appendix B)
11
12
13
14
15
16
12
13
14
15
16
17
18
19
20
Title
Effect of pesticides
on intermediary meta-
bolism. Perrine, Chamblee
Non-primate teratology
studies, Perrine
PCB bladder cancer
studies.
Chamblee
Single pregnancy (days
7-15) studies. Chamblee
Neurotoxicity screen-
ing (chickens). Chamblee
Provide baseline clin-
ical profiles of pri-
mates. Perrine
Influence of pesti-
cides on pituitary
hormone secretion and
correlation with EEC. Perrine
EM ultrastructure
studies.
Chamblee
Subacute toxicity
(including chronicity
factors and single gen-
eration reproduction Chaffiblee
studes).
Effects of pesticides
on behavior. Perrine
FY 73 Resources Needs -(SOOO/MY)
Suggested PresentMinimallyOptimal
Location Adequate
39,3/2.0 81,0/3,0 121,5/4.0
27
i0/1-3 81.0/3,0 108.0/4,0
27.0/1.3 30.5/1.5 44.0/1.5
27.0/1.3 37.8/1.5 . 43.2/20
27,0/1.3 40.2/1.5 42.8/1.5
108,0/4.0 216.0/8.0
27,0/1.3
27.0/1.3
27
27,0/1.3
10,0/0.0
102.5/4.0 210.0/6.0
§0/1>3 61.2/2,0 82.5/2.5
37.8/1.2 ' 43.2/1.5
44.5/2.0 91.2/3.0
-------
Page 3
PERRINE PESTICIDES
Task
Priority
Ranking
Program
Structure
Reference
(Appendix B)
Title
FY 73 Resources Needs ($000/MY)
Suggested PresentMinimallyOptimal
Loca ti on Adeq uate^
21
21
22
23
24
28
29
22
23
24
25
26
27
25
26
27
28
29
Pesticide pharmacody- Perrine, Chamblee
namics in rodents and
primates (distribution,
metabolism, and excretipn)t
Clinical pathology,, Chamblee
Heme synthesis and
metabolism. Chamblee
Biochemical NMR studies
of the mechanism of in-
teractions of toxicants
with proteolytic
enzymes. Perrine
Measurement of exposure
under field construction. Wenatchee
Correlation of exposure
indices. Wenatchee
General pathology sup-
port of int.eragency
toxicology rodent
studies.
General biochemical
and analytical sup-
port of intcrag«ncy
toxicology.
Perrine, Chamblee
4085/2.0 81.0/3.0 121.5/4.0
27,0/1.3 60,0/2.0 95.5/3.5
40.0/1.3 108,0/4.0 162.0/5.0
81.0/4.0
n.,o/o.o
«
8,5/0.6 37.0/1.0 55.5/2.0
98,0/5.2 162.0/5.0 205.2/6.5
120.5/4,0 137.7/5.0
31.4/2.0 45.7/3.0
Perrine, Chamblee 54.Q/2.6 108.0/4.0 162.0/6,0
Evaluation and Review of Health
Effects Research. Perrine
855/5'. 0 1,50n/10 8208,1/172.0
TOTALS 2170.0/69.0 5,046.4/102 8208.1/172.0
.en
-------
A 17
A. PROGRAM ELEMENT NUMBER; 510501
B. TITLE; Pesticides Effects Upon Human Health
PREPARED BY: R. D. Courter DATE: December 29, 1971
C. PROGRAM JUSTIFICATION; The pesticide registration and labelling obligations
of EPA require that the Agency determine the effects of pesticides on human
health. Changes in labelling or withdrawal of registration necessitate
cost-benefit assessment of the proposed changes. Such judgments must be founded
on Quantitative estimates of the health risks associated with pesticide usage.
Human health effects studies are indispensable to these control activities.
D- OBJECTIVES: To provide the health intelligence needed for scientifically
defensible pestfcide registration and labelling actions and to confirm .safety
in usage.
E. SCOPE: Four tasks are included in this program element. First, close
clinical and biochemical surveillance of temporarily registered pesticides with
emphasis .upon those likely to be particularly hazardous or to involve large
population exposures. Second, planning and implementing an acute poisoning
reporting system that will assure detection to 90% of incidents and accidents
involving pesticides and other related chemicals. Third, retrospective
human morbidity and mortality studies of population cohorts heavily exposed to
pesticides. Fourth, prospective epidemic!ogic studies of occupationally exposed
groups in 14 geographically dispersed study areas.
F. RESULTS: The research tasks described will provide data necessary to evalu-
ate more completely the potential hazards of temporarily registered pesticides,
to elucidate DH acute pesticide poisoning problems caused by mislabelling and
to assess the chronic disease risks associated with pesticide usage.
G. APPROACH: The Pesticides Registration Division will provide copies of
temporary registrations and make arrangements with the registrants to institute
clinical and biochemical surveillance of people utilizing these chemicals.
Expansion of pesticide accident reporting and investigational network
involving Federal, State and local governmental agencies will be accomplished.
Retrospective mortality and morbidity studies will identify occupational and
general population cohorts heavily exposed to pesticides in the past. Death
records and illness records, where available, would be utilized along with
appropriate actuarial procedures to assess any increase in risk attributable to
pesticides. Prospective studies of occupationally exposed cohorts in the 14
community pesticide study.areas will continue utilizing selected clinical and
biochemical health indicators.
H. SUPPORTING CONTRACTS: Included are 14 community study contracts with State
health departments or universities plus additional contracts with other groups
for reporting pesticides accidents.
-------
A 18
I. SPECIAL FACILITIES: Clinical biochemistry and physician services, adequate
data processing hardware and software and residue analysis laboratories are
needed.
J. INTERMEDIA RELATIONSHIPS: 'Exist with all media programs.
K. COORDINATION: With other health effects research programs, other Agency
research programs and with NIEHS, NIOSH, FDA, NSF, NCHS, DOD and AEC.
L. UNRESOLVED POLICY ISSUES; None
-------
PRIORITY LISTING PESTICIDES EFFECTS ON HUMAN HEALTH TASKS
Task
Priority
Ranking
1
Program
Structure
Reference
(Appendix B)
1
3
4
Ti tl e
Surveillance of Exnerineital Pesticides
Users
Investination of Acute Pesticide
Poisonings
Retrospective Human Morbidity and
Mortality Studies
Prospective Em'da^iolonic Studies
FY 73 Resources Needs ($000/MY)
Suggested PresentMinimallyOptimal
Location Adequate
Chamblee 100/3.0 125/4.0 150/4.0
Chanblee 270/10.0 305/12.0 .350/14.0
Charnhlee 119/2.0 175/3.0 219/3.0
Chamblee 3711/17.0 3911/17.0 4200/17.0
TOTALS .
4200/32 4516/36 4919/38
-------
A 20
A. PROGRAM ELEMENT NUMBER: None Assigned
B. TITLE: Radiation Health Effects
PREPARED BY: Edythelena Tompkins DATE: January 15, 1972
C. PROGRAM JUSTIFICATION: Proliferation of nuclear power plants in the near
future requires EPA to provide maximum assurance of safe population exposure
to the principle radionuclides released from nuclear power reactors and fuel
reprocessing plants. Present reactors release tritium and krypton; breeder
reactors release plutonium as well. Present standards for maximum exposure
to these radionuclides are calculated values derived from dose-effect studies
at high-level total body exposures. .The adequacy of these standards, especially
with reference to internal alpha and beta emitters, has not been experimentally
evaluated.
Populations are extensively exposed to electromagnetic radiation from the
communications industry, these sources will continue to increase in number.
No standard exists for exposure of the general population to these nonionizing
radiations, especially for chronic low-dose levels. Research on molecular,
biochemical, genetic and functional changes induced by electromagnetic radiation
exposure must be conducted to provide an adequate base of health intelligence
for appropriate regulatory action.
D- OBJECTIVES: To provide EPA with a scientific basis to select and support
environmental standards for radionuclides emitted by nuclear power generating
plants and for electromagnetic radiations generated by the communications industry.
E. SCOPE: Doses received by communities adjacent to large sources of radionuclides
and electromagnetic radiation will be defined. Long-term effects of human exposure
to ionizing radiation will be documented through epidemiologic studies of populations
with known high level exposure. Experimental animal exposure will be employed at
graded dose levels to determine dose-effect relationships. Ionizing and nonionizing
radiation induced carcinogenic and mutagenic effects will be studied as well as
other toxicologic endpoints including physiologic and behavioral changes and
cellular repair. Emphasis will be placed on tritium, krypton, plutonium and
electromagnetic radiation.
F. RESULTS: The knowledge gained through community and biomedical studies will
be made available in a series of intramural and published reports relating
toxicological information to radiation exposures of the population. These
reports will provide health effects information for the setting and appraisal
of radiation standards. The studies on krypton, tritium and plutonium will con-
tribute to EPA's ability to assure human safety associated with the proliferation
of nuclear power plants and will further the development of these needed facilities
under least social cost standards which adequately protect the public.
-------
A 21
G. APPROACH: The radiation health effects program is an integrated series
of epidemiologic and toxicological studies utilizing both community exposures
and experimental animal exposures to ionizing and nonionizing radiation.
Specific dose levels of radiaitbn are generated and monitored. Exposures are
both acute short-term and chronic in form. Sensitive biologic endpoints in
humans and animals are applied to detect both clinical and pre-clinical effects.
Animal toxicology is designed to obtain dose-effect relationships at levels
pertinent to human exposures.
H. SUPPORTING CONTRACTS: Animal holding facilities and electromagnetic
radiation dose assessment will be provided through existing contracts and
interagency agreements. Other research contracts and grants with universities
and private research organizations are developed to comploment in-house projects
I. SPECIAL FACILITIES: Housing for a cat colony utilized in studies of the
health effects of ionizing radiation. Equipment for measuring ionizing and
electromagnetic radiation is widely employed.
J. INTERMEDIA RELATIONSHIPS: With other EPA health program elements and with
air and water media offices.
K. COORDINATION: Liaison with AEC, NCI, DoD, DHEW.
L. UNRESOLVED POLICY ISSUES: None.
-------
PRIORITY LISTim OF RADIATION TASKS
Program
Task
Priority
Ranking
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Structure
Reference
(Appendix B)
A4
A8
A6
A9
B2
B5
A5
R4
R3
A3
A10
Bl
A7
A2
Title
Dose response effects studies of tnjbiun
Z+f3ZZr;.ja'
Radioactive oarticle studies
Dose-response effects studies of ^Krypton
Biokinetic studies of tritium
Mutagenic effects of nonionizinn radiation
Radiation renair and carcinoqenesis
Age sensitivity to radiostrontiim
and other nuclides
Population exnosure to environmental
nonionizing radiation'
Physiologic and behavioral effects of
nonionizing radiation
Enideniologic studies of long-term
effects of ionizing radiation
Plutonium exposure and effects studies
Fundamental models of action of
nonionizing radiation
Beta & alpha dosimetrv for DODU! . studies
Validation of assumptions inherent in
Suggested
Location
Twin brook
HERL
EERL
HERL
Twinbrook &
EERL
Twinbrook
Twinbrook
Twinbrook
Twinbrook
ABCC &
Twinbrook
WERL
Twinbrook
Twin brook
Twinbrook
FY 73 Resou
Present
110/3.0
44/2.5
60/2.0
59/4.0
120/3.5
141/4.3
549/17.0
21/2.3
192/4.5
226/6.5
0/0.0
100/3.0
,29/1.0
86/2.0
rces Needs (
Minimally
Adequate
135/4.0
70/3.5
" 80/3.0
240/8.0
226/6.5
210/5.3
660/20.0
400/3.5
237/7.5
449/8.5
200/11.0
114/4.0
58/2.0
375/5.0
^UUU/MY;
Optimal
185/6.0
110/5.0
140/5.0
240/8.0
301/3.5
320/7.3
1000/25.0
588/6.0
365/9.5
1245/16.5
200/11.0
193/6.0
77/3.0
375/5.0
dose-response models used for standards
PO
no
-------
PRIORITY LISTING OF RADIATION TASKS
Task
Priority
Ranking
15
16
17
Program
Structure
Reference
(Appendix
BS
Al
All
B)
Ti tl e
FY 73 Resources Needs ($000/MY)
Suggested PresentMinimallyOptimal
Location Adequate
Determination of innact of environmental Twinbrook
s.ynerqists on radiation standards
Definition of radiation dose to residents Twinbrook
around nuclear facilities
210
Pb as a biological indicator of radon
exposure
HERL
TOTALS
82/3.. 2 260/6.7 438/7.7
28/2.2 700/10.0 700/10.0
0/0.0 55/3.0
70/5.0
1847/61 4469/112 6547/140
*See Appendix 3
**Exceeds ORM projection by 158K an amount equal to the projected
budgets of the MERL and JEERL tasks.
IN3
CO
-------
A 24
A. PROGRAM ELEMENT NUMBER: (Not yet assigned)
B. TITLE: Health Effects of Solid Waste Disposal (only one project)
PREPARED BY: J. F. Finklea DATE: 7 January 1972
C. PROGRAM JUSTIFICATION: Disposal and reuse of solid wastes involve large
public and private investments in research and development of new techniques
in capital investments, and in operating expenses. Disposal practices for
hazardous substances represent special problems as dp incineration of
sewage sludge and reuse of papeK Guidelines for performance and emissions
standards for these facilities must be established by the Federal Government.
D. OBJECTIVES: To quantitate the health effects of existing solid waste
disposal practices utilizing human health and toxicologic studies and to
predict adverse health effects that might result from advanced solid waste
disposal practices.
E. SCOPE: Epidemiologic and clinical studies in thirty to forty urban
communities would be included. Special attention would be focused upon
communities utilizing differing advanced waste disposal techniques including
newer municipal and sewage sludge incineratprs,
*
F. RESULTS: Assurance of human safety of propos.ed advance solid waste
techniques would be possible by 1978 if adequate resources are allocated.
G' APPROACH: Human studies will utilize exposure surveillance and standardized
epidemiologic endpoints including pollutant burdens in tissues and alterations
in enzyme activity profiles. Toxicologic studies will utilize tissue culture
monolayers, isolated perfused organ systems and standardized toxicologic tests
in laboratory animals.
H. SUPPORTING CONTRACTS: Contracts with institutions and research organizations
would be complemented by intramural research efforts.
! SPECIAL FACILITIES: Included would be exposure and holding facilities for
laboratory animals, analytical capability for trace elements, a mobile CLEVER
unit (Clinical Environmental Ejn'demiologic Research laboratory) as well as
tissue culture and biochemistry laboratories.
J. INTERMEDIA RELATIONSHIPS: Air, water, pesticides and multimedia toxic
substances.
K. COORDINATION: With media and category programs and with ORM CHESS and Bio-
medical research programs.
L. UNRESOLVED POLICY ISSUES: None
-------
PRIORITY LISTING OF HEALTH EFFECTS OF SOLID WASTES TASKS
Program
Task Structure
Priority Reference
Ranking (Appendix B)
Title
FY 73 Resources Needs ($000/MY)
Suggested PresentMinimallyOptimaT
Location Adequate
Human Health Studies to Assure Safety
of Solid Wastes Disposal and Reuse
Procedures.
600/10
900/15
Toxicologic Studies of Human Exposures
to Toxic Trace Elements, Microbial
Agents and Noxious Chemicals from New
Solid Waste Techniques.
600/10
900/15
TOTALS
1200/20
1800/30
-------
A 2G
A. PROGRAM ELEMENT NUMBER:
B. TITLE: Health Effects Research - Water
PREPARED BY: L. J. McCabe DATE: January 14, 1972
C. PROGRAM JUSTIFICATION: A most important consideration in the setting of
water quality standards should be human health. Little specific research has
been done on the relationship of water quality to health, except for the
infectious diseases and drinking water. Chemical standards for drinking
water have been set on the basis of literature reviews of toxicologic research
on other problems and are not directly related to water problems. Large safety
factors must be used that possibility result in excessive pollution control
cost.
D. OBJECTIVES: To provide a scientific basis for establishing water quality
standards designed to protect human health.
E. SCOPE: Epidemiologic and Toxicologic studies of the health effects of
water pollutants will be focused on three areas:
1. Research to establish and suooort safe drinking water
standards with 12 tasks,
2. Research to establish and suoport safe recreational water
quality standards with 4 tasks, and
3. Research on human health criteria for water quality standards
for fish, shellfish, and irrigation with 5 tasks.
F. RESULTS: The knowledge gained through this research will be made available
in a series of intramural and published reoorts which will provide the health
effects base for water quality standards. Studies will orovide the control
efficiencies that must be met by the treatment technology research and indicate
areas where water supply practices must be improved.
G. APPROACH: Epidemiologic and toxicologic competence will be developed initially
with an in-house research program. Activities will then be extended to provide
coverage of more situations with contracts. Grants will be used to stimulate
research in areas that need exploratory work.
H. SUPPORTING CONTRACTS: Contracts with non-government organizations will be
used to extend and support in-house research. PL 480 funds will be used when
suitable projects can be developed.
I. SPECIAL FACILITIES: The following snecial facilities are required: chemistry,
microbiology and toxicology laboratories; small animal facilities; and computer
availability for data analyses. These facilities are available at the NERC
(Cincinnati)'s central and satellite laboratories.
-------
A 21
J. INTERMEDIA RELATIONSHIPS: Most of the water contaminants are also present
in other media and several of the-research tasks specify work on this inter-
relationship to study contributions to total body burden.
K. COORDINATION: Liaison with MCDC, NIEHS and FDA and non-qovernment
scientists.
L. UNRESOLVED POLICY ISSUES: Federal authority to set drinkinq water standards
is not available excent for contaminants that relate to communicable disease.
-------
PRIORITY LISTING OF HEALTH EFFECTS RESEARCH - WATER TASKS
Program
Task
Priority
Ranking
1
?
3
4
5
6
7
8
9
10
11
Structure
Reference
(Appendix B)
A4
A3
Al
A5
A7
R2
A6
A10
Cl
83
A8
12
All
Title
Chemical Characterization and Toxicity
Studies of Undefined Organic Connounds
in Drinkinq Water
Water's Contribution to Tracejtetal Body
Burden
Correlation of Hater Ouality and Chronic
Disease Morbidity and Mortality
Toxic Effects of Known Inorganic Chenical
ConDounds ~"
Occurrence of Human Enteric Viruses in Hater NEUL
Ouantitation of Ponulation Exnosed to
Contaminated Recreational Haters
Eoidemiology of Waterborn Disease
Isolation of Infectious Hepatitis Virus
from Water
Assessment of Problems Associated with Food
Produced in Polluted ''later
Cinn.
Bacteriological Techniques for Bathing Haters MEWL
Protocol Development for Testina of Chemicals Cinn.
and Products used ip Hater Treatment, Storage
and distribution
Physiological Availability of Metals from
i-'ater
Cinn.
FY 73 Resources Needs ($000/MY)
Suggested
Location
Cinn/NEWL
Cinn.
Cinn.
Cinn.
NEUL
Cinn.
Cinn.
Present
'246.4/6
6/0.4
30/1.8
49.7/3.4
109.2/7.6
0/0.0
25/1.1
0/0.0
Minimally
Adequate
510/12.0
140/4.0
250/10.0
160/9.0
200/8.0
100/3.0
140/7.0
20/1.0
Optimal
1200/20
300/4.0
1350/14.0
400/15.0
200/8.0
500/4.0
497/12.0
20/1.0
0/0.0 60/3.0
0/0.0 60/3.0
180/3.0
142/5.0 240/10.0 240/10.0
16/1.O' 270/3.0 270/3.0
180/4.0
-------
Page 2
PRIORITY LISTING OF HEALTH EFFECTS RESEARCH - WATER TASKS
Program
Task
Priority
Ranking
13
14
15
16
17
18
19
20
21
22
Structure
Reference
(Appendix B)
PI
A2
A9
C2
B4
A12
C3
C4
C5
A.I 3
Title
Em'deniological Assessment of Recreational Cinn.
'later Safety
Health Effects of Hater Nitrates Cinn.
Exolore Safety of Haste Hater Reuse Cinn.
Accumulation of Contaminants by Fish & NEWL &
Shellfish Gulf Coast
Etriological Study of the Agent for Amebic Cinn.
Meningoencephali ti s
Patterns of Hater Consumotion Cinn.
Toxicology of Accumulated Contaminants in NEWL
Fish & Shellfish to Test Animals
Accumulation and Survival of Contaminants Cinn.
in Irrigated Crops
Toxicology of Contaminants in or on Crons Cinn.
Research Grants for Health Effects - 'later Cinn.
TOTALS
FY 73 Resources Needs ($000/MY)
Suggested PresentMinimallyOptimal
Location
Adequate
0/0.0 340/11.0 460/13.0
18/1.0 250/10.0 250/10.0
0/0.0 280/4.0 500/6.0 [1500]
62.8/2.9 80/4.0 80/4.0
36/1.7
0/0.0
50/3.0
100/3.0
0/0.0 40/2.0 160/3.0
58.6/3.3 140/7.0 140/7.0
20/1.0
70/1.0
0/0.0 20/1.0 70/1.0
0/0.0 1500/8 2250/10
799.9/35.2 4870/124 9417/156
*[1500] Higher fundina necessary if it is decided that EPA policy is to promote the reuse of waste water for drinking.
ro
10
-------
A 30
A. PROGRAM ELEMENT NUMBER:
B. TITLE: Health Effects of Multimedia Toxic Substances
PREPARED BY: Douglas I. Hammer DATE: January 8, 1972
C. PROGRAM JUSTIFICATION: Environmental chemicals are constituents of
virtually everything we use. The manufacture and consumption of this
large array of chemicals creates multiple problems with waste discharge
and disposal. Chemicals safe in original form may thus undergo unde-
sirable changes during the cycle of use, disposal and return to the
environment. The result is that human exposure is universal, complex,
rapidly changing and often unpredictable. Chemicals which themselves
are not readily absorbed by humans can interact with known air, water,
and food hazards to become more readily available and absorbed into
body tissues. Health effects resultinq from these exposures are often
subtle, delayed and costly.
D. OBJECTIVE: To assess the human health effects of exposure to multi-
media toxic substances and to confirm the human safety of new and old
chemical compounds.
E. SCOPE: The work will involve clinical laboratory, toxicologic and
epidemiologic studies conducted by the Federal government, universi-
ties and private institutions.
F. RESULTS: With adequate funding, baseline data on a hazard awareness,
and the confirmation of human safety can be available by 1978.
G. APPROACH: A broad multidisciplinary approach involving all sectors
of society will be utilized.
H. SUPPORTING CONTRACTS: A number of supporting contracts deal inn
with information systems, hazard identification, exposure surveillance,
tissue monitoring and effects assessment have been discussed in other
tasks in this program element.
I. SPECIAL FACILITIES: Discussed in task statements.
J- INTERMEDIA RELATIONSHIPS: With all media and category programs.
K. COORDINATION: Coordination will be required with other ORM health
effects research program elements and with the research proarams of
other agencies including DOD, NIEHS, NIOSH, NSF and AEC.
L. UNRESOLVED POLICY ISSUES: None.
-------
PRIORITY LISTING OF TOXIC SIF.STANC^ TASKS
Program
Task
Priority
Ranking
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Structure
Reference
(Appendix B)
Al
B3
B9
B2
Rl
B8
A3
R4
B5
A5
B7
A2
A4
B6
FY 73 Resources Needs ($000/MY)
Title
Establish a connrehensive information systen
Huantitate health impact of accidental
releases
Develoo predicted population at risk and
health cost nodels
Enidemiolonic surveillance of exceptionally
exposed
Establish biochemical and cytological alarm
systems
Establish national tissue bank
Develop rapid j_n_ vivo an-d i_n_ vitro screening
methods
Evaluate imnact on other environmental
standards
Model biological effect other than cancer,
terata and mutation
Assure that reuse and recycling do not
endanger man
Devise and denloy personal surveillance
sys terns . .
Snonsor briefing and training sessions
Identify previously unrecognized human exposures-
Establish community surveillance networks
See Appendix P.
Suggested
Location
i
-
-
-
-
-
]
-
-
-
-
- .
;ures-
-
TOTALS
Present Minimally
Adequate
1000/4.0
600/8.0
1020/13.0
600/15.0
1600/16.0
2800/24.0
750/15.0
1100/15.0
1033/14.0
750/5.0
1020/13.0
100/5.0
1250/16.0
1380/17.0
15003/180
OptimaJ
1500/6.0
900/12.0
1530/20.0
900/22.0
2400/24.0
4200/36.0
1075/22.0
1650/23.0
1546/21.0
1025/8.0
1530/20.0
150/7.0
1825/24.0
2070/25.0
22301 /ly)
-------
A 32
A. PROGRAM ELEMENT NUMBER: (Not yet assigned)
B. TITLE: Health Effects of Noise (only one project)
PREPARED BY: John F. Finklea DATE: January 8, 1972
C. PROGRAM JUSTIFICATION: Increasing ambient urban noise levels threaten
the quality of life and human health. Federal performance standards for noise
emanating from many processes and products may be established or altered in
the near future. Except for hearing loss, the needed health effects information
for these standards is inadequate. Behavioral effects are less well documented
and the full impact of noise upon stress-related disorders, including cardio-
vascular diseases, is unknown. Noise standards based solely upon hearing loss
would ignore these potentially costly health effects.
D. OBJECTIVES: To assure that risk-benefit calculations for future standards
are based upon a realistic assessment of population exposures, and to assure
that existing and proposed noise standards do not allow unacceptable behavioral
impairments and chronic disease risks in urban man.
E. SCOPE: Included are first assessment of ambient noise exposures in
typical residential communities and in known high level noise areas; second,
construction and instrumentation of suitable exposure chambers for human
volunteers and experimental animals; third, selection of appropriate
behavioral and performance indices. Both intramural and contract efforts
would be required.
F. RESULTS: With adequate funding a firm assessment of non-auditory health
impairments and realistic estimates of the magnitude of the risks of existing
and projected noise exposures would be available by 1977.
G. APPROACH: Three separate tasks are proposed. First, ambient noise
monitors distinguishing both the quality and intensity of sound will be
installed at the CHESS-CHAMP stations already located in 30 to 40 urban
residential communities. Volunteer panelists, already participating in CHESS
studies will be asked to carry miniature recorders during their daily activities.
The integrated noise exposures of housewives, children and workers can thus be
quantitated. Playback of tapes will allow identification of important noise
sources. Appropriate transducers will convert tape data into standard sound
exposure units for further computer processing. Second, rodents,' primates and
other appropriate experimental animals would be exposed to noise levels relevant
to existing and projected urban noise levels. Necessary allowances for diurnal
variation would be made. Behavioral and performance tests would be administered
and chronic disease risk factors assessed. Third, anechoic chambers would be
constructed as an adjunct to the ORM CLEANS (CLJnical Evaluation and Assessment
of Noxious Substances) program. Healthy human volunteers, would be subjected
to relevant noise exposures for up to ten days and the effects on behavioral
tests, performance tests and neurophysiologic indicators would be periodically
assessed. In addition the CLEVER (mobile CLJnical Environmental Epidemiologic
Research unit) would be deployed in CHESS communities where ambient and personal
noise levels were under-surveillance. Residents of several areas that comprised
a dose gradient for noise exposure would be asked to volunteer for the appropriate
-------
A 33
behavioral, performance and neurophysiologic testing. In addition field
surveys on the sociologic impact would be carried out.
H. SUPPORTING CONTRACTS: Noise monitoring systems would be fabricated and
deployed by a contractor according to Federal protocols as would data on
persona-1 noise exposure. Intramural clinical and toxicologic research
programs would be supplemented by appropriate contracts.
I. SPECIAL FACILITIES: Community exposure monitoring stations, equipment
maintenance and repair laboratories, data transmission, central data monitoring
and computer facilities, anechoic chambers, electroencephalograph, psychological
testing apparatus, appropriate monitoring software and hardware, the CLEVER
mobile unit, laboratory animal facilities and biochemical laboratory.
J. INTERMEDIA RELATIONSHIPS: Exist with air and water
K. COORDINATION: Coordination is required with media and category programs
and with ORM CHESS and biomedical research programs. Interagency coordination
with DOC, DOT, DOD, NSF, NBS and DHEW is also necessary.
L. UNRESOLVED POLICY ISSUES: None
-------
PRIORITY LISTING OF HEALTH EFFECTS OF NOISE TASKS
Task
Priority
Ranking
1
P rog ram
Structure
Reference
(Appendix
1)
Title
Suggested
Location
FY 73 Resources Needs ($000/MY)
Present
1
Ouantitate population chronically exoosed
to noise levels above nostulated irritation
and hearinn loss thresholds
Determine spectrum and severity of patho-
physioloqic effects attributable to noise
exposure through animal experimentation
Determine threshold of behavioral chanqes in
humans associated with chronic exoosure to
low level noise.
TOTALS
Minimally
Adequate
300/7.0
400/7.0
Optimal
450/11.0
600/11.0
300/10.0 450/15.0
1000/24
1500/37
CO
-------
A 35.
A. PROGRAM ELEMENT NUMBER: (Not Assigned)
B. TITLE: National Center for Toxicologic Research (NCTR)
PREPARED BY: Morris Cranmer DATE: January 15, 1972
C. PROGRAM JUSTIFICATION: Toxicologic screening of new environmental chemicals
prior to release into the environment is a most economic and desirable method
to protect the public against chemical toxicants. The federal government must
provide leadership for developing standardized protocols for toxicologic screening,
for evaluating the adequacy of non-government safety tests prior to registration and
use of new environmental chemicals and for developing research data that, will facilitate
extrapolation. NCTR will be the federal governments only environmental health
laboratory whose mission is to serve as a watchdog and scientific leader in
evaluating the safety of new environmental chemicals.
D. OBJECTIVES: (1) To develop improved methodologies for evaluating the safety
of. environmental chemicals, (2) to determine the adverse health effects resulting
from long-term, low-dose exposure to environmental chemicals, (3) to determine the
metabolic processes for chemical toxicants in animal organisms, and (4) to develop
scientific data that facilitate extrapolation from animal to man.
£ SCOPE: NCTR will operate a core program in four areas of toxicologic research:
(1) acute and subacute toxicity studies in which short duration tests will be
conducted to identify health indicators and background data necessary for chronic
lifetime studies, (2) chronic toxicity studies to determine carcinogenic and other
life shortening effects of environmental chemicals, (3) teratogenic research on
chick and mammalian embryos to determine teratogenicity of environmental chemicals
and (4) mutagenic research to develop improved testing procedures for evaluating
genetic effects of environmental chemicals.
F. RESULTS: The knowledge gained from toxicologic screening of new environmental
chemicals will be of direct relevance to EPA's mission of controlling population
exposure to environmental toxicants. The adequacy of industry's own screening
programs prior to registration or marketing of new chemicals will be judged from
the point of view of protector of the public health. Neede'd long-term toxicity
studies, including carcinogenic and mutagenic screening, will be provided.
G. APPROACH: Toxicologic studies utilizing animal, organ and cell culture systems
will be employed following standardized and scientifically sound protocols. Dose-
response curves for carcinogenic, teratogenic, mutagenic and chronic toxicologic
endpoints will be provided.
H. SUPPORTING CONTRACTS: Contracts with industry, private research organizations
and universities are needed to supplement the core program of NCTR and to provide
supporting services such as processing of specimens for pathological and biochemical
analysis.
-------
A 36
I. SPECIAL FACILITIES: Construction of special facilities is required and has
been extensively described in the detailed NCTR Technical Plan prepared jointly
by EPA and FDA.
J. INTERMEDIA RELATIONSHIPS: With all other health program elements in ORM and with
media and categorical offices.
K. COORDINATION: With FDA, NIEHS, NIOSH, and NCI.
L. UNRESOLVED POLICY ISSUES: None
-------
PRIORITY LISTING OF NATIONAL CENTER FOR TOXICOLOGICAL RESEARCH TASKS
Task
Priority
Ranking
Program
Structure
Reference
(Appendix B)
Title
FY 73 Resources Needs ($000/MY)
Suggested PresentMinimallyOptimal
Location Adequate
1
1
Establishment of NCTR
Pine Bluff 4000/3 5790/3
8000/3
-------
Appendix B
Proposed EPA Health Effects
Program Structure
-------
Table of Contents
Program Element Page
Biomedical Research (Air)
A. Summary 1
B. Task Statements - CLEANS
1. TASK 1.
Effects of CO in Persons with Coronary Artery Disease 5
2. TASK 2.
Effect of CO in Myocardial Infarction 6
3. TASK 3.
Procurement of Human Environmental Exposure Facilities 7
4. TASK 4.
Instrumentation of Human Exposure Facilities 8
5. TASK 5.
Investigation of Growth of Lung Function in Children 9
6. TASK 6.
Development of Techniques for Studying Metabolism and
Physiology of Isolated, Perfused Organs 10
7. TASK 7.
Development of Sensitive Neurophysiologic Measuring
Techniques 11
8. TASK 8.
Effect of CO Exposure on Human Performance Related
to Vehicle Driving Tasks 12
9. TASK 9.
Metabolic Effects of Long-Term Exposure to Lead
Sesquioxide Aerosol in Humans 13
10. TASK 10.
Development of New Programs Including a Health
Information System 14
C. Task Statements - CLEVER
1. TASK 1.
Acquisition, Instrumentation and Shakedown
Operations of a Mobile Laboratory 15
2. TASK 2.
Pollutant Induced Changes in Subjects with Asthma
and Chronic Bronchitis 16
3. TASK 3.
Effects of N02 and CO on Cardiovascular Physiologic
Parameters in Subjects with Clinical and Subclinical
Heart Disease 17
-------
C. Task Statements: - CLEVER (Continued).
4. TASK 4.
Effects of Oxi.dants, NO*, Trace Metals, Synthetic
Organics and Atmospheric Polycyclic Aromatics on
Responses which are Sentinels for Cancer or
Genetic Mutations 18
5. TASK 5.
Neurophysiologic Effects of Exposure to CO, N02,
Oxidants, Noise, Odors and Electromagnetic Radiations 19
6. TASK 6.
Effects of Short-Term Exposure Variations in Oxidants,
NOX, SOX, Total and Fine Particulate on Red Blood Cell
Membrane and Enzyme Characteristics in a Community Study 20
D. Task Statements - ACTIONS
1. TASK 1.
Effects of Air Pollutants on Pulmonary Defense
Mechanisms 21
2. TASK 2.
Influence of Hazardous Substances on Cellular
Physiology 23
3. TASK 3.
Physiologic and Pathologic Studies of Pulmonary Response
to Hydrocarbon Air Pollutants in Syrian Golden Hamsters 25
4. TASK 4.
Influence of Environmental Pollutants on Red Blood
Cell Function 27
5. TASK 5.
Interactions of Various Pollutants on the Causation
of Pulmonary Disease 30
6. TASK 6.
Biological Effects of Trace Substances and Tobacco
Smoke in Interactions with. Nitrogen Oxides 32
7. TASK 7.
Procurement and Preparation of Airborne Carcinogens 33
8. TASK 8.
Pulmonary Effects of Chronic Exposure to Oxidants,
Ionizing Radiation and Other Environmental Pollutants
and Contaminants 34
E. Task Statements - inhalation Toxicology
1. TASK 1.
Comparative Hazards of Mobile and Stationary Source
Emissions 36
2. TASK 2.
Maintenance and Observation of Female Beagles
Previously Exposed for 5 Years to Auto Exhausts
and Other Pollutants. 39
3. TASK 3.
Analysis for Biochemical Changes in Laboratory Animals
Exposed to Fuel Emissions and/or Trace Metals 41
-------
m
E. Task Statements - Inhalation Toxicology (Continued)
4. TASK 4.
Behavioral and Neurological Effects of Trace Metals
and Fuel Emissions 43
5. TASK 5.
Assessment of Pulmonary, Cardiovascular and Renal
Function Following Inhalation of Atmospheres
Containing Trace Metals or Fuel Emissions 45
6. TASK 6.
Assessment of Absorption, Metabolic Fate, Excretion,
Acute and Subacute Toxicity of Trace Metals and
Other Chemical Pollutants 48
F. Table 1 - Resource Estimate 50
II. CHESS (Air)
A. Summary 52
B. Task Statements - Data Collection
1. TASK 1. .
CHESS New York Metropolitan Studies 56
2. TASK 2.
CHESS Southeastern Studies 58
3. TASK 3.
CHESS Chattanooga Studies 60
4. TASK 4.
CHESS Utah Area Studies 62
5. TASK 5.
CHESS Los Angeles Basin Studies 64
6. TASK 6.
St. Louis Regional Air Pollution Studies 66
7. TASK 7.
Chicago Stationary Source 68
8. TASK 8.
CHESS Southwest Studies 70
9. TASK 9.
CHESS Mountain Studies 72
10. TASK 10.
CHESS Northwest Studies 74
11. TASK 11.
CHESS Coastal Studies 76
12. TASK 12.
CHESS Lakes Studies 78
13. TASK 13.
CHESS Selected Source Exposures 80
C. Task Statements - Information Synthesis.
1. TASK 1.
CHESS Investigations of the Dose-Response Relationships
Between the Frequency of Chronic Respiratory Disease
Symptoms and Ambient Air Pollutant Levels of Oxides of
Nitrogen (NO*), Oxides of Sulfur (SOX), Photochemical
Oxidants (Ox), Total Suspended Particulates (TSP) and
Respirable Suspended Particulates (RSP). 82
-------
C. Task Statements - Information Synthesis (Continued)
2. TASK 2.
CHESS Investigations of the Dose-Response Relationships
Between the History of Acute Lower Respiratory Infection
(LRI) and Ambient Air Pollutant Levels of Oxides of
Nitrogen (NOx), Oxides of Sulfur (SO*), Photochemical
Oxidants (Ox), Total Suspended Particulates (TSP), and
Respirable Suspended Particulates (RSP) 84
3. TASK 3.
CHESS Investigations of the Dose-Response Relationships
Between Incidence of Acute Respiratory Tract Disorders
and Ambient Air Pollutant Levels of Nitrogen Oxides (NOX),
Sulfur Oxides (SOX), Photochemical Oxidants (Ox),
Total Suspended Particulates (TSP), and Respirable
Suspended Particulates (RSP) . 86
4. TASK 4.
CHESS Investigations of the Dose-Response Relationships
Between Pulmonary Function Test Performance and Ambient
Air Pollution Levels of Oxides of Nitrogen (NOX), Oxides
of Sulfur (SOX), Photochemical Oxidants (Ox), Total
Suspended Particulates (TSP), and Respirable Suspended
Particulates (RSP) 88
5. TASK 5.
CHESS Investigations of the Dose-Response Relationships
Between the Frequency of Acute Irritation Symptoms of
the Eye and Respiratory Tract Disability and Physician
Visits and Acute Ambient Air Pollution Episodes involving
Oxides of Nitrogen (NOx), Oxides of Sulfur (SOx), Photo-
chemical Oxidants (Ox), Total Suspended Particulates (TSP),
and Respirable Suspended Particulates (RSP) 90
6. TASK 6.
CHESS Investigations of the Dose-Response Relationships
Between the Aggravation of Symptoms in Panels of Elderly
Persons either Well or Afflicted with Chronic Heart
and/or Lung Disease and Acute Ambient Air Pollution
Levels of Nitrogen Oxides (NOx), Sulfur Oxides (SOx),
Photochemical Oxidants (Ox), Total Suspended Particulates
(TSP) and Respirable Suspended Particulates 92
7. TASK 7.
CHESS Investigations of the Dose-Response Relationships
Between the Aggravation of Asthma and Acute Ambient Air
Pollution Levels of Oxides of Nitrogen (NOx), Oxides of
Sulfur (SOx), Photochemical Oxidants (Ox), Total
Suspended Particulates (TSP), and Respirable Suspended
Particulates (RSP) 94
8. TASK 8.
CHESS Investigation of the Dose-Response Relationships
Between Human Pollutant Burdens Assayed in Hair, Blood,
and Tissues and Environmental Pollutants (including
Metals such as As, Cd, Cr, Cu, Pb, Mn, Hs, Ni, V, Zn
and Synthetic Organic Materials including Aromatic and
Aliphatic Halides such as PCB). This Task also Inves-
tigates the Relationship between Human Pollutant Burdens
and Disease using the CHESS Tissue Bank. 96
-------
C. Task Statements - Information Synthesis (Continued)
9. TASK 9.
CHESS Investigations of the Dose-Response Relationships
Between Excess Daily Mortality and Acute Ambient Air
Pollution Episodes (NOx, SOx, Ox, TSP, RSP) and Between
Coronary Artery Disease Deaths and Acute Air Pollution
Exposure (CO). 98
10. TASK 10.
CHESS Statistical Technique Improvements to Overcome
Problems Relating to Serial Correlation, Modeling
Human Exposure Assessment of Populations at Risk,
Censored Data, Analysis of Mixed Model (Categorical -
Continuous) Data, and CHESS Data Systems. 100
11. TASK 11.
Health Costs of Ambient Air Pollution and Health
Benefits of Pollution Control as Delineated in the
CHESS Program. NOx, SOx, Ox, CO, TSP, RSP and the
Pollutants of Prime Interest 102
D. Task Statements - Bio-Environmental Measurements
1. TASK 1.
Evaluation and Adaptation of Continuous and Personal
Air Monitoring Techniques for Use in Health Effects
Studies 104
2. TASK 2.
Establishment, Operation and Maintenance of Regular CHESS
and CHESS Continuous Health Air Monitoring Program (CHESS-
CHAMP) Stations. 106
3. TASK 3.
Evaluation of Special Human Exposures Related to Airports,
and Selected Stationary Sources, Including Fossil-Fuel
Power Plants, Incinerators, and Petrochemical Complexes 108
4. TASK 4.
CHESS Investigations of Human Exposure to Metallic and
Synthetic Organic Pollutants via Household Dust, Soil,
Tap Water, Food and Tissue Residues 110
5. TASK 5.
Laboratory Analyses of Routine Aerometric Specimens
Collected in CHESS 112
6. TASK 6.
Indoor Generation of Air Pollutants 113
E. Task Statements - New Health Indicators
1. TASK 1.
Dose Relationship Between Erythrocyte Damage and Exposures
Involving Ambient Air Pollutants, Trace Metals and Other
Environmental Contaminants as Indexed by Mechanical
Fragility, Osmotic Fragility and Centrifigation Assay of
Cell Age Distribution 114
-------
VI
E. Task Statements - New Health Indicators (Continued)
2. Task 2.
Dose Relationship Between Shifts in Oxyhemoglobin
Dissociation Curves and Exposures to Ambient Air
Pollution Including CO, NOx, SOx, Ox, and Trace
Metals 116
3. TASK 3.
Dose Relationships Between Indices of Erythrocyte
Damage and Air Pollution Exposures to CO, NOx, Ox,
SOx, and Trace Metals. Indices Include Lipid
Peroxidation, Sodium, and Potassium Flux Across the
Cell Membranes. The Indices in this Task may be
more easily Studied in the Field than the Direct
Effects Listed in TASK 1 118
4. TASK 4.
Dose Relationship Between Indices of Erythrocyte
Metabolism Including Methemoglobin, 2-3 Diphospho-
glyceraldehyde, Lactate/Pyruvate Ratios, Hemoglobin
Electrophoretic Mobility Patterns, Ami no-Acid
Profiles as well as Glucose-6 Phosphate
Dehydrogenase Levels 120
5. TASK 5.
Dose Relationship Between Alterations in Metal!oenzyme
Levels or Kinetics and Trace Metal and Synthetic
Organic Pollutant Exposures. Candidate Enzymes Include
Carbonic Anhydrase, Alkaline Phosphatase, Superoxide
Dismutase and Carboxypeptidase. Special Attention Will
Also Be Focused on Human Placenta! Biochemistry Effects. 122
6. TASK .6.
Cytological Location of Metallic Pollutants Will Indicate
Which Organelles and Cellular Processes Might Be Best
Indexed by Enzymatic Assay 124
7. TASK 7.
Assessment of Increased Cancer Risk by Exfoliative Cytology
Relating Cytologic Chances to Ambient Air Pollutants, Metals
and Synthetic Organics 126
8. TASK 8.
Dose Relationship Between Immunologic Deficits, Ambient
Air Pollutants and Metals 128
9. TASK 9.
Use of Leucocyte Metabolism as a Health Effects Indicator.
Indices Could Include Protein and Nucleic Acid Synthesis,
Lipid Metabolism and Antibody Production 130
10. TASK 10.
Use of Plasma Enzymes, Circulating Hormone Levels, Critical
Substrate Concentrations and Seminal Plasma Metabolic
Profiles as Health Indicators 132
-------
Vll
E. Task Statements - New Health Indicators (Continued)
11. TASK 11.
Cytogenetic Abnormalities Induced by Air Pollutants
Including Oxidants, Oxides of Nitrogen, Carbon
Monoxide, Suspended Particulates, Oxides of Sulfur,
Trace Elements and Selected Organic Compounds 134
12. TASK 12.
Research Grants Program to Qualitatively Define
Contribution of Air Pollutants to Acute and
Chronic Diseases of Major Public Health Significance 135
F. Table 1 - Resource Estimate
III. Pesticides Health Effects Research (OR&M in FY '72)
A. Summary 140
B. Task Statements
1. TASK 1.
Maintain Experimental Animal Facility 144
2. TASK 2.
Establish Primate Breeding Colony 145
3. TASK 3.
Effects of Long-Term Pesticide Exposure on EE.G and
EKG in Primates . 146
4. TASK 4.
Effects of Pesticides on Drug Metabolizing Enzymes 147
5. TASK 5.
General Analytical Support of Intralaboratory Toxicology 148
6. TASK 6.
Primate Teratology 149
7. TASK 7.
General Pathology Support of Intralaboratory Toxicologic
Studies 150
8. TASK 8.
F2a Reproduction Studies in Rodents 151
9. TASK 9.
Acute LD5Q, Oral and Dermal 152
10. TASK 10.
Effect of Pesticides on Neuromuscular Function and
Peripheral Synaptic Performance 153
11. TASK 11.
Effect of Pesticides on Intermediary Metabolism 154
12. TASK 12.
Non-Primate Teratology 155
13. TASK 13.
Polychlorinated Biphenyl-Bladder Cancer Study 156
14. TASK 14.
Single Pregnancy Studies 157
15. TASK 15.
Neurotoxicity Screening 158
-------
B. Task Statements (Continued)
16. TASK 16.
Provide Baseline Clinical Profiles of Primates 159
17. TASK 17.
Influence of Pesticides on Pituitary Hormone Secretion
and Correlation with EEG 160
18. TASK 18.
Electronmicroscopy-llltrastructural Studies of Specific
Organs 161
19. TASK 19.
Subacute To-xicity Including Chronicity Factors 163
20. TASK 20.
Effects of Pesticides on Behavior 164
21. TASK 21.
Pesticide Pharmacodynamics in Rodents and Primates
(Distribution, Metabolism, and Excretion) 165
22. TASK 22.
Clinical Pathology 166
23. TASK 23.
Heme Synthesis and Metabolism 167
24. TASK 24.
Biochemical Nuclear Magnetic Resonance (NMR) Studies
of the Mechanism of Interactions of Toxicants with
Proteolytic Enzymes 168
25. TASK 25.
Measurement of Exposure Under Field Conditions 169
26. TASK 26.
Clinical Investigations Related to Field Exposure 170
27. TASK 27.
General Pathology Support of Interagency Toxicology
Rodent Studies 171
28. TASK 28.
General Biochemical and Analytical Support of
Interagency Toxicology 172
29. TASK 29.
Evaluation and Review of Health Effects Research Grants 173
C. Table 1 - Resource Estimate 174
IV. Pesticides Effects Upon Human Health. (PPP in fY .'72).
A. Summary 176
B. Task Statements
1. TASK 1.
Surveillance of Experimental Pesticides; Us;ers 180
2. TASK 2.
Investigation of Acute Pesticide Poisonings 182
3. TASK 3.
Retrospective Human Morbidity and Mortality Studies 184
4. TASK 4.
Prospective Epidemiological Studies: 186
C. Table 1 - Resource Estimate 189
-------
V. Radiation Health Effects
A. Summary 190
B. Task Statements - Standards for Nuclear Facilities
1. TASK 1.
Definition of Radiation Dose to Residents Around
Nuclear Facilities 194
2. TASK 2.
Validation of Assumptions Inherent in Dose-Response
Models Used for Standards 196
3. TASK 3.
Epidenriologic Studies of Long-Term Effects of
Ionizing Radiation 198
4. TASK 4.
Dose-Response Effects Studies of Tritium 200
5. TASK 5.
Age Sensitivity to Radio-Strontium and Other Nuclides 202
6. TASK 6.
Dose-Response Effects Studies of Krypton-85 Exposure 204
7. TASK 7.
Beta and Alpha Ray Dosimetry for Population Studies 206
8. TASK 8.
Radioactive Particle Studies 208
9. TASK 9.
Biokinetic Studies of Tritium 210
10. TASK 10..
Plutonium Exposure and Effects Studies 211
11. TASK 11.
Lead - 210 as a Biological Indicator of Radon Exposure 212
C. Task Statements - Standards for Electromagnetic Radiation
1. TASK 1.
Fundamental Modes of Action of Nonioni.zing Radiation 214
2. TASK 2.
Mutagenic Effects of Nonionizing Radiation 216
3. TASK 3.
Physiological and Behavioral Effects of Nonionizing
Radiation 218
4. TASK 4.
Population Exposure to Environmental Nonionizing
Radiation 220
5. TASK 5.
Radiation Repair and Carcinogenesis 221
6. TASK 6.
Determination of Environmental Synergists on Radiation
Standards 224
D. Table 1 - Resource Estimate 228
-------
VI. Health Effects of Solid Wastes
A. Summary 230
B. Task Statements
1. TASK 1.
Human Health Studies to Assure the Safety of Solid
Wastes Disposal and Reuse Procedures 233
2. TASK 2.
Toxicologic Studies to Prevent Dangerous Human
Exposures to Toxic Trace Elements, Microbi.al Agents
or Noxious Chemicals Arising from Newer Solid Waste
Disposal Techniques 234
C. Table 1 - Resource Estimate 235
VII. Health Effects Research - Water
A. Summary 236
B. Task Statements - Standards for Drinking Water
1. TASK 1.
Correlation of Water Quality and Chronic .Disease
Morbidity and Mortality 240
2. TASK 2.
Health Effects of Water Nitrates 243
3. TASK 3.
Water's Contribution to Trace Metal Body Burden 247
4. TASK 4.
Chemical Characterization and Toxicity Studies of
Undefined Compounds in Drinking Water 252
5. TASK 5.
Definition of the Toxic Effects of Known Chemicals
Encountered in Drinking Water, Singly and in
Combination 255
6. TASK 6.
Epidemiology of Waterborne Disease 259
7. TASK 7.
Occurrence and Fate of Viruses in Drinking W.ater 260
8. TASK 8.
Protocol Development for Testing of Chemicals and
Products Used in Water Treatment, Storage and
Distribution 262
9. TASK 9.
Explore Safety of Waste Water Reuse 263
10. TASK 10.
Isolation of the Infectious Hepatitis Virus from Water 264
11. TASK 11.
Physiological Availability of Metals from Water 265
12. TASK 12.
Patterns of Water Consumption 266
13. TASK 13.
Research Grants Program to Qualitatively Define
Contribution of Water Pollution to Acute and Chronic
Diseases of Major Public Health Significance 267
-------
XI
VII. Health Effects Research - Water (Continued)
C. Task Statements - Standards for Recreational Water
1. TASK 1.
Epidemiological Assessment of Recreational Water
Safety 269
2. TASK 2.
Quantitation of Population Exposed to Contaminated
Recreational Waters 272
3. TASK 3.
Bacteriology of Recreational Water 274
4. TASK 4.
Etiological Study of the Agent of Amebic
Meningoencephalitis 276
D. Task Statements - Human Health Criteria for Fish, Shellfish
and Irrigation Water Quality Standards
1. TASK 1.
Assessment of Problems Associated with Food Produced
with Polluted Water 277
2. TASK 2.
Accumulation of Contaminants by Fish and Shellfish 278
3. TASK 3.
Toxicology of Accumulated Contaminants in Fish and
Shellfish to Test Animals 279
4. TASK 4.
Accumulation and Survival of Contaminants in
Irrigated Crops 280
5. TASK 5.
Toxicology of Contaminants in or on Crops 281
E. Table 1 - Resource Estimate 282
VIII. Health Effects of Multimedia Toxic Substances
A. Summary 285
B. Task Statements - Hazard Awareness
1. TASK 1.
Establish a Comprehensive Environmental Information
System Which Will Include Data Relating to Toxicity,
Usage and Human Exposure 288
2. TASK 2.
Sponsor Briefings and Training Courses for Research.
and Development Scientists to Foster a Free Flow of
Timely Information 289
3. TASK 3.
Develop Rapid Relevant Standardized in vivo and
in vitro Screening Methods to Serve as Models
for Industry 290
4. TASK 4.
Identify New and Previously Unrecognized Human
Exposures to Toxic Substances 291
5. TASK 5.
Assure That Recycling and Reuse of Solid Wastes and
Water Does Not Unduly Increase Human Exposure to Toxic
Substances . 292
-------
xn
VIII. Health Effects of Multimedia Toxic Substances (Continued)
C. Task Statements - Confirmation of Human Safety
1. TASK 1.
Establish a Biochemical and Cytological Alarm System
Utilizing Sensitive Indicators of Adverse Health
Effects in Vulnerable Populations 293
2. TASK 2.
Surveillance of Specific Relevant Morbidity and
Mortality Patterns and Trends in Exceptionally
Exposed Groups and the General Population 294
3. TASK 3.
Quantitate the Effects of Accidental Release of
Environmental Chemicals Using Mobile Clinical
Laboratory Teams, Mobile Exposure Monitors and
Intensive Study of Exposure Victims 295
4. TASK 4.
Evaluate Impact on Existing and Pending Media and
Categorical Standards Through Laboratory Models
Using Cells, Organ Cultures, Intact Animals and
Human Volunteers 296
5. TASK 5.
Biological Models to Evaluate Impact of Toxic Substances
on Important Health Effects Other Than Cancer, Mutations
and Congenital Abnormalities 297
6. TASK 6.
Establish Exposure Surveillance Networks for Community,
Home and Highest Level Areas 299
7. TASK 7.
Devise and Deploy Surveillance Systems to Quantitate
Personal Exposure 300
8. TASK 8.
Establish a National Tissue Bank to Determine Human
Pollutant Burdens 301
9. TASK 9.
Develop Population at Risk and Health Cost Models from
Usage Patterns, Effluent Profiles, Exposure Data and
Predicted Effects 302
D. Table 1 - Resource Estimate 303
IX. Noise Health Effects Research
A. Summary 304
B. Task Statements
1. TASK 1.
Quantitate Population Chronically Exposed to Noise Levels
Above Postulated Irritation and Hearing Loss Thresholds 308
2. TASK 2.
Determine the Spectrum and Severity of Pathophysiologic
Effects Attributable to Noise Exposure Through Animal
Experimentation 310
3. TASK 3.
Determine the Threshold of Behavioral Changes in Humans
Associated With Chronic Exposure to Low Level Noise
Through Clinical Studies of Human Volunteers 311
X. National Center for Toxicologic Research (No Tasks Submitted)
A. Summary 313
-------
110203
PROGRAM ELEMENT NUMBER
RESOURCES STATUS SUMMARY
Biomedical Research
PROGRAM ELEMENT TITLE
EPA FY '73 Plan
B 1
Funding Type
$ (1000)
Positions
In-House
Grant
Contract
1516
1000
603
81
i
1
Program Element Total
3119
81
-------
B 2
A. PROGRAM ELEMENT NUMBER: 110203
B. TITLE: Biomedical Research
PREPARED BY: J. F. Finklea DATE: January 4, 1972
C. PROGRAM JUSTIFICATION: Assessment of the real or potential effects of
erivironmenta 1 pol 1 u tants on human health and welfare necessitates direct
studies of both human and animal systems to validate results of epidemiologic
studies; to develop new health indicators or techniques applicable to
epidemiologic studies; or to give indications of the potential toxicity
of new materials that might be introduced into the environment. Such studies
are essential to the establishment of defensible environmental standards not
excessively punative to industry yet adequate for the protection of human
health and welfare.
D. OBJECTIVES: To develop health effects information that will facilitate the
development or revision of criteria and standards for environmental pollutants;
to test the adequacy of current primary standards in protecting human health;
to identify hazardous materials which may need control actions; and to define
the biologic effects of pollutants singly, in combination, or as they are
affected by other environmental factors and at various levels of exposure.
E. SJflPE: The Biomedical Research Program consists of laboratory and clinical
studies of the effects of pollutants on human health. Emphasis currently is
placed on studies of carbon monoxide, nitrogen oxides, photochemical oxidants
and the toxicity of automotive emissions. Some effort is expended to assess
the carcinogenicity of airborne polycyclic organic matter and the toxicity
of selected trace substances. Studies undertaken include development of
techniques or methods for assessing the effects of particular pollutants,
assessment of the direct effects at various levels of exposure, assessment
of the effects of exposure on susceptibility or potentiation of other
diseases, and the development of appropriate instrumentation or techniques
that will permit measurements of the effects in CHESS.
Research tasks are grouped into four projects. CLEANS (CJinical Laboratory
^valuation and Assessments of hJpxious Substances) utilizes controlled dosing
of human volunteers and includes ten tasks. CLEVER (CLinical Environmental
Epidemiology Research) using a sophisticated mobile laboratory includes six
tasks. ACTIONS (Assessment of Cellular Tpxicity and Interactions Of Noxious
Substances) utilizes cells from animals and tissue culture and involves eight
tasks. Inhalation Toxicology utilizes controlled exposure of experimental
laboratory animals and involves six tasks.
F. RESULTS: The knowledge gained through Biomedical research will be made
available in a series of intramural and published reports relating
toxicological information to environmental quality. These reports will
provide health effects information for application toward epidemiological
studies as well as direct intelligence for the appraisal and setting of
environmental standards. The studies on carbon monoxide, oxidants and
nitrogen oxides will contribute to the revision of the respective criteria
and NAAQS. Other studies will assist in formulating decisions on the control
of fuel additives or other environmental pollutants.
-------
B 3
G. APPROACH: The Biomedical research program in an integrated series of
toxicological studies utilizing both animal and human inhalation exposure
facilities. Specific pollutant atmospheres are generated, monitored, and
provided to the experimental animals or subjects for specified periods of
time. Exposures may be of an acute short-term nature or of the chronic
long-term type. Effort is also directed toward defining the biologic fate
of environmental contaminants as well as the development of improved
methodology (animal model systems and measurement techniques) which may be
applied for the detection of pre-clinical effects and subsequently utilized
in epidemiological studies.
Animal toxicology is conducted to identify, quantitatively and
qualitatively the primary effects and target system; examine pollutants of
such character and/or concentration unsuitable for human studies due to
ethical as well as medical-legal limitations; provide in vitro manipulative
approaches to develop techniques for subsequent application to clinical and
epidemiological investigations; and provide chronic exposure conditions for
identifying potential carcinogenic, teratogenic and mutagenic effects.
Laboratory clinical investigations are used to develop improved methodology
for epidemiological studies; varify extrapolation of animal effects to man;
and test, in a cause and effect manner under controlled conditions,
correlative epidemiological results.
H. SUPPORTING CONTRACTS: (a) Experimental planning utilizes data available
through NADIS and Office of Fuels and Additives Registration; (b) Information
from BMSPC is needed for facility design for toxicity assessment of mobile
emissions; (c) Contracts: CRC-APRAC provides cooperative funds for effects
studies related to carbon monoxide. Contracts with non-government organizations
provide support to in-house programs in the areas of pollutant interaction and
carcinogenesis. The current contract effort utilizes $900,000 per year;
(d) Grants: support for research grants for the same type of work done under
this element total $785,000.
I. SPECIAL FACILITIES: The following special facilities are required:
Ta~) Automotive engines, dynamoneters, dilution systems, irradiation chambers,
animal exposure chambers; (b) Human environmental chambers. Beyond the
state-of-the-art, the following is required: (a) Equipment for telemetering
physiologic parameters; (b) Complex behavioral testing equipment for EEG,
time, object and pattern discrimination; and task performance with associated
program control computer.
J. INTERMEDIA RELATIONSHIPS: Anticipate relationships with other EPA Offices on
effects of pollution research.
K. COORDINATION: Liaison with AEC, NIEHS, FDA, NCI.
L. UNRESOLVED POLICY ISSUES: None
-------
BIOMEDICAL RESEARCH
SUMMARY COMPARISON
($ Million/MY)
Optimum
Minimum
Adequate
Add on*
Current*
FY 73
15.8/240
8.0/168
5.0/111
3.1/81
FY 74
16.1/234
9.0/162
6.0/111
FY 75
14.0/230
9.9/162
6.6/111
FY 76
14.1/220
11.0/162
7.3/111
FY 77
14.3/220
12,1/162
8.0/111
*Add on program level becomes the current program level in FY 1974 - FY 1977.
DO
-------
B 5
PROGRAM ELEMENT: 110203
PROJECT A - CLEANS
TASK 1. Effects of CO in persons with coronary artery disease,
A. PROGRAM JUSTIFICATION: CO interfers with tissue oxyqenation. Tissues
such as the heart which depend on an uninterrupted 02 sunply for survival,
might be particularly susceptible to hypoxid effects of CO. Exercise
electrocardiography is a useful and relatively sensitive noninvasive method
for evaluating myocardial oxygen supply relative to demand; measurement of
systolic time intervals before and after exercise gives information about
myocardial function. CO in low concentrations (100 pom) has been shown to
cause an increased incidence of abnormalities on exercise EKG's and altered
systolic time intervals in asymptomatic middle-aged men, who are known to
have a high incidence of asymptomatic coronary disease. Patients with
angina pectoris, who have a more serious degree of coronary disease, might
be even more susceptible to effects of CO.
B. OBJECTIVE: To determine the effects of 100 ppm CO on exercise electro-
cardiography and systolic time intervals in patients with stable angina
pectoris.
C. SCOPE: Experimental methods and instruments are currently operational
at N.C. Memorial Hospital. Exposure of 12 subjects and analysis of data
will be completed within the next 8-12 months.
D. RESULTS: Patients with angina pectoris may have decreased exercise
tolerance and oain threshold, more markedly abnormal exercise EKG's, and
abnormal systolic time intervals following CO exposure.
E. APPROACH: Twelve patients with stable angina pectoris will be recruited
from the outpatient department at N.C. Memorial Hospital. On each of 5 suc-
cessive days, they will be exposed to either air, 50 pom CO, or 100 ppm CO,
for 5 hours in a double blind manner. Following exposure, they will undergo
exercise electrocardiography and measurement of systolic time intervals before
and after exercise. Expired air and blood COHb levels will be measured before
and after each exposure.
F. SUPPORTING CONTRACTS: Contract with UNC School of Medicine, Department
of Cardiology.
G. SPECIAL FACILITIES: Provided by UNC per contract.
H. INTERMEDIA RELATIONSHIP: None
I. COORDINATION: None
J. UNRESOLVED POLICY ISSUES: None
-------
B 6
PROGRAM ELEMENT: 110203
PROJECT A - CLEANS
TASK 2. Effect of CO in myocardial infarction.
A. PROGRAM JUSTIFICATION: Both theoretical and epidemiological data suggest
an increased morbidity in patients with ischemic heart disease when exposed
to air pollution. Data from a prospective study evaluating the effects of
chronic low-levels of carbon monoxide, as are often seen in urban areas and
in smokers, on the prognosis of myocardial infarctions are needed.
B. OBJECTIVE: To determine the role of carbon monoxide in the natural
history of ischemic heart disease.
C. SCOPE: The scope of this task will be limited to the proposed approach
(vide infra), but more subtle parameters of cardiac function could be
investigated.
D. RESULTS: It is expected that there will be a statistically significant
increase in morbidity, and possible mortality, in the pigs exposed to
carbon monoxide.
E. APPROACH: Pigs will have a myocardial infarction induced by placing an
Ameroid constrictor around a coronary artery. In a controlled method, half
of the pigs will be exposed to 100 ppm CO. Parameters to be followed for
each group include: length of survival, incidence and arrhythmias, and
oathological examination.
F. SUPPORTING CONTRACT: Animal care facilities will be arranged.
G. SPECIAL FACILITIES: Both an animal operating room and exposure chambers
are required.
H. INTERMEDIA RELATIONSHIP: None.
I. COORDINATION: None.
J. UNRESOLVED POLICY ISSUES: None.
-------
B 7
PROGRAM ELEMENT: 110203
PROJECT A - CLEANS
TASK 3. Procurement of human environmental exposure facilities.
A. PROGRAM JUSTIFICATION: Controlled laboratory studies of physiologic
and behavioral responses in humans exposed to selected air pollutants,
odors, noise and microwave radiation are important to EPA objectives.
Procurement and installation of human exposure facilities should be
undertaken as a separate task.
B. OBJECTIVE: To provide EPA with intramural capability in human
environmental health effects research.
C. SCOPE: Specifications have been written for human environmental
exposure chambers. Procurement and installation will be coordinated
with construction of the Clinical Research Center.
D. RESULTS: An intramural human environmental exposure facility will be
available to respond to EPA requirements for data relating human health and
welfare to environmental conditions.
E. APPROACH: Procurement is pending approval.
F. SUPPORTING CONTRACTS: All hardware acquisition will be through usual
Federal procurement channels.
G. SPECIAL FACILITIES: This task is for procurement, installation,
and "shakedown" operation of referenced special equipment.
H. INTERMEDIA RELATIONSHIP: None.
I. COORDINATION: In-house investigative program.
J. UNRESOLVED POLICY ISSUES: None.
-------
PROGRAM ELEMENT: 110203
PROJECT A - CLEANS
TASK 4. Instrumentation of Human Exoosure Facilities,
A. PROGRAM JUSTIFICATION: Controlled laboratory studies of physiologic
and behavioral responses in humans exposed to selected air pollutants,
odors, noise and microwave radiation are important to EPA objectives.
Instrumentation and "shakedown" operation of projected exposure facilities
should be planned and undertaken as a separate task.
B. OBJECTIVE: To provide EPA with intramural capability in human environ-
mental health effects research.
C. SCOPE: Physiologic and behavioral monitoring sensors will be interfaced
with signal conditioning, data display, data storage and on-line process
control instrumentation. These will provide for controlling the environment,
determining human responses to the controlled environment, and analyzing
portions of the data in real time so that studies may be modified as may be
indicated by experimental results.
D. RESULTS: An intramural human environmental exposure facility will be
available to fulfill EPA requirements for data relating human health and
welfare to environmental conditions.
E. APPROACH: EPA Bio-Engineers are preparing specifications for the
referenced instrumentation. They will coordinate procurement and instal-
lation of these instruments from the appropriate vendors with procurement
and installation of the exposure facilities from a prime contractor.
F. SUPPORTING CONTRACTS: All hardware acquisition will be through usual
Federal procurement channels.
G. SPECIAL FACILITIES: This task is for procurement, installation, and
"shakedown" operation of referenced special equipment.
H. INTERMEDIA RELATIONSHIP: None
I. COORDINATION: In-house investigative program.
J. UNRESOLVED POLICY ISSUES: None
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B 9
PROGRAM ELEMENT: 110203
PROJECT A - CLEANS
TASK 5. Investigation of Growth of Lung Function in Children
A. PROGRAM JUSTIFICATION: As a result of limited methods available for
testing lung function in children, the established normal values are incomplete
(especially in the preschool age) and imprecise. Adaptation and supplementa-
tion of presently used pulmonary function tests for children, with longitudinal
study of a group of children would provide improved methods and more precise
normal values upon which to base future studies of the effect of environmental
pollution on the growth of lung function in children.
B« OBJECTIVE: To improve noninvasive methods for studying static and
dynamic characteristics of lung function in young children, and establish
more complete and precise ranges of normal values.
C. SCOPE;
(1) Collect and assemble required equipment
(2) Select and train subjects while determining which tests will
be most appropriate and informative
(3) Subject testing to include study of lung volumes, airway
conductance and flow distribution of ventilation, frequency dependent
of compliance and airway closure characteristics
(4) Approximately 50 subjects (ages 6 weeks to 5 years) to be included
initially for longitudinal testing. Additional 200 subjects (ages 6-
12 years) to be tested less frequently.
D. RESULTS: Improved techniques for testing small children and the
normal data obtained in this study will provide background and control
values for comparison with future studies of growth of lung function in
children resident in areas of environmental pollution.
E. APPROACH: Noninvasive tests such as spirometry, plethysmography, or
analysis of expiratory gas concentration curves will be used. The
possibility of mild exercise exposing more subtle abnormalities in lung
function will be investigated.
F. SUPPORTING CONTRACTS: Frank Porter Graham School, Child Development
Center for laboratory space.
G. SPECIAL FACILITIES: A pulmonary function laboratory will be
established at the Child Development Center. Dedicated data acquisition
instruments will be assembled from components.
H. INTERMEDIA RELATIONSHIPS: None
I. COORDINATION: None
J. UNRESOLVED POLICY ISSUES: None
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B 10
PROGRAM ELEMENT: 110203
PROJECT A - CLEANS
TASK 6. Development of Techniques for Studying Metabolism'and Physiology
of Isolated, Perfused Organs
A. PROGRAM JUSTIFICATION: Metabolic and physiologic studies of the effects
of pollutants on isolated organs can provide information on environmental
hazards more directly related to clinical effects than can studies in
unicellular systems.
B- OBJECTIVE: To adopt and improve existing techniques for studying
the function of intact, isolated, perfused organs, as well as develop
new techniques as necessary. Control and manipulation of the environmental
co-variables will provide a sensitive system for studying biological
effects of environmental agents.
C. SCOPE: Construction of necessary apparatus for maintaining function
of the isolated organ will be followed by in-house studies to establish
normal values for metabolic and physiologic function.
D. RESULTS: A biological system which minimizes intra-organism
covariates and gives maximal control over environmental covariates
will be produced for use in EPA environmental health research.
E. APPROACH: Techniques for studying isolated perfused lung will be
established first, followed by kidney and liver.
F. SUPPORTING CONTRACTS; None
G. SPECIAL FACILITIES: Perfusion apparatus will be constructed in EPA shops,
H. INTERMEDIA RELATIONSHIPS: Air, Water, Pesticides, Radiation Programs
I. COORDINATION: With media and category programs
J. UNRESOLVED POLICY ISSUES: None
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B 11
PROGRAM ELEMENT: 110203
PROJECT A - CLEANS
TASK 7. Development of Sensitive Neurophysiologic Measuring Techniques
A. PROGRAM JUSTIFICATION: Due to the extreme difficulty in measuring
and determining the physiological effects of low levels of pollutants on
man, it is necessary to continue the search for new measurement techniques
and efforts to improve the sensitivity and accuracy of established methods.
Independent studies have indicated subtle behavioral changes in human
exposure to carbon monoxide with possible changes in the surface negative
slow potential (CNV) of the brain. The combination of CNV and behavioral
changes with state-of-the-art electronics should permit the development
of a useful method for determining the effects of pollutants on man.
B. OBJECTIVE: To determine the influence of environmental pollutants on
the surface negative slow potential (CNV) in the human brain while
performing time discrimination tasks.
C. SCOPE: A preliminary system will be designed and operated within
approximately 6 months. This model system will provide information
necessary to refine the approach for further studies should the methods
prove feasible.
D. RESULTS: Methods will be developed and improved to measure subtle
changes in man as he is exposed to low levels of pollutants. Instruments
will be assembled from components.
E. APPROACH: In the first phase of the project, a temporary human CO
exposure system will be constructed with a time discrimination panel to
study the conditional reflexes of the exposed subjects. Several channels
of EEG signals will be recorded with the response of the subject to the
stimuli. A computer will be used to correlate the recorded data of CNV,
behavioral response, and pollutant concentration. The subjects will be
exposed to low and ambient levels of carbon monoxide.
F. SUPPORTING CONTRACTS: Computer processing of recorded data required.
G. SPECIAL FACILITIES: A man-size sound proof exposure booth with
appropriate safety, monitoring, calibrating, and stimuli equipment with
a bio-engineering support laboratory.
H. INTERMEDIA RELATIONSHIPS: The techniques developed should provide a
means for determining safe levels of many pollutants found in the environment.
I. COORDINATION: None at present
J. UNRESOLVED POLICY ISSUES: None
-------
PROGRAM ELEMENT: 110203
PROJECT A - CLEANS
TASK 8. Effect of CO Exposure on Human Performance Related to Vehicle
Driving Tasks
A. PROGRAM JUSTIFICATION: Previous studies have suggested that low
levels of COHb are associated with decrements in reflex time or visual
response, and as such could lead to serious secondary effects particularly
since CO is closely associated with the automobile. Therefore, in
cooperation with the Coordinating Research Council (CRC-APRAC) contractual
studies are being undertaken to determine the levels of CO or COHb that
might be associated with reduced driving ability.
B- OBJECTIVE: To determine the effects of CO exposure (or COHb level)
on actual or simulated driving performance.
C. SCOPE: Contracts have been awarded to investigators at Harvard and
at Ohio State University. At Harvard laboratory, tests of visual
sensitivity are conducted while at Ohio road tests are carried out.
Increased funding would permit an increased range of exposures and the
addition of further response parameters for measurement.
D- RESULTS; Information obtained will be directly applicable to the
revision of the Air Quality Criteria for Carbon Monoxide.
E. APPROACH: Contracts have been awarded to two institutions, one of
which tests subjects for the effects of COHb levels on response reactions
that are related to uriviny situations and the other conducts actual
road tests. The combination of these approaches permits one set of
investigations to be verified by the other.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: Harvard contractor has special exposure facilities
and Ohio State contractor has facilities for monitoring CO levels while
subjects are driving.
H. INTERMEDIA RELATIONSHIPS: None at present
I. COORDINATION: None at Present
J. UNRESOLVED POLICY ISSUES: None
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B 13
PROGRAM ELEMENT: 110203
PROJECT A - CLEANS
TASK 9. Metabolic Effects of Long-term Exposure to Lead Sesquioxide Aerosol
in Humans
A. PROGRAM JUSTIFICATION: The toxic effects of exposure to low levels
of lead is not completely understood and as a consequence control actions
related to airborne lead have of necessity been taken on the basis of
less than adequate information. This program is designed to provide
sufficient data to determine the adequacy of these actions.
B' OBJECTIVES: To determine the effect of continuous exposure to low
levels of lead on body balance or tissue loading. In addition, the
effect of exposure on selected metabolic parameters such as delta ala
in urine or in serum is determined as is the effect on other selected
enzymes.
C. SCOPE: The model of exposure and parameter measurement has been
developed and is implemented for one substance at one exposure level with
the present level of funding. With increased support, effort will be
expanded in a modular fashion to include additional exposure facilities,
an expanded exposure schedule, an increase in the metabolic parameters
measured, or an increase in the substances to which subjects are exposed.
D. RESULTS: Information obtained will be directly applicable to the
determination of appropriate control actions necessary to protect against
lead toxicity.
E. APPROACH: Studies call for direct exposure of human volunteers at
constant levels of atmospheric lead. Balance is determined by estimating
total intake and total excretion. Selected enzyme levels are measured
or determined from tests of blood or urine.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: Contractor has special facilities for exposing
human subjects.
H. INTERMEDIA RELATIONSHIPS: None at present
I. COORDINATION: Liaison with NIEHS, NIOSH
J. UNRESOLVED POLICY ISSUES: None
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B 14
PROGRAM ELEMENT: 110203
PROJECT A - CLEANS
TASK 10. Development of New Programs Including a Health Information System
A. PROGRAM JUSTIFICATION: Protection of human health against environmental
hazards is a tremendous task which requires constant development of new
approaches and new techniques to meet the challenge. Imperative to this
effort is a system whereby Health Information is available to permit
identification of potential problems and provide maximum information
related to these problems in the shortest possible time.
B. OBJECTIVE: A health information capability will be developed to
contain the best possible capability for reviewing lists of potential
environmental hazards, identifying the probable most significant health
problems and recommending research priorities.
C. SCOPE: At the present level of funding no work can be done in this
area. However, at the indicated minimal adequate level the program
would be initiated by using our present research staff. With increased
support additional staff would be hired and computer back-up would be
obtained to permit the greatest depth of readily available information.
^' RESULTS: Information would be directly applicable to the establishment
of future research priorities and hopefully would assure that more often
than at present effects data would be available at the time it is needed.
£ APPROACH: The health information capability will be developed from
present staff initially by assigning researchers to part-time participation.
Eventually, some of the staff would be full-time and given the responsibility
of summarizing information relative to particular problems and doing the
staff work necessary for assigning future research priorities.
F. SUPPORTING CONTRACTS: This effort probably would be supported by
contract arrangements with NLM or other library services.
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIPS: None
I. COORDINATION: Liaison would be necessary with many agencies
J. UNRESOLVED POLICY ISSUES: None at Present
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B 15
PROGRAM ELEMENT: 110203
PROJECT B - CLEVER
TASK 1. Acquisition, Instrumentation and Shakedown Operations of a
Mobile Laboratory
A. PROGRAM JUSTIFICATION: Air Quality Standards are established for
the purpose of protecting the health of populations against the effects
of ambient levels of environmental pollution. To determine the effects
produced by these ambient levels of pollutants the CHESS program has
been established. However, to provide a capability for evaluating and
validating the results of epidemiology studies in the same ambient
situations, a mobile laboratory will be developed to permit the utili-
zation of more sophisticated research tools.
B. OBJECTIVES: Develop the capability for conducting high level testing
of people in the neighborhoods in which they live, for testing the differences
in selected health parameters is so called "hot spots" of pollution or for
testing the effects of short term episodes of pollution on population when-
ever and where ever they occur.
C. SCOPE: A mobile laboratory containing all of the laboratory equipment
necessary for making comprehensive measurements of pulmonary or cardiac
function will be designed and developed for use in areas of high or low
pollution. Present funding will permit basic necessary equipment only.
As support is increased, additional and refined equipment such as continuous
air-monitoring instruments will be added as will a small computer to assist
in assimilating the information obtained.
D. RESULTS: Development of this mobile capability will permit an evaluation
and verification of epidemiologic results that will not otherwise be available.
Until such verification is obtained, results of epidemiologic studies will
almost certainly be attacked.
E. APPROACH: Several designs will be developed and appraised for cost and
information to be obtained. Once a decision on the best design is made, bids
from contractors will be solicited for its construction.
F. SUPPORTING CONTRACTS: For construction.
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIPS: None
I. COORDINATION: None at present.
J. UNRESOLVED POLICY ISSUES: None at Present
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B 16
PROGRAM ELEMENT: 110203
PROJECT B - CLEVER
TASK 2. Pollutant induced changes in subjects with asthma and chronic
bronchitis.
A. PROGRAM JUSTIFICATION: Field Studies have given indications of
variations in attack rates for asthmatics that are associated with
air pollution levels. Using the mobile laboratory, from which sophisticated
measurements of pulmonary function can be made, these results will be
evaluated in the same panel members utilized in the field studies and in
the same environment.
B. OBJECTIVES: To evaluate and verify the association between air
pollution and attack rates in asthmatics indicated by field epidemiologic
studies.
C. SCOPE: With present funds, the mobil laboratory will be used to varify
epidemiologic study in one area by studying subjects for a short time.
With additional support, the duration of study would be extended or
the number of areas in which the evaluation would be undertaken will be
increased.
D. RESULTS: Information obtained will be utilized directly to support or
refute field studies and through them the documents on Air Quality Criteria.
E. APPROACH: The population groups studied by means of epidemiologic
techniques will be studied more carefully and thoroughly by puting a
mobile laboratory in the area in which the subjects reside.
F. SUPPORTING CONTRACTS: None.
G. SPECIAL FACILITIES: The mobile laboratory is a unique facility essential
to this study.
H. INTERMEDIA RELATIONSHIPS: None.
I. COORDINATION: None.
J. UNRESOLVED POLICY ISSUES: None
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B 17
PROGRAM ELEMENT: 110203
PROJECT B - CLEVER
TASK 3. Effects of N02 and CO on Cardiovascular Physiologic Parameters
in Subjects with Clinical and Subclinical Heart Disease.
A. PROGRAM JUSTIFICATION: Epidemiologic studies have shown evidence of
association between air pollution and incidence of cardiovascular illness.
Such evidence is most useful for supporting or establishing environmental
criteria and standards but varifications of the indicated associations is
essential to judging the adequacy of control actions taken.
B. OBJECTIVE: To evaluate effects of diurnal variations of N02 and CO
on cardiovascular function in CHESS urban areas. Similar studies may be
undertaken should accidental releases of hazardous substances occur.
C. SCOPE: Initially, with present funding, studies will be limited to
evaluating CHESS results, with added support similar investigations will
be undertaken in other high pollution areas.
D. RESULTS: Information obtained will be directly applicable to setting
of adequate air quality standards to protect human health.
E. APPROACH: Using a mobile facility providing comprehensive laboratory
capabilities, the technique developed on the CLEANS project will be employed
with CHESS heart disease panelists to evaluate effects of diurnal variations
in N02 and CO on cardiovascular function.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: The mobile laboratory is a unique facility essential
to this study.
H. INTERMEDIA RELATIONSHIPS: None at present.
I. COORDINATION: None at present.
J. UNRESOLVED POLICY ISSUES: None
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B 18
PROGRAM ELEMENT: 110203
PROJECT B - CLEVER
TASK 4. Effects of oxidants, Nox, trace metals, synthetic organics and
atmospheric polycyclic aromatics on responses which are sentinels
for cancer or genetic mutations.
A. PROGRAM JUSTIFICATION: Epidemiology studies have demonstrated gross
direct association between higher pollution levels and increased incidence
of illness. It would be highly desirable to undertake more sophisticated
studies in the same areas and using the same subjects to develop more
accurate information that would be more applicable to a standard setting
need.
B. OBJECTIVE: To evaluate CHESS participants for cytogenic effects on
cultured blood cells and for cytologic changes in exfoliated lung cells.
C. SCOPE: At present funding levels studies will be limited to small
groups of subjects in a single CHESS area from whom sputum specimens can
be obtained. Cytological examinations would be made for inflammatory
and metaplastic changes. With additional support, additional studies
would be undertaken including staining for mucopolysaccharide production,
enzyme levels possibly associated with inflammatory responses, phagocytic
activity and trace element concentration.
D. RESULTS: Information collected would provide much better data than
are now available relative to air pollution and the incidence of lung
cancer. Previous studies have shown higher incidence of lung cancer in
urban areas even among non-smokers, but these have not been associated
with specific pollutants or levels of pollution. This study will begin
to gather these specific data.
E. APPROACH: Previous studies have demonstrated the feasibility of
collecting sputum specimens from human subjects. This technique will be
applied in CHESS areas to evaluate volunteers for cytological changes in
exfoliated lung cells and also for cytogenic effects suggestive of carcino-
genic activity.
F. SUPPORTING CONTRACTS: None.
G. SPECIAL FACILITIES: The mobile laboratory represents a unique facility
essential to this study.
H. INTERMEDIA RELATIONSHIPS: None at present.
I. COORDINATION: Liaison with NCI and NIEHS.
J. UNRESOLVED POLICY ISSUES: None.
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B 19
PROGRAM ELEMENT: 110203
PROJECT B - CLEVER
TASK 5. Neurophysiologic effects of exposure to CO, N02, oxiciants, noise,
odors and electromagnetic radiations.
A. PROGRAM JUSTIFICATION: Epidemiologic studies have indicated that ambient
air pollution levels do have adverse effects on human health and have provided
some information on the levels at which the effects occur. To obtain more
precise information on the mechanisms of these effects and the minimum
increases in pollution that will produce them, sensitive neurophysiologic
and behavioral measures developed in the CLEANS project will be deployed in
CHESS areas by utilizing the mobile laboratory capability, to evaluate the
effects of diurnal variations in pollutants on sensitive and subtle endpoints
of response.
B. OBJECTIVE: To validate and evaluate the results of epidemiologic studies
which have provided gross information on the association of increased health
risks with higher air pollution levels.
C. SCOPE: Plans and equipment are designed for and capable of studying CO,
N02> oxidants, noise, odors, electromagnetic radiations, or any other pollu-
tant. At present funding levels the materials can be studied one at a time
and approximately four studies can be completed each year. With increased
funding additional materials could be studied with the maximum of about 12
studies per year being limited only by the number of people that can operate
in the mobile facility.
D. RESULTS: Information obtained from these studies will be directly appli-
cable to standard setting processes or decisions concerning other control
actions.
E. APPROACH: Using the mobile laboratory facility which provides the capa-
bility of taking sophisticated laboratory equipment and techniques into resi-
dential areas, the same populations included in CHESS will be studied more
comprehensively to validate the epidemiologic results, and to indicate more
precisely the mechanisms of action and the pollution levels at which they are
initiated.
F. SUPPORTING CONTRACTS: None.
G. SPECIAL FACILITIES: The mobile laboratory constitutes a unique facility
essential to this study.
H. INTERMEDIA RELATIONSHIPS: None.
I. COORDINATION: Liaison with NIEHS and NIOSH.
J. UNRESOLVED POLICY ISSUES: None.
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B 20
PROGRAM ELEMENT: 110203
PROJECT B - CLEVER
TASK 6. Effects of Short-term Exposure Variations in Oxidants, NOX, SOX,
Total and Fine Particulate on Red Blood Cell Membrane and Enzyme
Characteristics in a Community Study
A. PROGRAM JUSTIFICATION: The responsibility of EPA is the protection
of human health against hazardous environmental pollution. This
responsibility is fulfilled by determining in the laboratory the initial
subtle effects that may serve as sentinels of pollution effects, developing
techniques for measuring these effects in the field and finally determining
the ambient levels of pollution at which these initial indications, of
effects can be detected in populations. This program represents the final
step in this procedure.
B. OBJECTIVES: Using techniques and methods developed on the CLEANS
project, pollutant induced changes in rbc membranes and enzyme function
will be determined in selected CHESS areas.
C. SCOPE: Studies are designed in modules. At present funding levels
the CLEANS project will proceed more slowly and consequently this study
will be delayed. Initial investigation would consist of limited study in
a single CHESS area of rbc morphology and activity of one or two enzymes.
Additional support would speed the CLEANS project and permit this study
to develop more rapidly. Optimum support would permit comprehensive study
in a minimum of three areas with measurement of at least six parameters.
D. APPROACH: Methods and techniques for studying sensitive health
indicators are developed on the CLEANS project and then applied to field
situations by utilizing a mobile laboratory facility. Usually the site
of the field studies are CHESS areas in which data are utilized to evaluate
and verify the results of epidemiologic studies.
E. RESULTS: Information obtained is directly applicable to the standard
setting processes or decisions concerning other control actions because all
data relate to the effects of pollution in ambient situations.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: The mobile laboratory represents a unique facility
essential to this study.
H. INTERMEDIA RELATIONSHIPS: None
I. COORDINATION: Liaison with NIEHS and NIOSH
J. UNRESOLVED POLICY ISSUES: None
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B 21
PROGRAM ELEMENT: 110203
PROJECT C - ACTIONS
TASK 1. Effects of Air Pollutants on Pulmonary Defense Mechanisms
A. PROGRAM JUSTIFICATION: Many studies have demonstrated increased
incidence of disease in areas of higher air pollution. This task is
designed to determine the mechanism of pollutant action that produces
this greater level of illness and the dose response relationships at
various exposures.
B. OBJECTIVES: To evaluate the effects of inhalation of selected
pollutants on the pathogenesis of pulmonary disease. Specifically
these studies will relate to the effects of HC1.
C. SCOPE:
Present
1. Evaluation of the
effect of inhalation of
pollutant gas and an
infectious bacterium.
Test parameters:
a. Mortality
b. Growth and persis-
tence of microbes in the
lung.
c. Invasion of the
blood.
2. Evaluation of the
effect of pollutant gas
on the pulmonary defenses,
Test parameters:
a. Alveolar macrophage
viability.
b. Alveolar macrophage
stability.
c. Alveolar macrophage
morphology.
d. Alveolar macrophage
function (phagocytic).
3. Pathological examination
of exposed and normal tissue.
a. Light microscope
Minimal Adequate
1. All of the minimal
effort plus the evalu-
ation of the effect of
inhalation of a pollutant
gas and a viral agent.
Test parameters:
a. Same as found in
minimal effort plus
additional immunolog-
ical indicators such as:
1) Antibody production
2) Antibody persistence
2. Intracellular effect
of pollutant on alveolar
macrophage.
a. Acid phosphatase
. b. Lysozyme
c. Beta glucuronidase
3. Pathological exami-
nation of exposed and
normal tissue.
a. Light microscope
b. Electron microscope
Optimal
1. All of the min-
imal adequate effort
plus the following
investigations.
a. Evaluation of
immunoglobulin re-
sponse. Test param-
eters will be:
(1) Serum, IgA, IgM,
19 i
(2) Serum C's com-
plement.
2. Effects or,
acellular milieu.
a. Surface active
properties.
b. Protective nature.
3. Alteration of
mechanical defense.
a. Mucociliary
clearance.
b. [^ucus production.
4. jn vitro exposure
of continuous cultures
of human and animal cell
lines to gaseous pol-
lutants. The cell lines
which could be used ar
HeLa, WI-38, normal
deploid or others. ELx-
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B 22
Optimal (Continued)
posures would include
both .acute & chronic
conditions and para-
meters studied will be:
a. Cellular division
b. Chromosome
analysis
c. Cell morphology
d. Nucleic acid
synthesis.
D. RESULTS: Present funding: Information relative to the effects of
inhalation of HC1 on bacterial infections will be available in FY 1974 and
can be utilized to support air quality standards. Information on viruses,
immunoglobulins or -mechanical defenses would not be available at this time.
Minimal adequate funding: Information for both bacterial and viral
agents would become available, in FY 1974 or FY 1975. Studies of immuno-
globulin and mechanical defense systems would still be delayed.
Optimal funding: In FY 1974 or FY 1975 data on bacterial agents,
viral agents and mechanical defense systems will be available to assist
with the development of adequate control of HC1 pollution.
E. APPROACH: A mode system has been developed that can be utilized for
these studies. Therefore, funding level limits the number or variety of
infectious agents that can be studied and the specific parameters that
can be utilized to determine effects.
F. SUPPORTING CONTRACTS: Contract work with the Illinois Institute of
Technology in the amount of $100,000 annually has assisted with the
development of techniques and methods used in the model system. This
contract work will continue but will not study HC1.
G. SPECIAL FACILITIES: Gas generating and monitoring capability for
exposure chambers.
H. INTERMEDIA RELATIONSHIPS: None at Present
I. COORDINATION: NIEHS, NCI.
J. UNRESOLVED POLICY ISSUES: None
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B 23
PROGRAM ELEMENT: 110203
PROJECT C - ACTIONS
TASK 2. Influence of Hazardous Substances on Cellular Physiology
A. PROGRAM JUSTIFICATION: The greatest concern of environmental pollution
control officials is the protection of human health or welfare against the
effects of chronic exposure to low levels of toxic materials. Information
related to these types of effects can be obtained first from in vitro
systems to learn something of the dose response relationships~Tnd~th₯
mechanisms of action. These preliminary data provide the basic tools
with which studies of animals or humans can be undertaken.
B. OBJECTIVES: Cell and organ culture techniques are employed to screen
for potentially hazardous substances and to determine the mechanisms of
cytotoxicity.
C. SCOPE:
Present
1. Each pollutant is test-
ed in "acute" experiments in
an alveolar macrophage
system ^n_ vitro.
2. Parameters investigated:
a. total cell counts
b. differential cell
counts
c. response to exposure
including:
(1) stability
(2) viability
(3) morphology
(4) function
(5) quantitation of
trace element uptake
3. C.yto-toxicological
evaluation of each
pollutant in three human
cell lines in "acute"
and "chronic" studies.
4. Parameters investigated:
a. chromosome numbers and
karyology
b. total cell counts or DNA
Minimal Adequate
1. All of minimal s'tart
up effort plus: "recovery"
studies in alveolar macro-
phage and tissue culture
systems.
2. Addition parameters
investigated:
a. response to exposure:
(1) hydrolytic enzyme
activities (macrophages)
a) acid phosphatase
b) lysozyme
c) beta-glucuronidase
(2) uptake and incor-
poration of labeled and
unlabeled pollutants
(both systems)
(a) autoradiography
(b) differential
centrigugation
(c) beta and gamma
isotope counting
(d) stable form analysis
(3) isotopic study of DNA,
RNA, and protein bio-
synthesis in both systems.
Optimal
1. All of minimal
adequate effort
plus:
a. detailed invest-
igation of:
(1) toxic effect
at various staces
of cell growth and
division cycle
(using synchronized
cells).
(2) enzymatic a--1
macromolecular
interation (in
both systems).
(3) specific effects
on differentiated
systems using oraan
culture techniqjes.
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B 24
Present (Con't) Minimal Adequate (Con't)
c. mlcrobial- contamination (4) detcrmination of
d. response to exposure: mitotic indices and de-
tailed karyological
1 growth analysis (tissue culture
(2) DNA content system)
(3) morphology
(4) cell size
(5) total protein
content
(6) quantitation of
trace element uptake
D. RESULTS: Present funding will permit limited study of three substances
a year. Additional funds would be utilized to provide additional and more
comprehensive studies of these carefully selected substances rather than
undertaking a cursory screening survey of many materials. Optimal funding
would permit extensive study of approximately five substances per year.
E. APPROACH: Established techniques are utilized for culturing in vitro
systems to be exposed to various levels of the pollutants. At basic
funding levels studies are limited to gross cellular alterations effected by
pollutants. As additional funds become available the model is modified
very little, but the studies of effects on physiology become increasingly
sophisticated.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIP: EPA media offices
I. COORDINATION: NIEHS, NIOSH, NCI
J. UNRESOLVED POLICY ISSUES: None
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PROGRAM ELEMENT: 110203
PROJECT C - ACTIONS
B 25
TASK 3. Physiologic and Pathologic Studies of Pulmonary Response to Hydro-
carbon Air Pollutants in Syrian Golden Hamsters
A. PROGRAM JUSTIFICATION: Much information has been collected on the
identification of airborne hydrocarbons as carcinogens in particular
experimental situations. However, little is known concerning thp
efficiency of the carcinogens when inhaled or about dose-response
relationships.
B- OBJECTIVES: Develop and utilize a model system using inhalation
techniques to study the dose-pathologic and physiologic response relation-
ships between animals and hydrocarbons previously shown to be carcinogenic
by intratracheal methods.
C. SCOPE:
Present
1. Dose-Pathologic
Response Studies using
BaP, Fe^03, & BaP + f'e203.
Determination of Dose
Exposure of animals
Pathologic Study
2. Dose-Physiologic
Response Studies
Clearance of BaP
following a single dose.
Cellular response
following a single dose.
Parameters:
Macrophage number
Viability
BaP content
Mi n i mn1 Adcquate
1. All of minimal
start up effort.
2. Dose-Physiologic
responso studies
following multiple
exposures.
Clearance of BaP
Cellular response
Parameters:
Macrophage number
Viability
BaP content
Function
Optimal
1. All of minimal
adequate level.
2. Studies using
air particulate,
other carcinogens
and other cofactors,
Determining dose-
pathologic
response.
Determining dose-
physiolorric
response.
3. Studies using
macrophage free
hamsters.
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B 26
D' RESULTS: Infonnation obtained from these studies are directly
applicable to one of the most significant public health problems facing
the world's population today. At the present level of funding, eight
years will be required to produce the same results that can be obtained
in less than three years at optimal funding level.
E. APPROACH: A model system is being developed for these studies. Our
approach is to undertake basic studies and gross examinations at lowest
levels of funding and then to increase sophistication and comprehensiveness
as more support is made available.
F. SUPPORTING CONTRACTS; Atmospheric particulates are collected and
extractions are made under contract with the Pressure Chemical Company
of Pittsburgh, Pennsylvania. The prepared extracts are utilized in an
aerosol generator also developed by this contractor.
G. SPECIAL FACILITIES: A uniform and consistent aerosol generator and
adequate exposure facilities are necessary for these studies.
H. INTERMEDIA RELATIONSHIPS: None
I. COORDINATION: NCI, NIEHS, FDA, AEC
J. UNRESOLVED POLICY ISSUES: None
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j B 27
PROGRAM ELEMENT: 110203
PROJECT C - ACTIONS
TASK 4. Influence of Environmental Pollutants on Red Blood Cell Function
A. PROGRAM JUSTIFICATION: Health effects of pollutants begin as subtle
alterations in metabolic or physiologic activity which only after increased
or extended exposure develop into significant illness. Since blood is the
second interface between man and his environment it is logical that many
of these subtle effects may occur here. Blood changes could be determined
relatively easily in populations also if the laboratory studies could
develop appropriate tests to be used.
B. OBJECTIVES: Determine the effect of pollutants on the ability of
blood to transport oxygen and maintain viable erythrocytes.
C. SCOPE;
Description # of Items Cost
Water Baths 2 1,200.
Flame Photometer 1 2,800.
TOTAL 18 83,000.
Levels of Effort
Present
1. NO tested in "acute" and "chronic" phase at three dose levels, and four
time intervals using a total of 400 animals with 8 animals per group.
2. Parameters.
a. hematocrit.
b. sodium and potassium levels.
c. 2,3-DPG levels.
d. Oxygen dissociation on 13% of group samples.
e. mechanical fragility on 13% of group samples.
f. hemoglobin levels.
g. methemoglobin levels in 50% of group samples.
h. pyruvate/lactate ratios in 25% of group samples.
i. lactic dehydrogenase and glucose-6-P04 dehydrogenase activity in 25% of
group samples.
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B 28
Minimal Adequate
1. N02 tested in "acute" and "chronic" phase at three dose levels and four time
intervals using a total of 800 animals with 16 animals .per group.
2. Parameters.
a. hematocrit.
b. sodium and potassium levels.
c. 2,3-DPG levels.
d. oxygen dissociation on 191 of group samples.
e. hemoglobin levels.
f. mechanical fragility on 30% of group samples.
g. methemoglobin levels in 75% of group samples.
h. pyruvate/lactate ratios in 20% of group samples.
i. lactic dehydrogenase and glucose-6-PO« dehydrogenase activity in 20%
of group samples.
Optimal
1. NOp tested in "acute" and "chronic" phase at three dose levels and four time
intervals using a total of 800 animals with 16 animals per group.
2. Parameters.
a. hematocrit.
b. sodium and potassium levels.
c. 2,3-DPG levels.
d. oxygen dissociation of 19% of group samples.
e. hemoglobin levels.
f. mechanical fragility on 50% of group samples.
g. study on mechanism of action of 2,3-DPG regulation.
h. methemoglobin levels in 100% of samples.
i. pyruvate/lactate ratios in 50% of group samples.
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B 29
j. lactic dehydrogenase and glucose-6-PO^ dehydrogenase activity in 50%
of samples.
k. hemoglobin and erythrocyte membrane protein profiles.
1. lipid peroxidation determinations.
m. serum protein profiles.
n. serum lipoprotein profiles.
o. RBC membrane lipid profiles.
D. RESULTS: Data obtained from this study could be most useful in
epidemiologic studies of populations. In addition, the greater the
sophistication introduced into the laboratory effort the greater the
liklihood that useful tools will result that can assess the effects of
exposure to ambient levels of pollution.
E< APPROACH: A model system.is being developed whereby rbc's can be
exposed to pollutants. Once the model is established with the basic
funding, additional support will be utilized to increase the comprehensiveness
of the effort to determine initial metabolic, physiologic or morphologic
alterations that can be usefully applied to field studies.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: Special facilities for effecting exposure to
pollutants are necessary for these studies.
H. INTERMEDIA RELATIONSHIPS: Liaison is maintained with other EPA
offices interested in health effects.
I. COORDINATION: NIEHS, NIOSH, AEC, FDA
J. UNRESOLVED POLICY ISSUES: None
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B 30
PROGRAM ELEMENT: 110203
PROJECT C - ACTIONS
TASK 5. Interactions of Various Pollutants on the Causation of Pulmonary
Disease
A. PROGRAM JUSTIFICATION: Previous efforts have developed a model system
in which air pollutants at very low levels encourage the development of
bacterial and viral pneumonias. For instance, a two-hour exposure to 3.5
ppm and as little as three months intermittent exposure to 0.5 ppm N02
have been shown to enhance bacterial pneumonias. Interaction with tobacco
smoke further enhances the effect of N02 in promoting bacterial and viral
penumonias in mice and squirrel monkeys. This work has produced a very
significant amount of data utilized in the air quality criteria document
on N02-
B. OBJECTIVE: The purpose of the extension of this contract is twofold:
(1) to pursue the effect of NQ2 exposure on the immune systems and to
explore the relative weight of peaks versus steady dose in effect of N02
and (2) to pursue the effect of trace metals singly and in interaction
with N02 to determine whether there is synergism.
C. SCOPE: Present funding - The scope of the contract will be altered to
provide for quantative measure of immune response in vaccinated animals
exposed to N02- Considering the interaction of trace metals, a preliminary
feasibility study will be undertaken for the contractor to develop
information and preliminary data on the following problems.
(1) Availability of trace elements of respirable size
(2) Analysis of deposition and retention of the particles
(3) Development of aerosol capabilities
Input from DER will determine selection of dose levels and selection of which
metals should be tested, taking into consideration the availability of
particles suitable for aerosolization as well as program needs.
Minimal adequate funding or optimal funding would permit an
additional contract to validate information obtained and to develop
information relative to other trace materials.
D. RESULTS: This is a continuing contract from which considerable
information relative to the effects of N02 on the causation of disease
has been obtained in the past. The data obtained have been relevant to
the standard setting process and it is expected that subsequent data
would be equally relevant to determining the need for control actions for
trace materials.
-------
6 3]
E. APPROACH: The contractor (IIT) has unusual competence and facilities
for undertaking these studies. The model systems developed with NOg
exposure is being extended to study other pollutants. At higher levels
of funding this contract would be extended or expanded to cover a greater
number of trace materials, but new contracts will be negotiated in
addition so that the widest variety of test parameters and competencies
could be applied to the studies.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES; Contractor has developed special exposure
facilities and the staff competencies for undertaking these studies.
H. INTERMEDIA RELATIONSHIPS: Other interested research units within
EPA are kept abreast of developments on this contract.
I. COORDINATION: Liaison with NIEHS
J. UNRESOLVED POLICY ISSUES: None
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B 32
PROGRAM ELEMENT: 110203
PROJECT C - ACTIONS
TASK 6. Biological Effects of Trace Substances and Tobacco Smoke in Inter
Actions with Nitrogen Oxides
A. PROGRAM JUSTIFICATION: N0£ is known to be a significant lung irritant.
However, less is known about the secondary effects of N0£ exposure or
effects of known combinations of NO/ and other materials. In ambient
atmosphere, N0£ never occurrs alone. In fact, the same processes that
lead to higher levels of NOX usually produce other pollutants as well.
Consequently, information on the effects of exposure to low levels of
the combinations of pollutants is needed for the establishment of adequate
environmental standards.
B. OBJECTIVE: To determine in animals the effect of exposure to
simulated ambient combinations of NOX and trace substances on biological
parameters such as body weight, respiratory rate, rbc counts or rbc
morphology.
C. SCOPE: Under previous contract a research model was developed for
studies of biological effects of NOX exposure. The present work represents
an extention of this effort. At present funding levels exposure schedules
are simple and measurements of effects based on gross observations. As
support is increased the number of parameters is to be increased and the
sophistication of measuring effects is improved.
D. RESULTS: Information obtained is highly relevant to determinations
of type and extent of control actions that might become necessary.
E. APPROACH: The exposure model has been developed and utilized for
some time. The funds that can be made available determine the variation
in exposure schedules that can be studied as well as the number of health
parameters that can be observed.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: Contractor at the Stanford Research Institute has
developed the special exposure facilities necessary for the studies.
H. INTERMEDIA RELATIONSHIPS: None
I. COORDINATION: Liaison with NIEHS
J. UNRESOLVED POLICY ISSUES: None
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B 33
PROGRAM ELEMENT: 110203
PROJECT C - ACTIONS
TASK 7. Procurement and Preparation of Airborne Carcinogens
A. PROGRAM JUSTIFICATION: Carcinogenic properties of many hydrocarbons
have been adequately demonstrated. However, the relationships between
inhaling ambient levels of hydrocarbons and the incidence of cancer are
unknown, and efforts in this area of research are just beginning. It is
imperative that the EPA obtain as much data as possible to permit the
establishment of adequate control procedures.
B. OBJECTIVES: Provide quantities of crude airborne particulates suitable
for dispersion in animal exposure chambers in test of their carcinogenicity.
C. SCOPE: At present levels of funding sufficient material is obtained
to undertake in-house studies of carcinogenesis. At increased levels
additional material would be obtained so that duplicate tests might be
conducted in other laboratories and that further purification of the
materials might be made or that more comprehensive exposure schedules
for animals can be planned to provide maximum evidence relative to the
carcinogenicity of the material and the kinds of exposure which enhance
its activity.
D. RESULTS: Information is directly applicable to the determination
of the type and extent of control actions necessary.
E. APPROACH; Previous studies have demonstrated the carcinogenicity
of many hydrocarbons when administered by routes other than inhalation.
The proved carcinogens will be utilized but studies will determine the
incidence of illness when exposure is by the inhalation route.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIPS: Relationships have been established with
other EPA offices interested in carcinogenesis.
I. COORDINATION: Liaison with NCI, NIEHS, AEC, FDA
J. UNRESOLVED POLICY ISSUES; None
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B 34
PROGRAM ELEMENT: BIOMEDICAL RESEARCH - 110203
PROJECT C: ACTIONS
TASK 6. Pulmonary Effects of Chronic Exposure to Oxidants, Ionizing Radiation
and other Environmental Pollutants and Contaminants.
A. PROGRAM JUSTIFICATION: Effects of simultaneous exposure to many pollutants
are not well defined.For example, oxidants such as ozone, ionizing radiation,
trace metals, such as cadmium and manganese, and pesticides are known to cause,
individually, relatively serious pulmonary effects when inhaled. Since a definite
possibility for simultaneous exposure to these pollutants exist, some indication
of the type of effect produced is essential to determine adequacy of existing
standards.
B. OBJECTIVE; To establish the response differences between individual and
multiple pollutant exposures.
C. SCOPE: The scope of this task is one of providing the information to fill
the "gaps" in the existing knowledge concerning effects of multiple exposure.
An evaluation of the problem of multiple exposure points up several combinations
of pollutants that are, at the present time, likely to be encountered. Therefore,
those combinations which are most relevant will be attacked first using short-
term studies in animals to obtain the needed biological data.
D. RESULTS: With proper funding it is expected that information necessary to
confirm the adequacy of or need to change existing standards will be obtained.
E. APPROACH: Briefly, the approach entails a systematic series of animal ex-
posures. The animals will be exposed to realistic levels of various combinations
of environmental pollutants. Initial concern is with ozone inhalation combined
with periodic external gamma exposure, to simulate the diagnostic x-ray exposure
of the urban resident from known high ozone areas. The next combinations of
apparent high priority is ozone and pesticide exposure. Two pesticides of immediate
concern are Captan and Difolitan. Each will be studied in combination with ozone.
The effects will be measured using early-occurring indices such as cytogenetic
changes, enzymatic changes, and other physiological alterations. In selected
instances some animals will be retained for longer study. In most cases, screening
studies will be less than one year in duration.
F. SUPPORTING CONTRACTS: Pathology support will be obtained from one of two area
universities (Oklahoma State U. or Colorado State U.).
G. SPECIAL FACILITIES: Requires some modifications of existing exposure chambers.
All other facilities and pollutant generators are available.
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B 35
H. INTERMEDIA RELATIONSHIPS; Air
I. COORDINATION: Dr. David Coffin, RTP.
.0. UNRESOLVED POLICY ISSUES: None
-------
B 36
PROGRAM ELEMENT: BIOMEDICAL RESEARCH - 110203
PROJECT D: INHALATION TOXICOLOGY
TASK 1: Comparative Hazards of Mobile and Stationary Source Emissions,
A. PROGRAM JUSTIFICATION: Experimental data concerning relative hazards to
health and welfare from emissions of various mobile and stationary enerqy and/or
disposal systems are required due to a leqislative mandate. Adequate data is
lacking. This task is designed to produce required data, through controlled
laboratory investigation, in time required by EPA program.
B. OBJECTIVE: Evaluate comparative environmental health and welfare hazards
of emissions from several mobile (automotive, diesel, aviation) and stationary
(heating) fuel-combustion, and from waste disposal (urban waste and sewage sludge
incineration) systems.
C. SCOPE:
LEVEL OF EFFORT:
Subtasks: Hazards evaluation of PRESENT MINIMUM ADEQUATE OPTIMAL
1. Automotive emissions + v + +
2. Diesel emissions + + +
3. Stationary fuel emissions + +
4. Aviation fuel emissions +
5. Sewage sludge incineration + +
effluents
6. Municipal waste incineration + +
effluents
Test Parameters for above studies:
Short term exposures--
Mortality + + +
Body weight +(lim.) + ++
Morbidity, etc. + + +
Neurobehavioral +(lim.) + +
Pathologygross, micro +(lim.) + ++
OtherOncogen, plants, aquatic +(lim.) + ++
Biochemistry +(lim.) + +
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B 37
LEVEL OF EFFORT:
Subtasks: Hazards evaluation of PRESENT MINIMUM ADEQUATE OPTIMAL
Subacute
Body weight, morbidity, etc. +(1im.) + +
Mortality + + +
Reprod. Funct., neonate survival +(1im.) + +
Teratogenicity +(lim.) +
Oncogenicity +(lim.) +
Cell culture system +(lim.) +
Pathology--gross +(lim.) + +
micro + + +
-EM +(lim.) +
Neurobehavioral +(lim.) + +
Biochemicaleffects +(lim.) + ++
tissue anal. +(lim.) +
Hematology, CO-Met-Hb +(lim.) + +
Lung defense systems + +
Immunol. competence +(lim.) + +
Aquatic life system +(lim.) + +
Vegetation-soil system +(lim.) + +
Suscept. to physical stress + +
Aerobiology +
Cytogenetics +(1im.) +
Longevity effects +(lim.) +
Cardiopulmonary studies +(lim.) +
D. RESULTS: "Present level"--information concerning relative severity of acute
effects of emissions from gasoline and diesel systems, comparing 4-5 fuels
(gasoline, and 2 diesel types), 1 or 2 fuel additives, and an emission control
device, E.G. catalytic muffler; also, subacute effects1 severity comparing 2
selected generation variables stationary source and waste incineration studies.
Optimal -- broader spectrum studies of aviation and sewage incineration effluents.
E. APPROACH: Expose selected subjects to emissions at gradient exposure levels
generated by appropriate model or simulator systems, and make numerous biological
determinations at appropriate stages and with respect to parameters of biomedical
importance. Also perform analyses to define fuel (or waste) and the emissions,
for correlating with effects.
F. SUPPORTING CONTRACTS:
Analytical, pathology, bacteriology,
immunology, pulmonary defenses..
6. SPECIAL FACILITIES: Additional generator systems for "min. adequate" level;
irradiation, exposure, and animal care for "optimal" level available presently
in NERC, Cincinnati.
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B 38
H. INTERMEDIA RELATIONSHIPS: Coordination with air, solid waste, ecological
groups as well as with health effects; results should be of interest to several
programs.
I. COORDINATION: NIEHS, NCI; intra-EPA centers and programs.
J. UNRESOLVED POLICY ISSUES: Should have information from policy levels regarding
current research need priorities for maximal pertinence of this program's efforts.
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Program Element 110203-/ Biomedical Research
Project D: Inhalation Toxicology
B 39
TASK 2.
Maintenance and Observation of Female Beagles previously exposed for 5 years to
Auto Exhausts and Other Pollutants. (Continuing task, contract CPA 66-02-0323 -
University of California)
A. JUSTIFICATION:
It is essential to continue the observations of the effect of prior chronic exposure
to fuel emissions and other pollutant on aging processes in female beagles. These
animals were exposed for 5 years to high community levels of pollution.
B. OBJECTIVES:
To determine the effects of chronic exposure to auto exKausf,'SOx" and MOX "atmospheres
on subsequent development of diseases associated with aging processes.
C" SCOPE:
Second year (FY "73) contract .(renewable for a period of 1-3 years). Provide
housing, care, hematologic measurements and physical examinations for the re-
mainder of CAE study survivors (presently 89) ; also necessary necropsies and
tissue processing for histopathology. Data evaluation. and reporting is
included .
w
'D. RESULTS: .
Quarterly reports with quantitative data and clinical observation. Data obtained
will relate to the adequacy of present air quality standards to protect against chronic
effects of exposure to these pollutants.
E. APPROACH;
Provide, housing, animal care, clinical cate ^ exan.inatlons^hematologlc
measurements, attritional necropsies and t.ssue Pro«"^ £o. foimerly e..Pos
dogs during development of senescence processes, and assess the effects
exposure .
F. SirPPORTINS CONTRACTS;
.
histopathology, data processing, and other biological determinates .
G.
Provided by contractor.
H. iNmsRMiDT^MJ^n
None anticipated.
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B 40
I. COORDINATION:
Contractor: In-house staff coordination essential for satisfactory conduct
and results.
J. UNRESOLVED POLICY ISSUES;
Need to establish criteria determining duration of observation, i.e., if
and v;hen to terminate study, sacrifice animals. This will be done on a
consultant basis with a panel of pathologists, (estimated additional cost
in FY '73 - $2,000) .
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B 41
Program Element 110203c Biomedical Research
Project D: Inhalation Toxicology
TASK 3.
Analysis for Biochemical Changes in Laboratory Animals Exposed to Fuel
Emissions and/or Trace Metals.
A. JUSTIFICATION:
Fuel emissions, trace metals and various other pollutants are known to
interfere with many important metabolic reactions in normal metabolism.
We propose to investigate the effects of fuel emissions and trace
elements in accordance with the Sections 103 and 104 of the Clean Air
Act.
B. OBJECTIVE:
To investigate acute and subacute biochemical effects of fuel emissions
and/or trace metals at the cellular and subcellular levels using known
sensitive indicators. In part, this is a feasibility study to see if
certain enzymes or other biochemical parameters may be used as sentinels
of early biochemical damage and how these systems change in response to
exposure to fuel emissions.
When this biochemical screening system is established it should be a
useful tool for community studies such as CHESS and CLEANS especially
since the blood, along with other tissues will be studied.
C. SCOPE:
All experimental animals will be obtained from projects under TAME. Specific
plans and schedule of animal exposure are described in TAME project protocols.
The activity of 6-aminolevulinic acid dehydratase, glucose-6-phosphate
dehydrogenase and fatty acid synthetase which represent hematopoietic
system glycolytic metabolism and fatty acid metabolism, respectively,
will be determined.
D. RESULTS:
This study should contribute significantly to the A1r Quality Standards
by providing nsw and/or additional Information on the adverse effects
of fuel emissions and/or trace ratals.
L. APPROACH;
Twenty males and twantv females from each of ten acute and two subacute
studies (please refer to TAME protocol for details) will be subjected
to biochemical screening as described atovo.
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B 42
F- SUPPprJIMG CONTRACT;
Nona (unfor "Prosnnt" and "Minimal Adequate"). One ("Optimal").
Re-cording spectre-photometer - $16,000.00.
None,
I. COORD I NAT I (-M:
Nons.
None.
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B 43
j
Program Element 110203: Biornedical Research
Project D: Inhalation Toxicology
TASK a.
Behavioral and Neurological Effects of Trace Metals and Fuel Emissions.
A . JUSTIFICATION :
To determine and enforce standards for fuel emission levels in the air
it is important to know hov? emissions from different types of fuels
and engines compare in their effect on behavior and the nervous system.
Presently there are no data available making this comparison.
B. OBJECTIVE;
Experiments will determine the effects of different types of fuel emis-
sions on the structure and functioning of the nervous system of devel-
oping and adult animals.
A
C. SCOPE ;
At the present level locornotor activity and reflexes of rats will be
measured. The minimally adequate experiments to obtain information
required by legislation would also include tests of memory and avoidance
behavior, EEC, and evoked potentials in offspring and adult rats and
haras ters. The optimal level would also include measurements of food
and water intake, and learning as well as detailed neurohistology and
neurochemistry. -
D. RESULTS :
Data will be reported as publishable scientific papers which can be
used to set or enforce standards.
t. APPROACH ;
This is part of an integrated effort to find the total toxicological
effects of fuel emissions on living organisms. Animals will be tested
either during or just following exposure to engine exhaust emission.
F SUFPO,RTI]iG CONTRACTS;
Unless additional personnel and facilities are provided, performance of
detailed neurohistopathology and neurochemsitry must be done under con-
tract (estimated cost $7»1>K) .
Equipment for neurohistology nncl eloctrophysiology of young animals
is; needed if these aspects of the tank are. to be performed in-house.
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B 44
RELATIONSHIPS :
None.
I. COORDINATION;
None .
l] UNRESOLVED POLICY ISSUES:
None.
-------
B 45
Program Element 110203: Biomedical Research
Project D: Inhalation Toxicology
TASK 5.
Assessment cf pulmonary, cardiovascular and renol function following inhalation
of atmosphere? containing trace metals or fuel emission?.
A. OUSTIflCATTO[[:
The hazards rcsultinn from inhalation of airborne pollutants ultimately
depend on the dose (and dose rate) delivered to various tissues and unon
the toxicity of each substance involved. Retention., clearance f.nd trans-
location of inhaled particles ere larnely physiologic, although solubility
end particle size influence kinetics in the respiratory tract.
Pulmonary function is an obvious physiological parameter that might be
affected as a result of .inhaled material. Hov/ever, it v/ould most likely
be altered by acute hioh»concentration doses or by material that causes
specific harmful action to lung tissue. An example of this is fuel emissions.
Long-term lcv;-dc-ss exposure to agents not particularly har.nfu.1 to lung mny
pass on through to other tissues causing more subtle primary effects. An
example of this, is cadmium.
CadiiyiiiiTi: Moriy of the cedrniunMriduced physiological chsnpes can be inter-
7?rci"c''J""t'.s resiHtinn -frc.r-i kidney tubular desnaee, Kidney tubular dr.niaoc-: by
cadmium lias been v/oll doci.':r.ontC'd« Fov/ if any kidney function studies have
been done on nan or animals relating function to kidney tissue cadmium levels,
nor have any been'done relatino kidney function to atmosphere or diet levels
of cadmium.
Fuel [iTiir.sjcn?: A rapid but effective method for testing toxicological pro-
peYt~fbs~ol "pTcTsent ajid to-be»dsv(»lopsd riarket fuel emission is necessary,
Atmospheric pollution caused bv their use is of major concern, Exposure of
an animal to such an atmosphere yields a complex ansv/er;' hov;;>ver, early chcrioes
in the resniratory system and the circulatory system may shcv; pj2,r3..rj/ har=:ifi.il
effects. These changes are possibly reversible if the animal is relieved of
the burden, but if exposure continues indefinitely, secondary and tertiary
effects are more difficult to define.
B. OBJECTIVE:
The ultimate coal of this task is to determine the lov.'ost concentrations of
atmospheric pollutants* soccifical Vly 3 trace metis Is and fuel emission mnterial..
that will adversely effect physiological function. Principally, inhalation
-------
B 46
ensure v,l, be «:,d.
the mam cxperte^l cnirsl CC!ls- /-is vlll be' done so that sniwble
pulnonary ond rcr.M syit.,-.'* ol .expo «« "«ls « jni to bo thc fl
concentrations of coll^^ts cicbt ^ "-" -
.
concentrations of coll^^ts c;icbt ^ "-" h-,,s1oloo1cai effects iae to
netal.stu.Hcd in ^ co^.rcN-nMVC «av. Also. PJ,s« <> effccU beci.J5
gasoline engine cxurur.t will p.cc-,..- wji- dcvelooad for thes
rA-si^^arr^^^
"
ci.J5C
hese
" 1C, Effects
as an extramural contract, wo shall attempt to investigate.
effect to kidney damage,
2. DW»n1cs of pul^nary absorption, cle.rance and translation of
CdCl2 in pnouiiionectoraized and normal oog^.
perfused kidney system,
5. An estate of cardlo-pulmonary function in rats after exposure
to fuel emissions,
C. SCOPE:
PRESENT; LEVEL MIHIWU.Y.
Can be comoletcd oxcent Completed.
for electron microscopy.
Methods extended to
other trace rnetals
. effects of fuel eiri
s i ons.
Preliminary evaluation
of the an 1m?Is only.
Completed, Equipment
needed.
Methods can be developed, Completed.
Study could be essen-
tially extended to
other atmospheric
pollutants.
Could be done in much
Ir-ss time if more
p e rs o nn e 1 \ve re a v a i 1 -
able.
-------
B 47
Laboratory can be
established but not
staffed-~so~e sub-
stance tostinq can
bo done,
Full tirre quality
technician needed to
run tests in this or-
gan leboratory.
Completed?
Increase the nurber
of species tested.
Extend the number of
tests on eec'n snirral.
D. ,
This work should provide specific inforr.ation for the estsblishr.ent of'air
quality standards plus- acplicable methods that can be utilized for further
studies of this nature.
E. APPROACH;
In general, a variety of anin-al species are to bo used, primarily as docs,
rats and Guinea cics. In rrost studies they vnll be tested under normal
physioloficrl end uru-.nesthetized .conditions ciu! v/ith accented rnethcds. 'Pol
Intent, \.'hethc:r tr?ce r.r-i;al cr fuel emission, ranges v.'ill be suitable to
existing envirci^ental problems.
F* SUPPORT I'JG COiiTP.ACTS;
Contract needed for electron microscopy kidney,
' SPECIAL FACT LITIES:
Presently available,
!!. INTERIM PI A RE1. ATI OMSKIPS ;
None.
I. COORD I HAT I Oil;
None.
None.
-------
j B 48
Program Element 110203: Biomeuical Research
Project D: Inhalation Toxicology
TAS£ 6. _ ,
Assessment of Absorption, Metabolic Fate, Excretion, Acute and Subacute
Toxicity of Trace Metals and other chemical pollutants.
A. JUSTIFIC/VnOi-l;
The results derived from experiments on acute toxicity, chronic toxicit.y,
perinatal toxicity, metabolic fate, teratogenesis, local irritation,
etc. form tho basis for the evaluation of the possible hazardous
properties of a potentially toxic substance. These basic tests or
studies must be run on many of the new compounds that are being introduced
into the environment in order to assass their toxicity to man and
animals. The types of studies to be carried out on each of the hazardous
substances will vary depending on what additional information is needed
in order to develop guidelines.
E." OBJECTIVE:
The purpose of this task is to assess the toxicity of various pollutants
when administered through natural portals of entry and at dose levels
which include those which may be found in the environment.
c- SCOPE:
Present Level
1. Effect of different chemical forms of cadmium upon pulmonary absorption
following inhalation.
Compounds to be studied: a, cadmium chloride
. b. cadmium acetate
c. cadmium oxide
d. cadmium sulfate
2. Influence of different dietary components on gastrointestinal absorption
of cadmium. Effects of vitamin D, calcium and zinc.
3. Development of in vitro and in vivo bioassay system for testing the toxicity
of different chemical pollutants and trace metals.
-------
B 49
Minimally Adequate
Experiments described above plus
1. Influence of different concentrations of cadmium upon absorption.
2. Effects of nickel upon the cytodynamics of pulmonary <>lveolar cells.
Optimal
In addition to the above experiments
1. Initiate studies on manganese and vanadium especially antiknock compounds
containing rnanoanese.
K. 'RESULTS.:
Hill provide data on different pollutants.
E. APJIROACH.:
Details of each of the experiments are given in the protocol.
F- SUPPORT IjJ.fi CO'ilRACTS;
None.
Most of the equipment is currently available with the exception of tissue
culture equipment and microscope.
H. 'INTERMEDIA RELATIONSHIPS:
The pollutants to be studied are multimedia oriented and thus the data will
be of benefit in establishing guidelines for all the media.
I. "COORDINATION:
Will bo established with Research Triangle and others working on similar
type studies.
UNRESOIVED POLICrISSUES;
None.
-------
PROGRAM ELEMENT NUMBER: 110203
WORK PLAN RECIPIENT: Director, NERC/RTP
OR&M
FY '73 Work Plans
TITLE: Biomedical Research
PROGRAM ELEMENT MANAGER: Vaun A. Newill
Task
PROJECT
1A
2A
3A
4A
5A
6A
7A
8A
9A
10A
Resource Estimate
Present/MY
A - CLEANS (Cli
150/2.5
47/1-0
100/0.4
110/2.0
120/1.6
118/1.5
105/1.5
90/0.1
50/0.1
890/10.7
Add-On/MY
nical Laborato
238/3.0
47/3.0
100/0.7
200/2.0
175/2.5
153/3.0
190/2.5
122/0.1
135/0.2
1360/18.0
Min. Adequate/MY
ry Evaluation and A
238/3.5
47/3.0
100/2.0
200/2.3
175/3.0
173/3.0
190/2.5
122/0.2
150/0.3
1000/5.0
2395/24.8
Optimum/MY
ssessment of Noxious Substances)
390/8.0
55/3.0
115/5.0
290/3.0
250/7.0
250/6.0
265/6.0
215/0.5
175/1.0
1100/6.0
3105/45.5
PROJECT
IB
2B
3B
4B
5B
6B
!
- CLEVER (Clinical Laborato
166/3.0
90/2.0
90/2.0
70/1.0
60/1.0
60/1.0
536/10.0
237/5.0
170/3.0
170/3.0
170/3.0
170/2.0
170/2.0
1087/18. 0
ry Evaluation and Va
237/5.0
180/5.0
180/5.0
180/5.0
180/5.0
180/5.0
1137/30.0
i
lidation of Epidemiologic Research)
320/15.0
250/7.0
250/7.0
250/7.0 1
250/7.0 \
250/7.0
1570/50
co
en
O
-------
Task
PROJECT
1C
2C
3C
4C
5C
6C
7C
8C
Resource Estimate
Present/MY
C - ACTIONS (As
145/4.5
130/4.5
98/4.0
75/4.0
220/0.2
198/0.1
45/0.1
0/0.0
911/17.4
Add-On/MY
sessment of Cel
250/7.0
225/6.6
200/6.0
134/6.0
220/0.2
198/0.1
45/0.1
80/0.0
1352/26.0
Min. Adequate/ MY
lular Toxicity and :
550/9.0
400/7.0
348/7.0
337/8.0
475/1.2
485/0.9
73/0.1
130/6.5
2798/39.7
Optimum/MY
Interactions of Noxious Substances)
1800/12.0
1750/12.0
920/8.0
840/7.0
1725/6.0
1610/6.0
85/0.5
130/6.5
8860/58.0
PROJECT
ID
2D
3D
4D
5D
6D
RJF
C1N
TOTAL
} - Inhalation
300/15.0
52/0.1
50/2.5
75/3.6
305/15.3
6.5
.782/45.0
3119/81*
Toxicology Proc
405/20.0
57/0.2
97/4.8
80/3.0
104/5.0
357/16.0
11 00/49.0
4970/m.P
ram
500/25.0
110/0.5
237/7.0
145/5.0
172/7.0
390/22.5
1554/67
8014/168
660/31.0
110/0.5
274/8.0
311/8.0
292/7.0
495/26.0
2142/80.5
15807/240.5
Cincinnati BMRR will be forced to reduce from ceiling of 43 to 36.5
CO
en
-------
J
B 52
RESOURCE STATUS SUMMARY
110201
PROGRAM ELEMENT NUMBER
CHESS
PROGRAM ELEMENT TITLE
EPA FY '73 Plan
Funding Type
In-House
Grant
Contract
Program Element Total
$ (1000)
1415
1730
3130
Positions
107
107
Program Element Total
with FY '73 Add-on
6435
137
-------
B 53
A. PROGRAM ELEMENT NUMBER; 110201
B. TITLE: Community Health and Environmental Surveillance Systems (CHESS)
PREPARED BY: J. F. Finklea DATE: January 5, 1972
C. PROGRAM JUSTIFICATION: The initial purpose of the CHESS program is to
define, in ambient situations, the effects of environmental pollution on
human health and welfare; and then subsequently to determine the benefits
derived from improving environmental quality. The information obtained
from the CHESS program is directly applicable to the standard setting
process and to the assessment of the adequacy of standards once they are
established.
D. OBJECTIVES: To develop and utilize in populations sensitive indicators of
human health, to determine dose-response relationships with environmental
pollutants singly or in combination. It is expected that the information
obtained from these studies will enable the development of defensible
environmental standards, the measurement of benefits derived from improving
environmental quality, and determination of the adequacy of standards
established.
E. SCOPE: CHESS currently covers only four (particulate, sulfur dioxide,
nitrogen oxides, and photochemical oxidants) of the pollutants covered by
the National Ambient Air Quality SDandards. For carbon monoxide there is no
indication yet that it is possible to assess its effects in human populations
through epidemiologic studies; there are no health effects as such that can
be related to hydrocarbons. Trace metals are being studied insofar as they
can be traced through all environmental pathways and their burdens determined
for one group of communities. Additional pollutants, such as PCB and
pesticides, are also included in the CHESS program.
CHESS includes four projects. Data Collection with 13 tasks, Information
Synthesis with 12 tasks, Bioenvironmental Measurements with 6 tasks, Develop-
ment of More Sensitive Health Indications with 12 tasks.
F. RESULTS: The knowledge gained through CHESS will be documented in a series
of intramural and published technical reports relating health impact
indicators and important health covariates to environmental quality.
At least 8 reports per year are planned, one for each of the health indicators
currently utilized. The technical reports will also summarize the progress
in the research carried out as part of the health status evaluations and
body burden studies. The reports will provide health effects intelligence
for appraisal and setting of environmental standards.
G. APPROACH: CHESS is an integrated series of epidemiologic studies designed,
coordinated and largely funded by the Federal government. Under contract,
local health departments, universities or survey research organizations
operate special neighborhood environmental monitoring stations and collect
data from citizen volunteers living in communities with an exposure gradient
for specified pollutants. Bioenvironmental measurements are performed
in the field and in a Federal laboratory. A federal research group
synthesizes information from the data to produce intramural and published
technical reports. This Federal group is also responsible for research and
-------
B 54
development to find more sensitive impact indicators suitable for field
surveys, to improve bioenvironmental exposure monitoring and to refine
statistical procedures. As feasibility studies proceed, new health impact
indicators and pollutants will be integrated into the studies and indicators
no longer found useful will be eliminated.
H. SUPPORTING CONTRACTS: Under contract, local health departments, universities
or survey research organizations operate special neighborhood environmental
monitoring stations and collect data from citizen volunteers living in com-
munities with an exposure gradient for specified pollutants.
The CRC-APRAC provides some support for carrying out studies that are the
same as the CHESS. The Health Research Council of New York provides approxi-
mately $20,000 a year for the New York area CHESS.
Interage.ncy Agreements: The Bureau of Occupational Safety and Health provides
trace metal analyses for one of the studies.
I. SPECIAL FACILITIES AND EQUIPMENT: Beyond the state-of-the-art, there are
requirements for developing procedures and instruments as follows: (a)
compact instrument package to measure indoor air quality; (b) automated
procedure for analysis of chromosomal aberration and exfoliative cytology;
(c) direct telemetry capability from continuous ambient air monitors to
the data bank; (d) better methods for trace elements analysis, i.e., alpha
scatter, ASV; (e) personal air quality monitors; (f) better methods for
particulate measurement, both as to the size and chemical composition;
(g) capability to measure metallo-enzyme kinetics.
J. INTERMEDIA RELATIONSHIPS; Human pollutant burden studies of metals and
synthetic organic materials involve the Water Quality, Solid Wastes, and
Pesticides elements of EPA. Data from the food and milk sampling program
of the Radiation element could be integrated into CHESS. Monitoring
exposure to ionizing and non-ionizing radiation and the effects of the
latter might be approached through CHESS.
K. COORDINATION: Research personnel from each media office have been briefed
in CHESS.Very close working liaison is maintained with the Biomedical
Research element. The studies utilize the data available through NADIS.
Meteorologists required for analysis of the data are provided by the
Meteorological Support Element. The Biomedical Research element consists
of work closely related to CHESS; effects and pollutants identified and
studied under Biomedical Research are utilized to guide epidemiological
studies and vice-versa.
L. UNRESOLVED POLICY ISSUES: None
-------
CHESS
SUMMARY COMPARISON
($ Million/MY)
CHESS
Optimum
Minimum
Adequate
Add on*
Current*
FY-73
27.6/442
19.1/329
6.44/137
3.14/107
FY 74
27.5/438
21.5/368
6.89/140
FY 75
26.5/438
21.0/359
7.37/145
FY 76
25.5/434
19.3/3bO
7.89/145
FY 77
24.0/400
18.0/345
8.44/145
*Add on program level becomes the current program level in FY 1974 - FY 1977.
CO
en
en
-------
B 56
PROGRAM ELEMENT 110201: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT A - CHESS DATA COLLECTION
TASK 1. CHESS New York Metropolitan Studies
A PROGRAM JUSTIFICATION: New Yorkers are exposed to complex urban air
pollution mixtures including particulates, oxides of sulfur, carbon mono-
xide, oxides of nitrogen, trace metals, and products of combustion inclu-
ding fossil fuels and solid wastes. Possible adverse health effects due
to these multimedia exposures must be determined.
B. OBJECTIVE: To quantitate possible adverse health effects in urban
populations simultaneously exposed to particulates, carbon monoxide, oxides
of sulfur and nitrogen, trace metals and products of fossil fuel combustion
and waste disposal.
C. SCOPE:
Populations
Studied
Present and Add-on Minimally Adequate
All of the present
plus high risk groups
due to exposure from
1. Industry
2. Traffic mobile
sources
3. Stationary Sources
1.
2.
3.
4.
5.
6.
Children
Aged
Asthmatics
Cardiacs
Chronic
Bronchi tics
Well Adults
Indicators 1.
Used
2.
3.
4.
5.
6.
Chronic respi-
ratory disease
symptoms
Acute respi-
ratory disease
Reversible
pulmonary
function changes
Acute irritation
symptoms
Human pollutant
burdens
Aggravation of
cardiac symptoms
All of the present
plus more sensitive
indicators such as
1. Critical enzymes
2. Cardiac status
3. Exfoliative
cytology
4. Assessment of
immune responses
5. Assessment of
RBC function
and longevity
Optimal
All of the minimally
adequate plus spe-
cial susceptible
high risk groups
such as
1. Blood
dyscrasias
(sickle cell
anemia)
2. Pregnant women
3. Low income
groups
All of the minimally
adequate plus
1. Attitudes toward
pollution
2. Social cost
evaluations
3. New and more
sensitive indi-
cators
-------
J
B 57
Present & Add-on . Minimally Adequate
Optimal
Neighborhoods
Studied
Measuring
Stations
Per
Community
Pollutant
Measurements
1 outdoor
(Present) Eight
pollutants are
measured daily and
2 monthly. (Add-on)
CHESS CHAMP monitoring
20 environmental
measurements continuous
with real time telemetry
to RTP.
10
1 outdoor, 4 rotating
indoor, 9 personal
monitors are added.
Same as Add-on.
3 outdoor and 16
rotating indoor,
36 personal monitors
Same as Add-on.
D. RESULTS: Raw data collected from the New York CHESS network will be fed
to CHESS information synthesis and data analysis. These results will be used
to establish pollution standards and to evaluate the health effects of controls
reducing pollution levels.
E. APPROACH: Current CHESS New York area programs will form the basis for
continued studies. Refinements in protocols, based upon previous experience,
will increase effectiveness of data in measurement collection. New health
indicators, pollution measurements, and populations at risk must be added
for an optimal program.
F. SUPPORTING CONTRACTS: A contract for data collection with the local
health department is the basis for this program.
G. SPECIAL FACILITIES: Air monitoring stations, computer opti-scan devices
and computer data feedback to central data banks.
H. INTERMEDIA RELATIONSHIPS: Exist with each of the media and categorical
programs.
I. COORDINATION: Coordination between other ORM health effects research
program elements and other agencies such as DHEW, NIOSH, and NIEHS will be
necessary.
J. UNRESOLVED POLICY ISSUES: None.
-------
B 58
PROGRAM ELEMENT 110201: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT A - CHESS DATA COLLECTION
TASK 2. CHESS Southeastern Studies
A. PROGRAM JUSTIFICATION: Possible adverse health effects due to exposures
to high levels of particulates with low levels of other pollutants can be
determined uniquely in the Southeast.
B. OBJECTIVE: To quantitate possible adverse health effects in urban populations
exposed primarily to particulate matter.
C. SCOPE:
Populations
Studied
Present & Add-on
1.
2.
3.
4.
5.
6.
Children
Aged"
Asthmatics
Cardiacs
Chronic
Bronchi tics
Well Adults
Indicators 1.
Used
2.
3.
4.
5.
6.
Chronic respi-
ratory disease
symptoms
Acute respi-
ratory disease
Reversible
pulmonary
function changes
Acute irritation
symptoms
Human pollutant
burdens
Aggravation of
cardiac symptoms
Minimally Adequate
All of the present
plus hinh risk groups
due to exposure from
1
2.
Industry
Traffic mobile
sources
Stationary sources
All of the present
plus more sensitive
indicators such as
1. Critical enzymes
2. Cardiac status
3. Exfoliative
cytology
4. Assessment of
immune responses
5. Assessment of
RBC function
and longevity
Optimal
All of the minimally
adequate plus spe-
cial susceptible
high risk groups
such as
1. Blood
dyscrasias
(sickle cell
anemia)
2. Pregnant women
3. Low income
groups
All of the minimally
adequate plus
1. Attitudes toward
pollution
2. Social cost
evaluations
3. New and more
sensitive indi-
cators
-------
B 59
Present & Add-on Minimally Adequate
Optimal
Neighborhoods
$
StudiecT
Measuring
Stations
Per
Community
Pollutant
Measurements
1 outdoor
12
1 outdoor, 4 rotating
indoor, 9 personal
monitors.
CHESS CHAMP moni-
toring 20 environ-
mental measurements
continuously with
real time telemetry
RTP.
Same as Add-on.
15
3 outdoor and 16
rotating indoor,
36 personal monitors
Same as Add-on.
D. RESULTS: Raw data collected from the Southeast CHESS network will be fed
to CHESS information synthesis and data analysis. These results will
be used to establish pollution standards and to evaluate the health effects of
controls reducing pollution levels.
E. APPROACH: Current CHESS Southeast area programs will form the basis for
continued studies. Refinements in protocols, based upon previous experience,
will increase effectiveness of data in measurement collection. New health
indicators, pollution measurements, and populations at risk must be added
for an optimal program.
F. SUPPORTING CONTRACTS: Contracts for data collection with local health
departments and universities.
G. SPECIAL FACILITIES: Air monitoring stations, computer opti-scan devices
and computer data feedback to central data banks.
H. INTERMEDIA RELATIONSHIPS; Exist with each of the media and categorical
programs.
I. COORDINATION: Coordination between other ORM health effects research
program elements and other agencies such as DHEW, NIOSH, and NIEHS will be
necessary.
J. UNRESOLVED POLICY ISSUES: None.
-------
B 60.
PROGRAM ELEMENT 110201: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT A - CHESS DATA COLLECTION
TASK 3 CHESS Chattanooga Studies
A. PROGRAM JUSTIFICATION: Possible adverse health effects due to a primary
source of nitrogen oxide exposure with relatively low levels of other pollutants
can be uniquely evaluated in Chattanooga.
B. OBJECTIVE: To quantitate possible adverse health effects in urban popu-
lations primarily to higher levels of nitrogen oxides, but to other
pollutants associated with an industrialized area as well.
C. SCOPE:
Populations
Studied
Indicators 1.
Used
2.
3.
4.
5.
6.
Present and Add-on Minimally Adequate
All of the present
plus hinh risk groups
due to exposure from
1. Industry
2. Traffic mobile
sources
3. Stationary sources
1.
2.
3.
4.
5.
6.
Children
Aged"
Asthmatics
Cardiacs
Chronic
Bronchi tics
Well Adults
Chronic respi-
ratory disease
symptoms
Acute respi-
ratory disease
Reversible
pulmonary
function changes
Acute irritation
symptoms
Human pollutant
burdens
Aggravation of
cardiac symptoms
All of the present
plus more sensitive
indicators such as
1. Critical enzymes
2. Cardiac status
3. Exfoliative
cytology
4. Assessment of
immune responses
5. Assessment of
RBC function
and longevity
Optimal
All of the minimally
adequate olus spe-
cial susceptible
high risk groups
such as
1. Blood
dyscrasias
(sickle cell
anemia)
2. Pregnant women
3. Low income
groups
All of the minimally
adequate plus
1. Attitudes toward
pollution
_2. Social cost
evaluations
3. New and more
sensitive indi-
cators
-------
B 61
Present & Add-on Minimally Adequate
Neighborhoods
Studied
Measuring
Stations
Per
Community
Pollutant
Measurements
1 outdoor
(Present) Eight
pollutants are
measured daily and
2 monthly. (Add-on)
CHESS CHAMP monitoring
20 environmental meas-
urements continuously
with real time telemetry
to RTP.
1 outdoor, 4 rotating
indoor, 9 personal
moni tors.
Same as Add-on.
Optimal
8
3 outdoor and 16
rotating indoor,
36 personal monitors
Same as Add-on.
D. RESULTS: Raw data collected from the Chattanooga CHESS network will be fed
to CHESS information synthesis and data analysis. These results will
be used to establish pollution standards and to evaluate the health effects
of controls reducing pollution levels.
E. APPROACH: Current CHESS Chattanooga area programs will form the basis for
continued studies. Refinements in protocols, based upon previous experience,
will increase effectiveness of data in measurement collection. New health
indicators, pollution measurements, and populations at risk must be added
for an optimal program.
F. SUPPORTING CONTRACTS: Contracts for data collection are with a Non-profit
Research Institute and a local Technical Institute.
G. SPECIAL FACILITIES: Air monitoring stations, computer opti-scan devices
and computer data feedback to central data banks.
H. INTERMEDIA RELATIONSHIPS: Exist with each of the media and categorical
programs.
I. COORDINATION: Coordination between other ORM health effects research
program elements and other agencies such as DHEW, NIOSH, and NIEHS will be
necessary.
J. UNRESOLVED POLICY ISSUES: None.
-------
B 62
PROGRAM ELEMENT 110201: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT A - CHESS DATA COLLECTION
TASK 4. CHESS Utah Area Studies
A. PROGRAM JUSTIFICATION: Possible adverse health effects due to primary
exposure to sulfur oxides with low levels of other pollutants can be deter-
mined uniquely in Utah.
B. OBJECTIVE: To quantitate possible adverse health effects due primarily
to sulfur oxide exposures.
C. SCOPE:
Populations
Studied
Add-on
1. Children
2. Aged'
3. Asthmatics
4. Cardiacs
5. Chronic
Bronchi tics
6. Well Adults
Indicators 1.
Used
2.
3.
4.
5.
6.
Chronic respi-
ratory disease
symptoms
Acute respi-
ratory disease
Reversible
pulmonary
function changes
Acute irritation
symptoms
Human pollutant
burdens
Aggravation of
cardiac symptoms
Minimally Adequate
All of the present
plus hiph risk groups
due to exposure from
1. Industry
2. Traffic mobile
sources
3. Stationary sources
All of the present
plus more sensitive
indicators such as
1. Critical enzymes
2. Cardiac status
3. Exfoliative
cytology
4. Assessment of
immune responses
5. Assessment of
R3C function
and longevity
Optimal
All of the minimally
adequate Dlus spe-
cial susceptible
high risk groups
such as
1. Blood
dyscrasias
(sickle cell
anemia)
2. Pregnant women
3. Low income
groups
All of the minimally
adequate plus
1. Attitudes toward
pollution
2. Social cost
evaluations
3. New and more
sensitive indi-
cators
-------
B 63
Add-on
Minimally Adequate
Optimal
Neighborhoods
35
di
Studied
Measuring
Stations
Per
Communi ty
Pollutant
Measurements
1 outdoor
CHESS CHAMP moni-
toring 20 environ-
mental measurements
continuously with
real time telemetry
to RTP.
1 outdoor, 4 rotating
indoor, 9 personal
moni tors
Same as Add-on.
3 outdoor and 16
rotating indoor,
36 personal monitors.
Same as Add-on.
D. RESULTS: Raw data collected from the Utah CHESS network will be fed
to CHESS information synthesis and data analysis. These results will
be used to establish pollution standards and to evaluate the health effects of
controls reducing pollution levels.
E. APPROACH: Current CHESS Utah area programs.will form the basis for
continued studies. Refinements in protocols, based upon previous experience,
will increase effectiveness of data in measurement collection. New health
indicators, pollution measurements, and populations at risk must be added
for an optimal program.
F. SUPPORTING CONTRACTS: A contract for data collection with the local
health department is the basis for this program.
G. SPECIAL FACILITIES: Air monitoring stations, computer opti-scan devices
and computer data feedback to central data banks.
H. INTERMEDIA RELATIONSHIPS: Exist with each of the media and categorical
programs.
I. COORDINATION: Coordination between other ORM health effects research
program elements and other agencies such as DHEW, NIOSH, and NIEHS will be
necessary.
J. UNRESOLVED POLICY ISSUES: None.
-------
J
B 64
PROGRAM ELEMENT 110201: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT A - CHESS DATA COLLECTION
TASK 5. CHESS Los Angeles Basin Studies
A. PROGRAM JUSTIFICATION: Los Angeles Basin residents are exposed to complex
urban air pollution mixtures of photochemical oxidants associated with mobile
source emissions. Possible adverse health effects due to these multimedia
exposures must be determined.
B. OBJECTIVE: To quantitate exposures to photochemical oxidants and to
determine any possible adverse health effects resulting from these exposures.
C. SCOPE:
Populations
Studied
Indicators 1.
Used
2.
3.
4.
5.
6.
Present and Add-on Minimally Adequate
All of the present
plus hi ah risk groups
due to exposure from
1. Industry
2. Traffic Mobile
sources
3. Stationary sources
1.
2.
3.
4.
5.
6.
Children
Aged"
Asthmatics
Cardiacs
Chronic
Bronchi tics
Well Adults
tiptimal
All of the minimally
adequate plus spe-
cial susceptible
risk groups
as
Blood
dyscrasias
(sickle cell
anemia)
Pregnant women
Low income
high
such
1
2.
3.
groups
Chronic respi-
ratory disease
symptoms
Acute respi-
ratory disease
Reversible
pulmonary
function changes
Acute irritation
symptoms
Human pollutant
burdens
Aggravation of
cardiac symptoms
All of the present
plus more sensitive
indicators such as
1. Critical enzymes
2. Cardiac status
3. Exfoliative
cytology
4. Assessment of
immune responses
5. Assessment of
RBC function
and longevity
All of the minimally
adequate plus
1. Attitudes toward
pollution
2. Social cost
evaluations
3. New and more
sensitive indi-
cators
-------
B 65
Present & Add-on Minimally Adequate
Optimal
Neighborhoods
Studied
Measuring
Stations
Per"
Community
Pollutant
Measurements
1 outdoor
10
1 outdoor, 4 rotating
indoor, 9 personal
monitors are.added.
12
(Present) Eight Same as Add-on.
pollutants are meas-
ured daily and 2
monthly. (Add-on)
CHESS CHAMP monitoring
20 environmental meas-
urements continuously
with real time telemetry
to RTP.
3 outdoor and 1C
rotating indoor,
36 personal monitors,
Same as Add-on.
D. RESULTS: Raw data collected from the Los Angeles CHESS network will be fed
to CHESS information synthesis and data analysis. These results will
be used to establish pollution standards to evaluate the health effects of controls
reducing pollution levels.
E. APPROACH: Current CHESS Los Angeles area programs will form the basis for
continued studies. Refinements in protocols, based upon previous experience,
will increase effectiveness of data in measurement collection. New health
indicators, pollution measurements, and populations at risk must be added
for an optimal program.
F. SUPPORTING
with
CONTRACTS: A contract for data collection will be negotiated
the local Health Department, a University or a Research Organization as
determined by established federal procedures to provide the best data
collection resources.
G. SPECIAL FACILITIES: Air monitoring stations, computer opti-scan devices
and computer data feedback to central data banks.
H. INTERMEDIA RELATIONSHIPS: Exist with each of the media and categorical
programs.
I. COORDINATION: Coordination between other ORM health effects research
program elements and other agencies such as DHEl-/, NIOSH, and NIEHS will be
necessary.
J. UNRESOLVED POLICY ISSUES: None.
-------
B 66
PROGRAM ELEMENT 110201; COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT A - CHESS DATA COLLECTION
TASK 6. St. Louis Regional Air Pollution Studies
A. PROGRAM JUSTIFICATION: Possible adverse health effects due to exposures
specified stationary sources, including airports, have not been well defined.
These effects can be ideally studied in the St. Louis area.
B. OBJECTIVE: To quantitate possible adverse health effects in urban popu-
lations exposed to stationary sources of air pollution.
C. SCOPE:
Populations
Studied
Indicators 1.
Used
2.
3.
4.
5.
6.
Add-on
1. Children
2. Aged"
3. Asthmatics
4. Cardiacs
5. Chronic
Bronchi tics
6. Well Adults
Chronic respi-
ratory disease
symptoms
Acute respi-
ratory disease
Reversible
pulmonary
function changes
Acute irritation
symptoms
Human pollutant
burdens
Aggravation of
cardiac symptoms
Minimally Adequate
All of the present
plus hioh risk groups
due to exposure from
1. Industry
2. Traffic mobile
sources
3. Stationary sources
All of the present
plus more sensitive
indicators such as
1. Critical enzymes
2. Cardiac status
3. Exfoliative
cytology
4. Assessment of
immune responses
5. Assessment of
RBC function
and longevity
Optimal
All of the minimally
adequate plus spe-
cial susceptible
high risk groups
such as
1. Blood
dyscrasias
(sickle cell
anemia)
2. Pregnant women i
3. Low income
groups
All of the minimally
adequate plus
1. Attitudes toward
pollution
.2. Social cost
evaluations
3. New and more
sensitive indi-
cators
-------
B 67
Add-on
Neighborhoods
Studied
Measuring
Stations
Per
"Community
Pollutant
Measurements
1 outdoor
CHESS CHAMP
monitoring 20
environmental
measurements
continuously
with real time
telemetry to RTP.
Minimally Adequate
10
1 outdoor, 4 rotating
indoor, 9 personal
monitors are added.
Same as Add-on.
Optimal
12
3 outdoor and 16
rotating indoor,
36 personal monitors,
Same as Add-on.
D. RESULTS: Raw data collected from the St. Louis CHESS network will be fed
to CHESS information synthesis and data analysis. These results will
be used to establish pollution standards to evaluate the health effects uf controls
reducing pollution leveU.
E. APPROACH:
St. Louis'
will increase effectiveness
Current CHESS area proorams will form the basis for CHESS
studies. Refinements in protocols, based upon previous experience,
of data in measurement collection. New health
indicators, pollution measurements, and populations at risk must be added
for an optimal program.
F. SUPPORTING CONTRACTS: Contract for data collection will be negotiated
with the local Health Department, a University or a Research Organization.
G. SPECIAL FACILITIES: Air monitoring stations, computer opti-scan devices
and computer data feedback to central data banks.
H. INTERMEDIA RELATIONSHIPS: Exist with each of the media and categorical
programs.
I. COORDINATION: Coordination between other ORM health effects research
program elements and other agencies such as DHEW, NIOSH, and NIEHS will be
necessary.
J. UNRESOLVED POLICY ISSUES: None.
-------
B 68
PROGRAM ELEMENT 110201: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT A - CHESS DATA COLLECTION
TASK 7. Chicago Stationary Source
A. PROGRAM JUSTIFICATION: Possible adverse health effects due to exposures
to specified sources of air pollution have not been well defined. These effects
can readily be studied in Chicago.
B. OBJECTIVE: To quantitate possible adverse health effects in urban popu-
lations exposed to stationary sources of air pollution.
C. SCOPE:
Populations
Studied
Indicators 1.
Used
2.
3.
4.
5.
6.
Add-on^
1. Children
2. Aged"
3. Asthmatics
4. Cardiacs
5. Chronic
Bronchi tics
Chronic respi-
ratory disease
symptoms
Acute respi-
ratory disease
Reversible
pulmonary
function changes
Acute irritation
symptoms
;iuman pollutant
:jrdens
jgravation of
cardiac symptoms
Minimally Adequate
All of the present
plus hi ah risk groups
due to exposure from
1. Industry
2. Traffic mobile
sources
3. Stationary sources
All of the present
plus more sensitive
indicators such as
1. Critical enzymes
2. Cardiac status
3. Exfoliative
cytology
Assessment of
4.
5.
immune responses
Assessment of
RBC function
and longevity
Optimal
All of the minimally
adequate plus spe-
cial susceptible
high risk groups
such as
1. Blood
dyscrasias
(sickle cell
anemia)
2. Pregnant womeni
3. Low income
groups
All of the minimally
adequate plus
1. Attitudes toward
pollution
2. Social cost
evaluations
3. New and more
sensitive indi-
cators
-------
B 69
Add-on
Minimally Adequate
Optimal
Neighborhoods
Studied
Measuring
Stations
Per
Community
Pollutant
Measurements
1 outdoor
1 outdoor, 4 rotating
indoor, 9 personal
monitors are added.
CHESS CHAMP moni-
toring 20 environ-
ments continuously
with real time tele-
metry to RTP.
Same as add-on.
3 outdoor and 16
rotating inaoor,
36 personal monitors
Same as add-on.
D. RESULTS: Raw data collected from the Chicago
to CHESS information synthesis and data analysis.
CHESS network will be fed
These results will
be used to establish pollution standards to evaluate the health effects of
controls reducing pollution levels.
E- APPROACH: Current CHESS area p roc ranis will form the basis for Chicago
CHESS studies. Refinements in protocols, based upon previous experience,
will increase effectiveness of data in measurement collection. New health
indicators, pollution measurements, and populations at risk must be added
for an optimal program.
F. SUPPORTING CONTRACTS: Contract for data collection will be negotiated
with the local Health Department, a University or a Research Organization.
G. SPECIAL FACILITIES: Air monitoring stations, computer opti-scan devices
and computer data feedback to central data banks.
H. INTERMEDIA RELATIONSHIPS: Exist with each of the media and categorical
programs.
I. COORDINATION: Coordination between other ORM health effects research
program elements and other agencies such as DHEW, NIOSH, and NIEHS will be
necessary.
J. UNRESOLVED POLICY ISSUES: None.
-------
B 70
PROGRAM ELEMENT 110201: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT A - CHESS DATA COLLECTION
TASK 8. CHESS Southwest Studies
A. PROGRAM JUSTIFICATION: Possible adverse health effects due to total integrated
environmental insult has not been well defined. These effects can be investigated
in this study as well as inner city communities and exposures to specified sources
of environmental contaminates.
B. OBJECTIVE: To quantitate possible health effects to total integrated environ-
mental insult gradient and the effects from specified sources.
C. SCOPE:
Populations
Studied
Present 5 Add-on
No program
Indicators
Used
No program
Minimally Adequate
A. Normal exposed groups
1. Children
2. Aged
3. Asthmatics
4. Cardiacs
5. Chronic
Bronchi tics
B. High risk groups due
to exposure from
1. industry
2. traffic-mobile
sources
3. stationary sources
A. Health indicators
1. Chronic respiratory
disease symptoms
2. Acute respiratory
disease
3. Reversible pulmonary
4. Acute irritation
symptoms
5. Human pollutant
burdens
6. Aggravation of
cardiac symptoms
B. More sensitive indicators
such as
1. Critical enzymes
2. Cardiac status
3. Exfoliative cytology
4. Assessment of RBC
function and longevity
Optimal
All of the minimally
adequate plus special
susceptible high risk
groups such as
1. Blood dyscrasias
(sickle cell anemia)
2. Pregnant women
3. Low income groups
All of the minimally
adequate plus
1. Attitudes toward
pollution
2. Social cost
evaluations
3. New and more
sensitive indicators
-------
B 71
Present & Add-on
Minimally Adequate
Optimal
Nei ghborhoods
Studied
Measuring
Stations
Per
Community
Pollutant
Measurements
10
No program. 1 outdoor, 4 rotating
indoor, 9 personal
monitors.
No program. CHESS CHAMP monitoring
20 environmental meas-
urements continuously
with real time telemetry
to RTP.
12
3 outdoor and 16
rotating indoor,
36 personal monitors
Same
D. RESULTS: Raw data collected from thc-Southwest CHESS network will be fed
to CHESS information synthesis and data analysis. These results will be used
e h'alth *
E. APPROACH: Current CHESS area programs will form the basis for Southwest
CHESS studies. Refinements in protocols, based uoon previous experience
will increase effectiveness of data in measurement collection. New hea*lth
indicators, pollution measurements, and populations at risk must be added
for an optimal ..program.
F. SUP£QJJJN1,.C,QNIR1CLS: A contract for data col lection with the local
health department is the basis for this program.
G. SPECIAL FACILITIES: Air monitoring stations, computer opti-scan devices
and computer data feedback to central data banks.
H. INTERMEDIA RELATIONSHIPS: Exist with each of the media and categorical
programs .
I. COORDINATION: Coordination between other ORM health effects research
program elements and other agencies such as DHEW, NIOSH, and NIEHS will be
necessary.
J. UNRESOLVED POLICY ISSUES: None.
-------
PKObRAM
PROJECT A - CHHS5 DATA COLLECTION
TASK 9- CHESS Mountain Studies
B 72
-WluM.nY Hr.A!.i'H AND r-'iVlKOui
RYLlLLr-NCl: STUDltS (CiitSS)
A- PROGRAM JUSTIrlCATION; Possible adverse health
environmental insult has not been well defined. These et.vi:5.;
in this study as well as inner cify coirarium'ties and exposures io speci:''
of environmental contaminates. '
B. OBJECTIVE; To quantitate possible health effects to total integral/-.
mental insult gradient and the effects from specified source:;.
C. SCOPE:
Populations
Studied
Present £ Add-on Minimally Adequate
No program
Indicators
Used
No program
A. Normal exposed groups
. 1. Children
2. Aged
3. Asthmatics
4. Cardiacs
5. Chronic
Bronchi tics .
B. High risk groups due
to exposure from
1. industry
2. traffic-mobile
sources
3. stationary sources
A. Health indicators
T. Chronic respiratory
disease symptoms
2. Acute respiratory
disease
3. Reversible pulmonary
4. Acute irritation
symptoms
5. Human pollutant
burdens
6. Aggravation of
cardiac symptoms
B. More sensitive indicators
such as
1. Critical enzymes
2. Cardiac status
3. Exfoliative cytology
4. Assessment of RBC
function and longevity
Optimal
All of the minimally
adequate plus special
susceptible high risk
groups such as
1. Blood dyscrasias
(sickle cell anenvi
2. Pregnant women
3. Low income groups
All of the minimally
adequate plus
1. Attitudes toward
pollution
2. Social cost
evaluations
3. New and more
sensitive indicators
-------
B 73
Present & Add-on
Minimally Adequate
Optimal
Neighborhoods
Studied
Measuring
Stations
Per
Community
Pollutant
Measurements
10
No program 1 outdoor, 4 rotating
indoor, 9 personal
monitors.
12
3 outdoor and 16
rotating indoor,
36 personal monitors,
No program CHESS CHAMP monitoring Same
20 environmental meas-
urements continuously
with real time telemetry
to RTP.
D. RESULTS: Raw data collected from the Mountain CHESS network will be fed
to CHESS information synthesis and data analysis. These results will be used
to establish pollution standards and to evaluate the health effects of controls
reducing pollution levels.
E. .APPROACH: Current CHESS Mountain area programs will form the basis for
continued studies. Refinements in protocols, based upon previous experience,
will increase effectiveness of data in measurement collection. New health
indicators, pollution measurements, and populations at risk must be added
for an optimal,program.
F. .SUP.PO.RT.ING,.CQNIRACLS: A contract for data collection with the local
health department is the basis for this program.
G. S P E CIAL FA CI LIT T E S: Air monitoring stations, computer opti-scan devices
.and computer data feedback to central data banks.
H. INTERMEDIA RELATIONSHIPS: Exist with each of the media and categorical
programs.
I. COORDINATION: Coordination between other ORM health effects research
program elements and other agencies such as DHEH, NIOSH, and NIEHS will be
necessary.
J. UNRESOLVED POLICY ISSUES: None.
-------
J
B 74
PROGRAM ELEMENT ilu20l: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT A - CHESS DATA COLLECTION
TASK 10. CHESS Northwest Studies .. v- ;
A. PROGRAM JUSTinCATION: Possible adverse health effects due to total integrated
environmental insult has not been well defined. These effects can be investigated
in this study as well as inner city communities and' exposures to specified sources
of environmental contaminates. .... « . .
,
B. pBJECn_VJE_: To quantitate possible health effects to total integrated environ-
mental insult gradient and the effects from specified sources.
C.. SCOPE:
Populations
Studied
Present & Add-on Minimally Adequate
No program
Indicators
Used
No program
A. Normal exposed groups
1. Children
2. Aged
3. Asthmatics
4. Cardiacs
5. Chronic
Bronchi tics
B. High risk groups due
to exposure from
1. industry
2. traffic-mobile
sources
3. stationary sources
A. Health indicators
1. Chronic respiratory
disease symptoms
2. Acute respiratory
disease
3. Reversible pulmonary
4. Acute irritation
symptoms
5. Human pollutant
burdens
6. Aggravation of
cardiac symptoms
B. More sensitive indicators
such as
1. Critical enzymes
2. Cardiac status
3. Exfoliative cytology
4. Assessment of RBC
function and longevity
Optimal
All of the minimally
adequate plus special
susceptible high risk
groups such as
1. Blood dyscrasias
(sickle cell anemia)
2. Pregnant women
3. Low incorfie groups
All of the minimally
adequate plus
1. Attitudes toward
pollution
2. Social cost
evaluations
3. New and more
sensitive indicators
-------
B 75
Present & Add-on
Neighborhoods
$
01
Studied
Measuring
Stations
Per
Community
Pollutant
Measurements
No program.
No program.
Minimally Adequate
10
1 outdoor, 4 rotating
indoor, 9 personal
monitors.
CHESS CHAMP monitoring
20 environmental meas-
urements continuously
with real time telemetry
to RTP.
Optimal
12
3 outdoor and 16
rotating indoor,
36 personal monitors
Same
D. RESULTS: Raw data collected from the Northwest CHESS network will be fed
to CHESS information synthesis and d?.ta analysis. These results will be used
to establish pollution standards and to evaluate the health »f*>c*s o* co^rols
reducing pollution levels.. -i...tvb u. co,,,rois
E. APPROACH: Current CHESS area programs will, form the basis for i-lorthw.est
un"b studies. Refinements in protocols, based .upon previous experience,
v/ill increase effectiveness of data in measurement collection. New health
indicators, pollution measurements, and populacicub at risk iiiust be added
for an optimal.program.
F- .SyP,PORJING,.C,QNIRACIS: A contract for data collection with the local
health department is the basis for this program.
G. SPECIAL FACILITIES: Air monitoring stations, computer opti-scan devices
.and computer data feedback to central data banks.
H. INTERMEDIA RELATIONSHIPS: Exist with each of the media and categorical
programs.
I. COORDINATION: Coordination betv/een other ORM health effects research
program elements and other agencies such as.DHEW, NIOSH, and NIEHS will be
necessary.
J. UNRESOLVED POLICY ISSUES: None.
-------
B 76
PROGRAM ELEMENT 110201: CGnr-itfil f y iiE.ii.TH A;!;) ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS) .,
PROJECT A - CHESS DATA COLLECTION'
CHESS
TASK 11- Coastal Studies
A. PROGRAM JUSTIFICATION: Possible adverse health effects riue to total integrate-:!
environmental insult has'not been v^'il defined. These 'effects can bt- investigated
in this study as well as inner city communities and exposures to specified sources
of environmental
contaminates
B. OBJECTIVE: To quantitate possible health effects to total integrate:! environ-
mental insult gradient and the effects from specified sources.
C. SCOPE:
Populations
Studied
Present & Add-on Minimally Adequate
No program
Indicators
Used
No program
A. Normal exposed groups
1. Children
2. Aged
3. Asthmatics
4. Cardiacs
5. Chronic
Bronchi tics..
B. High risk groups due
to exposure from
1. industry
2. traffic-mobile
sources
3. stationary sources
A..Health indicators
1. Chronic respiratory
disease symptoms
2. Acute respiratory
disease
3. Reversible pulmonary
4. Acute irritation
symptoms
5. Human pollutant
burdens
6. Aggravation of
cardiac symptoms
B. More sensitive indicators
such as
1. Critical enzymes
2. Cardiac status
3. Exfoliative cytology
4. Assessment of RBC
function and longevity
Optimal
All of the minimally
adequate plus special
susceptible high risk
groups such as
1. Blood dyscrasias
(sickle cell anemia)
2. Pregnant women-
3. Low income groups
All of the minimally
adequate plus
1. Attitudes toward
pollution
2. Social cost
evaluations
3. New and more
sensitive indicators
-------
J
B 77
Present & Add-on Minimally Adequate
Optimal
Neighborhoods
I
Studied
Measuring
Stations
Per
Community
Pollutant
Measurements
10
No program 1 outdoor, 4 rotating
indoor, 9 personal
monitors.
12
3 outdoor and 10
rotating indoor,
36 personal monitors
Same
No program CHESS CHAMP monitoring
20 environmental meas-
urements continuously
with real time telemetry
to RTP.
D. RESULTS: Raw data collected from the Coastal CHESS network will be fed to
CHESS information synthesis and data analysis. These results will be used to
establish pollution standards and to evaluate the health effects of controls
reducing pollution levels.
..E. APPROACH: Current CHESS area programs will form the basis for Coastal
CHESS studies. Refinements in protocols, based upon previous experience,
will increase effectiveness of data in measurement collection. New health
indicators, pollution measurements, and populations at risk must be added
for an optimal.program.
F. jyPPjORTING._QQNIRACI5: A contract for data, collection with the local
.health department is the basis for this program.
G. SPECIAL FACILITIES: Air monitoring stations, computer opti-scan devices
.and computer data feedback to central data banks.
H. INTERMEDIA RELATIONSHIPS: Exist with each of the media and categorical
programs.
I. COORDINATION: Coordination between other ORM health effects research
program elements and other agencies such as DHEW, NIOSH, and NIEHS will be
necessary.
J. UNRESOLVED POLICY ISSUES: None.
-------
B 78
" ' J
PROGRAM ELEMENT l'ii/201: CO.-ii'lUNITY HEALTH AND ENVIROii.'tfNTAi.
SURVEILLANCE STUDIES (CHESS) ..
PROJECT A - CHESS DATA COLLECTION
TASK 12. CHESS Lakes Studies "-> ;
A. PROGRAM JUSTIFICAT/OH: Possible adverse health effects due to total
" not been well defined. These effects can be i
inner city communities and' exposures to specified sources
environmental insult "hV
in this study as well a
of environmental contaminates.
B' OBJECTIVE: To quantitate possible health effects to total integrated environ-
mental insult gradient and the effects from specified sources.
C.. SCOPE:
Populations
Studied
Present f. Add-on
No program
Indicators
Used
No program
Minimally Adequate
A. Normal exposed groups
1. Children
2. Aged
3. Asthmatics
4. Cardiacs
5. Chronic
Bronchi tics
B. High risk groups due
to exposure from
1. industry
2. traffic-mobile
sources
3. stationary sources
A. Health indicators
1. Chronic respiratory
disease symptoms
2. Acute respiratory
disease
3. Reversible pulmonary
4. Acute irritation
symptoms
5. Human pollutant
burdens
6. Aggravation of
cardiac symptoms
B. More sensitive indicators
such as
1. Critical enzymes
2. Cardiac status
3. Exfoliative cytology
4. Assessment of RBC
function and longevity
Optimal
All of the minimally
adequate plus special
susceptible high risk
groups such as
1. Blood dyscrasias
. (sickle cell anemia)
2. Pregnant women
3. Low incuiiie yrOups
All of the minimally
adequate plus
1. Attitudes toward
pollution
2. Social cost
evaluations
3. New and more
sensitive indicators
-------
B 79
Present & Add-on
Neighborhoods
Studied
Measuring
Stations
Ver
Community
Pollutant
No program
No program
Minimally Adequate
10
1 outdoor, 4 rotating
indoor, 9 personal
monitors.
CHESS CHAMP monitoring
20 environmental meas-
urements continuously
with real time telemetry
to RTP.
Optimal
12
3 outdoor and 16
rotating indoor,
36 personal monitors
Same
D. RESULTS: Raw data collected from the Lakes CHESS network will be fed
to CHESS information synthesis and data analysis. These results will be used
to establish pollution standards and to evaluate the health °ff°c^s o* controls
reducing pollution levels.. -T.x.b o, controls
E. APPROACH: Current CHESS . .area programs..will form the basis for Lakes
CHESS studies. Refinements.in protocols, based upon previous experience,
will increase effectiveness of data in measurement collection. New health
indicators, pollution measurements, and populations at risk must be added
for an optimal,program.
F. ..SyPPpjniNG..jCQNIRAC.LS: A contract for data collection with the local
health department is the basis for this program.
G. SPECIAL FACILITIES: Air monitoring stations, computer opti-scan devices
.and computer data feedback to central data banks.
H. INTERMEDIA RELATIONSHIPS: Exist with each of the media and categorical
programs.
I. COORDINATION: Coordination between other ORM health effects research
program elements and other agencies such as DHEW, NIOSH, and NIEHS will be
necessary.
0. UNRESOLVED POLICY ISSUES: None.
-------
B 80
PROGRAM ELEMENT 110201
Community Health and Environmental
Surveillance Studies (CHESS)
PROJECT A - CHESS Data Collection
TASK 13. CHESS Selected Source Exposures
A. PROGRAM JUSTIFICATION: Adverse health effects resulting from exposure to selected
pollutant sources of national importance have not been documented. Sources include
municipal incinerators, power plant facilities, landfills, petrochemical complexes,
airports and other municipal, domestic and industrial processes. Basic methods of the
CHESS Data Collection system will be applied to communities exposed to the above pol-
lutant sources. Health intelligence derived from these community studies will provide
a unique and necessary data base for control of major emission sources.
B* OBJECTIVE: To quantitate possible health effects to total integrated environ-
mental insult gradient and the effects from specified sources.
C. SCOPE:
Populations
Studied
Present 5 Add-on Minimally Adequate
No program
Indicators
Used
No program
A. Normal exposed groups
1. Children
2. Aged
3. Asthmatics
4. Cardiacs
5. Chronic
Bronchitics
D LKrit-, vti-l, rtv^r-,,1-- -l..r-
u. liiyii i ioi\ yi uupo uuc
to exposure from
1. industry
2. traffic-mobile -
sources
3. stationary sources
A, Health indicators
1. Chronic respiratory
disease symptoms
2. Acute respiratory
disease
3. Reversible pulmonary
4. Acute irritation
symptoms
5. Human pollutant
burdens
6. Aggravation of
cardiac symptoms
B. More sensitive indicators
such as
1. Critical enzymes
2. Cardiac status
3. Exfoliative cytology
4. Assessment of RBC
function and longevity
Optimal
All of the minimally
adequate plus special
susceptible high risk
groups such as
1. Blood dyscrasias
(sickle cell anemia)
2. Pregnant women
3. Low incoiiis groups
All of the minimally
adequate plus
1. Attitudes toward
pollution
2. Social cost
evaluations
3. New and more
sensitive indicators
-------
B 81
Present & Add-on
linimally Adequate Optimal
Neighborhoods
Studied
Measuring
Stations
Per
Community
Pollutant
Measurements
10
No program 1 outdoor, 4 rotating
indoor, 9 personal
monitors.
3 outdoor and 16
rotating indoor,
36 personal monitors
No program CHESS CHAMP monitoring Same
20 environmental meas-
urements continuously
with real time telemetry
to RTP.
D. RESULTS; Raw data collected from the Special Source Exposure CHESS network
will be fed to CHESS information synthesis and data analysis. These results
will be used to establish pollution standards and to evaluate the health effects
of controls reducing pollution levels.
E. APPROACH: Current CHESS area programs will form the basis for Special Source
Exposure CHESS studies. Refinements in protocols, based upon previous experience,
will increase effectiveness of data in measurement collection. New health indi-
cators, pollution measurements, and populations at risk must be added for an
optimal program.
F. SyP£QlT.INO,QfiLRACIS: A contract for data collection with the local
health department is the basis for this program.
G. SPECIAL FACILITIES: Air monitoring stations, computer opti-scan devices
and computer data feedback to central data banks.
H. INTERMEDIA RELATIONSHIPS: Exist with each of the media and categorical
programs.
I. COORDINATION: Coordination between other ORM health effects research
program elements and other agencies such as DHEW, NIOSH, and NIEHS will be
necessary.
0. UNRESOLVED POLICY ISSUES: None.
-------
PROGRAM ELEMENT 110201:
B 82
COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT B - CHESS INFORMATION SYNTHESIS
TASK 1. CHESS investigations of the dose-response relationships between the
frequency of chronic respiratory disease symptoms and ambient air pollutant
levels of oxides of nitrogen (NOX), oxides of sulfur (SQX), photochemical
oxidants (Ox), total suspended particulates (TSP) and respirable suspended
particulates (RSP).
A. PROGRAM JUSTIFICATION: Air quality control actions are by law primarily
based upon a recognized need to protect human health. Revisions of existing
air quality standards and promulgation of new standards require additional
health effects information. Chronic respiratory disease symptoms have been
linked to ambient air pollution in many epidemiologic studies. Further quantv
tation of these dose-response relationships is needed.
B. OBJECTIVE: To quantitate the relationship of chronic respiratory disease
symptoms (.CRD) to NOX, SOX, Ox, TSP and RSP over an exposure-dose gradient.
C. SCOPE:
Population
Studied
Indicator
Used
Present^vAd
-------
B C3
F. SUPPORTING CONTRACTS: Raw data for CHESS Information Synthesis are generated
through contracts with local health departments, universities and private industries.
G. SPECIAL FACILITIES: Environmental monitoring stations, opti-scan devices,
laboratory support and data feedback to central data banks.
H. INTERMEDIA RELATIONSHIPS; Exist with all media and categorical programs.
I. COORDINATION: Coordination with other ORM health effects research program
elements, other EPA offices, and selected other Federal and non-Federal agencies
will be necessary.
J. UNRESOLVED POLICY ISSUES: None
-------
B 84
PROGRAM ELEMENT 110201:
COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT B - CHESS INFORMATION SYNTHESIS
TASK 2. CHESS investigations of the dose-response relationships between
the history of acute lower respiratory infection (LRI) and ambient air
pollutant levels of oxides of nitrogen (NOX), oxides of sulfur (SOX), photo-
chemical oxidants (Ox), total suspended particulates (TSP), and respirable
suspended particulates (RSP).
A. PROGRAM JUSTIFICATION: Air quality control actions are by law primarily
based upon a recognized need to protect human health. Revisions of existing
air quality standards and promulgation of new standards require additional
health effects information. Acute lower respiratory diseases have been linked
to ambient air pollution in many epidemiologic studies. Further quantisation
of these dose-response relationships is needed.
B. OBJECTIVE: To quantitate the relationship of acute lower respiratory
disease frequency to NOX, SOX,. Ox, TSP and RSP over exposure-dose gradients.
C. SCOPE:
Population
Studied
Indicators
Used
Frequency
Pollutant Area
Sets Studied
Present and Add-on
Children from birth
through age 12.
History of bronchitis,
croup, pneumonia, other
deep chest infection and
hospitalization during
preceding three years.
Every 2 yrs.
(Present) Three area
sets with 17 commun-
ities. (Add-on) Seven
area sets with 39 com-
munities.
Minimally Adequate
Same
Same
Optimal
Same
Same
Same
Twelve area sets
with 69 commun-
ities
Same
Thirteen sets
with 75 commun-
ities
D. RESULTS: Technical reports elucidating the dose-response relationship between
air pollutants and acute lower respiratory disease frequency will provide necessary
health support for the promulgation of new air quality controls and the revision
of existing air quality standards.
-------
B 85
J
E. APPROACH: Parents of elementary school children complete self-administered
opti-scan questionnaires as specified by Federal protocols for CHESS data
collection contracts. Records are validated by consultation with physicians.
The effects of demographic and personal covariates are apportioned and the
effects of pollutants are assessed after appropriate adjustments.
F. SUPPORTING CONTRACTS: Raw data for CHESS Information Synthesis are generated
through contracts with local health departments, universities and private
industries.
G. SPECIAL FACILITIES: Environmental monitoring stations, opti-scan devices,
laboratory support and data feedback to central data banks.
H. INTERMEDIA RELATIONSHIPS: Exist with all media and categorical programs.
I. COORDINATION: Coordination with other ORM health effects research program
elements, other EPA offices, and selected other Federal and non-Federal agencies
will be necessary.
J. UNRESOLVED POLICY ISSUES: .None
-------
B 86
PROGRAM ELEMENT 110201: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT B - CHESS INFORMATION SYNTHESIS
TASK 3. CHESS investigations of the dose-response relationships between
incidence of acute respiratory tract disorders and ambient air pollutant
levels of nitrogen oxides (NOx), sulfur oxides (SOx), photochemical
oxidants (Ox), total suspended particulates (TSP), and respirable
suspended particulates (RSP).
A. PROGRAM JUSTIFICATION: Air quality control actions are by law primarily
based upon a recognized need to protect human health. Revisions of existing
air quality standards and promulgation of new standards require additional
health effects information. The incidence of acute respiratory disease
has been linked to ambient air pollution in many epidemfqlqcn'c st.iidi>s-.
quantisation of these dose-response relationships is needed.
B. OBJECTIVE: To quantitate the relationship between the incidence of
acute respiratory disease and NOx, SOx, Ox, TSP and RSP over exposure-
dose gradients.
C. SCOPE:
Population
Studied
Indicators
Used"
Present and Add-on
Volunteer families
with elementary
school children
residing in CHESS
communities. 300
families in each
community are
studied.
Incidence and
severity of acute
upper and lower
respiratory dis-
orders. Frequency
of bacterial com-
plications and
frequency and
severity of acute
non-respiratory
disorders.
Minimally Adequate
Same
Optimal
Same
Same
Same
-------
B 87
Frequency Queried every two Same Same
weeks during school
year.
Pollution Area (Present) Three Twelve area sets Thirteen area
Sets Studied area sets with 17 with 69 communities sets with 75
communities. (Add- communities
on) Seven area sets
with 39 communities.
D. RESULTS: Technical reports elucidating the dose-response relationship
between air pollutants and acute respiratory disease incidence will provide
necessary health support for the promulgation of new air quality controls
the revision of existing air quality standards.
E. APPROACH: Families are selected according to predetermined criteria
from respondents to a health questionnaire administered through community
schools. Volunteer families are queried every two weeks by telephone
regarding the onset, duration and severity of illness. Illness rates,
adjusted for appropriate personal and demographic cofactors, are related
to air pollutant exposures.
F. SUPPORTING CONTRACTS: Raw data for CHESS Information Synthesis are
generated through contracts with local health departments, universities
and private industries.
G. SPECIAL FACILITIES; Environmental monitoring stations, opti-scan
devices, laboratory support and data feedback to central data banks.
H. INTERMEDIA RELATIONSHIPS: Exist with all media and categorical programs.
I. COORDINATION: Coordination with other ORM health effects research
program elements, other EPA offices, and selected other Federal and non-
Federal agencies with be necessary.
J. UNRESOLVED POLICY ISSUES: None.
-------
PROGRAM ELEMENT 110201:
J
COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT B - CHESS INFORMATION SYNTHESIS
TASK 4. CHESS investigations of the dose-response relationships between
pulmonary function test performance and ambient air pollution levels of
oxides of nitrogen (NOx), oxides of sulfur (SOx), photochemical oxidants
(Ox), total suspended particulates (TSP), and respirable suspended
particulates (RSP).
A. PROGRAM JUSTIFICATION: Air quality control actions are by law primarily
based upon a recognized need to protect human health. Revisions of existing
air quality standards and promulgation of new standards require additional
health effects information. Decrements of pulmonary function have been
linked to ambient air pollution in many epidemiologic studies. Further
quantitation of these dose-response relationships is needed.
B. OBJECTIVE: To quantitate the relationship of pulmonary function and
exposure to NOx, SOx, Ox, TSP and RSP over exposure-dose gradients.
C. SCOPE:
Population
Studied
Indicators
Use?
Frequency
Present and Add-on
Elementary school
children
0.75 second forced
expiratory vol. (FEV)
Three times yearly
Minimally Adequate
Optimal
Same Same
(Also, see tasks 6 and 7)
Sets. Studied
Pollutant Area (Present) Three area
sets with 17
communities (Add-
on) Seven area sets
with 39 communities
2 additional tests
Same
Twelve area sets
with 69 communities
2 additional tests
Same
Thirteen area
sets with 72
communities
D. RESULTS: Technical reports elucidating the dose-response relationship
between air pollutants and pulmonary function in children will provide
necessary health support for the promulgation of new air quality controls and
the revision of existing air quality standards.
E. APPROACH: Children attending elementary schools located in CHESS areas
representing an exposure gradient for specified pollutants volunteer for
ventilatory testing during periods when pollutant levels are seasonally
lower and when they are elevated. Thus the relative effects of season,
acute pollution exposure and chronic pollutant exposure can be assessed as
can the effects of appropriate covariates. Pulmonary function test data
are collated with data abstracted from family health questionnaires completed
under CHESS data collection contracts".
-------
B 89
J
F. SUPPORTING CONTRACTS: Raw data for CHESS Information Synthesis are
generated through contracts with local health departments, universities and
private industries.
G. SPECIAL FACILITIES: Environmental monitoring stations, opti-scan devices,
laboratory support and data- feedback to central data banks.
H. INTERMEDIA RELATIONSHIPS: Exist with all media and categorical programs.
I. COORDINATION: Coordination with other ORM health effects research program
elements, other EPA offices, and selected other Federal and non-Federal agencies
will be necessary.
J. UNRESOLVED POLICY ISSUES: None.
-------
B 90
PROGRAM ELEMENT 110201:
COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT B - CHESS INFORMATION SYNTHESIS
TASK 5. CHESS investigations of the dose-response relationships between
the frequency of acute irritation symptoms of the eye and respiratory tract
disability and physician visits and acute ambient air pollution episodes
involving oxides of nitrogen (NOX), oxides of sulfur (SOx), photochemical
oxidants (Ox), total suspended particulates (TSP), and respirable suspended
particulates (RSP).
A. PROGRAM JUSTIFICATION: Air quality control actions are by law primarily
based upon a recognized need to protect human health. Revisions of existing
air quality standards and promulgation of new standards require additional
health effects information. Acute irritation symptoms and disability have
been linked to ambient air pollution in several epidemiologic studies. Further
quantisation of these dose-response relationships is needed.
B. OBJECTIVE: To quantitate the relationship of chronic respiratory disease
symptoms (CRD) to NOx, SOx, Ox, TSP and RSP over an exposure-dose gradient.
C. SCOPE:
Population
Studied
Indicator
Used
Frequency
Pollutant Area
Sets Studied
Present and Add-on
300 families living
in each CHESS com-
munity.
Frequency of eye
symptoms, respiratory
tract symptoms, assoc-
iated disability and
physicians visits
One control period and
at least one period of
increased pollution in
each area set each year.
[Present) Three area
sets with 17 commun-
ities. CAdd-on) Seven
area sets with 39 com-
munities.
Minimally Adequate Optimal
Same
Same
Same
Same
Same
Same
Twelve area sets
with 69 commun-
ities
Thirteen area
sets with 72
communities
D. RESULTS: Technical reports elucidating the dose-response relationship between
air pollutants and acute irritation symptom prevalence will provide necessary
health support for the promulgation of new air quality controls and the revision of
existing air quality standards.
-------
B 91
E. APPROACH: Families participating in CHESS studies of acute respiratory
disease incidence are queried during periods of low and elevated ambient air
pollutions. The relative effects of weather and specific pollutant sets can
be quantitated. Appropriate adjustments are made for reporting bias and other
cofactors. Repeated studies will allow construction of dose-response curves
for the effect of important ambient pollutants on children and adults.
F. SUPPORTING CONTRACTS: Raw data for CHESS Information Synthesis are generated
through contracts with local health departments, universities and private industries,
G. SPECIAL FACILITIES: Environmental monitoring stations, opti-scan devices,
laboratory support and data feedback to central data banks.
H. INTERMEDIA RELATIONSHIPS: Exist with all media and categorical programs.
I. COORDINATION: Coordination with other ORM health effects research program
elements, other EPA offices, and selected other Federal and non-Federal agencies
will be necessary.
J. UNRESOLVED POLICY ISSUES: None
-------
J
B 92
PROGRAM ELEMENT 110201:
COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT B - CHESS INFORMATION SYNTHESIS
TASK 6. CHESS investigations of the dose-response relationship between
the aggravation of symptoms in panels of elderly persons either well or
afflicted with chronic heart and/or lung disease and acute ambient air
pollution levels of nitrogen oxides (NOx), sulfur oxides (SOx), photo-
chemical oxidants (Ox), total suspended particulates (TSP) and respirable
suspended particulates (RSP).
A. PROGRAM JUSTIFICATION: Air quality control actions are by law primarily
based upon a recognized need to protect human health. Revisions of existing
air quality standards and promulgation of new standards require additional
health effects information. Chronic respiratory and heart disease symptoms
in the elderly have been linked to ambient air pollution in several
epidemiologic studies.. Further quantitation of these dose-response relation-
ships is needed.
B. OBJECTIVE: To quantitate the relationship of chronic respiratory and
heart disease symptoms to NOx, SOx, Ox, TSP and RSP over exposure-dose
gradients.
C. SCOPE:
Population
Studied
Present and Add-on
Minimally Adequate
Indicators
Used"
Frequency
Pollution Area
Sets Studied
1. Well elderly people
2. Elderly people with
chronic lung disease(CRD)
3. Elderly people with
chronic heart disease
4. Elderly people with
both chronic heart and
chronic lung disease
1. Prevalence of
disease symptoms
2. Fluctuations in
severity of disease
symptoms
3. Changes in disability
Daily
(Present) One area set
with 3 communities (Add-
on) Seven area sets with
39 communities
Same
Optimal
Same
Changes in
ventilatory
function.
Same
Twelve area sets
with 69 communities
Changes in
sputum cytology
and histochemistry
Same
Thirteen area sets
with72 communities
-------
B 93
J
D. RESULTS: Technical reports elucidating the dose-response relationship
between air pollutants and chronic respiratory and heart disease symptom
prevalence and incidence will provide necessary health support for the
promulgation of new air quality controls the revision of existing air
quality standards.
E. APPROACH: Panelists are recruited through local physicians, golden age
clubs, churches and other social mechanisms. Personal and demographic
cofactors are quantitated by an interviewer-administered opti-scan question-
naire. Volunteer panelists record their symptoms on opti-scan diaries which
are validated by the staff of the CHESS data collection contractor and
forwarded for data processing and appraisal.
F. SUPPORTING CONTRACTS: Raw data for CHESS Information Synthesis are
generated through contracts with local health departments, universities and
private industries.
G. SPECIAL FACILITIES: Environmental monitoring stations, opti-scan devices,
laboratory support and data feedback to central data banks.
H. INTERMEDIA RELATIONSHIPS: Exist with all medial and categorical programs.
I. COORDINATION: Coordination with other ORM health effects research program
elements, other EPA offices, and selected other Federal and non-Federal agencies
will be necessary.
J. UNRESOLVED POLICY ISSUES: None.
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B 94
PROGRAM ELEMENT 110201: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT B - CHESS INFORMATION SYNTHESIS
TASK 7. CHESS investigations of the dose-response relationships between the
aggravation of asthma and acute ambient air pollution levels of oxides of
nitrogen (NOx), oxides of sulfur (SOX), photochemical oxidants (Ox), total
suspended particulates (TSP), and respirable suspended particulates (RSP).
A. PROGRAM JUSTIFICATION: Air quality control actions are by law primarily
based upon a recognized need to protect human health. Revisions of existing
air quality standards and promulgation of new standards require additional
health effects information. Chronic respiratory disease symptoms have been
linked to ambient air pollution in many epidemiologic studies. Further quanti-
tation of these dose-response relationships is needed.
B. OBJECTIVE: To quantitate the relationship between aggravation of asthma
and NOX, SOX, Ox, TSP and RSP over exposure-dose gradients.
C. SCOPE:
Population
Studied
Indicator
Used"
Frequency
Pollutant Area
Sets Studied
Present and Add-on
Fifty volunteer panel-
ists with a history of
asthma .in each CHESS
community.
Frequency of acute
attacks and severity
of acute attacks
Every 6 hours
(Present) Three area
sets with 17 commun-
ities (Add-on) Seven
area sets with 39 com-
munities
Minimally Adequate
Same
Twice daily ventilatory
function as an addi-
tional indicator
Same
Twelve area sets with
69 communities
Optimal
Same
Same
Same
Thirteen area sets
with 75 communities
D. RESULTS: Technical reports elucidating the dose-response relationship between
air pollutants and aggravation of asthma will provide necessary health support for
promulgation of new air quality controls and the revision of exts-tfna afr aual
air poiiutanrs ana aggravation or astnma win provide necessary neaitn support ror
the promulgation of new air quality controls and the revision of exts-tfna atr quality
standards.
E. APPROACH: Asthma panelists are recruited from individuals completing the CHESS
family health questionnaire and through cooperation of physicians, clinics, and
neighborhood drugists. Appropriate demographic information is obtained by a personal
interview prior to entry into the study. Panelists then complete weekly diaries
recording onset frequency and severity of asthma symptoms. Air quality data will be
obtained from CHESS CHAMP stations. Data processing and technical reports will be
accomplished intramurally.
-------
B 95
F. SUPPORTING CONTRACTS: Raw data for CHESS Information Synthesis are generated
through contracts with local health departments, universities and private industries,
G. SPECIAL FACILITIES: Environmental monitoring stations, opti-scan devices,
laboratory support and data feedback to central data banks.
H. INTERMEDIA RELATIONSHIPS; Exist with all media and categorical programs.
I. COORDINATION: Coordination with other ORM health effects research program
elements, other EPA offices, and selected other Federal and non-Federal agencies
will be necessary.
J. UNRESOLVED POLICY ISSUES: None
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B 96
PROGRAM ELEMENT 110201: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT B - CHESS INFORMATION SYNTHESIS
TASK 8 - CHESS investigation of the dose-response relationships between
human pollutant burdens assayed in hair, blood, and tissues and environmental
pollutants (including metals such as As, Cd, Cr, Cu, Pb, Mn, Hs, Ni, V, Zn
and synthetic organic materials including aromatic and aliphatic halides such
as PCB). This task also investigates the relationship between human pollutant
burdens and disease using the CHESS tissue bank.
A. PROGRAM JUSTIFICATION: Air quality control actions are by law primarily
based upon a recognized need to protect human health. Revisions of existing
air quality standards and promulgation of new standards require additional
health effects information. Increased human pollutant burdens have been linked
to environmental pollution in several epidemiologic studies. Further quantita-
tion of these dose-response relationships is needed.
B. OBJECTIVE: To quantitate the relationship between pollutant burdens
human tissues and trace element and synthetic organic pollutants in the
environment.
C. SCOPE:
in
Present
Population 25 tissue sets,
Studiedcomposed of placenta,
scalp hair, pubic
hair, maternal blood,
and fetal blood are
collected in each
CHESS Community.
Scalp hair is also
collected from 300
families in each
CHESS area. Tap
water, soil and
house dust are ob-
tained from these
households.
Feasibility studies
of tissue collection
at surgery and autopsy
will be completed.
Add-on Minimally Adequate Optimal
National Studies of 3 especially
tissue vulnerable groups in-
bank will eluding blood specimens
be begun, from inner city children
and appropriate controls.
Same.
-------
B 97
Present
Indicators Tissue levels of
Used four metals moni-
tored routinely.
Preliminary
studies of 12
other metals
and PCB are
underway.
Frequency Every 2 years.
Add-on
Tissue levels
of 16 metals
and residues
of 4 impor-
tant synthetic
organic pollu-
tants.
Minimally Adequate
Same
Optimal
Same
Pollutant
Area Sets
Studied
Three areas with
17 communities.
Yearly
Seven areas
with 39
communities.
Same
Twelve areas
with 69 com-
munities.
Same
Thirteen
areas with
75 communi-
ties.
D. RESULTS. Technical reports elucidating the dose-response relationship
between air pollutants and human pollutant burdens will provide necessary
health support for the promulgation of new air quality controls the revision
of existing air quality standards.
E. APPROACH: CHESS contractors provide an administrative mechanism to collect
tissues and personal health information according to Federal protocols. Tissue
pollutant burden levels are assayed by intramural laboratories complemented by
contracts with universities and other research organizations. Data collation,
processing, appraisal and preparation of appropriate technical reports are
intramural activities.
F. SUPPORTING CONTRACTS: Raw data for CHESS Information Synthesis are generated
through contracts with local health departments, universities and private industries,
G. SPECIAL FACILITIES: Environmental monitoring stations, opti-scan devices,
laboratory support and data feedback to central data banks.
H. INTERMEDIA RELATIONSHIPS: Exist with all media and categorical programs.
I. COORDINATION: Coordination with other ORM health effects research program
elements, other EPA offices, and selected other Federal and non-Federal agencies
will be necessary.
0. UNRESOLVED POLICY ISSUES: None.
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B 98
PROGRAM ELEMENT 110201:
COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT B - CHESS INFORMATION SYNTHESIS
TASK 9 - CHESS investigations of the dose-response relationships between
excess daily mortality and acute ambient air pollution episodes (NO , SO ,
0 , TSP, RSP) and between coronary artery disease deaths and acute air
pollution exposure (CO).
A. PROGRAM JUSTIFICATION: Air quality control actions are by law primarily
based upon a recognized need to protect human health. Revisions of existing
air quality standards and promulgation of new standards require additional
health effects information. Increases in daily mortality have been linked
to ambient air pollution in many epidemiologic studies, further quanti.tati.on
of these dose-response relationsips is needed.
B. OBJECTIVE:
mortality to
C. SCOPE:
NOX,
To quantitate the relationship of fluctuations in daily
, TSP and RSP over exposure-dose gradients.
sox,
Present
Completion of daily
mortali ty model.
Application of model
to New York City &
Philadelphia. Model
will be developed
for every SMSA with
over 1,000,000
population.
Add-on Minimally Adequate
Same Model will be applied to
all CHESS regions and all
other SMSA over 1,000,000.
Included is purchase of
current mortality records
by date of death.
Optimal
Same.
D. RESULTS: Technical reports elucidating the dose-response relationship
between air pollutants and changes in daily mortality will provide necessary
health support for the promulgation of new air quality controls the revision
of existing air quality standards.
E. APPROACH: Daily mortality tapes will be obtained from DHEW or state and
local health departments. Daily pollutant measurements will be obtained
from other EPA units. Data processing and technical reports will be prepared
intramurally. Mortality models for any major metropolitan region would be
made available upon request to any regional EPA office.
F. SUPPORTING CONTRACTS; Daily mortality data will be purchased through
contracts with local health departments or through interagency agreements.
G. SPECIAL FACILITIES: Environmental monitoring stations, opti-scan devices,
and data feedback to central data banks.
H. INTERMEDIA RELATIONSHIPS: Exist with all media and categorical programs,
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B 99
I. COORDINATION: Coordination with other ORM health effects research program
elements, other EPA offices, and selected other Federal and non-Federal agencies
will be necessary.
J. UNRESOLVED POLICY ISSUES: None.
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B TOO
PROGRAM ELEMENT 110201
COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT B - CHESS INFORMATION SYNTHESIS
Task 10. CHESS statistical technique improvements to overcome problems
relating to serial correlation, modeling human exposure assessment of
populations at risk, censored data, analysis of mixed model (categorical -
continuous) data, and CHESS data systems.
A. PROGRAM JUSTIFICATION: Air quality standards must be establised which
are adequate to protect the public from recognized health dangers. The
synthesis of the monitoring and effects data collected in CHESS into
technical reports for support of air quality standards requires extensive
data processing and statistical analyses. The large-scale field studies
introduce many analysis problems such as missing observations, time
dependent observations, serial correlations, censored samples, non-response
and reporting bias. Better techniques are urgently needed to more appropriately
adjust for those situations.
B. OBJECTIVE: To provide optimal translation of the health and environmental
data collected in CHESS into quantitative dose-response relationships for setting
air quality standards.
C. SCOPE:
Present
Hith Add-on
Present plus
Minimally Adequate
Add-on plus
Optimal
M. A. plus
Proper use of
censored data
Optical scan
form develop-
ment
Time series analysis Basic human exposure
for panel studies models for CHESS
populations
Non-response bias
Better data record
linkage
Better human
exposure models
Computer simul-
ations
Mixed cate-
gorical-
continuous
data analysis
Invalid response
bias
Stratified sampling
techniques
Duster analysis
Statistical
analysis computer
program packages
(for current
CHESS program)
Estimation of
missing obser-
vations
Likelihood ratio
procedures
Discriminant
analysis
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B 101
D. RESULTS; The research findings will be incorporated into the
routTne statistical analysis and data processing protocols for the
CHESS Information Synthesis Project. The resulting technical reports
will provide more defensible air quality standards.
E. APPROACH: The appropriate scientific literature will be thoroughly
reviewe~cTTheoretical and empirical models will be constructed and
employed. The computer provides the primary means of evaluating the
efficiency of these new procedures and is essential for the simulation
results. The findings will be distributed to other EPA research com-
ponents such as Community Pesticides Program and Radiological Health
Program.
F. SUPPORTING CONTRACTS: Contracts with universities or private
research institutes such as RTI or the Mitre Corporation are
desirable and may be required.
G. SPECIAL FACILITIES: Because of the direct dependence on the computer
and other data processing equipment such as on-line terminals and opti-
scan devices, adequate access to these facilities is essential.
H. INTERMEDIA RELATIONSHIPS: Exist with the Community Pesticide Program,
and with the Water, Radiation, Solid Waste and Toxic Research Efforts.
I. COORDINATION: Coordination is required with other EPA research
programs, NIOSH, NIEHS, Census Bureau, NCHS.
J. UNRESOLVED POLICY ISSUES: None.
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B 102
PROGRAM ELEMENT 110201:
J
COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT B - CHESS INFORMATION SYNTHESIS
TASK 11. Health costs of ambient air pollution and health benefits of
pollution control as delineated in the CHESS program. NOx, SOx, Ox,
CO, TSP, RSP are the pollutants of prime interest.
A. PROGRAM JUSTIFICATION: Air quality standards are by law based on a
recognized need to protect human health. However, the health costs and
health benefits of control options must be considered together. Quantitation
of health costs is needed for more complete evaluation of control options.
B- OBJECTIVE: To provide urgently needed inputs to cost-benefit appraisal
of air pollution control options by quantitating the health costs to the
American public of the major air pollutants.
C. SCOPE:
Present
Current CHESS
health indica-
tors provide
quantitative
health burden
of pollution
Add-on
Estimate na-^
tional costs
for CHESS
health indica-
tor categories
Minimally Adequate
Illness specific na-
tional costs for all
major mortality and
morbidity indicators
National estimates of
sub-clinical illness
prevalence
Optimal
U.S. population at
risk to major air
pollutants
Quantitation in
CHESS populations of
national health cost
estimates
D. RESULTS: The findings will be utilized in the choice between competing
pollution control options. These urgently needed results will allow rational
decisions which, insure that the health costs of control do not exceed the
health benefits of control.
E. APPROACH; Dose-response analysis of current CHESS health indicator data
will quantitate health cost of major air pollutants on these few health
categories. National estimates can be determined for these same health
categories. More complete consideration of mortality, morbidity, and sub-*
clinical illness categories is urgently needed. Pollution monitoring data
and population at risk estimates for various levels of the major air pollutants
Inter-agency cooperation is imperative.
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B 103
F. SUPPORTING CONTRACTS: Contracts with universities or with research
institutes such as RTI or the Mitre Corporation would be desirable.
G. SPECIAL FACILITIES: Adequate computer and data processing facilities
must be available.Linkage capability between mortality-morbidity records
and social security files would be very valuable (see Task 9B)
H. INTERMEDIA RELATIONSHIPS: Exist with all media and categorical programs.
I. COORDINATION: Coordination with other ORM health effects research program
elements, other EPA offices, Census Bureau, NCHS, and other selected Federal
and non-Federal agencies will be necessary.
J. UNRESOLVED POLICY ISSUES: None.
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B 104.
PROGRAM ELEMENT 110201: COMMUNITY HEALTH ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT C - CHESS BIO-ENVIRONMENTAL MEASUREMENT PROVIDES FOR
BIOLOGICAL AND ENVIRONMENTAL SURVEILLANCE NECESSARY
FOR HEALTH EFFECTS STUDIES. IN THIS PROJECT,
ENVIRONMENTAL SURVEILLANCE AND QUALITY CONTROL METHODS
ARE SPECIFIED; AIR MONITORING STATIONS ARE ESTABLISHED
FOR CHESS COMMUNITIES; ENVIRONMENTAL AND BIOLOGICAL
.SAMPLES CONVEYED FROM THE FIELD ARE ANALYZED AND APPRO-
PRIATE ATMOSPHERIC MODELS ARE CONSTRUCTED. RESULTS ARE
FORWARDED FOR INFORMATION SYNTHESIS.
TASK 1. Evaluation and adaptation of continuous and personal air monitoring
techniques for use in health effects studies.
A. PROGRAM JUSTIFICATION; The monitoring and acquiring of aerometric
pollutant data involves the use of sophisticated electro-chemical sensors
and complex data acquisition systems. As technology advances and refine-
ment of systems increases, pilot feasibility studies are needed to inte-
grate the new technology into the operational Bio-environmental monitoring
program.
B. OBJECTIVES: To evaluate, test, and adapt new instrumentation to the
highly specialized environmental monitoring program used in the assessment of
human exposure studies. To adapt the latest automatic data acquisition principles
in acquiring and remotely transmitting collected pollutant data.
C. SCOPE:
1. Present
Evaluation of start-up operation of continuous monitoring systems
can be accomplished. Method and form of data acquisition can be re-
fined to insure greater reliability of sensor operation through use of
electronic quality control sensor monitors. A minimum effort to update
sensor technology to include^onitoring of additional pollutants can be
accomplished. For personal monitoring, prototype systems can be evalu-
ated and field tested on a limited basis.
2. Add-on
Same as present level.
3. Minimum Adequate
In addition to refinement of present continuous air monitoring
methods, emphasis can be placed on applying new technological advances
to the system. As new pollutant measurement methods arise, they can be
evaluated by rigid field tests. Real-time computer techniques can be
implemented, and real-time quality assurance programs can be incorporated
into the operational sites. Feasibility of monitoring new pollutants can
be established as the need for new health indicators arise. Personal
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B 105
monitoring techniques can be field tested on an operational basis at
several of the CHESS field operational locations; data from the per-
sonal monitors can be evaluated and used in validating the need for
such monitors in human health effects studies.
4. Optimum
Increased effort could be put into the search for more efficient
methods of environmental pollutants. In the area of atmospheric par-
ticulates, the use of scanning electron microscopes and X-ray diffrac-
tion systems could be adapted and implemented in both qualitatively and
quantitatively identifying aerosols.
D. RESULTS: The evaluation and adaptation of instrumentation and methods
provides the CHAMP operational environment monitoring program with proven
standard reliable methods for health effects monitoring.
E. APPROACH: Communication with research and development groups is kept
up to date. Prototypes of new instrumentation is studied for application
to the health effect monitoring. Systems are adapted and evaluated in
real field monitoring situations. Present operating systems are continually
studied for updating.
F. SUPPORTING CONTRACTS: None.
G. SPECIAL FACILITIES: Prototype field monitoring sites. Automatic
Data Processing facility, methods and instrumentation.
H. INTERMEDIA RELATIONSHIPS: EPA Research and Development, ADP operations.
I. COORDINATION: NIEHS, NIOSH, NCI.
J. UNRESOLVED POLICY ISSUES: None.
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B 106
J
PROGRAM ELEMENT 110201: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT C - CHESS BIO-ENVIRONMENTAL MEASUREMENT PROVIDES FOR BIOLOGICAL AND
ENVIRONMENTAL SURVEILLANCE NECESSARY FOR HEALTH EFFECTS STUDIES.
IN THIS PROJECT, ENVIRONMENTAL SURVEILLANCE AND QUALITY CONTROL
METHODS ARE SPECIFIED; AIR MONITORING STATIONS ARE ESTABLISHED
FOR CHESS COMMUNITIES; ENVIRONMENTAL AND BIOLOGICAL SAMPLES CON-
VEYED FROM THE FIELD ARE ANALYZED AND APPROPRIATE ATMOSPHERIC
MODELS ARE CONSTRUCTED. RESULTS ARE FORWARDED FOR INFORMATION
SYNTHESIS.
TASK 2. Establishment, operation and maintenance of regular CHESS and CHESS
Continuous Health Air Monitoring Program (CHESS-CHAMP) stations.
A. PROGRAM JUSTIFICATION: Comprehensive environmental monitoring is needed for
coupling sensitive health indicators to existing environmental pollutant levels.
Data correlations are made between observed health effects and observed air
quality exposure. The correlations are used to evaluate existing environmental
standards, to quantitate pollutant burdens in exposed populations, and to quantitate
health benefits of pollution control.
B. OBJECTIVE; To establish and operate environmental monitoring stations which
will provide reliable multi-pollutant and other environmental data either on a
real-time or integrated sample basis. To acquire and process sensor data by use
of automatic data acquisition systems with use of remote access by telemetry.
C. SCOPE:
1. Present - the funding can provide the following environmental monitoring:
a. New York Metropolitan - integrated 24-hour sampling or major pollutants
( particularly S02, N02, etc.).
b. California (LA Basin) - continuous monitoring (electronic sensors)
of oxidants.
c. Chattanooga, Tenn. - integrated 24-hour and continuous monitoring for
oxides of nitrogen.
d. Operation of CHAMP prototype station.
2. Add-on - funding can provide CHAMP continuous monitoring of major pollutants
and the presently 24-hour integrated sampling technique in seven study areas;
namely, S.E. trio, NYC, Utah, California, Chattanooga, St. Louis and Chicago.
In addition, it will provide one mobile unit for calibration, episode and support
functions. Personal monitors could be deployed at selected study areas, with
significant in-door, out-door monitoring.
3. Minimum Adequate - In addition to study areas accomplished by add-on funding,
the environmental monitoring could be expanded to cover the major regions of
the country. Work could be expanded in Chicago, and six monitoring stations
could be established at each of the following locations; namely, Southwest U.S.,
Mountain Area, Northwest U.S., Coastal, and the Great Lakes Area.
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B 107
Two additional mobile units could be utilized in calibration, support,
and episode functions. The units would have automatic data acquisition and
remote telemetry capability.
Additional equipment, supplies and instrumentation would require approxi-
mately 1.6K of the funding. Personal monitoring could be expanded to all
study areas. All major pollutants would be monitored.
4. Optimum - Under the optimum funding all work under minimum adequate would
be accomplished and six additional mobile units would be added, three for
aerometric and environmental support monitoring, two for bio-medical validation
purposes.
An elaborate hydrocarbon monitoring program could be established; that is,
specific organic hydrocarbon concentrations found in ambient air could be
determined.
A more sophisticated definition of pollutant interaction could be determined
and resulting monitoring could be accomplished.
Study areas providing unique exposure situations for exposure
to highly important stationary or mobile sources will be established.
D. RESULTS: The data obtained from this study will be very valuable in that it
will provide environmental pollution data for use in health studies needed to
establish air quality standards. The real-time measurements will be extremely
useful in establishing defensible short-term environmental standards. In addition,
it will provide enormous information on man's exposure in different community
situations.
E. APPROACH: With present funding, sampling frequency and methodology have pro-
vided 24-hour integrated samples on an "every day" basis. The implementing of
continuous electronic sensors with real-time notation and computer handling of
data will provide an infinite number of ways that a given set of aerometric data
can be analyzed or presented.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIP: EPA Media Offices
I. COORDINATION: NIEHS, NIOSH, NCI
J. UNRESOLVED POLICY ISSUES:
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B 108
PROGRAM ELEMENT 110201: COMMUNITY HEALTH ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT C - CHESS BIO-ENVIRONMENTAL MEASUREMENT PROVIDES FOR
BIOLOGICAL AND ENVIRONMENTAL SURVEILLANCE NECESSARY
FOR HEALTH EFFECTS STUDIES. IN THIS PROJECT,
ENVIRONMENTAL SURVEILLANCE AMD QUALITY CONTROL METHODS
ARE SPECIFIED; AIR MONITORING STATIONS ARE ESTABLISHED
FOR CHESS COMMUNITIES: ENVIRONMENTAL AND BIOLOGICAL
SAMPLES CONVEYED FROM THE FIELD ARE ANALYZED AND APPRO-
PRIATE ATMOSPHERIC MODELS ARE CONSTRUCTED. RESULTS ARE
FORWARDED FOR INFORMATION SYNTHESIS.
TASK 3. Evaluation of special human exposures related to airports, and
selected stationary sources, including fossil-fuel power plants, incinerators,
and petrochemical complexes.
A. PROGRAM JUSTIFICATION: Performance and emissions standards for stationary
sources and airports are a vital part of our effort to achieve clean air.
Stationary source standards have thus far been based largely upon ambient air
quality standards. However, stationary sources engender a number of special
human exposures whose health impacts have not been ascertained. More adequate
health information would assure that stationary sources standards could protect
health without being unnecessarily restrictive.
B. OBJECTIVE: To provide health intelligence necessary to support existing
and proposed stationary source standards.
C. SCOPE:
Present Add-on Minimally Adequate Optimal
Human exposure Human expo- Human exposure near Human exposures
surveillance in sure near municipal incinerator. near petrochem-
the vicinity of sewage ical complexes
an airport and sludge and odor sources,
near point sources incinerator.
of S02 and N02.
D. RESULTS: Health effects intelligence for improved defensible stationary
source performance standards by 1975.
E. APPROACH: Exposures would be quantitated using standard aerometric techniques.
Pollutants of special interest include toxic trace metals, synthetic organic
residues, particularly chlorinated compounds, HC1, NH~, fuel additive residues,
combustible hydrocarbons, and other hydrocarbons including polycyclic organic
matter. Intramural efforts would be supplemented by appropriate contracts.
Aerometric data would be collated with health data in the CHESS information
synthesis project.
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B 109
F. SUPPORTING CONTRACTS: Raw data for CHESS Information Synthesis are generated
through contracts with universities and private industries which supplement
intramural activities.
G. SPECIAL FACILITIES: Environmental monitoring statipns, opti-scan devices,
laboratory support and data feedback to central data banks.
H. INTERMEDIA RELATIONSHIPS; Exist with all media and categorical programs.
I. COORDINATION: Coordination with other ORM health effects research program
elements, other EPA offices, and selected other Federal and non-Federal agencies
will be necessary.
J. UNRESOLVED POLICY ISSUES: N6ne.
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B 110
PROGRAM ELEMENT I 1020 I: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT C - CHESS BIO-ENVIRONMENTAL MEASUREMENT PROVIDES FOR BIOLOGICAL AND
ENVIRONMENTAL SURVEILLANCE NECESSARY FOR HEALTH EFFECTS STUDIES.
IN THIS PROJECT, ENVIRONMENTAL SURVEILLANCE AND QUALITY CONTROL
METHODS ARE SPECIFIED; AIR MONITORING STATIONS ARE ESTABLISHED
FOR CHESS COMMUNITIES; ENVIRONMENTAL AND BIOLOGICAL SAMPLES
CONVEYED FROM THE FIELD ARE ANALYZED AND APPROPRIATE ATMOSPHERIC
MODELS ARE CONSTRUCTED. RESULTS ARE FORWARDED FOR INFORMATION
SYNTHESIS.
TASK 4. CHESS investigations of human exposure to metallic and synthetic
organic pollutants via household dust, soil, tap water, food and
tissue residues.
A. PROGRAM JUSTIFICATION: In order to accurately assess the level of
exposure of the human population to various pollutants these studies must
be undertaken. In addition media other than human tissue must be assayed
to establish the primary sources of exposure.
B. OBJECTIVE: To determine levels of trace metals and synthetic organic
pollutants in human tissue and identify the various media serving as
primary transmission sources to man.
C. SCOPE;
Present - Analysts will be performed for cadmium, copper, lead, mangenese,
and zinc in a variety of media and selected human tissues
such as blood and hair.
Add-on - Same as present.
Minimal Adequate - Studies can be expanded to include several other
trace metals (nickel, beryl I rum, antimony and mercury)
and some synthetic organics in human hair and blood
as well as several other media. Studies can also be
extended to vulnerable human groups as well.
Optimum - Same as Minimal Adequate but in addition studies can be ex-
panded to include a large number of samples as well as human
biopsy material, placenta and blood and hair collected from
selected urban populations in several areas as well as
appropriate vulnerable populations.
D. RESULTS: Data obtained will provide knowledge of human tissue burdens
as welI as primary sources of contamination.
E. APPROACH; Standard methods of trace metal and organic analysis will be
used following validation tests for each media type.
-------
B in
J
F. SUPPORTING CONTRACTS; I. Trace Metal Analyses on Maternal-FetaI
Tissue Sets (RFP-DU-72-B-379 at ca $80,000)
2. Hair and House Dust Trace Metal Analyses
(RFP-DU-72-B-375 at ca $218,000)
G. SPECIAL FACILITIES: Storage capability for samples via a tissue bank
must be set up.
H. INTERMEDIA RELATIONSHIPS: EPA Media Offices.
I. COORDINATION: FDA, AEC.
J. UNRESOLVED POLICY ISSUES: None :
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B 112
PROGRAM ELEMENT I 1020 1: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT C - CHESS BIO-ENVIRONMENTAL MEASUREMENT PROVIDES FOR BIOLOGICAL
AND ENVIRONMENTAL SURVEILLANCE NECESSARY FOR HEALTH EFFECTS
STUDIES. IN. THIS PROJECT, ENVIRONMENTAL SURVEILLANCE AND QUALITY
CONTROL METHODS ARE SPECIFIED; AIR MONITORING STATIONS ARE
ESTABLISHED FOR CHESS COMMUNITIES; ENVIRONMENTAL AND BIOLOGICAL
SAMPLES CONVEYED FROM THE FIELD ARE ANALYZED AND APPROPRIATE
ATMOSPHERIC MODELS ARE CONSTRUCTED. RESULTS ARE FORWARDED FOR
INFORMATION SYNTHESIS.
TASK 5. Laboratory analyses of routine aerometrlc specimens collected
in CHESS.
A. PROGRAM JUSTIFICATION: In order to assess the health effects of any
airborne pollutant accurate data must be available on its concentration
and patterns of change. This program is designed to measure the concen-
tration of a score of these airborne pollutants.
B. OBJECTIVE; To monitor atmospheric levels of S02, N02> TSP, RSP, SO ,
NOX, and trace metals as well as organics throughout the CHESS network.x
C. SCOPE:
Present - Routine analysis is being performed throughout the CHESS
network with a. gradual phase-out of analysis as the CHAMP system takes
over. It is anticipated that current funding and manpower levels .will
not be increased.
Add-on - Same as Present.
Minimal Adequate - Same as Present.
Optimum - Same as Present.
D. RESULTS; Data collected in this program provides knowledge of the
levels of environmental pollutants which are used In correlating health
effects. Data will also serve to validate CHAMP network.
E. APPROACH; Routine laboratory analysis is used.
F. SUPPORTING CONTRACTS; None
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIPS; EPA Media Offices.
I. UNRESOLVED POLICY ISSUES: None
J. COORDINATION: None
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B 113
PROGRAM ELEMENT: BIOMEDICAL RESEARCH - 110203
PROJECT C: CHESS
TASK 6. Indoor Generation of Air Pollutants.
A. PROGRAM JUSTIFICATION; The contribution of indoor activities such as cooking,
heating, cigarette smoking, etc., to airborne pollutants for which Air Quality
Standards have been established is unknown. For example, are the outside
ambient levels of N02 and resirable participates which penetrates homes enhanced
by indoor activities? Are the current ambient level standards adequate to cover
the relative confinement of the home environment? These are some of the questions
which must be considered to evaluate the adequacy of current standards.
B. OBJECTIVE: To characterize and measure the N02 and respirable particulate
build-up under a simulated indoor environment. Also, by exposing animals to
this environment, obtain an indication of adequacy of present standards.
C.- SCOPE; The scope includes an evaluation of the contribution to air pollution
of indoor household activities. Secondly, there is involved some minor changes
to an existing specially fabricated mobile home to provide adequate exposure
facilities for research animals. Finally, the scope of the task will be concerned
with exposure of suitable animals and the selection of appropriate exposure levels
and response parameters to evaluate the effects.
D. RESULTS; With adequate funding realistic estimates of the contribution to
air pollution levels of indoor activities will be obtained along with an
indication of any potential effects from prolonged exposure.
E. APPROACH: Using an existing controlled environment facility, normal indoor
activities will be simulated. Cooking of food with a gas range, using a gas
space heater,'etc., are examples of the activities planned. Animals will be
exposed to this analyzed environment along with other common indoor contaminants
such as cigarette smoke and household aerosols.
Progress will be followed by quantitating cytogenetic changes, enzymatic
changes, and other early pulmonary changes, along with the later occurring
histopathology.
F. SUPPORTING CONTRACTS; None
G. SPECIAL FACILITIES: Trailer home, which is available.
H. INTERMEDIA RELATIONSHIPS: Air
I. COORDINATION: With Air Programs
J. UNRESOLVED POLICY ISSUES: None
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B 114
J
PROGRAM ELEMENT 110201: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT D - DEVELOPMENT OF MORE SENSITIVE HEALTH EFFECTS
INDICATORS FOR CHESS, INCLUDING BIOCHEMICAL
AND CYTOLOGICAL ALARM SYSTEMS.
TASK 1. Dose relationship between erythrocyte damage and exposures
involving ambient air pollutants, trace metals and other
environmental contaminants as indexed by mechanical fragility,
osmotic fragility and centrifigation assay of cell age
distribution.
A. PROGRAM JUSTIFICATION: A need exists to develop biochemical and
physiological indicators which will be reflective of change in cellular
metabolism following challenge by pollutants. These techniques will
allow for quantisation and differentiation of a variety of effects and
thus allow us to compare present air quality standards with known
health effects. Erythrocytes serve a particularly useful function in
this area because they are more easily collected and stored than other
types of tissue.
B. OBJECTIVE: To use the parameters of mechanical fragility, osmotic
fragility and cell sedimentation characteristics to quantitate pollutant
induced erythrocyte damage.
C. SCOPE:
Present - Effect of N02 only can be assessed on 5% of group
samples for all parameters studied. This includes both fragility
patterns as well as sedimentation characteristics.
Add-on - The number of samples assayed can be increased to
approximately 8%.
*
Minimal Adequate - The number of group samples studied can be
increased to 15% and in addition the studies can be expanded to assess
the effects of SOX and Ox as well as NOX.
Optimum - Same as minimal adequate.
D. RESULTS: The data obtained from this study will be useful in
epidemiologic studies of populations and provide insight into the use-
fulness of these indicators for large scale studies.
E. APPROACH: A model system for exposure of erythrocytes to pollutants
is being developed at present. Assay of the various changes will utilize
standard techniques. As additional funds are made available the number
of group sample studies will be increased to provide a more accurate
assessment of the results.
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B 115
F. SUPPORTING CONTRACTS: None.
G. SPECIAL FACILITIES: Special facilities for animal exposure are
necessary as well as some additional special equipment.
H. INTERMEDIA RELATIONSHIPS: EPA Media Offices.
I. COORDINATION: NIEHS, NIOSH, AEC, FDA.
J. UNRESOLVED POLICY ISSUES: None
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B 116
PROGRAM ELEMENT 110201: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT D - DEVELOPMENT OF MORE SENSITIVE HEALTH EFFECTS
INDICATORS FOR CHESS, INCLUDING BIOCHEMICAL
AND CYTOLOGICAL ALARM SYSTEMS.
TASK 2. Dose relationship between shifts in oxyhemoglobin dissociation
curves and exposures to ambient air pollution including CO,
NOX» S0x» Ox and trace metals.
A. PROGRAM JUSTIFICATION: It is known that by binding with hemoglobin
CO will decrease the amount of oxygen the blood will carry. In addition,
CO will interfer with the dissociation of hemoglobin as well. A study of
the oxyhemoglobin dissociation curves as effected by a variety of pollutants
singly or in combination will allow assessment of enhancing, antagonistic
or neutral effects of these various agents. In addition, it will be possible
to develop this parameter for use in evaluation of current or future air
quality standards.
B. OBJECTIVE: To determine the dose response profile of several pollutants
on shifts in oxyhemoglobin dissociation curves.
C. SCOPE:
Present - Dose relationships can be assessed in only 5% of group
samples and wilV be confined to NQx only at three dose levels and
four time intervals in animal only.
Add-on - The number of group samples analyzed can be increased to
10% but still confined to NOX only in animals.
Minimal Adequate - The number of group samples will be increased to
20% and be expanded to include studies with SOx, Ox and trace metals
in addition to NOX in both animals and selected human subjects. Some
aspects of expanded study will require contracted research.
Optimum - Same as minimal adequate.
D. RESULTS: The data obtained from this study will allow for use of this
parameter in establishing or reassessing air quality standards. In addition,
the impact of each pollutant on human health can be better evaluated, parti-
cularly in terms of the function integrity of erythrocytes.
E. Approach; At present, a model system is being developed to expose erythro-
cytes to these various pollutants. This baste model system, once developed,
can be expanded to be used for several animal species as well as select human
subjects. Once studies are completed, this parameter will be utilized to assess
these alterations in field studies of human populations.
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B 117
F. SUPPORTING CONTRACTS; None.
G. SPECIAL FACILITIES: Exposure chambers for both animal and human
studies will be necessary.
H. INTERMEDIA RELATIONSHIPS: EPA Media Offices.
I. COORDINATION: NIEHS, NIOSH, AEC, FDA.
J. UNRESOLVED POLICY ISSUES: None.
-------
B 118
PROGRAM ELEMENT 110201: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT D - DEVELOPMENT OF MORE SENSITIVE HEALTH EFFECTS
INDICATORS FOR CHESS, INCLUDING BIOCHEMICAL
AND CYTOLOGICAL ALARM SYSTEMS.
TASK 3. Dose relationships between indices of erythrocyte damage and
air pollution exposures to CO, NOx, Ox» SOX, and trace metals.
Indices include lipid peroxidation, sodium, and potassium
flux across the cell membranes. The indices in this task may
be more easily studied in the field than the direct effects
listed in TASK 1.
A. PROGRAM JUSTIFICATION: The integrity of the erythrocyte membrane is
a primary determinant of its functional soundness as a metabolizing cell.
Changes in this membrane induced by pollutants would be a useful indicator
of exposure level as well as cell health. Various oxidants such as NOX are
known to induce peroxidation of various unsaturated fatty'acids with a resultant
destruction of the lipoprotein complex and changes in membrane characteristics.
Therefore, a study of pollutant induced lipid peroxidation will allow quan-
titation of the degree of damage in particular if coupled with a study of
sodium/potassium flux which is a good indicator of membrane soundness. These
two parameters are more specific than mechanical and/or asmotic fragility
and in addition are more easily studied in the field.
B. OBJECTIVE: To use the indices of degree of lipid peroxidation and Na/K
flux patterns .as a measure of erythrocyte membrane integrity. These indices
will allow quantitation of pollutant induced effects in large populations in
the field.
C. SCOPE:
Present - Effect of NOX only can be assessed in 10% of group samples
and is confined to animals only.
Add-on - The effect of NOx and Ox can be assessed in 10% of samples,
but is still confined to animals only.
Minimal Adequate - The effect of NOX, Ox, SOX5 CO, and trace metals can
be assessed in 20% of group samples from animals and the study can be
expanded to include some samples collected from human populations in
the field as well as selected laboratory exposed human subjects. Some
of the human exposure studies or field samples may be contracted.
Optimum - Same as minimal adequate.
D. RESULTS: The data obtained from this study will be of great utility in
epidemiologic studies of populations and provide direct methods for assessment
of exposure levels as well as biochemical changes induced by these pollutants.
-------
B 119
E. APPROACH: A model system for erythrocyte exposure to pollutants is
being developed at present. Assay of changes will utilize standard methods.
As additional funds become available, the sample size and scope assayed will
be expanded.
F. SUPPORTING CONTRACTS: None.
G. SPECIAL FACILITIES: Animal exposure facilities are necessary as well
as some analytical instrumentation.
H. INTERMEDIA RELATIONSHIPS; EPA Media Offices.
I. COORDINATION: NIEHS, NIOSH, AEC, FDA.
J. UNRESOLVED POLICY ISSUES: None.
-------
B 120
PROGRAM ELEMENT 110201: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT D - DEVELOPMENT OF MORE SENSITIVE HEALTH EFFECTS
INDICATORS FOR CHESS, INCLUDING BIOCHEMICAL
AND CYTOLOGICAL ALARM SYSTEMS.
TASK 4. Dose relationship between indices of erythrocyte metabolism
including methemoglobin, 2-3 diphosphoglyceraldehyde, lactate/
pyruvate ratios, hemoglobin electrophoretic mobility patterns,
ami no-acid profiles as well as glucose-6 phosphate dehydrogenase
levels.
A. PROGRAM JUSTIFICATION; In order to better assess the effect of pollutants
on the functional integrity of the erythrocyte it is necessary to examine changes
at the molecular and enzymatic level. In this project a number of key substrates,
components and enzymes will be re-examined following challenges by various pollu-
tants at several dose levels. It is felt that changes induced in these parameters
will often preceed or closely parallel other more grossly observable damage and
will provide more sensitive and selective indicators for the assessment of pollu-
tant induced metabolic change.
B. OBJECTIVE: To develop a number of erythrocyte enzymatic and sub-
strate profiles as correlators of erythrocyte damage and pollutant
exposure.
C. SCOPE:
Present - Effect of N02 only can be assessed on 5% of group samples
at three dose levels and four time intervals in animals only. See
Project C - Action - Task 4.
Add-on - Effect of N02 only can be assessed in 10% of group samples
animals only.
*
Minimal Adequate - Program can be expanded to include studies of
other animal species, selected human subjects exposed under
laboratory conditions and samples collected in the field from human
populations. In this case only 20% of samples could be analyzed
but scope could be expanded to include N02, Ox, SOX and some trace
metals.
Optimum - Same as minimal adequate.
D. RESULTS: The data obtained from this study will provide the capability
of more precise assessment of pollutant induced subcellular and cellular
effects then presently available. These indices provide the capability
for rapid and specific assessment of pollutant damage in large populations.
They will also render the task of standard setting simpler and more
easily related to human health effects.
-------
B 121
E. APPROACH: At present a model system for erythrocyte exposure to
pollutants is under development. This system can be expanded to include
a variety of animal species and human populations. These indices when
developed will be taken to the field for studies of human populations.
F. SUPPORTING CONTRACTS: None.
G. SPECIAL FACILITIES: Exposure chambers for humans and animals will
be necessary.Some additional instrumentation is required.
H. INTERMEDIA RELATIONSHIPS: EPA Media Offices:.
I. COORDINATION: NIEHS, NIOHS, AEC, FDA.
J. UNRESOLVED POLICY ISSUES: None.
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B 122
PROGRAM ELEMENT 110201: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT D - DEVELOPMENT OF MORE SENSITIVE HEALTH EFFECTS
INDICATORS FOR CHESS, INCLUDING BIOCHEMICAL AND
CYTOLOGICAL ALARM SYSTEMS.
TASK 5. Dose relationship between alterations in metalloenzyme levels
or kinetics and trace metal and synthetic organic pollutant
exposures. Candidate enzymes include carbonic anhydrase,
alkaline phosphatase, superoxide dismutase and carboxypeptidase.
Special attention will also be focused on human placental bio-
chemistry effects.
A. PROGRAM JUSTIFICATION: Although some data is available which relates
to the effect of a few trace metals on several metalloenzymes most of this re-
search has been conducted in in vitro systems. By contrast rigorous
studies to equate these effects with known pollutant burdens or classes
in vivo have not been conducted on any meaningful scale. It is not only
clesirable but mandatory that such studies be conducted in order to fully
understand the singular or combined effects of these various trace metals
and for that matter the synthetic organic compounds as well. This
program will allow for studies designed to elucidate not only direct
effects of trace metals and synthetic organics on the several enzymes
chosen but will provide insight into the kinetics of inhibition, dose
response characteristics and again provide useful indices that can be
expanded to field studies of the population in general as well as selected
vulnerable groups.
Studies on human placental enzymes provide a unique opportunity to assess
the effect of various pollutants in situ using tissue which is more
easily collected and very active metabolically. Similarly since this
tissue is critically tied to fetal metabolism as well changes induced
in any of its systems can be expected to have effects in the fetus as well.
*
B. OBJECTIVE: To use the enzymes carbonic anhydrase, alkaline phosphotase,
superoxide dismutase and carboxypeptidase as indices of exposure to
trace metals and synthetic orqanics. In addition studies of placental
enzyme effects will be used to assess pollutant effects on highly
specialized tissue as well as general maternal and fetal health as well.
C. SCOPE:
Present - The effect of only a few (Cd, Pb and Hg) trace metals on
the various metalloenzymes can be studied and the current feasibility
studies on placental enzymes under contract will be interrupted.
Add-on - The effect of three additional metals as well as PCB's.
on the various metalloenzymes will be studied and the placental enzyme
biochemistry effects feasibility study will be completed.
-------
B 123
Minimal Adequate - The enzyme profile studies can be completed and
put into the field to assay the general population as well as some
select vulnerable populations as well. Field studies will assess Cd,
Pb and Hg in 2 urban areas.
Optimum - Field studies can be expanded to include PCBs Chromium,
Vanadium, Nickel and Selenium as well as Cadmium, Lead and Mercury in
three urban areas. Both the general populations and selected
vulnerable populations will be studies.
D. RESULTS: The data obtained from this study will allow an accurate
assessment of trace metal and synthetic organic effects on human health
and provide a sound basis for establishment or reevaluation of present
quality standards.
E. APPROACH; Model systems for human and animal exposure, tissue collection
and enzyme assay are currently being developed. The placental enzyme
project is underway and will be expanded as funds become available.
F. SUPPORTING CONTRACTS: PEAP.
G. SPECIAL FACILITIES: Animal and human exposure facilities are necessary
as well as some instruments.
H. INTERMEDIA RELATIONSHIPS: EPA Media Offices.
I. COORDINATION: NIEHS, AEC, FDA, University of Georgia.
J. UNRESOLVED POLICY ISSUE: None.
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B 124
PROGRAM ELEMENT 110201: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT D - DEVELOPMENT OF MORE SENSITIVE HEALTH EFFECTS
INDICATORS FOR CHESS, INCLUDING BIOCHEMICAL
AND CYTOLOGICAL ALARM SYSTEMS.
TASK 6. Cytological location of metallic pollutants will indicate which
organelles and cellular processes might be best indexed by
enzymatic assay.
A. PROGRAM JUSTIFICATION: In order to accurately assess the effect of
trace metals on human health studies of specific metalloenzyme systems is
desirable. The choice as to which enzymes will be assayed, however, is
dictated by their metabolic importance and by their subcellular localization
in relation to the various trace metal pollutants. Cellular fractions or
organelles which possess the highest concentrations of metal must be
identified or if gradients exist, their characteristics and flux patterns
must be specified. For example, cadmium is found exclusively in the
soluble cytoplasmic fraction and thus study of its toxicity is confined to
those susceptible enzymes in this fraction. With respect to the other
metals, little of the specific subcellular compartmentalization is known
and a rational choice of enzymes is rendered more difficult. In addition,
an understanding of subcellular localization of trace metals will provide
insight into their turnover or sequestery patterns as well as dictate
the type of pathology most likely to occur on initial challenge. It is
also necessary to define the types of compounds these metals are forming
within the cell as well since this factor is of great importance in
determining toxicity.
B. OBJECTIVE: To localize and quantitate trace metals at the subcellular
level in order to more accurately define potentially susceptible enzyme
systems.
C. SCOPE:
Present - No funds are available.
Add-on - Feasibility studies can be undertaken to measure Pb and Cd
only in several animal organs.
Minimal Adequate - Studies can be expanded to include several
other metals as well as their compounds in both exposed animals and
tissues collected from selectively exposed human subjects.
Optimum - Studies will include ten most important trace metals as
well as several of their compounds both in animajs, human subjects,
numerable populations and sample populations from several urban
study areas as well.
-------
B 125
D. RESULTS: Data from this study will provide knowledge of subcellular
compartmentalization of metals and their compounds as well as provide a
rational basis for metalloenzyme selection. In addition these data
will allow for more specific criteria necessary for setting of standards
for both the general population and for populations more specifically
exposed to one trace metal or compound.
E. APPROACH: Methods for subcellular fractionation will need to be developed
as well as methods for controlled exposure of either animals or humans at
various dose levels.
F. SUPPORTING CONTRACTS: None.
G. SPECIAL FACILITIES: Animal exposure and cellular fractionation apparatus
is needed.
H. INTERMEDIA RELATIONSHIP: EPA Media Offices.
I. COORDINATION: FDA, NIEHS, AEC, NIOSH.
J. UNRESOLVED POLICY ISSUES: None.
-------
B 126
TASK 7.
PROGRAM ELEMENT 110201 (CHESS)
PROJECT D - DEVELOPMENT OF MORE SENSITIVE HEALTH EFFECTS
INDICATORS FOR CHESS INCLUDING BIOCHEMICAL AND
CYTOLOGICAL ALARM SYSTEMS
Assessment of increased cancer risk by exfoliative cytology
relating cytologic chances to ambient air pollutants, metals
and synthetic organics.
A. PROGRAM JUSTIFICATION: Air quality standards should protect the
public from undue exposure to potentially carcinogenic pollutants. Excess
urban respiratory mortality can be attributed to carcinogenic pollutants
in ambient air that arise from mobile sources, fossil fuel combustion and
industrial activity. More adequate health intelligence is urgently needed
to establish defensible air quality controls for polycyclic organic matter
and other carcinogenic pollutants.
Establish the dose response relationships between air
pollutant exposures and cancer risk factors.
B. OBJECTIVE:
C.
Complete feasi-
bility study in
3 communities
comprising an
exposure gradi-
ent for oxides
of nitrogen.
With Add-on
Complete demon-
stration study on
an additional 3
communities com-
prising an expo-
sure gradient for
photochemical
oxidants.
Minimally
Adequate
Complete studies
on an additional
5 sets of three
communities com-
prising exposure
gradients for
particulates,
oxides of sulfur,
polycyclic organic
material, and trace
metals. Prospec-
tive studies would
be undertaken.
Optimal
Complete studies on
an additional 7 sets
of communities to
evaluate the impact
of specific station-
ary sources including
metallurgical opera-
tions, incinerators
and petrochemical
complexes. Prospec-
tive studies would
be undertaken.
D. RESULTS: Cytological evaluations would be merged with aerometric data
in the CHESS Information Synthesis Project. The resulting technical reports
should provide more defensible air quality standards.
E. APPROACH: Techniques for sputum collection, preservation, shipment and
processing have been established. Adults from families residing in CHESS
communities would be asked to submit a sample of sputum for cytological
evaluation. Environmental exposure data would be available from CHESS CHAMP
stations and tissue levels of metals and toxic substances ascertained under
the CHESS pollutant burden studies also would be related to cytologic
abnormalities.
-------
B 127
F. SUPPORTING CONTRACTS: Sputum collection and cytologic evaluation
would be accomplished according to Federal protocols by contracts or
grants to universities or research organizations. CHESS data collection
contracts would also support the effort.
G. SPECIAL FACILITIES: The contractor would require cytological
laboratory facilities.
H. INTERMEDIA RELATIONSHIPS: Exist with the community Pesticide Program
and with water, radiation, solid waste and toxic substance research efforts.
I. COORDINATION: Coordination is required with other EPA research programs,
NIOSH, NIEHS, NCI and HSMHA.
J. UNRESOLVED POLICY ISSUES: None.
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B 128
PROGRAM ELEMENT 110201: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT D - DEVELOPMENT OF MORE SENSITIVE HEALTH EFFECTS
INDICATORS FOR CHESS, INCLUDING BIOCHEMICAL
AND CYTOLOGICAL ALARM SYSTEMS.
TASK 8. Dose relationship between immunologic deficits, ambient
air pollutants and metals.
A. PROGRAM JUSTIFICATION: Air quality standards for oxides of nitrogen,
particulates and sulfur dioxide are in part based upon an increased risk
of acute and chronic respiratory diseases. Air quality controls for poly-
cyclic organic matter, trace metals and certain synthetic organic materials
will in part be based upon an increased risk of lung cancer. These disorders
are profoundly influenced by our immunologic competence. Preliminary animal
and human data hint that several components of the immune system may be
impaired by ambient air pollutants. Further investigation is required to
quantitate risks incurred by urban residents and to provide defensible air
quality standards.
B. OBJECTIVE: To quantitate adverse effects of air pollutants on the
immunologic system and thus provide an index of the increased risk to
respiratory and malignant disease so that air quality controls may most
efficiently protect public health.
C. SCOPE:
Minimally
Present Add-On Adequate Optimal
Complete feasibility Assess effects Assess effects Assess effects
study funded in FY71. of oxidants upon of NOX, SOX, of 10 addition-
five immunologic TSP, RSP, and al pollutant
parameters in two oxidants upon sets upon seven
communities ex- six immunologic immunologic
posed to differ- parameters in a parameters in a
ing oxidant levels. total of 30 total of 30
communities. additional
communities.
D. RESULTS: Data on immunologic status will be merged with exposure surveillance,
personal covariate and other health data collected in CHESS utilizing the CHESS
information synthesis project. The resulting technical reports should help
assure the air quality standards are based upon a defensible scientific
foundation.
E. APPROACH: Family members residing in CHESS communities would be asked to
donate a small sample of venous blood. Immunoglobulin levels would be quantitated
as would antibodies against selected respiratory agents. Leucocyte indices
would be quantitated to provide a rough estimate of cellular immunity and a
suitable index of complement activity would be measured. Under minimally adequate
and optimal programs, the immunologic respose to defined antigenie challenges
could be quantitated.
-------
B 129
F. SUPPORTING CONTRACTS: A small intramural program would coordinate
collection and analyses of specimens which would be accomplished under
contract or by grants to universities and research organizations. CHESS
data collection contracts would provide demographic support.
G. SPECIAL FACILITIES: Adequately equipped biochemistry laboratory and
adequate computing capability.
H. INTERMEDIA RELATIONSHIPS: Exist with media and categorical programs.
I. COORDINATION: Coordination is required with other ORM health effects
research programs and with DHEW.
J. UNRESOLVED POLICY ISSUES: None.
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B 130
PROGRAM ELEMENT 110201: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT D - DEVELOPMENT OF MORE SENSITIVE HEALTH EFFECTS
INDICATORS FOR CHESS, INCLUDING BIOCHEMICAL
AND CYTOLOGICAL ALARM SYSTEMS.
TASK 9. Use of leucocyte metabolism as a health effects indicator. Indices
could include protein and nucleic acid synthesis, lipid
metabolism and antibody production.
A. PROGRAM JUSTIFICATION: Like the erythrocyte the leucocyte serves as
an important cell in blood processes and as such can serve as an important
indicator of pollutant induced pathology. Biochemically the RBC is very unique
in that it is without a nucleus and is largely committed to oxygen
transport. The white blood cell is less unilateral in its metabolic
activity and as such would serve as a better indicator of general metabolic
processes such as nucleic acid synthesis, uptake of various non carbohydrate
precursors and generalized lipid metabolism. Like the RBC it is easily
collected and as such can serve as a critical indicator of pollutant
induced biochemical changes at.the second tissue interface.
B. OBJECTIVE: To study several metabolic processes of the leucocyte
and utilize these processes to indicate pollutant induced changes not
measurable in the erythrocyte.
C. SCOPE:
Present - No funds available.
Add-on - Feasibility studies will be undertaken to develop these
indicators in animals exposed to N02. In this case only 10% of group
samples can be studied.
Minimal Adequate - Studies will be expanded to include NOX, SOX, Ox,
trace metals and some synthetic organics. The majority of this work
will be conducted in animals with some work being done in selectively
exposed human subjects and some field samples.
Optimum - Same as minimal adequate except studies will be extended
to select populations in several urban areas as well as several
particularly vulnerable populations as well.
D. RESULTS: The data obtained from this study will provide several
other sensitive indices of human exposure to various pollutants as well
as enable more rigorous assessment of the selective health effects of
various agents.
-------
B 131
E. APPROACH: Model systems for WBC exposure to a variety of
pollutants will be developed and assay of changes will utilize standard
techniques. As additional funds become available sample size and
scope will be expanded.
F. SUPPORTING CONTRACTS: None.
G. SPECIAL FACILITIES: Animal exposure facilities are necessary as well
as some instrumentation.
H. INTERMEDIA RELATIONSHIPS: EPA Media Offices.
I. COORDINATION: NIEHS, NIOSH, AEC, FDA.
J. UNRESOLVED POLICY ISSUES: None.
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B 132
PROGRAM ELEMENT 110201: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT D - DEVELOPMENT OF MORE SENSITIVE HEALTH EFFECTS
INDICATORS FOR CHESS, INCLUDING BIOCHEMICAL AND
CYTOLOGICAL ALARM SYSTEMS.
TASK 10. Use of plasma enzymes, circulating hormone levels, critical
substrate concentrations and seminal plasma metabolic profiles
as health indicators.
A. PROGRAM JUSTIFICATION: In addition to the large number of specific
health indicators that are primarily intracellular in scope there exists
a number of cell free or circulating systems which are readily assayable
and serve as sensitive indicators of the overall metabolic state of humans
as well as animal species. Several classes of plasma enzymes are sensitive
indices of disease as are plasma levels of specific substrates such as
glucose^cholesterol, bilirubin, etc. In addition though present in
low concentrations circulating hormones are of great importance in both
initiation and control of a variety of interrelated metabolic processes.
These systems can serve as early warning sentinels of disease in
mammalian species and as such can be used to assess the effects of pollutants
in human health. They are more easily assayed than a number of parameters
and as such are particularly suited to the task in question. By the same
token little is known of the effects of various pollutants on reproducitve
competence and a study of seminal plasma enzymatic and substrate profiles
can serve as an indicator of pollutant induced changes. This latter
index although confined to males only is also readily collected and assayed.
B. OBJECTIVE: To use these cell free metabolic systems as indices of
pollutant induced changes in human health status. These parameters should
provide a more generalized picture of metabolic change which will
point toward more specific effects.
C. S'COPE:
Present - No funds available.
Add-on - Feasibility studies can begin with animals using NOX only,
assaying only 10% of group samples.
Minimal Adequate - Feasibility studies can be completed in animals
for NOX, SOX, Ox selected trace metals and some synthetic organics.
The studies can also be extended to experimentally exposed human subjects.
Optimum - Same as minimal adequate, except studies can be extended
for pollutants mentioned to several select urban populations as well
as vulnerable groups as well.
-------
B 133
D. RESULTS: These data wiII be of great importance in assessing some of
the more generalized changes in metabolism induced by specific pollutants
as well as allow for more rigorous establishment of environmental quality
standards.
E. APPROACH: Model systems for exposure of animals and 'humans will be
developed and standard assay methods will be used. Some methods will have
to be developed for both hormonal and seminal plasma studies.
F. SUPPORTING CONTRACTS; None.
G. SPECIAL FACILITIES: Animal exposure facilities are needed.
H. INTERMEDIA RELATIONSHIPS: EPA Media Offices.
I. COORDINATION: NIEHS, AEC, FDA, NIOSH.
J. UNRESOLVED POLICY ISSUES: None
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B 134
PROGRAM ELEMENT 110201: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT D - DEVELOPMENT OF MORE SENSITIVE HEALTH EFFECTS
INDICATORS FOR CHESS, INCLUDING BIOCHEMICAL
AND CYTOLOGICAL ALARM SYSTEMS.
TASK 11. Cytogenetic abnormalities induced,by air 'pollutants 'including oxidants,
oxides of nitrogen, carbon monoxide, suspended particulates, oxides of sulfur,
trace elements and selected organic compounds.
A. PROGRAM JUSTIFICATION: Minor abnormalities in the chromosomal pattern of
circulating lymphocytes are thought to represent an index of cellular damage
which may be related to increased risk of somatic mutations, malignancies and
genetic abnormalities. Ionizing radiation, ozone, certain pesticides and virus
infections have all been linked with these abnormalities. Quantisation of
minor chromosomal abnormalities in human populations would provide a bridge
between toxicologic studies and general population pollutant exposures. This
information would be utilized to quantitate the health costs of air pollution
and health benefits of pollution control.
B. OBJECTIVE; To support air quality standards and enforcement actions by
quantitating health risks.
C. SCOPE;
Present & Add-on Tlinifnally Adequate Optimal
No program ^ Karotype 200 individuals Karotype 200 individuals
"in 36 CHESS "neighborhoods " in 72 CHESS neighborhoods
D. RESULTS: Health effects intelligence for improved^.defensible standards for
stationary sources, mobile sources and ambient air quality by 1975.
E. APPROACH: Volunteers from CHESS neighborhoods would be asked to submit a venous
blood specimen for karotyping. Test results would be analyzed to determine the
effects of air pollutants after adjusting for appropriate personal and demographic
covariates. Statistical analyses and technical reports would be prepared intramurally,
F. SUPPORTING CONTRACTS: Blood would be collected under CHESS data collection
contracts and tested under contracts with industry, universities or private research
organizations.
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIPS: Exist with all media and categorical offices.
I. COORDINATION: FDA, NIOSH, AEC, NIEHS
J. UNRESOLVED POLICY ISSUES: None
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B 135
PROGRAM ELEMENT 110201: COMMUNITY HEALTH AND ENVIRONMENTAL
SURVEILLANCE STUDIES (CHESS)
PROJECT D - DEVELOPMENT OF MORE SENSITIVE HEALTH EFFECTS
INDICATORS FOR CHESS, INCLUDING BIOCHEMICAL
AND CYTOLOGICAL ALARM SYSTEMS.
TASK 12. Research Grants Program to Qualitatively Define Contribution
of Air Pollutants to Acute and Chronic Diseases of Major Public
Health Significance
A. PROGRAM JUSTIFICATION: Classical air pollution health effects studies have
focused on the role of air pollutants as lung irritants in relation to acute
and chronic respiratory disorders. The influence of environmental pollutants
on other major public health problems, including heart disease, cancer,
arthritis, congenital deformities and hypertention has not been evaluated.
To date, major causes of these widespread diseases have escaped identification.
As more refined and sophisticated methods to measure trace elements and
synthetic organic compounds in, human tissue are developed, increasing evidence
has accrued for the role of these environmental pollutants in disturbing
biochemical and physiologic pathways crucial to maintenance of good health.
A systematic effort to explore these leads is necessary to accomplish EPA's
function of achieving environmental quality for the protection of public
health at the least possible social cost. A health research grants program
motivated by the mission of a regulatory agency will focus the scientific
talents of the nation on studies assessing the causal role of trace substances
common to the environment in the development of major public health problems.
B. OBJECTIVES: To identify through a well planned, coordinated extramural
research grants program the contribution of environmental trace elements and
synthetic organic compounds to important acute and chronic diseases. These
results will provide new health indicators for input to the CHESS program,
where quantitative relationships between population exposure and disease
endpoints may be readily developed as a basis for appropriate environmental
control actions.
C. SCOPE:
Present & Add-on Minimal Adequate Optimal
No program 24 health research grants 51 health research grants
to identify contribution to identify contribution
of environmental "trace sub- pf environmental trace sub-
stances to the" following stances to the following
major public health prob- major public health prob-
lems i 1 ems;
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B 136
Present & Add-on
Minimal Adequate
1. Cancer of the bladder, colon
and prostate
2. Lung cancer
3. Congenital deformities
4. Genetic markers in relation
to disease
5. Aging
6. Heart disease
7. Hypertension
8. Diminution in sensory
perception including
smell, taste and adaptation
to darkness
9. Wound healing
10. Pollutant induced aggra-
vation of chronic cardio-
pulmonary diseases,
utilizing telemetered
physiologic measurements
11. Respiratory allergies
Optimal
Same as minimally
adequate; in addition:
1. Cataracts
2. Arthritis
3. Chronic kidney disease
4. Exercise tolerance and
. athletic performance
5. Diagnostic virologic
support for CHESS'
6. Skin diseases,
including neonatal
skin infections
7. Markers of chronic
respiratory disease,
including cytochemis--
tries, pulmonary
function, alpha-*!-*
antitrypsin, other
genetic markers.
8. Diabetes
9. Respiratory distress
in newborns
10. Postoperative
recovery
D. RESULTS: Minimally adequate funding: Qualitative identification of relation-
ships between listed diseases and environmental trace substances will provide new
and highly important health indicators for subsequent employment in the CHESS
program. Optimal funding: A well integrated and balanced research grants
program will be focused on major public health problems over a wide variety of
environmental exposures. This program will make a major impact on EPA's
need for health intelligence to control trace substances in the environment.
E. APPROACH: Research grants will be solicited from competent, proven, or
promising investigators; grant scopes of work will be carefully directed and
coordinated to achieve goals of EPA's regulatory mission, in accordance with
the new system for obtaining more mission-related research through the grant
program.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: As appropriate to the objectives of individual research
grants.
H. INTERMEDIA RELATIONSHIPS: All media and categorical offices within EPA.
I. COORDINATION: NIEHS, NIOSH, NCI, NCHS, NHLI, NIAID, DoD, NSF, USDA, FDA, WHO.
J. UNRESOLVED POLICY ISSUES: None
-------
PROGRAM ELEMENT NUMBER: 110201
OR&M
FY '73 Work Plans
TITLE: CHESS (Community Health and Environmental Surveillance System)
WORK PLAN RECIPIENT: Director, NERC/RTP
PROGRAM ELEMENT MANAGER: Vaun A. Newill
Resource Estimate
Task
Present/MY
Add on/MY
Min. Adequate/MY
Optimum/MY
PROJECT
1A
2A
3A
4A
5A
6A
7A
8A
9A
10A
11A
12A
13A
A - CHESS Data
420/2.0
245/1.5
420/2.0
1085/5.5
Collection
425/2.0
370/2.0
250/1.5
250/1.5
425/2.0
370/2.0
250/1.5
2340/12.5
425/2.0
370/2:0
350/1.5
250/1.5
425/2.0
370/2.0
475/2.0
500/2.5
500/2.5
475/2.0
500/2.5
500/2.5
5040/25.0
425/2.0
370/2.0
350/1 .5
250/1.5
425/2.0
800/4.0
875/4.0
500/2.5
500/2.5
475/2.0
bOO/2.5
500/2.5
700/4.0
6670/33.0
co
GO
--si
-------
B 138
Resource Estimate
Task
Present/MY
Add on/MY
Min. Adequate/MY Optimum/MY
PROJECT B
IB
2B
3B
4B
5B
6B
7B
8B
9B
10B
11B
12B
- CHESS Information Synthesis
120/6.0
120/6.0
120/6.0
120/6.0
120/6.0
120/6.0
120/6.0
100/5.0
100/5.0
120/6.0
80/4.0
1240/62
140/7.0
140/7.0
140/7.0
140/7.0
140/7.0
140/7.0
140/7.0
120/6.0
100/5.0
140/7.0
100/5.0
1440/72
240/12
240/12
240/12
240/12
240/12
240/12
240/12
320/15
160/8
450/15
500/16
300/6
3410/138
240/12
240/12
240/12
340/12
240/12
240/12
240/12
320/15
160/8
450/15
500/16
300/6
3410/138
PROJECT C
1C
2C
3C
4C
5C
6C
*Includes
- Bioenvi
40/2.0
475/23.5
120/6.0
100/5.0
_
735/36.5
ronmental Measurement
40/2.0
2075/29.5
20/1.0
120/6.0
100/5.0
_
2355/43.5
200/5
4740/60*
80/4
240/12
100/5
65/4
5325/90
300/10
6700/76
160/8
500/25
100/5
65/4
7825/128
CHESS CHAMP and mobile units.
-------
B 139
Resource Estimate
Task Present/MY Add on/MYMin. Adequate/MY Optimum/MY
PROJECT
ID
2D
3D
4D
5D
6D
7D
8D
9D
10D
no
12D
13D
D - Develop
-
20/1
20/1
20/1
60/3
More Sensitive
20/1.0
30/1.0
40/1.0
20/1.0
40/1.0
20/1.0
50/1.0
50/1.0
15/0.5
15/0.5
300/9
Indicators
220/3.0
220/3.0
220/3.0
220/3.0
500/4.5
220/6.0
480/8.0
450/12.5
220/6.0
450/8.0
720/6.0
1520/13.0
5290/76.0
220/3.0
220/3.0
220/3.0
220/3.0
800/21.5
400/11.0
730/21.0
750/21.5
300/7.0
600/8.0
Ii310/15.0
3690/26.0
9660/143.0
-------
B 140
RESOURCES STATUS SUMMARY
510101
PROGRAM ELEMENT NUMBER
Pesticides Health Effects Research
PROGRAM ELEMENT TITLE
EPA FY '73 Plan
Funding Type
$ (1000)
Positions
In- House
Grant
Contract
1315.0 64.0
855.0 5.0
Program Element Total
2170.0
69.0
-------
B 141
A. PROGRAM ELEMENT NUMBER: 510101
B. TITLE: Pesticides Health Effects
PREPARED BY: Morris Cranmer DATE: January 14, 1972
C. PROGRAM JUSTIFICATION: Section 4 of the Federal Insecticide, Fungicide
and Rodenticide Act (FIFRA) requires that every economic poison (oesticide^
shipped or marketed in interstate commerce shall be registered with EPA to
insure that such products shall be safe and effective. Also, Section 403(d)
of the Federal Food, Drug and Cosmetic Act provides that any person who has
registered or applied for registration of an economic poison under FIFRA
may submit a petition to establish a tolerance for this product on a raw
agricultural commodity. This responsibility covers both the occupationally
exposed and general population. Effects data from laboratory animals must be
generated and crosswalked with human situations if EPA is to be responsive
to these legislative mandates.
D. OBJECTIVES: To assure that safety in use patterns and human exposures to
pesticides are below that which will determentally affect the health and well
being of humans. The estimate of tolerable exposures will be developed from
relevant animal toxicology studies. To assure that sensitive indicators of
subtle but hazardous effects are available for human safety evaluation.
E. SCOPE: Pesticidal chemicals are one group of toxic agents which contribute
to environmental pollution and pose an unanswered challenge to man's health
either through the stress of one chemical agent or the potentiation by other
toxicants. The health effects from repeated acute exposures or long-term, low-
level and massive exposures are not unknown. The scope of this program is to
provide necessary toxicology information on health effects to support the
administrative decision with respect to cancelation or restriction procedures.
This effort at current funding supports 29 tasks describes as acute and subacute
toxicity testing in rodents, teratology in rodents and primates, development
and reproduction, pathology, biochemistry and metabolism, neurophysiology and
behavior, clinical studies, animal care and maintanence and grand review and
evaluation.
F. RESULTS: With adequate funding a predictive toxicology program would
provide the necessary toxicological information to support administrative
review of registrations, to provide sentinels of disease for human epidemiology
studies and to substantiate and provide mechanistic understandings of the effects
of pesticides on the general population and occupationally exposed. At the
current level of funding, a minimum predictive programs is operable with the
major effort allocated to the resolution of problems already identified as of
concern to the agency.
-------
' B 142
G. APPROACH: Through the use of relevant animal models including primates
controlled experiments v/ill be implemented to describe the developmental,
birth defect, metabolic and biochemical, neurophysiological and pathological
effects of pesticides. These studies will be designed to provide dose-
response and population at risk data as well as to elucidate mechanisms of
effects and to develop better sentinels of effects wliich can be used in
interpreting human population exposure to pesticides. These studies will be
of both short term and lifetime durations.
H. SUPPORTING CONTRACTS: Support for the maintenance of the primate breeding
colony will be contracted if implemented because of position ceilings.
I. SPECIAL FACILITIES: Additional cage washing capability will be constructed
to supplement the currently inadequate equipment and a close circuit T.V.
monitoring system will be installed in the primate breeding facility. More
adequate laboratory and animal facilities would enhance the efficiency of the
output of the Perrine, Chamblee and Wenatchee sites. A permenant central
facility would optimize output.
J. INTERMEDIA RELATIONSHIPS: Pesticides in air standards must be established
by FY 75. An air criteria document is required in FY 74. Water standards are
currently being revised. The disposal of pesticide tn a solid waste and air
pollution problem.
K. COORDINATION: Coordination is required with media and the Office of
Pesticides Programs and with Community Pesticides Studies and CHESS. Inter-
agency coordination with DOC, DOT, DOD, NSF and DHEW is also necessary.
L. UNRESOLVED POLICY ISSUES: New pesticide legislation. Transfer of
Community Studies Branch from Office of Pesticides Programs to OR&M.
-------
PESTICIDES HEALTH EFFECTS RESEARCH
Optimum
Minimally
Adequate
Current
FY 73
5.7/154.0
3.6/89.0
2.17/69.0
SUMMARY COMPARISON
($ Million/MY)
FY 74
6.1/194.0
3.9/113.0
2.3/75.0
FY 75
6.6/203.0
4.2/119.0
2.5/77.0
FY 76
7.0/209.0
4.4/122.5
2.7/80.0
FY 77
7.9/215.0
4.9/126.5
2.9/80.0
co
-------
B 144
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 1. Maintain Experimental Animal Facility.
A. PROGRAM JUSTIFICATION; Biomedical investigations of possible toxic
compounds to which man is exposed require the use of animal models and
controlled experiments from which reliable data may be derived and extrap-
olated to man. Both lower mammals and non-human primates are required
as animal models.
B. OBJECTIVES; (1) Provide healthy research animals of proper species,
strain, sex and age for the toxicologic problem under investigation.
(2) Provide professional veterinary medical care for all research animals,
including emergency care for ill or injured animals, and regualr physical
examinations. (3) Provide surgically prepared animal models when requested
by investigators. (4) Write research animal procurement specifications
which will ensure the receipt of animals that meet requirements. (5) Advise
laboratory personnel on matters pertaining to veterinary public health and
status of pending or in force laboratory animal welfare legislation.
C. SCOPE: The animal resources section maintains a stable research animal
population of approximately 250 non-human primates, and several hundred
laboratory rodents and other species as required.
D. RESULTS: Maintain animal mortality due to disease and other unplanned
causes at a minimum. Ensure uniformly healthy animal models on each experi-
ment.
E. APPROACH: Standard approved husbandry and veterinary medicine procedures
will be utilized.
F. SUPPORTING CONTRACTS: (1) Equipment maintenance. (2) Clinical laboratory
(microbiology).(3) Pest control program for animal facilities.
G. SPECIAL FACILITIES: Primate housing facilities.
H. INTERMEDIA RELATIONSHIPS: None
I. COORDINATION: None
J. UNRESOLVED POLICY ISSUES: None
-------
B 145
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 2. Establish Primate Breeding Colony
A. PROGRAM JUSTIFICATION: Primate toxicologic research in
reproduction and teratology require timed pregnancies. These
are inconvenient, costly, and sometimes impossible to acquire
from a commercial source.
B. OBJECTIVES: (1) Establish and maintain a closed primate
breeding colony for both Asian and South American primates.
(2) Produce, in addition to offspring needed for reproduction
and development studies, a surplus of offspring needed for other
non-human primate toxicologic research.
C. SCOPE: As staffing and facilities are expanded, the total
primate requirements of the Pesticides toxicologic research
program will be met.
D. RESULTS: Provide non-human primate research animals of
known age and genetic background for toxico-logic research.
E. APPROACH: Established primate breeding programs will be
utilized. If not established, they will be developed to
meet the programs specific needs.
F. SUPPORTING CONTRACTS: (1) Maintainance of physical
facilities. T2~] Pest control program.
G. SPECIAL FACILITIES: Primate housing facilities.
H. INTERMEDIA RELATIONSHIPS: None
I. COORDINATION: None
0. UNRESOLVED POLICY ISSUES: None
-------
B 146
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 3. Effects of long term pesticide exposure on EEG and
EKG in Primates.
A. PROGRAM JUSTIFICATION: Human populations are exposed to a
complex of environmental stressors including pesticides.
Individuals are exposed to these agents, most of which are
neurotoxins, throughout their lifetimes either chronically
or repeatedly and most often in very low concentrations.
The magnitude of the insult may be too slight to manifest
itself as an obvious functional deficit yet may result in
significant changes in the EEG.
B. OBJECTIVES: Extract information via computer-assisted,
time series analyses which will be indicative of low-level
exposure of primates to pesticides.
C. SCOPE: Selected pesticides, based on usage and potential
hazard, will be fed to non-human primates at low levels and
for prolonged (3 years or more) periods to rule out changes
that may be transient. On-line, computer processing of EEG
will be performed. The methadology and expertise developed
in these studies will be applied to EEG recordings obtained
from pesticide exposed humans in order to test the feasibility
of EEG as a monitoring procedure using a portable instrument
now under development.
D. RESULTS: It is anticipated that the utility of the EEG
recording will be extended to a monitoring technique for the
early detection of pesticide exposure at sub-clinical levels.
E. APPROACH: EEG recordings of pesticide fed monkeys will be
made with various lead arrangements in order to determine the
least number of lead pairs consistent with obtaining adequate
data. A portable EEG instrument is being developed for field
use in which the EEG recordings are stored on tape cassettes
for return to the Perrine Laboratory for computer processing.
F. SUPPORTING CONTRACTS: (1) Instrumentation maintenance
G. SPECIAL FACILITIES: (1) EEG recording facility.(2) Closed
circuit TV. (3) On-line Digital Computer.
H. INTERMEDIA RELATIONSHIPS: Air & Water
I. COORDINATION: NERC
J. UNRESOLVED POLICY ISSUES: None
-------
B 147
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 4. Effects of pesticides on drug metabolizing enzymes.
A. PROGRAM JUSTIFICATION: Exposure to pesticides can induce or
inhibit the metabolism of drugs. This can result in increased
or decreased susceptibi 1 ity .to the drug and thus markedly
influence its therapeutic efficacy. Such drug-pesticide
interactions must be recognized in order to effectively evaluate
and/or predict the therapeutic course associated with drug
administration.
B. OBJECTIVE: (1) Develop an in vi vo method to evaluate liver
microsomal enzyme induction applicable to human studies.
(2) To study effects of pesticides on activities of drug-metaboli
ing pathways.
C. SCOPE: Studies will include: (1) Development of an in vitro
procedure for the metabolism of lindane to chlorophenols
(2) Correlation of rate of appearance of organophosphorus pesti-
cide metabolites to level of liver microsomal mixed function
oxidases as an in vivo index of enzyme induction. (3) Effects of
Arochlors on drug-metabolizing pathways and cytochrome levels.
Changes will be related to dose, length of exposure and tissue
levels of test compounds.
D. RESULTS: The data obtained will aid in establishing safety
levels for pesticides and combinations of pesticides.
E. APPROACH: Selected compounds, singly and in combinations,
will be administered to rats, guinea pigs and monkeys. Blood,
urine and feces will be analyzed for metabolites of the admin-
istered compound(s). Liver microsomal enzyme activity will be
measured and correlated with rates of excretion of pesticide
metabolites.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIPS: Air & Water
I. COORDINATION: NERC
J. UNRESOLVED POLICY ISSUES: None
-------
B 148
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 5. General analytical support of intralaboratory toxicology.
A. PROGRAM JUSTIFICATION: Studies on the biological effects of
pesticides and their metabolism must be accompanied by determ-
inations of the levels of pesticides and/or metabolites in body
tissues and excretions in order to verify the relation between
exposure and effect. This support is essential therefore to the
total toxicology effort.
B. OBJECTIVE: To furnish analytical support in studies of the
biological effects and pharmacodynamics of pesticides.
C. SCOPE: Expertise in analytical methadology will be maintained
within each laboratory in order to provide data on pesticide levels
in tissues of animals exposed to pesticides.
D. RESULTS: Analytical data in support of toxicologic research
E. APPROACH: Standardized methods for extraction of pesticides
from animal tissues will be used. Gas chromatographic, thin
layer, spectrophotometric, and isotopic techniques will be used
to identify and quantitate the residues.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIPS: None
I. COORDINATION: NERC
J. UNRESOLVED POLICY ISSUES: None
-------
B 149
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 6. Primate Teratology
A. PROGRAM JUSTIFICATION: Congenital malformations, fetal
wastage, and impaired neonatal development are a source of major
medical and sociological problems in todays society. The cause
of the majority of these problems is unknown. One possible
source that has yet to be evaluated to any extent is low grade
toxicity to the mother or the fetus from ubiquitous environ-
mental pollutants such as organic and/or heavy metal pesticides.
B. OBJECTIVES: To provide information on the fetal effects of
pesticides in non-human primates
C. SCOPE: The program will utilize primates in the study of
compounds which have been shown to possess teratogenic effects
in laboratory rodents and will coordinate with the teratology
program of NCTR, Pine Bluff.
D. RESULTS: The data obtained will aid in establishing human
relative risks associated with pesticide exposure.
E. APPROACH: Selected compounds will be administered to monkeys
before and/or at specific times after conception. Offspring will
be examined for functional and morphological deficits during
development.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: Primate housing facilities
H. INTERMEDIA RELATIONSHIPS: Air & Water
I. COORDINATION: NCTR (Pine Bluff), NERC
J. UNRESOLVED POLICY ISSUES: None
-------
B 150
PROGRAM ELEMENT; PESTICIDES. HEALTH EFFECTS RESEARCH
TASK 7. General pathology support of intralaboratory toxicologic
studies.
A. PROGRAM JUSTIFICATION: In order to properly evaluate the
effects of pesticides the determination of pathological changes
in animals exposed to these compounds is important. The findings
recorded in the course of pathological studies will support regu-
latory efforts and will help establish meaningful standards in
outlining exposure levels for the general population and also
high exposure groups.
B. OBJECTIVE: Autopsies will be performed on animals dosed
orally or dermally with pesticides and the effects on the organs
evaluated by macroscopic and microscopic study. The animals are
obtained from subacute and chronic feeding studies and reproduc-
tion studies performed in our own laboratory or occasionally
other laboratories within the EPA and rarely other government
agencies.
C. SCOPE: In FY1973 organs of rats fed different dietary levels
of SB 1382 (a pyrethrum compound), Paraquat, Disulfoton and
hexachlorobenzene will be studied. In addition examination of
organs of rats fed Aroclor 1260 and Aroclor 1254 will be com-
pleted. Long term reproduction studies have been performed with
most of these animals prior to sacrifice.
D. RESULTS: At autopsy gross findings will be recorded. Slides
for microscopic study will be prepared from sections of organs.
These slides will be studied and the results of the evaluation
recorded. In connection with the reproduction or other studies
these results will then be summarized and published in scientific
journals and also submitted to EPA in support of any regulatory
actions or as information for the establishment of tolerance
1evels.
E. APPROACH: Groups of 10 animals are exposed in the diet or
dermally to the above mentioned pesticides over varying periods
of time. The feeding studies are usually long term studies while
the dermal exposure is at the most terminated after 30 days. All
animals are autopsied at the end of exposure and their organs
studied after organ weights are obtained. Unless autolysis is
severe autopsies are also performed on all animals that die
during the course of the experiments.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIPS: Air & Water
I. COORDINATION: NERC
J. UNRESOLVED POLICY ISSUES: None
-------
B 151
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 8. F2a Reproduction Studies in Rodents
A. PROGRAM JUSTIFICATION: Some pesticides have been shown to
have deleterious effects on reproduction in several species of
mammals and further, show a more pronounced effect in the second
generation than in the first generation. These studies are
needed for use by the Agency in establishing safe levels of
exposure for these compounds in man.
B. OBJECTIVES: To determine the effect of paraquat, SBP-1382,
and hexachlorobenzene upon development of treated rats and upon
their reproduction through the F2a generation.
C. SCOPE: The study utilizes laboratory rats for initial testing
on reproduction and development.
D. APPROACH: Rats will be orally administered the test com-
pounds from the age of weaning, through maturity and pregnancy.
Their offspring will be retained on the same.pesticide intake,
allowed to mature and reproduce. Counts of viable offspring
will be made.
E. RESULTS: These studies will indicate the more hazardous
compounds with respect to reproduction and/or development impair-
ment and will permit efficient utilization of more expensive
primate testing.
F. SUPPORTING CONTRACTS; None
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIPS: Air & Water
I. COORDINATION: NERC, Chamblee and Perrine
J. UNRESOLVED POLICY ISSUES: None
-------
B 152
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 9. Acute LD5QJ Oral and Dermal
A. PROGRAM JUSTIFICATION: Information on the acute oral and
dermal toxicity of pesticide compounds is essential in order to
carry out further toxicologic research and field testing with
minimal hazard to occupational ly exposed humans. There are
pesticide compounds in use and under consideration for more
extensive use for which acute toxicity data is still insufficient
B. OBJECTIVE: Determine the oral and dermal LD,-n of selected
pesticides.
C. SCOPE- The acute oral and dermal toxicity of ,
Maretin(K) , tri cycl ohexyl tin hydroxide, and browacil will be
studied in laboratory rats and single dose LDsg values determined
for the adult male and female and for one sex of weanling age rats.
D. RESULTS: Acute toxicity. data are essential to the Agency
in establishing adquate labeling requirements.
E. APPROACH : Laboratory rats will be administered pesticide
compounds dermally or by stomach tube over a dosage range. Mortality
rate at each dose is observed and standard statistical methods
used to estimate the LD5Q.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIPS: Air & Water
I. COORDINATION: NERC, Chamblee and Perrine
J. UNRESOLVED POLICY ISSUES: None
-------
B 153
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 10. Effect of pesticides on neuromuscular function and
peripheral synaptic performance
A. PROGRAM JUSTIFICATION: In order to elucidate the effects of
pesticides on the EEG, a complex of biopotential transients of
the whole brain, there is a need for short-term experiments on
isolated peripheral preparations of rats such as the neuromuscular
junction and autonomic ganglia. The behavior of these simpler
systems will permit interpretations which will result in more
efficient use of costly non-human primate EEG studies.
B. OBJECTIVES: To study conduction of nervous activity in
peripheral pathways and its transmission across nerve-muscle
and nerve-nerve junctions following administration of pesticides.
To utilize this information in the interpretation of pesticide
induced changes of the complex EEG.
C. SCOPE: Laboratory rats are used and the procedures developed
permit the experimental data to be used as a screening test for
pesticide induced deficits of nervous system function as well as
for interpretation of the EEG.
D. RESULTS: Development of more sensitive methods of assessing
functional status of the nervous system.
E. APPROACH: Electrical activity of pre-junction nerve path-
ways, of the junction itself and of post-junctional pathways
will be measured simultaneously. Quantitative assessments of
the electrical activity as well as a response parameter such as
muscle contraction will be made.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIPS: Air & Water
I. COORDINATION: NERC
J. UNRESOLVED POLICY ISSUES: None
-------
B 154
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 11; Effect of Pesticides on Intermediary Metabolism
A. PROGRAM JUSTIFICATION; Pesticides have been shown to produce
changes in intermediary metabolic pathways. Examples are: Acquired
porphyria by alteration of heme synthesis, physiological and path-
ological changes produced by hormone imbalance and altered lipid
metabolism and changes in amino acids in the brain. Further data
is needed by the agency to establish threshold levels and set
minimum safety concentration levels in body tissues.
B. OBJECTIVE: To study the effects of pesticides on (1) pathways
of heme metabolism & porphyrin excretion, (2) steroid hormone
synthesis and degradation (3) energy metabolism and (4) lipid and
protein metabolism.
C. SCOPE: Small laboratory mammals and non-human primates will
be administered selected pesticides according to usage and/or
relative acute toxicity. Intermediary metab.olic pathways will be
assessed for rates of activity and abnormal performance. These
observations will be correlated with pesticide and/or metabolites
level in the body tissues. Changes will be related to dose and
duration of exposure.
D. RESULTS: The data obtained will aid in establishing safety
levels for pesticides and combinations of pesticides.
E. APPROACH: Selected compounds and mixtures of compounds will
be administered to experimental animals. Blood, urine, feces,
and tissues will be analyzed for the parent compound, its metabolites
and enzyme activities using standard analytical procedures.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIPS: Air & Water
I. COORDINATION: NERC, Chamblee and Perrine
J. UNRESOLVED POLICY ISSUES: None
-------
B 155
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 12. Non-primate Teratology
A. PROGRAM JUSTIFICATION: The investigation of congenital
malformations associated with pesticide exposure using non-human
primates is costly in time and money. In order to make optimum
use of the primates, preliminary screening of suspected compounds
should be accomplished using laboratory rodents.
B. OBJECTIVES: To provide information on the fetal effects of
phenoxy-acid herbicides and heavy metals in order to identify
those compounds which warrant further testing in primates.
C. SCOPE: The teratology studies are intended to form a compre-
hensive picture of effects on fetal development in a variety of
non-primate species (mouse, rat, hamster). The program will co-
ordinate with the teratology program of NCTR at Pine Bluff.
D. RESULTS: An adequate study of 3 agents selected on the basis
of relative hazard and usage will be completed in FY 73.
E. APPROACH: Compounds will be administered orally during the
period of organogenesis in at least two species. Fetuses will
be recovered before term and necropsied. When applicable,
additional techniques such as alizarin staining for skeletal defects
and assay for the compound in fetal tissue will be used.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIPS: Air & Water
I. COORDINATION: NERC, NCTR (Pine Bluff)
J. UNRESOLVED POLICY ISSUES: None
-------
B 156
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 13: Polychlorinated biphenyl-bladder cancer study.
A. PROGRAM JUSTIFICATION: During the course of a long term
oral toxicity study in Sherman strain rats, a malignant bladder
tumor was found in one of ten female rats at the dietary exposure
of 100 ppm Aroclor 1260 (a PCB). Spontaneous bladder cancers in
rats are almost non-existent. Since Aroclor 1260 is found in-
creasingly in the environment it is important to determine whether
this compound is a bladder carcinogen. Autopsies will be per-
formed at the end of the study and tissues, particularly the
bladder, examined microscopically.
B. OBJECTIVE: The purpose of this study is to determine in a
reasonably large number of animals whether the previously observed
bladder cancer was caused by the carcinogenic action of Aroclor
1260 or a metabolite thereof or whether it was an incidental
finding.
C. SCOPE: The study will be limited to the exposure of 200 rats
of one sex to one dietary level of Aroclor 1260 for the better
part of their lifetime. Information will be gathered on incidence
of tumors, weight gain, incidence of deaths -during the time of
exposure and signs of poisoning. The information obtained will
aid in establishing meaningful and intelligent safety regulations.
D. RESULTS: Macroscopic and microscopic findings will be reported
on autopsy reports and microscopic slides will be available for
review. These findings will be summarized in a paper for publi-
cation in a scientific journal and for in house reports.
E. APPROACH: 200 rats will be fed the polychlorinated biphenyl
Aroclor 1260 for 18 months and an equal number of animals will be
kept as controls. Food consumption will be measured, body weight
determined and symptoms of poisoning recorded.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: Electron Microscope
H. INTERMEDIA RELATIONSHIPS: None
I. COORDINATION: NERC
J. UNRESOLVED POLICY ISSUES: None
-------
B 157
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 14. Single Pregnancy Studies
A. PROGRAM JUSTIFICATION; Long term studies on pesticide-
induced alterations of reproduction cannot readily distinguish
between pre- and post-imp]atation effects. Studies in which the
pesticide compound is administered post-implantation are needed
to demonstrate effects on pregnancy per se.
B. OBJECTIVES; To determine the effect of paraquat, SBP-1382 and
hexachlorobenzene upon established pregnancy and development of
offspring to weaning age.
C. SCOPE; The study utilizes laboratory rats for rapid screening
of compounds for effects on pregnancy.
D. RESULTS; The data obtained will be used as a basis for
selecting compounds which warrant F2a reproductive studies.
E. APPROACH: Rats will be bred and the pesticides under study
will be orally administered each day from the 7th through the
15th day of pregnancy. Numbers of offspring -born and body weights
from birth to the age of 21 days will be recorded.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIPS: Air & Water
I. COORDINATION: NERC
J. UNRESOLVED POLICY ISSUES: None
-------
B 15C
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 15. Neurotoxicity Screening
A. PROGRAM JUSTIFICATION: Some organophosphorus pesticide agents
have been found to induce demyelination of peripheral nerves, and/
or paralysis in chickens. This reaction can serve as a screening
test to identify those compounds which are potentially most toxic
to the nervous system in repeated dosages.
B. OBJECTIVE: To determine if the organic phosphorous compounds
MonitorU), Torak(R), and MaretinlR> cause paralysis in chicken
hens when the compounds are administered subcutaneously at various
dosage 1 eve!s .
C. SCOPE: To utilize the particular susceptibility of the chicken
as a rapid screening procedure for organophosphate pesticides
effects on the nervous system.
D. RESULTS: Data required for safety regulations.
E. APPROACH: Administer test compounds subcutaneously at different
dosages and observe chickens for leg paralysis.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIPS; None
I. COORDINATION: NERC
J. UNRESOLVED POLICY ISSUES: None
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B 159
PROGRAM ELEMENT: PESTICIDE HEALTH EFFECTS RESEARCH
TASK 16. Provide Baseline Clinical Profiles of Primates
A. PROGRAM JUSTIFICATION: Baseline clinical values for blood
and urine must be used as a basis upon which to evaluate possible
pesticide effects. Since baseline values can vary depending on
environmental conditions of the primates, there is a need to obtain
this information from the animals to be used for an experiment and
in the locale of the experiment.
B. OBJECTIVES: Provide clinical support as an essential aid to
the carrying out of controlled experiments, to include: hematology,
microbiology, and parasitology.
C. SCOPE: The animal resources section maintains a stable research
animal population. The bulk of the primates are purchased through
various approved suppliers although as staffing and facilities are
expanded the in house breeding program will furnish most of our
needs.
D. RESULTS: Maintaining clinical profiles on experimental
primates ensures healthy subjects and makes available their pro-
files to the investigator in charge of the experiment.
E. APPROACH: Microbiological, parasitological and hematological
values are determined on conditioned primates prior to their assign-
ment on experiments and throughout the course of the experiment.
F. SUPPORTING CONTRACTS: (1) Equipment Maintainance, (2) Clinical
Laboratory (Microbiology), (3) Pest control program for animal
facilities .
G. SPECIAL FACILITIES: Primate housing facilities
H. INTERMEDIA RELATIONSHIPS: None
I. COORDINATION: NERC
J. UNRESOLVED POLICY ISSUES: NONE
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B 160
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 17. Influence of pesticides on pituitary hormone secretion
and correlation with EEG.
A. PROGRAM JUSTIFICATION: Low level chronic exposure to neuro-
toxins such as pesticides produce subtle alterations of central
nervous function including neuroendocrine activity. The magni-
tude of these changes needs to be evaluated in order to assess
the hazard of these environmental pollutants to human health.
B. OBJECTIVES: Determine the electrophoretic profile of pituitary
hormones from pesticide-treated animals. Correlate these findings
with electrical activity of neuroendocrine centers in the hypo-
thai amus .
C. SCOPE: Obtain pituitary glands from pesticide treated rats
and perform gel electrophoresis on the homogenates. Recover
fractions and correlate with specific hormones. Program will be
extended to primates when it is possible to measure circulating
pituitary hormone levels.
D. RESULTS: The data obtained will be useful in determining
relative risks associated with usage of a given compound or
mixtures of compounds.
E. APPROACH: Acrylamide gel electrophoresis of pituitary homo-
genates and recovery of the separated fractions. Bioassay of the
fractions to establish thetr hormone content. Measurement of
hypothalamic electrical activity to establish correlation between
this and neurosecretory activity.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACTILITIES: None
H. INTERMEDIA RELATIONSHIPS: Air & Water
I. COORDINATION: NERC
J. UNRESOLVED POLICY ISSUES: None
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B 161
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 18. Electronmicroscopy-Ultrastructural Studies of Specific
Organs.
A. PROGRAM JUSTIFICATION: Many pesticides induce changes in organs
that seem rather insignificant when studied under the light micro-
scope, for example, the liver enlargement caused by chlorinated
hydrocarbons. Examination of this tissue under the electron micro-
scope shows that pronounced changes have occurred in the ultra-
structure of the cell. Another application of the electron micro-
scope is in the study of grossly detectable lesions caused by pesti-
cides in order to give a better understanding of the lesion and
possibly mechanism of action of the pesticide. The obtained infor-
mation will aid in setting tolerance levels and will give informa-
tion on the nature of the effect that can be expected from the
pesticides.
B. OBJECTIVE: It is the purpose of this study to examine the
liver lesion produced by Aroclor 1254 in rats in a previous study.
Once the lesion is established in the animals exposure to the
chemical will be discontinued and it will be established whether
the liver damage is permanent or whether the liver goes back to
normal - after preliminary light microscopic studies the effect of
pentachlorophenol on the liver will also be investigated.
C. SCOPE: In the study the rats will be fed the pesticide in the
diet. Immediately at the end of exposure or at intervals there-
after the rats will be sacrificed and liver tissue obtained for
study under the electron microscope. All tissue studied under the
electron microscope is also always studied under the light micro-
scope and the findings are compared.
D. RESULTS: Microscopic and ultrastructural findings will be
reported on autopsy sheets. Findings will also be summarized for
publication of papers in scientific journals.
E. APPROACH: Five exposed and 5 control rats will be sacrificed
6 months after onset of exposure to Aroclor 1254 and thereafter
the poisoned diet will be discontinued and the remaining animals
will be sacrificed at monthly intervals X 6 (5 exposed and 5 con-
trols at each sacrifice). The livers will be weighed and tissue
prepared and studied under the light and electron microscope. The
livers of the rats treated with pentachlorophenol will be treated
in similar fashion.
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B 162
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: Electron Microscope
H. INTERMEDIA RELATIONSHIPS: None
I. COORDINATION: NERC
J. UNRESOLVED POLICY ISSUES: None
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B 163
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 19. Subacute toxicity including chronicity factors.
A. PROGRAM JUSTIFICATION: In order to establish safe levels of
exposure to pesticides in occupationally exposed humans, the sub-
acute toxicity of repeated dosages must be determined. The 90-day
LD50 dose has been determined for only a few of the pesticides in
common usage. This data is essential to the Agency in setting
labeling requirements.
B. OBJECTIVE: To evaluate the subacute toxicity of pesticides
with common usage patterns.
C.
for
i common usage patterns.
SCOPE: Ninety-day subacute toxicity studies will be conducted
_ Monitor (R), Torak(R), and Maretin^) using laboratory rodents.
D. RESULTS: The data obtained will provide information on the
persistence of effect of a single dose of a pesticide agent.
E. APPROACH: Rats will be orally administered the pesticide
agent for 90-days at different dosages. The 90-day LDso will be
estimated using appropriate statistical methods. Together with
the single dose LD5Q, a chronicity factor (single-dose LDso [mg/kg]/
90-dose LDso [mg/kg/day]) will be estimated for one sex of rat for
each compound.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIPS: Air & Water
I. COORDINATION: NERC
J. UNRESOLVED POLICY ISSUES: None
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B 164
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 20. Effects of pesticides on behavior
A. PROGRAM JUSTIFICATION: Neurotoxic compounds including pesti-
cides are potentially capable of altering behavior patterns of
exposed animals. In order to evaluate the possible hazard to
human health, there is a need for carrying out animal experiments
designed to measure learning, memory, motivation, etc.
B. OBJECTIVES: Test the effects of pesticides on standard
instrumental measures of behavior in the laboratory rat.
C. SCOPE: Study the effects of carbaryl and at least one other
carbamate pesticide on operant-conditioning behavior in the rat.
As staffing and facilities permit, extend studies to pesticide-
fed primates.
D. RESULTS: Development of more sensitive methods for assessing
functional deficits in the nervous system.
E. APPROACH: Rats will be water or food deprived and trained to
lever press for reward. The response rate and latencies for a
series of fixed-ratio paradigms will be determined before and
after pesticide administration.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIPS: Air & Water
I. COORDINATION: NERC
J. UNRESOLVED POLICY ISSUES: None
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B 165
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 21. Pesticide pharmacodynamics in rodents and primates
(distribution, metabolism, and excretion).
A. PROGRAM JUSTIFICATION: In order to define and elucidate the
mechanism of action of a toxic agent, the route and rate of absorp-
tion, the distribution in the blood and organs and the route and
rate of metabolism has to be investigated.
B. OBJECTIVE: The purpose of the study is to determine the funda-
mental characteristics of absorption, distribution and metabolism
of selected toxic agents.
C. SCOPE: The study will be limited to selected compounds which
may present an environmental hazard.
D. RESULTS: The results expected should include detailed data
regarding rate of absorption of the compound in question. The
absorption and distribution studies will indicate length of
retention by the organism thereby clarifying, to some extent, any
hazard due to exposure. The metabolic studies will determine the
biotransformation products and/or detoxication mechanisms.'
E. APPROACH: Selected compounds will be administered to rats at
appropriate sub-lethal dosages. The organs, blood and excreta
will be analyzed for the parent compound as well as predicted
metabolites. Isotopically labelled compounds will be employed.
The rates of absorption and depletion of storage levels will also
be determined.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: none
H. INTERMEDIA RELATIONSHIPS: None
I. COORDINATION: NERC
J. UNRESOLVED POLICY ISSUES: None
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B 166
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 22. Clinical Pathology
A. PROGRAM JUSTIFICATION; Clinical pathology is a necessary adjunct
to toxicologic research. These studies will provide information
needed by the agency for regulatory purposes.
B. OBJECTIVE; To provide clinical pathology back up to pesticides
research on animals including man.
C. SCOPE; Provide clinical pathology expertise on an intermittent
basis when needed.
D. RESULTS; Blood chemistry, plasma protein electrophoretic
profiles and tests of renal and hepatic function will be done and
reports submitted.
E. APPROACH; Standard clinical pathology procedures will be
performed.
F. SUPPORTING CONTRACTS; None
G. SPECIAL FACILITIES! None
H. INTERMEDIA RELATIONSHIPS; None
I. COORDINATION; NERC
J. UNRESOLVED POLICY ISSUES: None
-------
B 167
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 23. Heme Synthesis and Metabolism
A. PROGRAM JUSTIFICATION; Exposure to pesticides can induce
alterations in heme synthesis and result in porphyria. Studies
on the specific enzyme vulnerabilities are essential to an
understanding of the mechanism of action of the toxic compounds and
are needed by the Agency to establish safety standards,
B. OBJECTIVE; To study the effects of pesticides on pathways of
heme metabolism, porphyrin excretion, and levels of exposure
necessary to produce porphyria.
C. SCOPE; Laboratory rats will be used in the study of effects
of environmental chemicals on heme synthesis and porphyrin excretion
as well as tissue cytochrome levels.
D- RESULTS; The data realized will aid in establishing safety
levels for pesticides and combinations of pesticides and/or other
environmental pollutants.
E. APPROACH; Selected compounds will be administered to rats,
Blood, urine, feces, and tissue will be analyzed for the parent
compound, metabolites, and enzyme activities.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES; None
H. INTERMEDIA RELATIONSHIPS; Air and Water.
I. COORDINATION; NERC
J. UNRESOLVED POLICY ISSUED: None
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B 168
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 24. Biochemical Nuclear Maanetic Resonance (NMR) Studies of the Mechanism
of Interactions of Toxicants with Proteolytic Enzymes.
A. PROGRAM JUSTIFICATION; Pesticides have been shown to affect
multiple enzymes, rather than a specific enzyme, by attaching to
groupings on the molecule common to all the enzymes it affects.
Biochemical NMR studies disclose the nature of the complexing and
identify vulnerable groups. These studies are essential for
predicting the total impact a pesticide toxicant will have on an
exposed animal.
B. OBJECTIVE! Recover enzyme-pesticide complexes from treated
animals and subject them to NMR spectroscopy, Derive the chemical
nature of the complexing from the spectrographic data.
C. SCOPE; The project will make use of pesticide-treated animal
tissues from other experiments thus extending the information
obtained from them.
D. RESULTS: Information on the chemical configuration of enzyme
vulnerable sites and the thermodynamics of the complexing will be
obtained. The data will be used to predict the full impact a pesti-
cide will have on enzyme systems-, will suggest possible antidotes,
and will be useful in planning costly animal experiments more
efficiently.
E. APPROACH: Selected pesticide compounds will be studied for
their complexing characteristics with several enzymes and at several
temperatures .
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES; Nuclear Magnetic Resonance Spectrometer.
H. INTERMEDIA RELATIONSHIPS; None
I. COORDINATION; NERC
J. UNRESOLVED POLICY ISSUES: None
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B 169
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 25. Measurement of exposure under field conditions.
A. PROGRAM JUSTIFICATION; It is important, to determine the magni-
tude of human exposure to various pesticides, particularly those
of high toxicity, under actual conditions of field application.
The information is needed in order to ensure the safety of field
applicators.
B. OBJECTIVE; To measure dermal and respiratory exposure of field
applicators as well as those living near treated fields.
C. SCOPE; Exposed workers and incidentally exposed individuals
will be studied to determine the route and rate of uptake for
different pesticide formulations.
D. RESULTS: The data obtained are needed to develop safe pesticide
application procedures.
E. APPROACH; Exposure to a number of pesticides will be measured
under actual field application conditions to workers (including
applicators, farmers, and crop workers) and the persons with
environmental exposure, including those living near treated fields.
Methods of measuring human exposure will be improved.
F.
G.
H.
I.
J.
SUPPORTING CONTRACTS: No
SPECIAL FACILITIES: None
INTERMEDIA RELATIONSHIPS:
COORDINATION: NERC
UNRESOLVED POLICY ISSUES:
None
None
-------
B 170
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 26. Clinical Investigations Related to Field Exposure.
A. PROGRAM JUSTIFICATION; Effects of heavy pesticide exposure
in humans such as pulmonary function, skin reactions and blood
cholinesterase must be recognized so that they in turn can be
used as indicators of pending excessive exposure,
B. OBJECTIVE; To study highly exposed applicators for adverse
effects incident to pesticide use and develop methods for
diagnosis and treatment of poisoning.
C. SCOPE ; Gather data from highly exposed field workers and
individuals living near pesticide treated fields.
D. RESULTS; Development of clinical parameters indicative of
heavy pesticide exposure. Experimentation to determine feasibility
of new diagnostic and treatment methods.
E. APPROACH; Monitor blood cholinesterase of workers exposed to
organophosphate and carbamate pesticides. Measure urinary
metabolites of pesticide exposed individuals. Conduct examinations
for adverse skin reactions.
F. SUPPORTING CONTRACTS; None
G. SPECIAL FACILITIES; None
H. INTERMEDIA RELATIONSHIPS: None
I. COORDINATION: NERC
J. UNRESOLVED POLICY ISSUES: None
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B 171
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 27. General pathology support of interagency toxicology
rodent studies.
A. PROGRAM JUSTIFICATION; In order to properly evaluate the effects
of pesticides the determination of pathological changes in animals
exposed to these compounds is important.
B. OBJECTIVE; Perform pathological examinations of pesticide-
treated animal tissues for other agency projects when otherwise
not available to them.
C. SCOPE; Limited support on a need basis and within the work
resources of the pathology group.
B. RESULTS; Pathology reports in support of any regulatory actions
or as information for the establishment of tolerance levels.
E. APPROACH; Standard pathology procedures will be used,
F. SUPPORTING CONTRACTS: None.
G. SPECIAL FACILITIES;. Electron Microscope,
H. INTERMEDIA RELATIONSHIPS; None
I. COORDINATION; NERC
J. UNRESOLVED POLICY ISSUES: None
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B 172
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 28: General Biochemical and Analytical Support of
Interagency Toxicology.
A. PROGRAM JUSTIFICATION; Sophisticated biochemical and
analytical procedures are often required in order to complete
meaningful toxicologic investigations. These are not always
available at each laboratory location.
B. OBJECTIVE: Furnish biochemical and/or analytical expertise
to interagency toxicologic research.
C. SCOPE; Limited support on a need basis and within the work
resources of the analytical group.
D. RESULTS; Analyses in support of any regulatory actions or
for establishment of tolerance levels.
E. APPROACH; Accepted biochemical analytical methods will be
used and reports of results prepared.
F- SUPPORTING CONTRACTS; None,
G. SPECIAL FACILITIES; None
H. INTERMEDIA RELATIONSHIPS; None
I- COORDINATION; None
J- UN-RESOLVED POLICY ISSUES; None
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B 173
PROGRAM ELEMENT: PESTICIDES HEALTH EFFECTS RESEARCH
TASK 29. Evaluation and Review of Health Effects Research Grants
A. PROGRAM JUSTIFICATION; The mission of Environmental Protection
Agency requires the knowledge of many areas which cannot be
supported by an inhouse effort. Certain areas may be so newly
developed or sophisticated that the development of an inhouse
capability could not be accomplished within the necessary timeframe.
Additionally it is necessary to have the flexibility of realignment
of program and the grant mechanism is an efficient mechanism.
B. OBJECTIVES; (1) To provide research information on specific
pesticide health effects problems. (2) To develop indicators of
disease and effect, e.g., grants for the development of cytogenetic
indicies. (3) To develop methodologies for specific pollutants and
effects. (4) To supplement the inhouse and contract effort of the
agency.
C. SCOPE; The pesticides health effect effort will be $755,000
and supports work in universities throughout the United States.
Research in any area relevant to the needs of pesticides health
effects will be considered.
D. RESULTS; Provide information outside the capability of the
inhouse research staff on issues pertinent to the review and
consideration of pesticides applications.
E. APPROACH; All disciplines needed to impact on pesticide health
effects are available. Funds will be allocated to universities and
research institutes in single year and continuation grants.
F. SUPPORTING CONTRACTS; None
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIPS: Coordination.
I. COORDINATION; With categorical and media grant programs to
eliminate duplication and provide a cohesive total program.
J. UNRESOLVED POLICY ISSUES: None
-------
OR&M
FY '73 Work Plans
PROGRAM ELEMENT NUMBER:
TITLE: Pesticides Health Effects
Research
WORK PLAN RECIPIENT; Director, NERC/RTP
PROGRAM ELEMENT MANAGER:
Vaun A. Newill
Resource Estimate
Task ! Present/MY | Min. Adequate/MY | Optimuir./MY
1.
2.
3.
4.
5.
6.
7.
8.
9.
220.0/11.5
27.0/1.3
40.5/2.0
241.8/12.0
30.5/2.0
27.0/1.3
18. 5/- 6
27.0/1.3
27.0/1.3'
1080.0/15.0
108.0/2.0
122.0/2.0
594.0/12.0
81.0/2.0
81.0/3.0
37.0/1.0
37.8/1.0
37.8/1.0
1360.0/42.0
216.0/4.0
806.0/3.0
925.8/23.0
121.5/3.0
108.0/4.0
51.6/1.5
43.1/1.5
43.2/1.5
10.
11.
12.
13.
14.
15.
27.0/1.3
39.3/2.0
27.0/1.3
27.0/1.3
27.0/1.3
27.0/1.3'
35.4/1.5
81.0/3.0
81.0/3.0
30.5/1.5
37.8/1.5
40.2/1.5
45.6/1.5
121.5/4.0
108.0/4.0
44.0/1.5
43.2/2.0
42.8/1.5
-------
OR&M
FY '73 Work Plans
PROGRAM ELEMENT NUMBER:
TITLE: Pesticides Health Effects
WORK PLAN RECIPIENT: Director f
Rese
NERC/RTP
PROGRAM ELEMENT MANAGER: Vaun A. Newill
Task
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
Resource Estimate
Prescnt/MY
27. O/ 1.3
27. O/ 1.3
27.0/1.3
27. O/ 1 .3
10.0/1.3
40. 5/ 2.0
27. O/ 1.3
40.0/2.i;
-8.5/.0
Min . AcLequate/MY
108.0/4.0
102.5/4.0
61.2/2.0
37.8/1.0
44.5/2.0
81.0/3.0
60.0/2.0
108.0/4.0
37.0/1.0
Optiiuuiri/MY
216.0/8.0
210.0/6.0
82.5/2.5 :
43.2/1.5
91.2/3.0
121.5/4.0
95.5/3.5
162.0/5.0
55.5/2.0
98.0/U.2
81.0/4.0
27. ! 10.0/0.0
28. 54. 0/2. C
1
r:n.
TOTAL
r '- ~. ' " O
"17Q.U/C:.0
i
162.0/5.0
120.5/4.0
31.4/2.0
108.0/4.0
3C4C.A/8S.O
205.2/6.5
137.7/5.0
45.7/3.0
162.0/6.0
b708. 1/1 154.0
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B 176
RESOURCES STATUS SUMMARY
(None Assigned) Pesticides Effects Upon Human Health
PROGRAM ELEMENT NUMBER PROGRAM ELEMENT TITLE
EPA FY '73 Plan
Funding Type $ (000) Positions
In-House 735 32
Grant
Contract 3465
Program Element Total 4200 32
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B 177
A. PROGRAM ELEMENT NUMBER; 510501
B. TITLE: Pesticides Effects Upon Human Health
PREPARED BY: R. D. Courter DATE: December 29, 1971
C. PROGRAM JUSTIFICATION: The pesticide registration and labelling obligations
of EPA require that the Agency determine the effects of pesticides upon human
health. Changes in labelling or withdrawal of registration necessitate a
cost-benefit assessment of the proposed changes. Such judgments must be founded
upon quantitative estimates of the health risks associated with pesticide usage.
Human health effects studies are indispensable to these control activities.
D. OBJECTIVES: To provide the health intelligence needed for scientifically
defensible pesticide registration and labelling actions and to confirm safety
in usage.
E. SCOPE: Four tasks are included in this program element. First, close
clinical and biochemical surveillance of temporarily registered pesticides with
emphasis upon those likely to be particularly hazardous or to involve large
population exposures. Second, planning and implementing an acute poisoning
reporting system that will assure detection to 90% of incidents and accidents
involving pesticides and other related chemicals. Third, conduct retrospective
human morbidity and mortality studies of population cohorts heavily exposed to
pesticides. Fourth, prospective epidemiologic studies of occupationally exposed
groups in 14 geographically dispersed study areas.
F. RESULTS: The research tasks described will provide data necessary to evalu-
ate more completely the potential hazards of temporarily registered pesticides,
to elucidate acute pesticide poisoning problems caused by mislabelling and
to assess the chronic disease risks associated with pesticide usage.
G. APPROACH: The Pesticides Registration Division will provide copies of temporary
registrations from the Pesticides Registration Division and make arrangements with
the registrants to institute clinical and biochemical surveillance of people
utilizing these chemicals. Expansion of pesticide accident reporting and investi-
gational network involving Federal, State and local governmental agencies will be
accomplished. Retrospective mortality and morbidity studies will identify occu-
pational and general population cohorts heavily exposed to pesticides in the past.
Death records and illness records, where available, would be utilized along witn
appropriate actuarial procedures to assess any increase in risk attributable to
pesticides. Prospective studies of occupationally exposed cohorts in the 14 com-
munity pesticide study areas will continue utilizing selected clinical and bio-
chemical health indicators.
H. SUPPORTING CONTRACTS: Included are 14 community study contracts with State's
health departments and universities and additional contracts with other groups
for reporting pesticides accidents.
-------
B 178
I. SPECIAL FACILITIES: Clinical biochemistry and physician services, adequate
data processing hardware and software and residue analysis laboratories are
needed.
J. INTERMEDIA RELATIONSHIPS: Exist with all media programs.-
K. COORDINATION; With other health effects research programs, other Agency
research programs and with NIEHS, NIOSH, FDA, NSF, NCHS, DOD and AEC.
L. UNRESOLVED POLICY ISSUES: None
-------
PESTICIDES EFFECTS UPON HUMAN HEALTH
SUMMARY COMPARISON
($ million/MY)
Optimum
Minimum
Adequate
Current
FY 73
4919/38.0
4516/36.0
4200/32.0
FY 74
5120/40.0
4764/38.0
4455/34.0
FY 75
5401/42.0
5026/38.0
4710/36.0
FY 76
5698/42.0
5302/38.0
4955/36.0
FY 77
6011/42.0
5594/38.0
5190/36.0
CO
10
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. . B 180
PROGRAM ELEMENT 510501: Pesticides Effects Upon Human Health
TASK 1. Surveillance of Experimental Pesticides
Users
Tlie current practice of the Agency is to
give a temporary registration for new pesticides for limited and
experimental use in the field under natural conditions. These
permits are based upon protocols presented by the manufacturer
giving primarily results of controlled laboratory tests on animals.
This proposal is for surveillance of the effects of these new*
products upon the health of individuals using them under experimental
field conditions. The data gathered will be used by regulatory
personnel in determining whether to grant regular use registration
for the products.
B< OBJECTIVES; This study will be designed to determine whether new
pesticides used under temporary permits are damaging the health of
the users under recommended field conditions prior to registration
for restricted or general usage.
_S_COPE: The studies will be on people using temporarily registered
pasticidf.s to determine their reactions to them.
D. RESULTS : The data and data analysis will be made available to
"regulatory personnel to be used as part of the information
for decision making in setting usage guidelines and in estab-
lishing regulations.
Copies of temporary registrations will be obtained from
the Pesticides Registration Division and arrangements will be made
with the registrants to test the people using the chemicals.
Clinical and biochemical tests will be made of the participants
before, during and after contact with the chemicals to determine
any changes in vital functions as a result of such exposure.
p. SUPPORTING CONTRACTS/. Much of this work can be done by health
departments and universities now under contract for other studies
on pesticides.
Clinical testing and biochemistry laboratory
services will be. needed; however, many of these are already available
and could give the needed support with a little expansion of their
activities.
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B 181
H. INTERMEDIA RELATIONSHIPS; Arrangements will need to be made with
the Pesticides Registrations Division to receive copies of temporary
permits (this is already agreed to) and to get from the permit
holder the names of the persons conducting the field trials. Amend-
ments for the work will then be made to existing contracts or new
ones would be executed.
I. COORDINATION: All activities will be coordinated by a small central
staff.
J. UNRESOLVED POLICY ISSUES; The only issue is what component of the
Agency will be given the responsibility and will be funded for
providing this support to the Pesticides Registrations Division.
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B 182
J
PROGRAM ELEMENT 510501: Pesticides Effects Upon Human Health
lasK £. Investigation of Acute Pesticide
Poisonings
3
Total validated statistics are not available
on the numbers of acute pesticide poisonings occurring each year in
the U. S. The annual report prepared by the HEW Poison Control Unit
had 5,700 alleged (human) adverse pesticide incidents reported in
1969. It is generally stated that there are at least ten unreported
poisonings for each one reported each year. Therefore, on the basis
of present pesticides usage adverse pesticide incidents involving
humans may be expected to number over 50,000 a year.
There is presently no formalized central clearing house to gather
and compile such information. Several governmental agencies have
responsibilities for investigating certain types of pesticide
mishaps. However, mishaps are more often not investigated
and too often cases have several separate investigations. There
is need to develop a single Federal investigational program on
pesticide and related chemicals which will provide maximum cooperation
vrith other government agencies.
Eased on present information, incidents occur each year due to the
use or misuse of pesticides. Some of these occur because of the
lack of complete toxicological data and/or complete label information.
Incidents 'must , therefore, be investigated both in the field,
where occurring, and in the pesticides registration review and
toxicological laboratory areas to determine cause and effect on
the environment .
General - Insure there is a reporting system which will give 90
percent assurance of incidents and accidents involving pesticides
and other related chemicals being reported; and provide for an
investigational program incorporating Federal, State and local
governmental agencies that will insure prompt and effective remedial
action.
FY 1972 - 197j_ - Increase the number of pesticide incident investigations
"from approximately 275 in FY 72 to 2,000 in FY 77 and provide for
data processing storage and retrieval of all data.
Starting with four regions in FY 1973 establish programs for joint
FederalState reporting and investigation of pesticide, accidents and
incidents. Have active programs in all ten regions by 1977.
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B 183
J3COPE : Assist State and local agencies in developing capabilities to
extend systems for reporting of pesticide incidents and iuvestij;at:b.ig
a representative sample of such incidents. Information data, one?.
gathered and edited , will feed into a computer data ban!-, that will
be utilized to pinpoint hazard trends and safety problemr, Label
review of hazardous pesticides will be placed under continuous review.
A public information program will alert users to the inherent dangers
in the. use of these chemicals.
Investigative data will provide information on product
and use violations; appropriate amendments in registration and
enforcement policies; identify use trends and enable the. analysis
of safety problems, particularly the persistence of toxic amounts
in the environment.
Information with regard to epidemiology, symptomatology and treatment
will be obtained for the toxicant. Reports for scientific and public
issuance x;ill be prepared.
E. APPROACH : Expanding the pesticide accident reporting and investigations.!
network through increased contacts with various Federal, State and
, local government agencies; developing investigational capabilities
at regional and State levels; using existing and developing new
analytical methods developed for the isolation and identification
of new or old pesticides that might be involved in a pesticide
exposure or poisoning.
Distributing toxicological and educational data derived from pesticide
accident -investigations .
Ft SUPPORTING COKTIlAC'f S : None
G«, SPE CT.AL F ACII, I TIE S : Laboratory capabilities will need to be
expanded beyond present facilities.
"' Iill?J^r^lA- ^M.-^!1:^' Results of investigations will influence
in appropriate cases techniques for disposal of pesticides wastes
and containers (Solid Wastes).
I . COORDINATION: None
v). UNKESOLVED POLICY ISSUES: Determination of which program has
primary responsibility for directing and coordinating the investigations
of incidents and subsequent actions; and insuring an effective data
storage and retrieval system.
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B 184
PROGRAM ELEMENT 510501: Pesticides Effects Upon Human Health
TASK 3. Retrospective Human Morbidity and
Mortality Studies
This tyPP- °f study is. one method of measuring
the health status of large numbers of people over desired periods
of time. It is a means of maintaining surveillance of selected
health indicators or chronic diseases in populations with destlnctive
characteristics. These studi.es will be on people who have or have
had extensive contacts with pesticides and have or have had chronic
diseases.
Pesticide chemicals usage is necessary for adequate production of
food, fiber, forest products and for the control of disease vectors
and other noxious insects. These poisons will continue to contribute
to economic production, agricultural products and prevention of
infectious diseases, however, these chemicals are health hazards
when not used properly. The Agency must maintain a surveillance
on environmental contamination resulting from the use of these
chemicals and to* determine the relative health hazards associated
with their proper use by the occupationally exposed and the general
population;
B. OBJECTIVES : The objectives are a review of health histories and
causes of death,? and the current health status to determine ar.y
differences in cohorts with high exposure, to pesticides and similar
cohorts with minimal exposure. The observations made will be
useful in determining what is indeed proper usage and whether
current guidelines and regulations are adequate for reasonable
protection of the environment.
C. SCOPE: Reviewing death record data should identify contribution
prolonged pesticide exposure might have on life expectancy. A
program will be developed to examine 'death record data for excessive
mortality in specified geographical areas and in certain selected
occupations. Death certificates usually coi!.tcii< among other things
the occupation, and residence at time of death, the cause of der.th
as well as description of the individual such as age, sex and race.
This allows analysis by various criteria.
The morbidity studies would be on case histories available in PHS,
VA and DOD hospitals. There are 416 Federal hospitals or about 5%
of the total in the U.S. and assuming that 75% of deaths pass through
hospitals there would be approximately 6,700 case histories of the
listed diseases. This would provide the basis for a rather large
case history study.
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B 185
A1 third, approach is through the use of data gathered, by the National
Center for Health Statistics which could provide, prevalence data
on users of pesticides,
MSP.HS: Tlie data "ill 'be analyzed to determine whether there is
a difference in the health status of people with high exposure
to pesticides and those with minimal or no exposure before the
advent of currently used chemicals. Should it be found thai:
pesticides as presently used in this country, are damaging human
health the data would be used in setting appropriate guidelines
and regulations by the agency which will prevent such damage.
y^H1 The ^eata records would be obtaiiied from state health.
department vital statistics and retrieval and. manipulation of -the
data will be done with a computer services. The same will be done.
with data obtained from case histories and other records. It is
fully expected that personal interviews will be needed to c.orrplete
many of the health histories. Most of the above will be donn through
contracts or grants to other agencies, e.g. the current coKuininity
studies and health departments.
There are 29 existing contracts with health-
departments and universities which can be amended to form a nucleus
for gathering the information.
G. _SPECT.AL_ FACILITIES : The only special facilities needed would be
approval of v;hatever forms or questionnaires are used and the
establishment; of computer capabilities.
11 ' I!Lr^'MJA.J^^^JP2lS].llZl: The data and conclusions, of course,
will be available to the tolerance setting and regulatory groups
within the Agency and those in the states responsible for pesticides
control. Arrangements will need to be mace with health departments
and hospitals for obtaining the desired information.
Ii COORDINATION : This will be provided by a small central staff of
epidemiologists and biostatisticians.
J. UNi\£SOU
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B 186
PROGRAM ELEMENT 510501: Pesticides Effects Upon Human Health
TASK 4. Prospective Kpidemiological Studies
PROGRAM JU-STIFICATION; In the. span of the last 30 years there has evolved
among the lay and scientific community an awareness of the proliferation
of synthetic and natural chemical agents which pollute nan's environment.
Pesticidal chemicals are one class of a group of toxic agents which
contribute to environmental pollution and pose a serious challenge to man's
health either through the stress of one chemical agent or the. pot.entia.tion
by other toxicants. There are numerous reports on the acute toxicity and
lethality of organochlorine and organophosphorus insecticides in wan
and animals. Despite the plethora of information on acute toxicity, health
effects from repeated acute exposures or long-term, lox-; and massive exposure
are not -known.
Current knowledge, on mechanisms of chronic disease induction, especially
neoplastic disease, necessitates that chronic!ty data be available for'
comprehensive evaluation of the stress under consideration. To ueet these
requirements, epidemiological studies must be pursued exploring,
retrospectively or prospec.Lively, the impact of a range of pesticide
exposures (low, median or high) on human population groups. These "huir.an
population laboratories" have as their purpose the developacnr. of findings
or information relevant to pesticide, exposure and ultimate effect of such
exposure in terms of human disease induction.
OBJECTIVES: General objectives are to determine in 14 study areas the levels
of selected pesticides in human tissues, and in environmental ir.e-dia such '
as food, water, air and soil; to study the effects of pesticides upon the
health status of a group of subjects selected for che known frequent
contact with these chemicals; to determine the types of pesticides to vaich
the human population within the 14 study areas are exposed, the ecologic
factors which may effect their health status and to undertake such specific
studies as may be necessary to provide specific information on individual
chemicals or attendant problems.
FY-7^ - Provide information impact of pesticides on human health with
respect to the human body burden through the collection and analysis of an
estimated 12,000 determinations on pesticide residues in human tissues and
body fluid samples and an estimated 2,500 environmental samples composed
of house dust, clu?t in ambient air, drinking water ?.nd various food stuffs;
to continue to evaluate the long-term effects of pesticides on hum^n health
through the continuing surveillance of approximately 3,000 volunteer study
subjects;
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B 187
to determine the pesticide use patterns within the defined study r,rc-.f> of:
each of the. 14 areas to study the association of certain disnasc conditions
with the use of pesticides;
to provide supplemental information on human health effects of pest:'icicle?-.,,
methods development and other related problems through specified investj.gr.izio,
of these and similar problems in each of the 14 study areas;
to complete the preliminary analysis of the data now on hand using the
MARK IV system.
FY 74-77 - to continue to monitor the health status of the study populations
in order to maintain a current awareness of the effects of pesticides on
man in his environment.
.C. J3COPE: Using suitable epidemiological and toxicological procedures, attempts
will be made in 14 geographical areas to delineate a cause and effect-
relationship between man's exposure to pesticides and disease. To provide
an assessment of the sources and magnitude of pesticide exposures from
these sources, which may be related to disease, extensive environmental
monitoring programs will be carried out associated with population groups
selected for study. Exposure surveys so essential in classification of
high- and low-risk groups for study will be facilitated by baseline data
from a pesticide use survey in the study area.
Q.. RESULTS PRODUCTS EXPECTED: Pesticide, residues in the tissues and. body
fluids of each study area population will be determined on a continuing
basis. Residues will be determined in environmental samples which nave
been obtained-from the homa and v.rork environment of the study subjects.
Pesticide poisoning cases occurring throughout the study area will be
investigated. The data which emanates from this project is 'made available
to the Tolerance and Registration Divisions of the Pesticides Office, EPA.
The basic Community Profile document, with its annual modifications provides
a current reference on pesticide usage patterns. The annual reports
arising from each project also summarize the status of pesticide use.
The data which is compiled from the physical examinations of the 3,000
volunteer study subjects, chemical and biochemical analyses and pesticide
residue values, is analyzed by each project, and forms the basis for'various
reports and publications in .appropriate scientific journals. These data
are further analysed by the data management section.
Reports en the progress being made in the individual special studies
will be received auarterly and the results obtained during the year will
be. received annually. The special studies will reveal tVie effects of
certain pestic.id.p. chemical?; upon e.nr-.'yme production and activity in animals
and they will a.1, so show r.ny neurological damage caused by specific, pesticides,
This kind of information could lead to a regulation in which people, having
a certain levt-.l of involve:::;;:.".t night ba prohibited from operating dangerous
machinorv such as auro-uebiles. Laboratory merhcds development will Dead
to the icc-:\t.;.iication of certain ce-ta:Aina:-.ts which new interr-nro. wit.h
the "readout" of the highly sophisticated instruments which hrve ou occasion
caused some hard to understand results.
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f B 1RP.
-^
^QIi: Approximately 3,000 people ±i\ occupational contact with t:he.se
chemicals are under intense surveillance to determine those illnesses o:-:
biochemical -changes which may occur, line health status of this g'''o\;p is-;
compared v?ith a similar group with a relatively minor degree -of e/.vosuri? <>
pesticides. This surveillance comprises an annual physical examine t:i.o:is
determination of pesticide residues, and a battery of different: bioohi-nlcaJ
tests to detenaine the functioning of the vital organs such a;;; the. liver }
kidneys, and. the cardiovascular, hematologic, gastro-intestinfl auc!
metabolic systems. These studies are located in 14 different areas
of the country selected because of heavy pesticide usage and demographic
and climatic characteristics.
Human tissues from the general population, will be analyzed for pesticide
residues. In addition, blood arid urine specimens will be analysed for the
presence of pesticide residues. Environmental samples including aii'.bj enf.
air, household dust, foods, water, clothing and other media will 'be
analyzed. As necessary, acute poisoning ca.ses will be investigated by
standard epidemiologic procedures.
The data used to develop the Community Profile is collected through
interviews with pesticide users, f ormulators , manufacturers, and through
the review of retail sales data in given areas.
syi'Z01lI^\i?_c?:l:TMcJ[§.'» Contracts are let to 14 States' health departments
and universities to carry out the program described.
SPECIAL FACILITIES /EOUIP^NT : Each of the 14 studies maintains its own
residua chemistry laboratory. Some of the laboratories perform their own
biochemical determinations while others utilize commercial -or institutional
laboratory facilities for this purpose.
!>'- 1 SRMZD I A RH I. AT ION S H IPS: Interaction between this program, the research
units and the regulatory activities of the registration and tolerance
setting i? important in that impact of the use of pesticides on hunan
h-2?.lth can best be evaluated through this program and that information
of this kind c?.n have considerable effect on decisions made in the other
.1. COQIiDINATT.CM : No coordination was needed prior to reorganization.
i'.. UNRESOLVED POLICY ISSUE: None
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OR&M
FY '73 Work Plans
PROGRAM ELEMENT NUMBER: 510501
WORK PLAN RECIPIENT:
Not Assigned
PROGRAM ELEMENT
MANAGER: Vaun A
Task
Resource
Present/MY
Estimate ($000)
Minimum, Adequate/MY
Optimum/MY
1
2
3
4
Total
100/3.0
270/10.0
119/2.0
3711/17.0
4200/32.0
125/4.0
305/12.0
175/3.0
3911/17.0
4516/36.0
150/4.0
350/14.0
219/3.0
4200/17.0
4919/38.0
TITLE: Pesticides Effects Upon Human Health
CO
oo
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B 190
RESOURCE STATUS SUMMARY
None Assigned
PROGRAM ELEMENT NUMBER
Radiation Health Effects
PROGRAM ELEMENT TITLE
EPA FY '73 Plan
Funding Type
In-House
Grant
Contract
$ (1000)
1238
291
318
Positions
61
0
0
Program Element Total
1847
61
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B 191
A. PROGRAM ELEMENT NUMBER: None Assigned
B. TITLE: Radiation Health Effects
PREPARED BY: Edythalena Tompkins DATE: January 15, 1972
C. PROGRAM JUSTIFICATION: Proliferation of nuclear power plants in the near
future requires EPA to provide maximum assurance of safe population exposure
to the principal radionuclides released from nuclear power reactors and fuel
reprocessing plants. Present reactors release tritium and krypton; breeder
reactors release plutonium as well. Present standards for maximum exposure
to these radionuclides are calculated values derived from dose-effect studies
at high-level total body exposures. The adequacy of these standards, especially
with reference to internal alpha and beta emitters, has not been experimentally
evaluated.
Populations are extensively exposed to electromagnetic radiation from the
communications industry; these sources will continue to increase in number.
No standard exists for exposure of the general population to these nonionizing
radiations, especially at chronic low-dose levels. Research on molecular,
biochemical, genetic and functional changes induced by electromagnetic radiation
exposure must be conducted to provide an adequate base of health intelligence
for appropriate regulatory action.
D. OBJECTIVES: To provide EPA v/ith a scientific basis to select and support
environmental standards for radionuclides emitted by nuclear power generation
and for electromagnetic radiation from the communications industry.
E. SCOPE: Doses to communities adjacent to large sources of radionuclides and
electromagnetic radiation will be defined. Long-term effects of human exposure
to ionizing radiation will be 'documented through epidemiologic studies of
populations with known high level exposure. Experimental animal exposure will
be employed at graded dose levels to determine dose-effect relationships for
ionizing and nonionizing radiation induced carcinogenic and mutagenic effects
and other toxicologic endpoints including physiologic and behavioral changes
and cellular repair. Emphasis will be placed on tritium, krypton, plutonium
and electromagnetic radiation.
F. RESULTS: The knowledge gained through community and biomedical studies
will be made available in a series of intramural and published results relating
toxicological information to radiation exposures of the population. These
reports will provide health effects information for the setting and appraisal
of radiation standards. The studies on krypton, tritium and plutonium will
contribute to EPA's ability to assure human safety associated with the proliferation
of nuclear power plants and will further the development of these needed facilites
under least social cost standards which adequately protect the public.
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B TK
G. APPROACH: The radiation health effects program is ah integrated series
of epidemiologic and toxicological studies utilizing both community exposures
and experimental animal exposures to ionizing and nonionizing radiation.
Specific dose levels of radiation are generated and monitored. Exposures are
both acute short-term and chronic in form. Sensitive biologic endpoints in
humans and animals are applied to detect both clinical and pre-clinical effects.
Animal toxicology is designed to obtain dose-effect relationships at levels
pertinent to human exposures.
H. SUPPORTING CONTRACTS: Animal holding facilities and electromagnetic
radiation dose assessment will be provided through existing contracts and
interagency agreements. Other research contracts and grants with universities
and private research organizations are developed to complement in-house projects,
I. SPECIAL FACILITIES: Housing of a cat colony for ionizing radiation health
studies is required.Equipment for measuring ionizing and electromagnetic
radiation is widely employed.
J. INTERMEDIA RELATIONSHIPS: With other EPA health program elements and with
air and water media offices.
K. COORDINATION: Liaison with AEC, NCI, DoD, DHEW.
L. UNRESOLVED POLICY ISSUES: None.
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Optimum
Minimally Adequate
Current
RADIATION HEALTH EFFECTS
Summary Comparison ($ Million/MY)
FY 73
6547/140
4469/112
1847/61
FY 74
6874/140
4692/112
2064/65
FY 75
6530/138
4882/110
2252/67
FY 76
6008/134
4638/110
2365/67
FY 77
5527/130
4406/108
2483/67
CO
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PROGRAM ELEMENT: RADIATION HEALTH EFFECTS B 194
PROJECT A -'STANDARDS FOR NUCLEAR FACILITIES
TASK 1. Definition of radiation dose to residents around nuclear
facilities.
A. PROGRAM JUSTIFICATION: EPA standards are being promulgated for
operation of nuclear facilities which limit the average radiation
dose to a population living within 50 miles of a nuclear facility
as well as limiting the dose calculations based on metered releases
of activity, meteorological data and in a few cases measurements
of ambient air levels of radionuclides. Assumptions are also made
that overlapping exposures from multiple facilities will cause no.
problems in the future and that there are no critical subsets of
the population. No data on actual radiation doses to individuals
living around nuclear facilities is available.
B. OBJECTIVE: Develop methodology for obtaining measurements of actual
exposure of individuals resulting from operation of nuclear facilities.
The variability of doses among individuals due to differences in
life style and age at given distances from a nuclear facility will
be defined. Refined methods for estimating the dose from a nuclear
facility in fetuses, infants, children, the aged, and the potentially
reproductive population will be developed. Patterns of exposure to
single populations from multiple nuclear sites will be evaluated.
C. SCOPE: Existing measurement data from ORM, ORP, and AEC will be gathered
together and'a boiling water reactor, pressurized water reactor, and a
fuel reprocessing plant will be identified for study as well at: tv:o
reactors within 100 miles of each other. Contracts will be negotiated
with appropriate health departments or universities to obtain nerjc.ssary
demographic data.
D. RESULTS: Data on actual exposures to populations living in the environs
of nuclear facilities will permit evaluation of adequacy of standards in.
minimizing risk to the public from operating nuclear facilities.
E. APPROACH: A careful review of available methodologies for individualizing
dose estimates will be made. Feasibility studies to evaluate degree of
cooperation which can be obtained for the most promisinr; methods will be
carried out. Protocols will be prepared, including methods to be u&ed
and sampling plans for detailed studies. Data V7i.ll be: gathered under
contract and analyses carried out by staff.
F. SUPPORTING CONTRACTS: Contracts with health departments and universities
to obtain necessary data.
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B 195
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIPS: None
I. COORDINATION: The program will be coordinated with the exoosure
studies being conducted around certain nuclear facilities by ORP,
EPA AND AEC.
J. UNRESOLVED POLICY ISSUES: Standards for light-water cooled power
reactors have been promulgated. No standards for operation of
nuclear fuel processing plants, breeder reactors, or permanent
storage facilities have been developed.
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PROGRAM ELEMENT: ./RADIATION HEALTH EFFECTS B 196
PROJECT A - STANDARDS FOR NUCLEAR FACILITIES
TASK 2. Validation of assumptions inherent in dose-response models
used for standards.
A. PROGRAM JUSTIFICATION: Radiation standards are currently based on four
assumptions on the development of effects following exposure to low
levels of exposure; no threshold, linear response down to zero dose,
all types of malignancies can be induced by radiation, and no difference
in effects between acute and chronic exposures. These assumptions are
thought to be conservative, but they may not be.
B. OBJECTIVES: (1) To define the dose-response curve for children exposed to
diagnostic levels of l^ll. (2) To determine relative organ sensitivity to
radiogenic tumor formation.
C. SCOPE: Protocols for definitive studies will be developed by sLnff and
contracts let for collection of data with multiple study centers which
have appropriate exposed populations. Analyses will be conducted by staff.
D. RESULTS: Actual data on the validity of assumptions currently employed
in estimating risks associated with exposure to low levels of radiation
will permit evaluation of adequacy of standards in minimizing risk to the
public from operating nuclear facilities.
E. APPROACH: A mail follow-up of 1000 children exposed to 1311 for diagnostic.
purposes before 1960 will be conducted through the treating centers."
Following evaluation of these data, the number of additional children
needed, if any, to complete the definition of the curve will be determined
and followed.
One large tumor treatment center will be used to determine the groups
of patients who have been treated for tumors with radiation and hove the
longest survival times which are best suited for study of latent develop-
ment of radiation induced tumors. Follow-up of these patients will yield
information necessary to plan sample size and details of protocol, for
cooperative study. Other centers, as needed, will then be brought into
the study.
F. SUPPORTING CONTRACTS: Contracts for collection of data with selected
treating centers.
G. SPECIAL FACILITIES: None.
H. INTERMEDIA RELATIONSHIPS: None.
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B 197
j
! -QP£Ldju2£ t i£n: Bureau of Radiological Health, HEW, is interested in doing
a clinical study of the children treated with 131I. The plans for our
study will be coordinated with them.
J. Unresolved Policy Issues: Standards for light-water cooled pov?er reactors
have been promulgated. No standards for operation of nuclear fuel process-
ing, plants,breeder reactors, or permanent waste storage facilities have
been developed.
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B TOP-
PROGRAM ELEMENT: RADIATION HEALTH EFFECTS
PROJECT A - STANDARDS FOR NUCLEAR FACILITIES
TASK 3. Epidemiologic studies of long-term effects of ionizing
radiation.
A. PROGRAM JUSTIFICATION: Quantification of various long-term health risks
associated with environmental exposure to radiation is the scientific
basis for protection standards. Current study of populations known to
have been exposed to radiation in the past permits the evaluation of
risks associated with these exposures, and projection of long-term risks
to be expected from exposures being accumulated by the population today.
With the projected increases in the nuclear industry, continued study is
essential to assure the safety of the population.
B. OBJECTIVE: To provide quantitative risk assessments for development of
specific disease states following exposure to known levels of radiation
to be used in establishing population exposure standards.
C. SCOPE: For each grouo under study, a protocol is developed, the study
population and controls defined, demographic data as well as exposure
and disease history determined, and present health status ascertained
for each individual in the study.
D. RESULTS: With quantification of risks associated with radiation exposure,
the risks to populations exposed to radiation from the operation of
specific nuclear facilities can be evaluated.
E. APPROACH; Each population will be studied by a contracting institution
or grantee or a combination of contracts for obtaining data with analysis
done by staff. The populations are: (1) Japanese exposed to atomic
homes; (2) Uranium miners; (3) Patients with body burdens of thorotrast;
(4) Persons exposed to uranium tailings used in construction.
F. SUPPORTING CONTRACTS: Contracts to obtain data are let with institutions
which own the individual records on exposure histories.
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIPS: None
I. COORDINATION: Close coordination is maintained with agencies such as
HEW, and AEC who are also conducting studies on long-term effects of
radiation.
J. UNRESOLVED POLICY ISSUES: No standards for operation of breeder reactors,
fuel reprocessing plants, or long time waste storage have been promulgated.
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B 199
I. COORDINATION: Bureau of Radiological Health, HEW, IsJnterested in
of Radiological Health, HEW, is interested ii
of the children treated with 13'l. The plai
doing a clinical study of the children treated with IJII. The plans
for our study will be coordinated with them,
J. UNRESOLVED POLICY ISSUES: Standards for light-water cooled power
reactors have been promulgated. No standards for operation of nuclear
fuel processing plants, breeder reactors or permanent waste storage
facilities have been developed.
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B 200
PROGRAM ELEMENT: RADIATION HEALTH EFFECTS
PROJECT A - STANDARDS FOR NUCLEAR FACILITIES
TASK 4. Dose-response effects studies of tritium.
A. PROGRAM JUSTIFICATION: EPA is responsible for setting environmental
radiation standards. Tritium and Krypton are the two principle radio-
nuclides released from nuclear power reactors and fuel-reprocessing
plants for which an environmental standard must be promulgated. The
present ICRP recommendation for the maximum exposure of individuals
in the general population to tritiated water (HTO) is a calculated
value. Further, the calculation was derived from dose-effect studies
employing high-level total body exposure to x and gamma radiation.
The adequacy of the ICRP recommendation for exposure to HTO has not
been experimentally investigated.
B. OBJECTIVES: The objective of this study is to provide the scientific
bases needed to select and support an EPA environmental standard for
tri ti urn.
C. SCOPE: This study will include investigation of some of the major somatic
and genetic consequences of radiation exposure and the development,
modification and application of a spectrum of neurochemical techniques
for assessment of damage to the particularly radiosensitive system.
D- RESULTS; Because of the dose ranges employed this task should provide the
experimental basis for the selection of an environmental HTO level which
produces "no detectable effect" in sensitive mammalian systems for the
types of observations made.
E. APPROACH: Investigations of the intermediate and long-term consequences
of irradiation with tritium are proceeding by employing:
1. exposure of rats to HTO, the predominant environmental form
of tritium.
2. activity ranges of 100-1000 approaching ICRP recommendations
at the lowest levels.
3. continuous lifetime exposures or exposures during the most
radiosensitive phases of mammalian development.
4. major somatic and genetic endpoints for the assessment of
effects.
Specific subtasks are:
Subtask 1. Tumorigenic potential of intrauterine exposure to HTO.
Subtask 2. Effects on the mammalian nervous system of intrauterine
exposure to HTO.
Subtask 3. Effects of lifetime parental exposure to HTO on the F2
generation.
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B 201.
F. SUPPORTING CONTRACTS:
1. Long-term holding and animal care fora* 1200 rats over a
2-3 year period will be required.
2. Radiation effects on .pre-implantation embryos in vitro
(Cornell University)
6. SPECIAL FACILITIES: This study will utilize glove Boxes for the
containmant of HTO during animal exposures along with liquid scintillation.
H. INTERMEDIA RELATIONSHIPS: None
I. COORDINATION; None
J. UNRESOLVED POLICY ISSUES; Promulgation of an environmental tritium standard.
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B 202
PROGRAM ELEMENT: RADIATION HEALTH EFFECTS
PROJECT.A - STANDARDS FOR NUCLEAR FACILITIES
TASK 5. Age sensitivity to radio-strontium and other nuclides,
A. PROGRAM JUSTIFICATION: The Environmental Protection Agency is responsible
for the development of environmental radiation standards. Some of the
environmental pollutants resulting from nuclear operations include radio-
strontium and iodine which are released in nuclear reactor and fuel-
reprocessing plant effluents; radio-plutonium and sodium are the major
radio-nuclides which are present in liquid-metal fast breeder reactors
to which a national commitment has been made. At present, the radiation
exposure recommendations of ICRP and others is based primarily upon
biological effects data on adult humans and animals. The indications
of the existence of more radiosensitive phases of life than the adult
have been reported but adequate investigations of the age-sensitivity
of mammals to environmentally important radio-nuclides have not been
undertaken.
B. OBJECTIVES: The objective of this study is to determine whether various
age groups have significant differences in response to irradiation from
some of the most probable environmental radiocontaminants, and to
investigate some of the unknown physiologic and kinetic characteristics
of radio-nuclides.
C. SCOPE: Present funding permits the study of the age-sensitive response
to a single dose-level of one radionuclide plus the necessary supportive
radio-nuclide metabolic studies. Increased funding would permit an
expansion of the number of radio-nuclides to be investigated and the
number of dose-levels employed.
D. RESULTS: Using the same radionuclide exposure level across several age
groups would permit identification of the most radiosensitive age for
exposure to a particular radio-nuclide and an estimate of the magnitude
of sensitivity difference from the adult. If the most sensitive group
was not the adult, these data would be used to provide a basis for
revision of the radiation exposure recommendations for the radio-nuclide
to protect the most critical sub-population.
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B 203
E. APPROACH: The experimental arrmals used in these studies are the domestic
cats supplied from our closed colony. The cat is particularly suited for
experiments designed to evaluate human guidelines for radio-nuclide
exposures because of their similarity to humans in metabolism and the
development of neoplastic diseases. The investigation of the influence
of age-sensitivity will proceed by:
1. chronic ingestion of radio-strontium, plutonium, iodine,
or sodium.
2. .establishment of the same radio-nuclide dose at each age
level.
3. age levels examined will be the embryo and fetus, weanling,
adolescent and adult.
4. examination of the pertinent radiation response parameters
strontium the short-term effects would be on the
hematopoietic system and long-term effects would be the
incidence of myeloproliferative diseases, osteosarcoma
and life span shortening.
Because of the differences in the age of the groups employed, differences
in the metabolism, distribution and retention of radio-nuclides are
expected. In order to induce the same radiation exposures supportive
metabolic studies are essential.
F. SUPPORTING CONTRACTS:
1. Contract 68-01-0403 with Hazleton Laboratories, Inc., Vienna,
Virginia for the technical assistance for the care and
maintenance of the feline colony.
2. Grant - Accumulation of Fallout Radio-nuclides in Teeth and
Bone - H. L. Rosenthal, Washington, St. Louis, Mo.
3. Grant - Comparative Effects of Two Radiation Regimes -
D. G. Willhoit, University of North Carolina, Chapel Hill, N.C.
G. SPECIAL FACILITIES; This study will utilize 2 single channel qamma analyzers
($1400), 2 Timer-readouts ($2700), 1 Low-energy Crystal ($1000), and
1 Radiation Glove Box ($1100).
H. INTERMEDIA COORDINATION: None
I. COORDINATION: Office of Radiation Programs.
J. UNRESOLVED POLICY ISSUES: None
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PROGRAM ELEMENT: RADIATION HEALTH EFFECTS
PROJECT A - STANDARDS FOR NUCLEAR FACILITIES
TASK 6. Dose-response effects studies of Krypton-S5 exposure.
B 204
A. PROGRAM JUSTIFICATION: Krypton-85 is a long-lived noble fission product
gas released to the atmosphere in large quantities primarily by reactor
fuel reprocessing plants. Federal and State regulations permit release
of 85
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B 205
Subtask 6.
Subtask 7.
Subtask 8.
Determine the bloodiair partition coefficient, the tissue:b1ood
partition coefficients and tissue:air partition coefficients for
most significant tissues/organ at saturation.
Determine the median lethal exposure to Kr under these
experimental conditions with guinea pigs, estimates of the
corresponding organ and whole body doses, differences in
lethality with sex and the time pattern of death.
Include values for the median lethal exposure for guinea pigs
under the postulated exposure conditions, the time pattern of
death, and the gross clinical effects produced. The data will
be compared to existing lethality data for guinea pigs exposed
to different radiation by other investigators.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: This study will utilize special apparatus built at
the University of Rochester for preliminary studies in this project and now
located at the Eastern Radiation Research Laboratory, Montgomery, Alabama.
This equipment includes 10 animal air-Krypton delivery manifold for
exposing guinea pigs to inhaled isotopes and a life support system and
8'xl6' tank for providing total body beta exposure in the same geometry
as anticipated in ICRP exposure standards, i.e.., infinite cloud approximation,
H. INTERMEDIA RELATIONSHIPS: None
I. COORDINATION:. The dosimetry for this study will be coordinated through
the Radio-nuclide Toxicology Branch, TRL.
J. UNRESOLVED POLICY ISSUES: An EPA environmental standard for 85Kr exposure.
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B 206
PROGRAM ELEMENT: RADIATION HEALTH EFFECTS
PROJECT A - STANDARDS FOR NUCLEAR FACILITIES
TASK 7. Beta and alpha ray dosimetry for population studies.
A. PROGRAM JUSTIFICATION; Estimates of the population exposures due to
radioisotopes entering the environment from the nuclear fuel cycle
depend critically on the models used to calculate the whole-body
dose and dose to critical organs. Presently available models are
not wholly suitable for evaluating the population exposure situations
encountered in nuclear fuel reprocessing, reactor effluents, and
the mining and processing of fissionable fuels.
B. OBJECTIVES: Because they do not consider adequately the exposure geometry
and the amount of absorbing material between the radioactivity and internal
organelless the objective of this study is to provide methods of evaluating
the absorbed dose delivered by beta and alpha ray emitters in the environment.
Particular attention will be given to exposure geometries corresponding to
Krypton-85 and Xe-133 in air, inhaled radioactivity, and metabolized isotopes.
Variation in the dose distribution pattern due to exposure geometry, the
size of the radioactive source, and anatomical features will be examined .
for a number of isotopes commonly encountered in the environment.
C. SCOPE: This study will be limited to a study of the dose delivered by
isotopes released in significant amount in the nuclear fuel cycle includ-
ing mining and reprocessing of spent nuclear fuels.
D. RESULTS; Internal and external scientific reports yielding information on:
1. The beta-ray dose delivered at various depths in tissue from
a cloud of Krypton-85 or Xenon-133.
2. The dose distribution from planar sources of alpha-ray activity
such as those contributing to the dose received by the lung
bronchi from inhaled radon daughters and plutonium.
3. The dose distribution within organs and cells containing such
beta ray emitting isotopes as tritium, iodine-131, cesium-137,
and all other principal beta-ray emitting fission products.
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B 207
(
j
E. APPROACH: Both theoretical and experimental studies will be needed to
provide a confirmed description of the dose distribution. Calculational
studies will include the extension of existing beta-ray source functions
to geometries of interest in environmental exposure situations, Monte
Carlo calculations of the dose from air to skin, and the development of
alpha-ray dose distribution functions. Experimental portions of this
study will concentrate on the beta-ray dose distribution at various depths
in the skin and other tissues from radioactive gases such as Krypton-85.
If possible, the experimental studies will be extended to other appropriate
geometries and microdosimetric dimensions.
F. SUPPORTING CONTRACTS; If funding permits, a $5,000 contract to the National
Bureau of Standards for Monte Carlo calculators of the beta-ray dose at an
air interface will be negotiated.
6. SPECIAL FACILITIES: The Krypton-85 exposure facilities at the Eastern
Environmental Radiation Laboratory will be used for a portion of the
experimental program.
H. INTERMEDIA RELATIONSHIPS: None
I. COORDINATION: This program will be coordinated with the dose calculation
studies performed by the National Bureau of Standards and the ORNL program
of dose calculations for the NCRP and ICRP.
J. UNRESOLVED POLICY ISSUES: None
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B 208
PROGRAM ELEMENT: RADIATION HEALTH EFFECTS
PROJECT A: STANDARDS FOR NUCLEAR FACILITIES
TASK 8. Radioactive particle studies.
A. PROGRAM JUSTIFICATION: The possibility of environmental, radioactive
contamination increases with the expanding use of nuclear energy. Regard-
less of the nature or origin of the contamination, or the protective safety
measures employed, a distinct possibility of inhalation and retention of
radioactive substances exists. Although studies concerned with oncogenic
effects from inhaled radioactive materials began during the first half of
this century with the investigation of lung cancer in miners, much is still
unknown. The exposure dose-effects relationships are poorly defined. The
mode of tumor induction is not understood. Even less well understood are
the problems associated with deposition non-uniformity, which is commonly
found following all types of aerosal exposures. These uncertainties surround-
ing carcinogenesis and the growing awareness that man's atmosphere is being
contaminated by ever-increasing types and amounts of pollutants necessitate
critical, periodic re-evaluation of existing safety standards.
B. OBJECTIVES: To accumulate sufficient biological data from animal experi-
mentation for evaluating the carcinogenic potential of inhaled radioactive
substances. Dose-effects relationship for radiogenic tumor induction and
any enhancing effect-of non-uniform distribution within the lung are principal
parameters of concern.
C. SCOPE: The scope entails a rigorous study of inhalation carcinogenesis
in suitable research animals (hamsters and dogs) using controlled exposure
techniques (implantation) and semi-controlled techniques (inhalation). Dose
response studies using various types of radiation under similar exposure
conditions will be used to evaluate carcinogenic potential and to determine
any enhancing factors associated with distribution peculiarities.
D. RESULTS: The information obtained from this task should provide a more
reliable basis for initiating the necessary changes in the radiation health
standards. The largest single problem is to obtain the necessary information
for changing the lung model. The expected results should provide a better
insight to a possible solution.
E. APPROACH: The approach combines both controlled (implantation) and
semi-controlled (inhalation) techniques to expose sufficient animals to
graded doses of various radioactive substances. Research animals of
choice are the hamster and dog, with any needed confirmatory work completed
in the burro or sub-human primate. Details of both techniques (implantation
and inhalation) are available as preprints or will appear in publication in
the near future. Necropsy of expiring animals, periodic serial sacrifice,
and histopathologic examination of selected tissues will be used to document
the expected neoplastic lung changes.
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B 209
F. SUPPORTING CONTRACTS: Histopathologic support will be obtained from one
of the veterinary colleges in the area (Oklahoma State University or Colorado
State University).
G. SPECIAL FACILITIES: All required facilities are available; e.g., housing
facilities, surgery room, inhalation apparatus.
H. INTERMEDIA RELATIONSHIPS: Air
I. COORDINATION; None
J. UNRESOLVED POLICY ISSUES: None
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B 210
PROGRAM ELEMENT: RADIATION HEALTH EFFECTS
PROJECT A: STANDARDS FOR NUCLEAR FACILITIES
TASK 9. Biokinetic studies of tritium.
A. PROGRAM JUSTIFICATION; The distribution of tritium in body hydrogen
following chronic exposure is not known. The quality factor for the
tritium beta is not known with certainty. Hence, since relatively high
environmental levels of tritium currently exist and nuclear power reactors
are continuing to add to environmental tritium, better biological information
is needed to develop realistic and reliable safety criteria.
B. OBJECTIVE; To determine the distribution of tritium in various parts of
body hydrogen and to determine a quality factor.
C. SCOPE: The scope involves the production of animal food in a uniformly
tritiated environment; the exposure of animals (via food, water and air)
through several generations; and the comparison of resultant effects with
those from a reference source of radiation.
D. RESULTS; The results are expected to solve the controversey over tritium
concentration in various organic molecules and provide a more reliable
indication of the true quality factor.
E. APPROACH: Alfalfa grown in a uniformly tritiated hydroponic solution will
be used as the sole source of food for rabbits. These animals will be main-
tained in a tritiated environment (water, food and air) through three
generations in an effort to reach equilibrium, and then sacrificed. Following
sacrifice, the three principal body hydrogen fractions (water, fat and protein)
will be analyzed for tritium to measure any concentration which might have
occurred. The second phase is simply two dose-response studies to determine
quality factor.
F. SUPPORTING CONTRACTS: Extramural contract for human tissue collection
($801]
G. SPECIAL FACILITIES; Greenhouse, feed grinder, feed pelletizer, etc.
H. INTERMEDIA RELATIONSHIPS: None
I. COORDINATION: None
J. UNRESOLVED POLICY ISSUES: None
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J B 211-
PROGRAM ELEMENT: RADIATION HEALTH EFFECTS
PROJECT A: STANDARDS FOR NUCLEAR FACILITIES
TASK 10. Plutonium exposure and effects studies.
A. PROGRAM JUSTIFICATION: Plutonium presently contaminates certain areas of
the countryside and represents a serious potential health hazard. The proposed
reprocessing plants and fast breeder reactors scheduled for installation in
several areas in the near future could be additional sources of plutonium.
While much work is currently underway with regard to the inhalation problem
associated with plutonium, little work has been done to define the contributory
role if ingestion, especially when the plutonium has been cycled through plant
or animal prior to ingestion.
B. OBJECTIVES; Obtain sufficient biological data to define biokinetics of
ingested, metabolized plutonium.
C. SCOPE: Involves collection of human tissue to obtain indication of tissue
distribution of plutonium in chronically exposed humans; the cycling of plutonium
through plants and animals to produce metabolized plutonium; and the exposure of
research animals.
D. RESULTS: Will permit an evaluation of ingestion as a route of exposure.
E. APPROACH: Food which has been labelled in vivo with plutonium will be feed
to suitable experimental animals. The uptake and tissue distribution will be
compared with those following a more classical type of exposure using pure
chemical compounds, such as plutonium citrate.
F. SUPPORTING CONTRACTS; Human tissue collection ($70K)
G. SPECIAL FACILITIES: Greenhouse, experimental farm, animal holding facilities,
H. INTERMEDIA RELATIONSHIPS; None
I. COORDINATION: None
J. UNRESOLVED POLICY ISSUES: None
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j B 212
PROGRAM ELEMENT: RADIATION HEALTH EFFECTS
PROJECT A: STANDARDS FOR NUCLEAR FACILITIES
TASK 11. Lead - 210 as a biological indicator of radon exposure.
A. PROGRAM JUSTIFICATION; At present, there is no adequate method for evalu-
ating the lung exposure of populations exposed to radon-222 and its progeny.
The two populations known to be exposed are the residents of Grand Junction,
Colorado, and the uranium miners. If the bio-assay procedure can be shown to
be quantitative, then it would yield more accurate data for dose assessment
in an individual than would any environmental measurement.
B. OBJECTIVE: To obtain necessary experimental data to supplement limited
human data to construct a more reliable dose-response curve which could be
used in establishing realistic exposure standards.
C. SCOPE: Suitable research animals will be exposed for different periods
of time to 10, 20, or 30 WL (cumulative) of radon. Urinary and fecal excretion
of 210 Pb and 210 Po recorded as a function of both cumulative exposure and
time will be used to evaluate any existing relationship. Human tissue samples
(lymph nodes and bone) and excreta samples (urine and feces) will be obtained
from hospitalized uranium miners in the Grand Junction and evaluated with the
animal data.
D. RESULTS: With adequate funding, this project will provide a biological
dosimeter for improving the estimate of radiation exposure to the principal
populations at risk (uranium miners and Grand Junction residents).
E. APPROACH: Groups of 100 rats will be exposed to a uniform radon concen-
tration in a chamber for 1, 2, or 3 months to give 3 different cumulative
exposures. Metabolic data, tissue distribution data, and histopathological
lesions will be used to develop any existing correlations with dose, cumulative
exposure, rate of exposure, etc. To supplement meager human data, excreta
samples from hospitalized miners and tissue samples, whenever possible, will be
collected and analyzed also.
F. SUPPORTING CONTRACTS: Contracts for human excreta collection and tissue
samples would be arranged through the service pathologist at St. Elizabeth's
Hospital in Grand Junction, Colorado.
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B 213
G. SPECIAL FACILITIES; Housing facilities, exposure chambers, and the
necessary analytical equipment are available.
H. INTERMEDIA RELATIONSHIPS: Air
I. CORRDINATION; None
J. UNRESOLVED POLICY ISSUES: None
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B 214
PROGRAM ELEMENT: RADIATION HEALTH EFFECTS
PROJECT B - STANDARDS ,'OR ELECTROMAGNETIC RADIATION
TASK 1. Fundamental modes of action of nonionizing radiation.
A. PROGRAM JUSTIFICATION: The entire population is exposed to electromagnetic
radiation from nuclear industry, radar, television, and communications systems.
The number and power of these sources will continue to increase. Though
microwaves and radiowaves at thermal intensities are known to cause adverse
biological effects, no standard exists for the exposure of the general
population to these nonionizing radiations. Before EPA can establish and
evaluate population exposure standards, the extent and importance of
molecular, biochemical, genetic and functional changes reported at low
intensities must be determined. The consequences of underestimating the
effects of long-term exposure are serious, especially if there are genetic
effects. The fundamental interactions between nonionizing radiation and
molecular systems, including the sites of energy deposition, and the basic
data needed to predict hazards at specific frequencies need to be determined.
B. OBJECTIVES: The objective of this task is to define the physical and
biological parameters tha-t determine the absorption of nonionizing radiation
by biologically important molecular systems.
C. SCOPE: The scope includes the development, evaluation and application of
biophysical and biochemical techniques which yield information on the
interaction of nonionizing radiation with biological systems.
D. RESULTS: This task will provide information which is necessary to formulate,
evaluate, and support standards on environmental levels of electromagnetic
radiation. Information will be communicated through intramural reports,
consultation, and publication. Results will be incorporated into studies to
predict cumulative and irreversible nonionizing radiation effects.
E. APPROACH: The task will be accomplished by intramural research with existing
special exposure facilities complemented by grants and contracts. Specifically:
(1) develop and apply a model protein system to test the flexible protein chain
theory of microwave radiation; (2) evaluate the instrumentation developed for
observing changes in absorption spectra during microwave irradiation; i.e.,
crossed-beam technique; (3) apply the crossed-beam technique to protein and
nucleic acid model systems to determine changes in conformation and function;
and (4) compare the free energy necessary for important macromolecular
transitions to energy supplied by microwave fields.
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B 215
F. SUPPORTING CONTRACTS; A grant assigned to EPA under Reorganization Plan
No. 3 has been identified with this task; namely, "macromolecular radiation
pathology" which is an electron microscope fine structure analysis of cells
irradiated with x ray.
G. SPECIAL FACILITIES: The system for controlling the temperature, humidity, and
gas composition in the environmental chamber installed in the anechoic room
will be completed in fiscal year 1972. Preliminary evaluation of the modified
spectrophotometer for the observation of absorption spectra during microwave
irradiation will also be completed during fiscal year 1972. Necessary additional
equipment includes a Gary 61 spectropolarimeter which can be modified to observe
optical rotatory dispersion during microwave irradiation.
H. INTERMEDIA RELATIONSHIPS: None.
J. COORDINATION: Coordination with other interested agencies is being developed,
particularly with DHEW and various laboratories of the Department of Defense,
such as School of Aerospace Medicine, Brooks AFB, Texas; Walter Reed Institute
of Research, Washington, D.C.; Naval Aerospace Medical Center, Pensacola, Florida.
K. UNRESOLVED POLICY ISSUES: Standards for permissible levels of nonionizing
radiation in the environment have not been promulgated.
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B 216
PROGRAM ELEMENT: RADIATION HEALTH EFFECTS
PROJECT B - STANDARDS FOR ELECTROMAGNETIC RADIATION
TASK 2. Mutagenic effects of nonionizing radiation.
A. PROGRAM JUSTIFICATION: The entire population is exposed to electromagnetic
radiation from the nuclear industry, radar, television, and communication
systems. The number of these sources will continue to increase. Though
microwaves and radiowaves at thermal intensities are known to cause adverse
biological effects, no standard exists for the exposure of the general
population to these nonionizing radiations. The consequences of under-
estimating the effect of long-term exposure are serious, especially if there
are genetic effects. Before EPA can establish and evaluate population
exposure standards, the extent and importance of molecular, biochemical,
genetic and functional changes due to electromagnetic radiation exposure
must be determined.
B. OBJECTIVE: The objective of this task is to determine the existence and
consequences of genetic alterations in biological important systems exposed
to electromagnetic radiation.
Tne scope includes the development, evaluation, and appl.i cation
of biological and. biochemical . systems which are sensitive indicators
of genetic damage.
D- , MS1M.S: This task will provide meaningful scientific data on
biological effects of electromagnetic radiation which is needed to
formulate, evaluate, arid support standards. This scientific infor-
mation will be communicated via intramural reports, publications,
and consultations.
E' MTJiQ.v.Q[: Genetic effects from electromagnetic radiation, including',
possible threshold levels and cumulative., irreversible components,
will be examined at several levels of biological complexity:
(1) Purified DNA will be exposed in selected environments and
examined for changes in its biological and physical chemical
properties. This model system will yield information concerning
the fundamental interaction effects of electromagnetic- radiation
with the chromosome. The development of this: mode], system is
presently nearing completion.
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B 217
(2) Relatively simple, well-defined genetic systems will be
used to seem the electromagnetic speetrum to examine frequeucy-
dependent interactions with the basic genetic apparatus in
living systems. This approach is presently being te.stcd with
the bacterial system, K. eoli.
(3) Mammalian cell culture model systems will be used to examine
parameters that affect mammalian cell response to electromagnetic
. radiation. Because of the more complex chromosome structure
and regulatory mechanisms, these systems may demonstrate more
subtle effects of electromagnetic radiation exposure.
(A) Animal and plant systems will be developed to examine
ce3J.ul.ar responses to electromagnetic radiation. These
systems will demonstrate the compensating mechanisms of the
whole organism to stresses introduced by exposure to electro-
magnetic radiation .
This researcli will be accomplished intrarnurally , supplemented by
grants and contracts.
F. SUPPORTING CONTRACTS: Contracts and grants will be awarded to extend the
frequency capabilities of the laboratory and to complement the intramural
research program. Grants that have been identified are:
(1) "Effects of Electromagnetic Fields on Genetic Phenomena,"
which is designed to detect genetic effects of microwaves in
Drosophila, and
(2) "Polarization Effects in Micro-organisms ," which is
designed to study non-thermal effects of polarized electro-
magnetic radiation.
G. SPECIAL FACILITIES: The system for controlling the temperature, humidity,
and gas composition in the environmental chamber installed in the anechoic
room will be completed in fiscal year 1972. Other available equipment includes
a radtofrequency source and a 250 KVCP x-ray source. Additional necessary
equipment includes monitoring facilities for the radtofrequency source and
generating and monitoring facilities for frequencies above 2.54 GHz.
H INTEKM£DIA RE I AT IONS! UPS : None at present stage of development.
T:l'QIi: Coordination with other interested agencies is being
TJc'veTcJpeciTparticul.arly with D1IEW and various laboratories of the
Department of Defense.
J l^rl^QI'v!^J^J:Q'_J:S;ii-1i§.: Standards for permissible levels of
nonT
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B 218
PROGRAM ELEMENT: RADIATION HEALTH EFFECTS
PROJECT B - STANDARDS FOR ELECTROMAGNETIC RADIATION
TASK 3. Physiological and behavioral effects of nonionizing radiation.
A. PROGMI-; JUSTIFICATION:
The entire population is exposed to electromagnetic radiation
from imclear industry, radar, television, and communication
systems. The number and power of these sources will continue
to increase. The effects of radiation, in particular non-
ionizing radiation, on physiological systems and behavioral
patterns have not been clearly defined. The assessment of
potential hazardous consequences must be made before standards
can be reasonably set. The literature implicates the nervous
system, the endocrine system, and cardiovascular system as
'being sensitive to nonionizing radiation.
B. OBJECTIVES:
The objective of this task is to determine and describe the
effects of nonionizing radiation exposures on the nervous
system and glands controlling physiological integration in
relation to age and dose of radiation.
C. SCOPE :
The scope includes the development, evaluation, and application
of physiological and behavioral techniques which yield infor-
mation on the interaction of nonionizing radiation with physio-
logical systems.
D. RESULTS:
Data necessary to develop standards v?i.ll be gathered and reports
of scientific findings will be published.
E. APPROACH;
The task will be accomplished by intramural research with
existing special exposure facilities complemented by grants and
contracts. Peripheral, autonomic , and central nervous system
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B 219
functions V73.ll be studied by analyzing signals recorded from
the bruin and sensory end organs. Behavioral tasks will be
utilized to explore tbe effects on activation level, learning,
memory, motivation and perception. Quantitative biochemical
analyses using optical and radio-isotope techniques will be-}
performed to determine changes in enzyme and hormone levels.
Short and long term irradiation regimens, immediate and delayed
effects, a7id age --sensitivity will be investigated.
F- SUPPORTING CONTRACTS :
Currently, a service contract provides clinical laboratory
analyses of serum for thyroid function determiTiations , and
an interagency contract provides for the part-time salary of
one investigator.
Grants that could be awarded to complement the intramural
program are identified as follows:
(1) "Behavioral Effects of Low Intensity UUP Radiation"
(2) "Cumulative Effects of Microwave Radiation on the
Eye"
(3) "Sensitivity of Man to Low Level, Low Frequency Fields"
(4) "Electromagnetic Radiation Effects on Chickens and
Rats"
(5) "Neurophysiological Effects of Microwave Radiation"
G. SPECIAL FACILITIES;
The environmental microwave chamber and associated control
system at the Rockville Laboratory will be in operation in FY'72.
Signal analysis and behavioral control equipment have been
ordered and should be operational by the end of FY '72. Shielded
rooms for neurophysiological recording and access to a computer
terminal are needed.
H INTERMEDIA RELATIONSHIPS:
None
I . COORDINATION:
Coordination will be necessary with research activities sponsored
by DOD and DHEW, and instrumentation development of National
Bureaii of Standards.
nfii
Standards for permissible levels of rionionizing radiation in
the environment have riot been promulgated.
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B 220
PROGRAM ELEMENT: RADIATION HEALTH EFFECTS
PROJECT B - STANDARDS FOR ELECTROMAGNETIC RADIATION
TASK 4. Population exposure to environmental nonionizing radiation.
A. PROGRAM JUSTIFICATION: Many persons are currently exposed to radiation fields
from microwave, radio frequency and other transmitters. Non-occupational
exposures are probably highest in urban areas. Exposures to non-ionizing
radiation may cause disease and chanaes in normal behavior in man. It is
projected that the number and power of transmitters being used will continue
to increase. No evaluation of the extent and level of exposure of the
population to environmental nonionizing radiation has been made.
B. OBJECTIVE: To determine the extent and levels of exposure of certain
urban populations to nonionizing radiation and project potential exposures
with increased use of nonionziing radiation in field of communications.
C. SCOPE: Included in the project will be the verification by direct measure-
ment of calculated exposure levels in selected areas of study cities. One
metropolitan area will serve as a pilot study city before expansion to
other metropolitan areas.
D. RESULTS:
Current population exposure to environmental nonionizing radiation
will be known and decisions can be made whether this type, of exposure is,
or is projected to become a health hazard to the population.
E. APPROACH: Iso-density tracings of power and frequency of fixed transmitters
are being obtained from Electromagnetic Compatibility Analysis Center, DOD.
Population density overlays are being obtained from US Census Bureau.
Confirmation of calculated exposure levels and evaluation of current extent
and levels of exposure and projections will be made by staff. Populations
which are defined as having unique exposures to nonionizing radiation will
be studied for effects related to exposures under grant or contract.
F. SUPPORTING CONTRACTS: t\n intcragency agreement has been made with DOD for
purchase of data on fixed sources of nonionizing radiation.
G. SPECIAL FACILITIES: Instrumentation and personnel will be required to measure
actual exposures in selected areas.
H. INTERMEDIA RELATIONSHIPS: None.
I. COORDINATION: Development of measurement equipment is currently under way
in EPA. Close coordination will be maintained with Division of Research,
Bureau of Radiological Health, HEW, where studies of effects of occupational
exposures to radar arc being conducted.
J. UNRESOLVED POLICY ISSUES: Standards' for population exposures to nonionizing
radiation hnve nor. bstui promulgated.
-------
_/ B 221
PROGRAM ELEMENT: RADIATION HEALTH EFFECTS
PROJECT B - STANDARDS FOR ELECTROMAGNETIC RADIATION
TASK 5. Radiation repair and carcinogenesis.
A. PROGRAM JUSTIFICATION:
Tumorigenesis is a biological endpoint of primary importance in
establishment of radiation standards and guidelines. For this
purpose tha induction of tumors is assumed to be linearly related
to radiation dose with no threshold, exposure. However, recent
results from several laboratories indicate that 1) viruses are. the
causative agents in many (including radiation induced leukemia s and
sarcomas) if not all, tumors and that ?.) repair of radiation damage
in humans is an important factor in radiation carcinogenesis . The
implication of repair in radiation carcinogenor-is suggests thresholds
may be present at Ic/; exposure. The existence and knowledge of con-
trolling mechanisms for threshold will be.coaia increasingly significant.
as decisions must be made on determining total allowable radiation
exposures from multiple sources when alternatives to operations which
increase radiation exposure are considered with their corresponding
detrimental eftects. Therefore characterisation of the role ol: repair
in radiation carcinogcnesis is of paramount importance, in particular,
with regard to viral induced tumori genesis . Because animal studies
involving tumor igene sis are both costly and time consuming, the tissue
culture approach v:hich allows rapid assay of carcinogenosis is developed
and employed to answer this problem.
The purposes of this task are to 1) develop tissue culture assay
systems to sea sure radiation enhanced tumor virus carcinoge.ner.is, 2) to
characterize repair of radiation damage in maomalian cells, and 3) to
determine the role of repair in the radiation enhanced viral carcinogenesis
C ' SCOPE :
This task employs mammalian calls and cell extracts fron various sninrals,
including r,nn and other primates. Viruses which infect man or other
primates are also used. The individual objectives are pursued con-
currently v;ith objective 1 expected to continue 1-2 years and objective 3
3-5 years.
-------
B 222
D. JR^jJl/rS:
The acco.T.plislrovi'nts of pas!: cmd present investigations hav-?. sbov.'n
th.nt ionising n:id noaionix.in,'', radi.at.iOii enbaacc viral o;;rc:ui.O;-,o.r.'CsiF-
and induction of tumor -viruses from iT'irnmalian cells. Other studios
have quantitatively detc-rininad relative reactivation abilitlc t; of
cells from different species, the. effects of lonixing and noiiloiiixinj.1,
radiations; on this reactivation ability, and the. effects of temperature
and repair inhibition. Further results will characterize the relation
of age to reactivation ability, the. possible induction of repair en;:y\n^
by radiation, the quantitative aspects of repair mechanisms, the rela-
tion of tim?. between irradiation and virus infection in carclno^evinpls
aad the role of repair in this phenomenon, and the dose response for
induction of tumor virus from cells by radiation. These combined
results can be used for guidance of animal studies and for esti;mtlon
of lo;v dose and low dose rates effects.
The virus infectivity and viral careinogenesis models developed and
used in these studies can be developed as rapid, reliable systems
for evaluating environmental agents with regard to 1) increasing
virus infections, ?.) synergisms with radiation responses, and 3)
, potential carcinogenic action. However, the present facilities
do not allow for adequate containment or disposal of hazardous
materials.
E. APPROACH:
This task is accomplished through intramural research including
collaborative efforts with investigators outside. EPA and through
grants. The experimental approach employs recently developed
microbiological and molecular biological techniques and methods.
The biological sources of materials are mammalian (when appropriate,
human). The specific subtasks designed for completion or initiation
in FY 73 include:
Subtask 1. Determine quantitatively the levels of rapair activity
e.s a function of in vivo and in vitro age for mammalian
cells.
Subtask 2. Determine the relation of time between initial exposure
to radiation and levels of repair activity for radiation-
enhanced reactivation.
Subtask 3. Development and application of a biochemical assay system
to determine repair enzyms levels.
Subtask 4. Development and application of molecular biological methcdi-.
to quantitate repair at the molecular- level.
-------
Subtaclc 5. Characterisation of ti:tD sequence of radiation enhance
ment of viral carcincf^enesis and determination of role
of re-pair In this p lien omen on.
Subtask 6. E>:amnntion of importance, of radiation quality in in-
duction of larc-nt tumor virus from mammalian cells and
determination of dose, response and role of repair in
this induction.
Sub task 7. Development of viral carcinogenesis assay method for
use in evaluat.ing carcinogenic, potential of other
e nv i r onro-3 i\ t a 1 a ge n t s .
None
G. S_PEC
In addition to special tissue culture, virology, and biochemical
facilities currently available, facilities and equipment for protein
isolation, purification, and characterization will be needed.
Liaison f.ncl soavn colli;bovative effort are maintained with investigators
of the Bureau of Radiological Health, FDA and the National Cancer In-
stitute, National Institutes of Health. Liaison with the other divisions
of ORM will be established and maintained regarding use of the viral. a??i/
systems as?. ;n?.ans of determining hazardous potential of environmental agsnts,
Liaison through intermedia relationships are used to coordinate develop-
ment of viral, assays for evaluation of hazardous potential of enviroanonr,' 1
agents.
M^I§2I^E D _? OLIC Y_I S S L[E 3 :
This task proposal presumes retention of the Twinbrook Research Building
and its associated faci.liti.es and equipment.
-------
B ?24
PROGRAM ELEMENT: RADIATION HEALTH EFFECTS
PROJECT B - STANDARDS FOR ELECTROMAGNETIC RADIATION
TASK 6. Determination of environmental synergists on radiation standards.
A. PROGRAM JUSTIFICATION:
Since the radiation sensitivity, radiation response and radionuclide
metabolism of aquatic and terrestrial organisms, including man, are
dependent upon the interaction of other environmental pollutants, such
as heavy metals, it is imperative to study the synergisms, interactions
and mechanism(s) of action which exist between radiation and other
environmental stresses in order to upgrade or reestablish radiation
standards (more stringent standards).
B. OBJECTIVES-.
Define health risk associated with co-insult by radiation and other
environmental stresses. In order to select those heavy matals which
are most apt to causa synergisms, be able to identify interactions
and oiechaniSLn(s) of action, screening techniques will be used to
evaluate the acute bioeffects of each matal separately, fro:;i radiation
alone and fro.Ti the co-insult using the same vital organ syste.-n(s) which
the metal and radiation affect independently as the supporting endpoint(s)
of lethality. Very high potential metal pollutants such as Cd, Pb, and
methyl mercury will be studied first because (1) each metal is accum-
ulating not only in food chains but in humans as well; (2) each metal
affects the same vital organ system(s) (hematopoietic and respiratory
in the cases of Cd and Pb or nervous system in the case of methyl
mercury) as does radiation alone; and (3) the synergistic bi.oeffec.ts
remain unknov/n. Other metals of high priority include Hg, Cu, Ag, Se,
HU, Cr, Zn, Ni, Sn, Te, An, Sb, Tc and Fe and will be screened thereafter.
Matals causing syuergistic biosffocts ;-;i.Lh radiation at acute levaIs
.'ill be rcevalv.iat.ed, using lower concentrations, independently and in
combination with radiation. The recvaluation will consist, of using
multiples of the environmental concentrations of each rastnl and acute
doses of radiation in tb-3 maaur.al. Aquatic organisms will be initially
screened at r.valtiples' of enviroyi'.iwnl-.al levels of each metal with moder-
ately lev doses of radiation (1.0 80 rads in the case of iia-nature
oysters). Hlstopathological, biochemical, and cytogenetic studies will
bo used to investigr.tr1 the syitergistic bioeffects noted in the initial
screening study.
-------
R 225
C. SCOPE:
The Task is a multldisciplinary program requiring the efforts of radiation
biologists, veterinary pathologist, hematologist, cytogeneticist, aquatic
biologists, neurologist, and supportive personnel. The Task was designed
bifactorially in the mammal and tri-factorially (metal, radiation and
temperature) in the oyster.
Subordinate tasks:
(a) Effect of heavy metals on the radiation response of a
mammal (Long Evans rat).
(b) Effect of heavy metals and temperature on the radiation
response of aquatic organisms (oyster, clam, fish).
D. JESUITS:
Acute screening studies of each co-insult will identify metals which act
synergistically with radiation causing bioeffects. Acute and secondary
chronic studies will investigate the interaction and mechanism(s) of action
of the co-insults. Chronic studies using low concentrations and radiation dose
will provide sound scientific data useful for recommending changes in
present standards concerned with maximum permissible limits of radioactive,
stable element and toxic compounds, and thermal discharges in our environs.
E. APPROACH:
Research efforts are being devoted to cadmium and lead bi-factorially
with radiation in tli2 Long Evans rat. The toxicity of cadmium chloride
and lead acetate .to tivs 30-dayold Long Evans rat will bs'determined
by injecting (I.P.) one nil. of various concentrations of each compound
twice weekly for 30 days. The concentrations of choice for cadmium
chloride will be 31,25, 62.5, 125, and 250 |ig/g solution since prelimi-
nary studies indicate that 125 ug/g causes mild but significant anemia
and satellite formations in lymphocytes and ueutrophils within 30 days.
Each group of animals (sample, size of 50) receiving such concentrations
will be subjected to 0, 425, 500, 575, 650 rads of x cays at the age
of 60 days or after 30 days of heavy matal insult and observed for
another 30 days (90 days of age) in order to identify changes in sur-
vival, I/J 50/30 values, RBC production via 59Fe incorporating, anemia,
hemaglobin content, hematocrit, mean cell volumes, leucopenia or
leucocytosio, including differential counts and satellite production,
and tUTiorf£?.n?.sis i?i rna-.uii.ary glands. Organ accumulation of cadmium or
lead V7ill be cleteriaui?.d via atomic absorption spectroscopy'and related
to bioeffects. Histopathology will be conducted, the extent of which1
will be dependent uyoo the findings. Chronic studies will be started
if screening studies identify Cd or Pb to act synargistically with
radiation. The effect of lead, as lead acetate, on the radiation
-------
, B 226
response of the rat xvil] be ccaciuclrt'd in a similar fashion, only
the concentrations finally iirlralivLstered in the; co-instill study
x\Till be different as determined by preliminary tosicity studies
in which 1 ml. of 100 |j.g, 1 rnvj, 10 rn-, and 100 m^/g solution will
be administered tv.Tice wiakly for 30 days. Screening of other uvutals,
listed above, will folio-.-; vas tiin-2 p?.n».its.
Research efforts are being devoted to cadmium, lead and copper tri-
factorially with radiation and temperature in two stages (developing
and immature) of three aquatic organisms (oyster, clam, fish). Sample
experimental design for determining bioeffects of cadmium, radiation
and temperature on developing or larval stage of the oyster will utilize
radiation loses of 10, 20, 40 and 80 rads; temperatures of 10, 20 and
30° C; and CdCl2 doses of 0.1, 0.2 and 0.3 ppm.
Survival, abnormalities, growth (size and weight), coloratic-.i, activity,
respiration and osraoregulatioa will be reported, Uptake, distribution
and retention studies for each bi-factcr (temperature and radiation)
will bs conducted using an Armac arid 3>:3" NaT. crystal. Organ accumula-
tion of Cd, Pb and Cu \vill be detenr.inod by aLojii.c absorption, and
related to bicsffects.
7>.-70 research grants or contracts will be tnada iraiediately one to Texas
Woman's University (Department of Radiation Biology) to study th-3
synergism between methyl mercury and radiation i\i the rat; the second
grant to tha University of Washington (College of Fisheries) to study
the synergisra between various fofui.s of Ag, Zn, Cr, Hg, and/or 1-in and
radiation in. the oyster and fish. Both grants will be three years
commitments and will cost $12,690 and approximately $125,000 respec-
tively. At least two lovvj-terai contracts will be awarded after 18
months of screening has been completed. Each chronic study would be ,
awarded for 3-5 years totally $150,000 - 200,003 each.
SPECIAL FACILITIES; .
Equipment assu\a^d available include (1) X-r&y Unit v:ith theriiioli.-.vlnascei
equipment, (2) Arainc whole-body gamma counter, (3) 3>:3" "a Crystal with
multichannel analyzer, Old Pe.rkin and Eliv^r Atonic Absorption. Unit, (4)
Instant Ocean Aquaria with temperature control, (5) Electron microscope
with histological laboratory, (6) Animal racks ana cn.ges, (7) Supply of
animals and (8) Laboratory space for supportive personnel.
New equipment and facilities needed Include (1) 403 Perkin and EJ.nisr
Atomic Absorption Unit, (2) continuous flow ocean aquaria, (3) c-duition
instant oceans, (4) top loading and fins met tier bula^oas and (5) more
appropriate laboratory space for supportive parscuno.l.
-------
H. I!^]^5.ll^.l'iMIlQ:i?.HiPS:
Continuous co.Tnr.mication will be. maintained with o^hsr go^ern-^-ical
agencies such as tha AEG (Oak Ridge National Labcralory - Stn.p. Auorbach)
and NCAA (Ted Rice - Beaufort, N.C.) and Universities interested in
synergisms between radiation and envirpnavsutal pollutants inclv-.-liug
hzavy ratals.
I. COO^i^ATION:
Cloye cujruiaatiua will be maintained v/ich the W-a.cion.aJ. EPA ccMLter in
Research Triangle Park, N,C. arid coounu.iication will bi aiaintnincd vith
EPA in Las Vegas, Nevada and Corvallis, Oregon.
^' UNRESOT.,VED POI.TCi' ISSUES:
Proposed budgets for. TY'1973-1976 are made ;vith the understanding that
equipment now available will remain with EPA.
-------
PROGRAM ELEMENT NUMBER: None Assigned
WORK PLAN RECIPIENT:
Director,
NERC/RTP
OR&M
FY '73 Work Plans
TITLE: Radiation Health Effects
PROGRAM ELEMENT MANAGER: Vaun A. Newill
TASK
PROJECT
1A
2A
3 A
4A
5A
6A
7A
8A
9A
IDA
11A
TOTAL
Resource Estimate
Present/MY
A - STANDARDS FOR
28/2.2
86/2.0
226/6.5
110/3.0
549/17.0
60/2.0
29/1.0
44/2.5
59/4.0
0/0,0
0/0.0
1191/40.2
Minimally Adequate/MY
i
NUCLEAR FACILITIES
700/10.0
375/5.0
449/8.5
135/4.0
660/20.0
80/3.0
58/2.0
70/3.5
240/8.0
200/11.0
55/3.0
3022/78.0
Optimum/MY
700/10.0
375/5.0
1245/16.5
185/6.0
1000/25.0
140/5.0
77/3.0
110/5.0
240/8.0
200/11.0
70/5.0
4342/99.5
DO
ro
ro
oo
-------
PROGRAM ELEMENT NUMBER: None Assigned
WORK PLAN RECIPIENT:
Director,
NERC/RTP
QR&M
FY '73 Work Plans
TITLE: Radiation Health Effects
PROGRAMTLTMENT MANAGER: Vaun A. Newill
TASK
PROJECT
IB
2B
3B
4B
5B
6B
TOTAL
Resource Estimate
Present/MY
B - STANDARDS FOR EL
100/3.0
120/3.5
192/4.5
21/2.3
141/4.3
82/3.2
656/20.8
Minimally Adequate/MY
ECTROMAGNETIC RADIATION
114/4.0
226/6.5
237/7.5
400/3.5
210/5.3
260/6.7
1447/33.5
Optimum/MY
193/6.0
301/3.5
365/9.5
588/6.0
320/7.3
438/7.7
2205/40
S3
-------
R 230
RESOURCES STATUS SUMMARY
(None Assigned)
PROGRAM ELEMENT NUMBER
Health Effects of Solid Wastes
PROGRAM ELEMENT TITLE
EPA FY '73 Plan
Funding Type
$ (000)
Positions
In-House
Grant
Contract
Program Element Total'
None
None
None
None
UJ.
-------
, R 231
A. PROGRAM ELEMENT NUMBER; (Not yet assigned)
B. TITLE; Health Effects of Solid Waste Disposal (only one project)
PREPARED BY; J. F. Finklea DATE; 7 January 1972
C. PROGRAM JUSTIFICATION; Disposal and reuse of solid wastes involve large
public and private investments in research and development of new techniques
in capital investments, and in operating expenses. Disposal practices for
hazardous substances represent a special problem as does incineration of
sewage sludge and reuse of paper. Guidelines for performance and emissions
standards will be established by the Federal Government.
D. OBJECTIVES; To quantitate the health effects of existing solid waste
disposal practices utilizing human health and toxicologic studies and to
predict any adverse health effects resulting from advanced solid waste disposal
practices.
E. SCOPE; Epidemiologic and clinical studies in thirty to forty urban
communities would be included. Special attention would be focused upon
communities utilizing differing advanced waste disposal techniques including
newer municipal and sewage sludge incinerators.
F. RESULTS: Assurance of human safety of proposed advance solid waste
techniques would be possible by 1978 if adequate resources are allocated.
G. APPROACH: Human studies will utilize exposure surveillance and standardized
epidemiologic endpoints including pollutant burdens in tissues and alterations
in enzyme activity profiles. Toxicologic studies will utilize tissue culture
monolayers, isolated perfused organ systems and standardized toxicologic tests
in laboratory animals.
H. SUPPORTING CONTRACTS; Contracts with institutions and research organizations
would be complemented by intramural research efforts.
I. SPECIAL FACILITIES; Included would be exposure and holding facilities for
laboratory animals, analytical capability for trace elements, a mobile CLEVER
unit (CLJnical Environmental Epidemiologic Research laboratory) as well as
tissue culture ancT biochemistry laboratories.
J. INTERMEDIA RELATIONSHIPS: Air, water, pesticides and multimedia toxic
substances.
K. COORDINATION; With media and category programs and with ORM CHESS and Bio-
medical research programs.
L. UNRESOLVED POLICY ISSUES: None
-------
SUMMARY COMPARISON
($ million/MY)
Solid Waste
Optimum
Minimum
Adequate
FY 73
1 .8/30
1.2/20
FY 74
2.8/40
1.8/30
FY 75
3.5/60
2.8/40
FY76
3.9/60
3.5/60
FY 77
4.2/62
3.9/60
Current
-------
3 2.33
PROGRAM ELEMENT: (SOLID WASTES)
PROJECT: HUMAN AND TOXICOLOGIC STUDIES
TASK 1. Human health studies to assure the safety of solid wastes disposal
and reuse procedures.
A. PROGRAM JUSTIFICATION: Solid waste disposal and reuse practices should
benefit, not endanger public health. Newer disposal techniques including
sewage sludge incineration and solid waste reuse can increase human exposure
to toxic trace elements and other noxious substances with subsequent adverse
effects on human health. Performance and emission standards cannot be
established or evaluated without additional health intelligence.
B. OBJECTIVE; To quantitate human exposures, and evaluate the adverse health
effects resulting from toxic substances originating from sewage sludge and
municipal incinerators.
C. SCOPE: Population exposures to trace metals,microbes and selected toxic
substances will be monitored and these exposures will be related to the stan-
dardized epidemiologic endpoints utilized in the CHESS program element and to
the clinical physiologic responses described in the CLEVER project of the
Biomedical program element.
D. RESULTS: Health evaluation of solid waste disposal practices which are
now being advocated as substitutes for ocean dumping, open burning and land-
fills.
E. APPROACH: Two (minimally adequate program) or four (optimal program)
communities adjacent to facilities employing newer solid waste disposal
techniques would be studied. Air, soil, housedust, water and selected foods
could be monitored. Health indicators include changes in pollutant burdens
in human tissues attributable to trace elements, changes in metalloenzyme
functioning, alteration is susceptibility to infection and aggravation of
existing chronic diseases.
F. SUPPORTING CONTRACTS: Data collection would be carried out according
to Agency protocols by a suitable contractor as would analysis of tissues
collected for trace element studies.
G. SPECIAL FACILITIES: CLEVER mobile units will be acquired under the
Biomedical program element.
H. INTERMEDIA RELATIONSHIPS: Air, water, pesticides, toxic substances.
I. COORDINATION: With media and category programs and with CHESS and
Biomedical research program elements.
J. UNRESOLVED POLICY ISSUES: None.
-------
B 234
PROGRAM ELEMENT: (SOLID WASTES)
PROJECT: HUMAN AND TOXICOLOGIC STUDIES
TASK 2. Toxicologic studies to prevent dangerous human exposures to toxic
trace elements, microbial agents or noxious chemicals arising from
newer solid waste disposal techniques,
A. PROGRAM JUSTIFICATION; The health effects of newer solid waste disposal
techniques including reuse of paper, incineration of sewage sludge and pyrolysis
should be carefully evaluated to assure that their future widespread use will
not endanger public health.
B- OBJECTIVE: To assure that solid waste disposal techniques, thought feasible
on the bases of research and development efforts, do not increase the true
social cost of solid waste disposal or result in environmental exposures that
invalidate already promulgated air and water quality standards.
C. SCOPE: Trace element and synthetic organic compound exposures from sewage
sludge incineration will be predicted.and dose response studies undertaken in
relevant experimental laboratory models. Interactions with imoortant water
tants, air pollutants and pesticides will be evaluated.
D. RESULTS; Health intelligence necessary to establish performance and
emissions standards for newly developed solid waste disposal techniques.inclu-
ding the effects on cell replication, cell transformation, and the structural
and functional integrity of isolated perfused organ systems. In addition,
toxicologic studies of intact animals will ascertain interactive effects on
resistance to disease and psychophysiologic function.
E. APPROACH: Tissue culture mqnolayers of diploid cells will be exposed to
relevant doses of the pollutants in question. Changes in morphology, meta-
bolic integrity and occurrence of malignant transformation will be monitored.
Isolated perfused lung or liver will be utilized to elucidate further the
effects of pollutants. Impact on susceptibility to infection and metabolism
of intact animals will be assayed in rodents, dogs or primates.
F. SUPPORTING CONTRACTS: Psychophysiologic function in primates would be
studies under contract with existing Federal primate research centers. Trace
element and residue analyses would also be performed under contract.
G. SPECIAL FACILITIES: Animal exposure chambers, tissue culture, and bio-
chemistry laboratories, organ perfusion apparatus all of which are in existence
in EPA National Environmental Research Centers.
H. INTERMEDIA RELATIONSHIPS: Air, water, pesticides.
I. COORDINATION: With media and category programs.
J. UNRESOLVED POLICY ISSUES: None.
-------
B 235
OR&M
FY '73 Work Plans
PROGRAM ELEMENT NUMBER: Not Assigned TITLE: SOLID WASTE
WORK PLAN RECIPIENT: Not Assigned
PROGRAM ELEMENT MANAGER: Vauh A. Newi11
Resource Estimate
Task Present/MY Minimum Adequate/MY Optimum/MY
1 - 600/10 900/15
2 - 600/10 900/15
Total - 1200/20 1800/30
r
-------
B 23f.
RESOURCES STATUS SUMMARY
None Assigned
PROGRAM ELEMENT NUMBER
Health Effects Research - VJater
PROGRAM ELEMENT TITLE
EPA FY '73 Plan
Funding Type
In-House
Grants
Contracts
Program Element Total
$ (000) Positions
676.7* 3b.2
-
123.0
799.7* 3L.ii
*Position and Funds from Program Elements:
329300 Standards and Regulation
310210 Development of Bathing Beach Criteria that were located
in the Water Supply Programs Division.
310210 Municipal Water Use
310208 Marine Recreation Use that were in the Office of Research
and Monitoring.
-------
237
A. PROGRAM ELEMENT NUMBER:
B. TITLE: Health Effects Research - Water
PREPARED BY: L. J. McCabe DATE: January 14, M-7?
C. PROGRAM JUSTIFICATION: A most important consideration in the setting of
water quality standards should be human health. Little snecific research has
been done on the relationship of water quality and health, except for the
infectious diseases and drinkinq water. Chemical standards for drinking
water have been set by literature review of toxicolcqy research on other
problems and are not directly related to water n^oblens. Larae safety
factors must be used and possibly result in excessive pollution control
cost to meet standards.
D. OBJECTIVES: To provide a scientific base for water quality standards that
are set for the protection of human health.
E. SCOPE: Health effects research will be conducted using epidemioloqy and
toxicology techniques on the contaminants of water. Activities are focused
on three areas:
1. Research to establish and suooort safe drinkinq water
standards with 12 tasks,
2. Research to establish and support safe recreational water
quality standards with 4 tasks, and
3. Research on human health criteria for water quality standards
for fish, shellfish, and irriqation with 5 tasks.
F. RESULTS: The knowledge gained through this research will be made available
in a series of intramural and published reports which will provide the health
effects base for water quality standards. Studies will nrovide the control
efficiencies that must be met by the treatment technology research and indicate
areas where water supply practices must be improved.
G. APPROACH: Epidemioloqy and toxicology competence will be first developed
with in-house research and activities extended to provide coverage of more
situations with contracts. Grants will be used to stimulate research in areas
that need exploratory work.
H. SUPPORTING CONTRACTS: Contracts with non-government organizations will be
used to extend and support in-house research. PL 480 funds will be used when
suitable projects can be developed.
I. SPECIAL FACILITIES: The following snecial facilities are required: chemistry,
microbiology and toxicology laboratories; small animal facilities; and computer
availability for data analyses. These facilities are available at the NERC
(Cincinnati)'s central and remote laboratories.
-------
°. 23?
J. INTERMEDIA RELATIONSHIPS: Most of the water contaminants are also present
in other media and several of the research tasks specify work on this inter-
relationship to study contributions to total body burden.
K. COORDINATION: Liaison with Water Supply Programs Division, NCDC, NIEHS
and FDA and non-government scientists.
L. UNRESOLVED POLICY ISSUES: Federal authority to set drinking water standards
is not available excent for contaminants that relate to communicable disease.
-------
Optimum
Minimally Adequate
Current
Health Effects Research - Water.
Summary Cornparison ($ Mi 11 ion/MY)
FY 73
9.5/156
4.D/124
0.8/36
FY 74
io.5/iyo
6.0/12:8
0.8/38
FY 75
10.9/196
6.Z/134
0.9/40
FY 76
11. 3/1 at,
b.4/ I4U
0.9/42
FY 77
ll.b/1%
6.5/146
1 .0/44
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PROGRAM ELEMENT: Health Effects Research - Water
PROJECT A. Health Effects Research to Establish
and Support Safe Drinking Water Standards
TASK 1. Correlation of Water Quality and Chronic Disease ^orbl d :;,;
and Mortality.
A. PROGRAM JUSTIFICATION:
There are marked geographic differences in mortality. Some
.of these differences may be related to drinking water quality,
several studies have indicated a correlation of higher heart
disease mortality in soft water areas. Lithium content of water
has been related to mental hospital admissions. Toxic organic
chemicals have been isolated from drinking water. Cancer mor-
tality has been related to trace metal content of river sys-
tems. Most such studies have made use or avail,'b"ie vital sta-
tistics and drinking water quality based on at most a few
samples collected at the water plant. Death rates have been on
a county or state bases.
B. OBJECTIVES:
To provide a more systematic assessment of the health ef-
fects of water quality on man's health. This will require
more specific health and drinking water quality data.
C. SCOPE:
Drinking water quality data has been obtained for samples
collected at the consumer's tap for all water supplies in
8 metropolitan areas during the Community Water Supply
Survey. More specific data on morbidity and mortality will be
obtained on the populations served by the 751 water supplies
in these areas. Consideration will be given to imocrtant
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P 241
environmental and demographic covariates - ionizing radiation,
pesticide usage, ambient air quality, climate and urbaniza-
tion - age, sex, ethnic grouo, population density and
socioeconomic status.
Increased fundinn will allow the extension to other metro-
politan areas. Analyses and data gathered will be modified
as preliminary results indicate.
n. RESULTS:
When sufficient results are obtained, drinking water stand-
ards can be set to protect the public fron adverse health
effects. It is likely that this more broad aoproach to health
studies will lead to the development of more specific studies
of populations using unique waters using more sensitive mea-
surements of physiologcal effects.
E. APPROACH:
Sufficient in house research capability will be developed
to work out the details of the research approach and
evaluation techniques. Replication of developed research
approaches to additional water consumer populations; to
obtain statistically significant results bv contract.
F . SLIP PC RTING CONTRACTS:
Mith optimal fund ino, contracts will be used to extend
study to four metropolitan areas in each region per year.
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242
G. FACILITIES:
Facilities of NERC(Cincinnati) will be used for laboratroy
analyses for in house research. Computer capability
there will be used in the evaluation of in house and
contract research .
n. INTERMEDIA RELATIONSHIPS:
Other media areas, the important environmental covariates
and total body burden are derived from the multi-media
exposure.
I. COORDINATION:
Planning will be conducted with other EPA organizations
to assure that data on environmental covariates will be
gathered for study areas.
j. UNRESOLVED POLICY ISSUES:
None.
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B 243
PROGRAM ELEMENT: Health Effects Research - Water
PROJECT A. Health Effects Research to Establish
and Support Safe Drinking Water Standards
TASK 2. Health Effects of Water Nitrates
PROGRAM JUSTIFICATION:
Elevated levels of nitrate in ground water are well known
in many areas of the United States and there are many
reports of infantile methemoglobinemia associated with
this high nitrate water. Nitrate in surface waters
rarely reaches the high level sometimes found in ground
water but in certain areas, increases have been observed
and in a few instances the nitrate levels have exceeded,
for a short period, the recommended limit of 45 milligrams
per liter as nitrate. In highly agricultural areas where
immense quantities of nitrogenous fertilizers are used
nitrate in surface waters has been found to increase.
There have been no reported increases of nitrate in our
major surface waters (Great Lakes, major rivers) to levels
that can produce nitrate toxicity in humans but a few
examples of nitrate increases of public health signifi-
cance are found in small rivers and lakes. There is
reason to believe that if the present imbalance in the
nitrogen cycle continues, the increase of nitrate in
surface water will continue. Therefore, it is important
to determine any possible effects to human health which
might result from consumption of this water.
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B. OBJECTIVES:
To obtain information by epidemioloqic methods on the
relation of high nitrates in surface water to human
health. This would include the study of both infants
and adults for clinical and/or sub-clinical illness,
observing as many of the important variables as feasible
that might be important in the development of a health
problem. This data would be valuable in providing more
scientific information to support the present Drinkine
Water Standard for nitrate.
Ct SCOPE:
The project will involve the use of prospective epidemiology
and will study people in several different areas using
water for drinking obtained from surface water high in
nitrate. Both young infants and adults will be studied
and information will be obtained concerning diet, daily
consumption of water, present illness, recurrent or
chronic illness, use of medication, sex, race, and for
infants birth weight and formula preparation used. Bio-
chemical assays might include methemoglobin levels, NADH
methemoglobin reductase levels, and catalase activity
within the red blood cells. In a limited number of
persons, 24-hour urine samples will be collected for
analysis of the total nitrate for 24 hours as an indi-
cation of the total exposure to nitrate per day from
all sources; from this, one can estimate the relative
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3 245
importance of nitrate from water in relation to total
exposure.
D. RESULTS:
With adequate funding it should be possible to define
present health problems, if any, resulting from nitrate
in surface waters at their present level. If oroblems
exist it should be possible to determine the level of
exposure to nitrate/nitrite that will produce a health
hazard. Prospective epidemiologic studies of this type
should also give a better scientific basis for the pre-
sent drinking water standard for nitrate, and may
necessitate changes depending upon the results of these
studies .
E. APPROACH:
This researdiwill be accomplished by grants and contracts
to research organizations as well as by in house research
and evaluation.
F. SUPPORTING CONTRACTS:
Supporting contracts will be granted as necessary to
achieve the research goals. The extent of contracts
granted will depend upon our own in house research
capabi1iti es .
G. FACILITIES:
This research will involve a number of field studies
and base of operations could be in NERC(Cincinnati) ,
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B 246
at least in the early stages. Laboratory support will
be necessary for analysis of water samples and various
biochemical assays; this is also avilable in Cincinnati.
Statisticians and persons trained in computer programming
will also be essential in the evaluation of the data
collected.
H. INTERMEDIA RELATIONSHIP:
The contribution of nitrogen oxides from air pollution
will be considered, both as a contribution to the
water concentration and direct exposure to man.
I. COORDINATION:
Support in the development of various biochemical assays
used in the study may be necessary in the early stages.
This could be accomplished through in-house research
or through grants to other research organizations.
J. UNRESOLVED POLICY ISSUES:
None.
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PROGRAM ELEMENT: Health Effects Research - Water
PROJECT A. Health Effects Research to Establish
and Support Safe Drinking Water Standards
TASK 3. Water's contribution to Trace Metal Body Burden
A. PROGRAM JUSTIFICATION:
While certain trace elements at low concentrations have
been shown to be essential and beneficial in human metabo-
lism, the same elements at higher concentrations and others
at even low concentrations may cause detrimental effects.
Examples of trace elements that are generally considered
at present to be neither essential or beneficial and that
exhibit toxic properties at relatively low concentration
are: lead, mercury, cadmium, arsenic.
Trace elements enter the body via these means: (1) orally
and absorption through the gastrointestinal tract, (2)
inhalation through the respiratory system, (3) absorption
through skin and mucous and mucous membranes. Thus, the
three principal environmental factors involved in human
exposure to trace elements are air, water, food, and the
total body burden may represent a combination of these
exposures .
Epidemic! ogical and animal studies can provide data that will
allow the setting of restrictions on total intake of indi-
vidual or combinations of trace elements; however, to
accurately apply these data in terms of air and drinking
water quality standards, it is necessary to be able to
-------
predict what portion of the total body burden will be
contributed via each route of exposure.
A further complication in determining the contribution of
body burden from dri'.k.ing water is the fact that even in
large public water supplies the concentration of trace
metals can vary throughout the distribution system depend-
ing upon the characteristics of the water and tyne of
piping used. The water at a customer's tap is not necessarily
the same quality as delivered from the treatment plant.
Thus, for a given group of people in a large metropolitan
area, trace metal exposure from drinking water and air
may vary considerably. It is anticipated that trace ele-
ments in food products consumed by a given group of oeople
would be relatively constant.
B. OBJECTIVES:
The primary objective is to provide a basis for
partitioning the total body burden between the routes of
exposure for contaminants found in food, air, water. A
second objective is to define those factors that influence
trace metal pick-up in water distribution systems.
C. SCOPE:
Present: Drinking water samples were obtained from
150 CHESS Study families in three areas of
an SMSA. The samples were analyzed for 11
trace metals (copper, iron, manganese, zinc,
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B 249
cadmium, chromium, lead, silver, cobalt,
nickel, mercury). Results are to be ana-
lyzed with other health and environmental data
2 . Minimal1y Adequate:
Samples will be obtained from three other
sets of CHESS cities. Laboratory capa-
bility will be developed to obtain concen-
trations of four more metals. Factors
influencing the metal pick-up in the water
distribution systems will be defined.
3. Optimal :
Six additional sets of CHESS cities will
be studied. Monitors will be used to
analyze fluctuations in metal concentra-
tions in the drinking water so as to obtain
an integrated dose to the water user.
D. RESULTS:
With adequate funding it is expected that an assessment
can be made of the contribution of trace elements in the
drinking water to total body burden of trace elements.
In addition, factors influencing the pick-up of trace
metals in the distribution systems will be more clearly
defi ned.
E. APPROACH:
The program is to be accomplished primarily through ir-house
research and evaluation. If optimally funded grants and/or
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B 250
contracts to institutions and research organizations
will be also utilized.
F. SUPPORTING CONTRACTS:
Supporting work on determining trace metal burden on the
human body will be accomplished by CHESS. It is expected
that hair, blood, and urine samples are to be analyzed.
Supporting work on determining respiratory exposure to
trace metals will also be accomplished by the Inhalation
Toxicology Program. It is expected that data are to be
obtained on overall ambient air quality of the immediate
area, and the specific air quality near each household as
measured by fall out in the soil and household dust. In
addition, it is anticipated that FDA will be asked to
contribute data regarding trace metal exposure from food
products .
G. SPECIAL FACILITIES:
Instrumentation (ten-channel atomic absorption unit plus
additional equipment) and personnel will be requested.
Space at NERC(Cincinnati) appears to be adequate.
H. INTERMEDIA RELATIONSHIPS:
Because of the various route of exposure to trace elements,
it is essential that air and food medias be involved.
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B 251
I. COORDINATION:
Analyses conducted on water samples and samnle collection
must be coordinated with CHESS. Close cooperation is nec-
essary for meaningful results. In addition, close coordina^
tion must be maintained with FDA.
J. UNRESOLVED POLICY ISSUES:
While standards have been promulgated for drinking water,
no standards for ambient air quality have been set. Re-
sults will be useful in helping to determine these stand-
ards and the proportioning of exposure between media.
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PROGRAM ELEMENT: Health Effects Research - Water
PROJECT A. Health Effects Research to Establish
and Support Safe Drinking Water Standards
TASK k. Chemical characterization and toxicity studies of undefined
compounds in drinking water.
A. PROGRAM JUSTIFICATION;
All water supplies contain some organic and inorganic compounds that
may adversely affect the health of the consumer. The type, number,
and concentrations of these chemicals varies widely with geographic
location and with time. Although only a few agents have been
identified, it is firmly believed that the substances are derived
from municipal, industrial, and agricultural waste treatment.
Only sparse data h.aye been generated to assess the acute and chronic
toxicity of these chemicals in aggregate in drinking water, and
to determine which agent or group of agents may be responsible for
undesired effects upon health. At ambient levels, the chemicals
in drinking water are more likely to produce chronic rather than acute
illness. In some cases, chronic exposure may lead to malignancies,
malformed offspring, degenerative diseases, etc. It is necessary
to identify such potential toxicity through animal experimentation
and to identify the causative agents. Such information should
lead to control actions such as appropriate standards, proper
treatment techniques, and monitoring strategies. In addition,
the results of animal studies may indicate disease sentinels that
can be used in epidemiological investigations.
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B 253
B. OBJECTIVES;
1. To determine the acute and chronic toxicity of organic
chemicals in drinking water and of fractions of these chemicals;
2. To chemically identify the toxicants;
3. To set reasonable and appropriate standards for these materials
in drinking water.
C. SCOPE;
This research effort will consist of the following endeavors:
1. Selection of the chemical samples and of the water supplies;
2. Concentration and extraction of the organics;
3. Fingerprinting the organics;
k. Partitioning the bulk of organics;
5. Identifying the organics;
6. Screening the bulk organics, the partitions, and the identified
organics for toxicity;
7. Studying in depth the toxicity of those fractions that appear
to be highly toxic.
D., RESULTS:
With optimal support, it is expected that the toxicity of the
organics in drinking water will be substantially elucidated by 1982.
However, reduction in support to minimal levels will prolong the
realization of these objectives to approximately 1986. At the
present rate of progress, the goals may never be achieved because
the nature of the problem may change in greater proportion to the
progress.
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3 254
E. APPROACH:
The scope of this research demands a multi-disciplinary approach,
employing not only elaborate in-house research capabilities but
also the talents of educational institutions via grants and of
private industry via contracts.
F. SUPPORTING CONTRACTS;
FACILITIES:
Presently, laboratories and animal facilities exist at the NERC,
Cincinnati, Ohio, to serve as the focal point of this work. In
addition, a core staff of 2 toxicologists, 1 organic chemist,
1 technician, and 1 animal caretaker are capable of initiating
the main thrust of the research effort at present support levels.
Additional facilities and personnel are also available at the
Northeast and Gulf Coast Water Supply Laboratories.
G. SPECIAL FACILITIES: Sophisticated analytical laboratory
capability.
H. INTERMEDIA RELATIONSHIPS;
Some of the compounds identified may also be found in air and in
foods. Information about total environmental exposure will be
important. Toxicity data from the oral route can also be used to
set more precise standards in all media.
I. COORDINATION:
Coordination will be maintained with the air media and with the
Food and Drug Administration, and each will be informed about
toxic effects as well as about the chemicals identified. Close
cooperation and coordination will be maintained with the Water
Quality Laboratory, NERC, Cincinnati.
J. UNRESOLVED POLICY ISSUES: None
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PROGRAM ELEMENT: Health Effects Research - Water
PROJECT A. Health Effects Research to Establish and
Support Safe Drinking Water Standards
TASK 5. Definition of the toxic effects of known chemicals encountered
in drinking water, singly and in combination.
A. PROGRAM JUSTIFICATION:
A number of chemicals are known to occur in drinking water supplies.
As a minimum, it is necessary to know what the possible hazards to
health associated with these chemicals are. Additionally, definition
of the toxic effects of each of these chemicals, whether in the
current drinking water standards or not, in specific terms and in
sufficient depth is required to set standards at a level which
would preclude subclinical damage that might result in long-term,
non-specific disease states and also not be unnecessarily restrictive
to increase pollution control cost or preclude use of some water resources.
3. OBJECTIVES;
To set up test systems for the effects of toxic chemicals, in vivo.
which have general application and yet sufficient sophistication to
incorporate a maximum in sensitivity. Then apply these methods
systematically to the study of chemicals known to occur in drinking
water and thus derive the dose-response data required for setting
of drinking water standards.
C. SCOPE;
Emphasis will be placed upon systems known to be operative both in
the test animals and in man. Where possible, without sacrificing
.sensitivity and specificity, parameters will be chosen that show
some promise for use in human screening. Where this is not possible,
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B 256
and effects are noted with a specific chemical, an indirect indicator
of the effect will be sought. The only restriction on the type of
compound which will be studied is that It be likely to occur in
drinking water supplies. The number of compounds which will be
examined will be governed by budgetary and manpower considerations.
Testing of combinations will be predicated on the likelihood of
synergisms based on the known chemical and biological properties
of individual compounds.
D. RESULTS;
This project will produce data from which health effects of
particular chemicals may be included in consideration of drinking
water standards. In addition, the test systems derived from this
study should have general application to other chemicals in
drinking water as they become identified.
E. APPROACH:
Current activities:
1. A test system has been developed to detect j_n_ vivo effects of
chemicals on the central nervous system. This technique involves
measurement of changes in oxidized-reduced states of electron chain
Intermediates in brain tissue exposed to short periods of electrical
stimulation. Kinetic measurements of these changes allow conclusions
to be made about the competency of the tissue in energy metabolism
and the functional inputs into energy metabolism. Using properly
designed electrical parameters effects on the excitability of the
.tissues will also be assessed. The technique has proved to be
sensitive in evaluating the damage produced in methyl mercury exposed
rats in preliminary studies.
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B 257
2. Liver microsomal enzymes comprise an important adaptive mechanism
of animals (and man) to chemical insult. Chemicals which affect
this complex of enzymes are very likely to alter the animal's ability
to survive exposure to other chemicals. A test system has been
designed to determine the effects of chemicals on these enzymes,
in vivo. Effects of a chemical on this system will be correlated
with synergisrns and antagonisms encountered upon simultaneous
exposure of the intact animal to a second chemical whose metabolism
depends on these enzymes. From this data the ability of the system
to predict synergisms and antagonisms between compounds will be
evaluated. This system has also been tested in animals exposed
to methyl mercury with promising results.
Proposed activities:
3. Extension of 1) to other soft tissues by modification. It will
be necessary to either find a means of increasing the functional
activity of the tissues of interest (a counterpart to the electrical
stimulation used in 1) of it will be necessary to work with isolated
mitochondria from the tissues of animals exposed to toxic chemicals.
The former approach is preferable because it provides information
about the functional integrity of the tissue as a whole whereas the
latter approach necessarily confines itself to the question of the
competency of energy metabolism of the particular tissue.
if. Set up short-term toxicologic screening tests to determine
LDrn's, cumulative effects and target organs for chemicals found
in water for which this basic information is lacking. After the
compound has been screened in this system the necessity for further
testing in-house or for long term toxicity studies will be decided.
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B 258
5. Study matrix effects on the toxicity of environmental chemicals.
Determination of the toxic equivalencies of chemicals administered
via the oral route in water compared to various natural foodstuffs.
6. Study of interactions between the "essential" trace elements
and the "toxic" elements. This would involve investigation of the
mutual influences on their respective absorption, distribution,
metabolism and excretion of each pair of elements.
F,. SUPPORTING CONTRACTS;
Supporting contracts will be required for two purposes: 1. Definition
of long-term dose-response relationships for effects which have
been noted in shorter exposure periods through the in-house effort.
2. To determine the carcinogenic potential of compounds found
in water for which adequate data is not available.
G- SPECIAL FACILITIES: Sophisticated analytical laboratory capability.
H. INTERMEDIA RELATIONSHIPS; Air & land.
I. COORDINATION; EPA Media and Categorical Offices.
J. UNRESOLVED POLICY ISSUES: Hone
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R 259
PROGRAM ELEMENT: Health Effects Research - Water
PROJECT A. Health Effects Research to Establish and
Support Safe Drinking Water Standards
TASK 6. Epidemiology of Waterborne Disease
A. PROGRAM JUSTIFICATION: Waterborne diseases still occurs with about one
waterborne outbreak per month. Primary notification on these outbreaks from
state agencies is received by the National Center for Disease Control. Determi-
nation of the deficiencies in the water system that allowed the outbreak to
occur is necessary.
Enteric disease occurs throughout the country and it is not known what proportion
of these are waterborne. This needs to be determined so corrective action can
be taken.
,
B. OBJECTIVE: To assure that waterborne disease does not occur in outbreaks
or in the endemic situation because of deficiencies in water supplies.
C. SCOPE: Disease outbreaks are investigated and causes are analyzed so repeti-
tions may be prevented. Records of reported incidents are analyzed and assistance
provided to NCDC in investigations.
Patterns of occurence of enteric diseases are analyzed to determine the role of
water in the occurence of these diseases.
D. RESULTS: Data on outbreaks are published and recommendations made for im-
provements of water supplies to prevent re-occurence of outbreaks. Changes in
program are made to correct deficiencies in water supply practices to control
the occurence of waterborne diseases.
E. APPROACH: Epidemiological investigations and studies with laboratory back-
up are conducted in cooperation with NCDC and state agencies.
F. SUPPORTING CONTRACTS: Grants or contracts will be used to extend studies
to other areas when study procedures are developed in-house with optimal funding.
G. SPECIAL FACILITIES: Facilities of NERC (Cincinnati) will be used with
requested laboratory assistance from other EPA laboratories during outbreak
field investigations.
H. INTERMEDIA RELATIONSHIPS: With optimal funding, investigations will be
extended to include follow-up upon spills of toxic substances to see if human
disease has resulted.
I. COORDINATION: Cooperation is maintained with the Epidemiology Branch, NCDC.
J. UNRESOLVED POLICY ISSUES: None
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R. 260
PROGRAM ELEMENT: Health Effects Research - Water
PROJECT A. Health Effects Research to Establish and
Support Safe Drinking Water Standards
TASK 7. Occurrence and Fate of Viruses in Drinking Water.
A. PROGRAM JUSTIFICATION: The transmission of human enteric viruses by water
route is well documented by reports of waterborne outbreaks of infectious
hepatitis and poliomyelitis. In the past three years, there has been one
major hepatitis outbreak per year reported in the states. Also, circumstantial
evidence indicates that some community supplies in this country are probably
polluted with low levels of enteric viruses. The growing evidence in association
of these viruses with incidence of serious diseases intensifies the urgency of
need in resolving this problem. Polluted surface water is increasingly becoming
the initial source of our daily water intake. Sound judgments regarding the
role of water in the transmission of disease by viruses are virtually impossible
without critical knowledge of their survival pattern in the water environment.
The intent of this project is to provide definitive information on virus survival
so that a realistic indication of the health hazards of viruses in water may be
intelligently assessed.
C. OBJECTIVE; To determine the survival characteristics of human enteric
viruses in the various aqueous environments used and consumed by man.
C. SCOPE: Nationwide
D. RESULTS: Longitudinal survey of raw and finished water supplies from
selected communities for viral pollutants. Data from the study would help
assess:
1. The effectiveness of the methods used.
2. Whether these supplies are potentially hazardous to man and animals.
3. Justification for surveillance of more water supplies.
4. Shed new light on the effectiveness of water treatment processes and
the relationship between viral survival and their practices in the
field.
E. APPROACH: A longitudinal survey of raw and finished water supplies from
selected communities will be made. In addition, a study of the characteristics
of human enteric viruses in water will be made in order to elucidate the relative
survival capability of such viruses in aquatic environments used by man. This
would involve definition of both the intrinsic and extrinsic factors affecting
their survivals in these environments including their fate. Finally an assess-
ment will be made of the role of natural waters in the transmission of virus
diseases based on the knowledge obtained by the above studies. The viral
survival pattern would then be compared with that of the indicator bacteria.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: None
I!. INTERMEDIA RELATIONSHIPS: Some interface could be possible with water
pollution.
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R 261
! COORDINATION: Headquarters Water Supply Programs Division
0. UNRESOLVED POLICY ISSUES: None
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B 262
PROGRAM ELEMENT: Health Effects Research - Water
PROJECT A. Health Effects Research to Establish and
Support Safe Drinking Water Standards
TASK 8. Protocol Development for Testing of Chemicals and Products used
in Water Treatment, Storage, and Distribution.
A- PROGRAM JUSTIFICATION: New products or modification of old products are
proposed for use by water supplies. Use of these chemicals and materials
can make the drinking water a hazard to health. Water utilities look to their
state's water supply program for advice and state agencies to the Federal water
supply activity for advice on the safety of these products. Suitable information
must be supplied by manufacturers so that the safety of the products may be
evaluated. Testing protocols must be developed on what information must be
obtained.
B. OBJECTIVES: To assure that the chemicals and materials used in water
storage, treatment and distribution do not create a health hazard to the con-
sumer by assuring that adequate information is presented to the regulatory
agency to judge safety.
C. SCOPE: Currently, the coagulant aids are the only class of products that
are reviewed in a systematic way and a list of approved products maintained.
Other-classes of products, paints, disinfectants, corrosion control, and
algaecides are considered on an ad hoc bases when advice requested by state
and Federal agencies.
D. RESULTS: Protocol and test procedures will be developed to be used by
manufacturers.
E. APPROACH: In-house toxicology and chemistry research will be used to
develop and test protocols.
F. SUPPORTING CONTRACTS: Contracts will be used under optimal funding to
consider the health hazards of new product classes.
a. FACILITIES: Facilities of NERC (Cincinnati) will be used.
H. INTERMEDIA RELATIONSHIPS: Similar activities are conducted by pesticide
registration.
I. COORDINATION: Liaison will be maintained with similar EPA activities.
J- UNRESOLVED POLICY ISSUES: To date only the safety of products have been
considered, not the utility of the product for water treatment, storage and
distribution.
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B 263
PROGRAM ELEMENT: HEALTH EFFECTS RESEARCH - WATER
PROJECT A: HEALTH EFFECTS RESEARCH TO
ESTABLISH AND SUPPORT SAFE
DRINKING WATER STANDARDS
TASK 9. Explore Safety of Waste Water Reuse.
A. PROGRAM JUSTIFICATION: Increased water consumption and use in the United
States has resulted in progressively decreasing resources of good quality
water for human use for drinking and culinary purposes. Although reuse of
waste water has been praticed for many years for agricultural and other less
direct uses than drinking water, there is a need to consider this direct reuse
as an element in our water resource planning. Health consideration will be
paramount to this consideration. Drinking water standards have been established
considering that relatively unpolluted water was used as a source and cannot
be applied to the reuse situation.
B. OBJECTIVES: To provide health criteria for the establishment of drinking
water standards for reuse.
C. SCOPE: Chemical, microbiological and toxicological analyses will be conducted
on product water produced from selected waste water reuse plants and water plants
treating highly polluted water. Epidemiological studies will be conducted on
populations using water produced in suitable plants.
D. RESULTS: The output from this task will provide data for evaluating the
safety of waste water reuse and provide criteria for standards. Protocol will
be developed for more specific studies that will be conducted under contract with
optimal funding.
E. APPROACH: Epidemiological and toxicological research conducted at NERC
(Cincinnati) and other location of waste water renovation and reuse research.
F. SUPPORTING CONTRACTS: Contracts will be used to extend the scope of the
research with optimal funding.
G. SPECIAL FACILITIES: Chemical, microbiological and toxicological laboratories
and animal facilities.
H. INTERMEDIA RELATIONSHIPS: None
I. COORDINATION: With Program Element 328108 Waste Water Renovation & Reuse
J- UNRESOLVED POLICY ISSUES: Resolution of EPA policy on the promotion of
waste water reuse.
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B 264
PROGRAM ELEMENT: Health Effects Research - Water
PROJECT A. Health Effects Research to Establish
and Support Safe Drinking Water Standards
TASK 10. Isolation of the Infectious Hepatitis Virus from Water.
A. PROGRAM JUSTIFICATION: The-most important infectious disease associated
with water in this country is Infectious Hepatitis. Knowledge of the water-
borne nature of this disease has been obtained by the epidemiological and
clinical approach. The etiological agent has not been isolated and can not
be studied in the laboratory or pilot plant. Knowledge about susceptibility
of this virus to water treatment is needed.
B. OBJECTIVE: To obtain the agent of infectious hepatitis and develop
laboratory techniques for its study.
C* SCOPE: Much competent research has been done in this area without success.
Research is continuing by many investigators. A liaison and planning activity
will be conducted to see what should be done by EPA.
D. RESULT: A program for EPA will be developed.
E. APPROACH: Liaison and planning.
F. SUPPORTING CONTRACTS: Depends on outcome of planning.
G. SPECIAL FACILITIES: NERC (Cincinnati)
H. INTERMEDIA RELATIONSHIPS: Liaison with health and virus researchers in
this country and abroad.
I. COORDINATION: Liaison
J. UNRESOLVED POLICY ISSUES; To be explored in the planning.
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PROGRAM ELEMENT: Health Effects Research - Water
PROJECT A. Health Effects Research to Establish
and Support Safe Drinking Water Standards
TASK 11. Physiological Availability of Metals from Water.
A. PROGRAM JUSTIFICATION: It is possible that the concentration of a metal in
food, water, or air is not as important as the chemical state that makes a dif-
ference as to its availability.
t5- OBJECTIVE: To determine the relative availability of trace metals that occur
in foods, water and air.
C. SCOPE: This is a cooperative effort to provide support for the water trace
metal aspect of this multimedia project.
0. RESULTS: To provide scientific base for apportioning of total body burden
exposure from air, food, and water when setting standards.
E. APPROACH; Animal feeding studies will be conducted with trace metals incor-
porated in foods during their growth and production, drinking studies with trace
metals in water, and inhalation studies with trace metal air pollutants. Cadmium
and calcium would be used to develop a model.
F. SUPPORTING CONTRACTS: Preliminary studies will develop in-house techniques
and optimal funding would allow extension to other metals with contracts.
G. SPECIAL FACILITIES: NERC (Cincinnati)
H. INTERMEDIA RELATIONSHIPS: The essence of the task.
I. COORDINATION; Cooperation with Inhalation Toxicology Laboratory.
J. UNRESOLVED POLICY ISSUES: None
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B 266
PROGRAM ELEMENT: Health Effects Research - Water
PROJECT A. Health Effects Research to Establish
and Support Safe Drinking Water Standards
TASK 12. Patterns of Water Consumption.
A. PROGRAM JUSTIFICATION: The average amount and the variability of water
ingested is not known.This is needed to determine a dose of contaminant
from a concentration established in drinkinq water standards.
B. OBJECTIVES; To determine water consumption patterns and attitudes about
drinking water to aid in setting standards.
C. SCOPE: Study populations in different climatic conditions will be selected
and data obtained on types of water used and factors effecting use.
D. RESULTS: Provide scientific base for setting drinking water standards and
assist in epidemiological studies.
E. APPROACH: In-house capabilities will be developed and study extended by use
of contracts.
F. SUPPORTING CONTRACTS: Optimal funding will allow extension of studies by
contract.
S.: SPECIAL FACILITIES: NERC (Cincinnati)
H. INTERMEDIA RELATIONSHIPS: None
I. COORDINATION: With other EPA attitudinal studies.
J. UNRESOLVED POLICY ISSUES: None
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B 267
PROGRAM ELEMENT: Health Effects Research - Water
PROJECT A: Health Effects Research to Establish
and Support Safe Drinking Water Standards
TASK 13. Research Grants Program to Qualitatively Define Contribution of
Water Pollution to Acute and Chronic Diseases of Major Public
Health Significance.
A. PROGRAM JUSTIFICATION: Research on health effects in years past has been
confined to the infectious diseases. Some later rather exploratory research
has indicated that the drinking water quality may be related to heart disease
and cancer. There are marked geographic differences in morbidity and mortality
and to date causes of these differences have escaped explanation. As more
refined and sophisticated methods to measure trace elements and synthetic
organic compounds in human tissue are developed, increasing evidence has accrued
for the role of these environmental pollutants in disturbing biochemical and
physiologic pathways crucial to maintenance of good health. A systematic effort
to explore these leads is necessary to accomplish EPA's function of achieving
environmental quality for the protection of public health at the least possible
social cost. A water health research grants program responsive to LPA's
regulatory mission will focus the scientific talents of the nation on con-
trol programs designed to minimize the true social cost of environmental
pollution.
B. OBJECTIVES: To identify through a well planned, coordinated extramural
research grants program the contribution of water pollutants to important acute
and chronic diseases. The results will provide health indicators for population
studies of effects of water pollutants where quantitative relationships between
population exposed and disease endpoints can be determined to provide a scienti-
fic base for water standards and appropriate control actions.
C. SCOPE: There is no current grants program and the proposed minimal adequate
program would allow for 26 health grants to identify contribution of water pollu-
tants to the causes of the major health problems. The optimal program would pro-
vide an expansion of this long neglected area of research support.
D. RESULTS: The results of research supported by these grants will assure that
the significant health problems are considered in the development of water
quality standards.
E. APPROACH: Research grant applications will be solicited from competent,
proven or promising investigators; grant applications will be carefully reviewed
and coordinated to achieve goals of EPA's regulatory mission. Geographic spread
will be considered to provide assessment of effects of geochemical pollutants
that are regional problems.
-------
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES; None
H. INTERMEDIA RELATIONSHIPS; All media and categorical offices within EPA.
I. COORDINATION: HEW Agencies.
J. UNRESOLVED POLICY ISSUES: None
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B. 269
PROGRAM ELEMENT: Health Effects Research - Water
PROJECT B: Health effects research to establish and
support safe recreational water quality
standards.
TASK 1. Epidemiological Assessment of Recreational Water Safety.
A. PROGRAM JUSTIFICATION:
Much of the impetus for water pollution control is to make
our streams and lakes suitable for recreation. The National
Academy of Science found that there was little scientific
bases to set water quality criteria for recreation. Con-
siderable sums are spent for waste treatment to meet arbitrary
standards with no certainty that health is being adequately
protected or that the cost is justified. Health is a most
important consideration with water contact recreation with
positive and negative effects expected. Health is of lesser
consideration for other forms of recreation, except recrea-
tional shell fishing, but most recreational exoeriences are
related to water.
B. OBJECTIVES:
To provide a scientific base for recreational water quality
criteria so that health will be adequately protected but
water pollution control cost not excessive. A need to bal-
ance costs and benefits is likely.
c. SCOPE:
Microbiological techniques for assessing human pathogens are
being developed and will be used to measure water quality at
selected recreational sites. Most easily monitored indicator
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F 270
organisms, i.e. fecal col i form and ./hers, will also be mea-
sured. Persons recreating at chosen sites will be followed
for illness or infection development usina most sensitive
epidemiological techniques. Water quality and degree of
contact will be related to health indices.
D. RESULTS:
Recreational water quality standards will be developed.
E. APPROACH:
Techniques of study will be developed in house with some
contracts for development of measuring instruments of health.
When study protocol is developed, it will be extended to
other areas with contracts to cover greater ranges of water
quality, types of water resource developments, and types
of contact.
F. SUPPORTING CONTRACTS:
Four contracts will be used to extend study to obtain signi-
ficant results and range of water quality.
G. FACILITIES:
Facilities at NERC(Cincinnati) will be used during the de-
velopment stage and other EPA Microbiological laboratories
when the study is extended to obtain coverage of more
climactic and hydrologic conditions.
H. INTERMEDIA RELATIONSHIPS:
Food expo'sures could be important for the infectious and
cooperation in study design will be sought with NCDC and
FDA. Other media are unlikely related to infectious diseases
but air pollution will be considered with eye irritation
syndrome. The Department of Interior's Bureau of Outdoor
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D 271
Recreation will be consulted.
I. COORDINATION:
Study will be coordinated with CHESS and other EPA copulation
studies if suitable recreational areas are nearby. These
study subjects could be included in other population samples or
at least other populations would provide base line health
indi ces .
J. UNRESOLVED POLICY ISSUES:
Swimming pools would be one extreme of quality and could be
included in EPA responsibility.
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3 272
PROGRAM ELEMENT: Health Effects Research - Water
PROJECT B': Health effects research to establish and
support safe recreational water quality
standards .
TASK 2. Quantisation of population exposed to contaminated
recreational waters.
A. PROGRAM JUSTIFICATION:
Water based recreation is increasing rapidly in this country,
but in some areas of development, this wholesome activity is
detered by the quality of water available. In many areas this
concern for the quality of the water is based on hearsay evi-
dence; the relationship between eutrophication and Quality of
water for body contact recreation is confusing.
R. OBJECTIVES:
To provide a systematic assessment of the quality of v»ater used
for recreation and recognized health problems. This will aid in
putting the problem in perspective with other environmental
health problems.
C. SCOPE:
Data will be obtained from state and local agencies on beach
and other recreational water surveillance. In suitable areas
with suitable infectious disease reporting and hospital records,
surveys will be conducted of records to obtain histories of
water based recreation.
D. RESULTS:
Review of available data will allow for selection of suitable
areas for more intensive study of the relationship of recrea-
tional water quality and health. The scope of the problem will
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R 273
be defined.
E. APPROACH:
Original activity will be in house research but grants wi11
be used to obtain coverage around the country with differing
types of recreation.
F. SUPPORTING CONTRACTS:
When suitable problem areas are found, contracts will be used
to obtain more specific data on recreation water quality and
reported disease by local health agencies.
G. FACILITIES:
Facilities of NERC (Cincinnati) will be used.
H. INTERMEDIA RELATIONSHIPS:
Other media population surveys will yield background data and
will be considered as primary sources of this data if located
in suitable areas. Results of etiologic study of amebic men-
ingoencephalitis will be pertinent to this study.
I. COORDINATION:
As mentioned in J.
J. UNRESOLVED POLICY ISSUES:
None.
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8 274
PROGRAM ELEMENT: Health Effects Research - Water
PROJECT B. Health effects research to establish and
support safe recreational water quality
standards.
TASK 3. Bacteriology of Recreational Water.
A. PROGRAM JUSTIFICATION: One of the major forces behind the drive to control
water pollution is the demand for clean water for recreation. Public health
officials have worked_for years to maintain certain bacterial quality standards
at bathing beaches. These standards are commonly based on the counts of the
coliform group, v/atch are also used to assess the quality of drinking
water. It is absolutely essential that a sound basis be established for bacte-
rial quality standards for recreational waters. Research is badly needed in
order to correlate currently used or new indicator organisms with waterborne
disease. In addition, there is a need to determine the relationship between
disease in swimmers at salt water beaches and the sanitary quality of the
bathing water as measured by any of several possible systems.
B. OBJECTIVES: To test the feasibility of a study to determine the relationships
between the incidence of disease in swimmers at salt water beaches and the sani-
tary quality of the bathing water as measured by any of several possible indicator
systems. To determine whether test beaches tentatively selected for the study
are suitable as regards sanitary pollution levels. To evaluate and as required
modify methods for the enumeration of possible indicators of sanitary pollution
and of selected pathogenic micro-organisms at the salt water beaches. To
develop guidelines for the sanitary control of bathing beaches. To develop
criteria for assessing the quality of water at bathing beaches.
C. SCOPE: Nationwide
D. RESULTS: Data will be obtained which will allow for the development of
bathing beach criteria for fresh and marine waters and studies of the correlation
of currently used or new indicator organisms with the disease incidence in swim-
mers. The establishment of standards to protect the health of swimmers.
E. APPROACH: Sampling for a variety of indicator organisms will be conducted
at the tentative test beaches. These data will be used in selecting the test
beaches. Laboratory and field studies with samples collected from the tentative
test beaches will be used to evaluate the microbiology assay methods for the
study; these include membrane filter methods for the enumeration of fecal
streptococci, staphylococcus aureus, vibrio paraphemolytices and pseudoreonas
aeruginosa. Membrane filter procedures for total and fecal coliforms, aeromonas
hydrophiTTa and salmonella will also be evaluated as they become available.
Basic approaches including contract work will be used to develop procedures for
determining illness among swimmers. The present study involving marine bathing
waters will be extended to studies of fresh water bathing areas.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: None
-------
275
H. INTERMEDIA RELATIONSHIPS: Considerable interface with water pollution will
be involved.
I. COORDINATION: Headquarters Water Supply Programs Division.
J. UNRESOLVED POLICY ISSUES: None
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B 276
PROGRAM ELEMENT: Health Effects Research - Water
PROJECT B. Health Effects Research to Establish and
Support Safe Recreational Water Quality
Standards.
TASK 4. Etiological Study of the Agent of Amebic Meningoencephalitis
A. PROGRAM JUSTIFICATION: This is a universally fatal disease that has been
associated with water-based recreation. Cases have not been frequent but have
occurred in Florida, Georgia, Virginia, and California. Occurence of a case
causes great concern and interferes with the enjoyment of water contact recreation.
Why cases occur in some situations and not others is not known.
B. OBJECTIVE: Develop an understanding of the occurence of the disease is
necessary to develop control techniques.
C. SCOPE: The etiologic agent of the disease is the ameba, Naegleria gruberi,
the free living form of this ameba is ubiquitous. Techniques have been developed
to differentiate the pathogenic strain from the free living form. The occurrence
of the pathogenic form will be determined.
D. RESULTS; Control procedures will be developed.
E. APPROACH; Cooperative research is conducted with other investigators. Studies
will be. carried to the field and the pathogenic strain sought in lakes. Conditions
effecting occurence of the pathogenic strain will be determined.
F. SUPPORTING CONTRACTS: Grants will be used to support cooperating investigators.
3. SPECIAL FACILITIES; NERC (Cincinnati)
H. INTERMEDIA RELATIONSHIPS; None
lm COORDINATION; With limnological studies of NERC (Corvalis) and NCDC disease
investigators.
J. UNRESOLVED POLICY ISSUES: None
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B 277
PROGRAM ELEMENT: HEALTH EFFECTS RESEARCH - WATER
PROJECT C: RESEARCH ON HUMAN HEALTH CRITERIA FOR
WATER QUALITY STANDARDS FOR FISH, SHELL-
FISH AND IRRIGATION WATER.
TASK 1. Assessment of Problems Associated with Food Produced with Polluted Water.
A. PROGRAM JUSTIFICATION: Foods produced with polluted water have caused human
illness from contamination with viruses, bacterial and hiqher micro-organisms.
Criteria on human health effects have not been developed to aid in the establish-
ment of water quality standards. The lack of information is particularly acute
on chemical contaminants.
B. OBJECTIVES: To provide a systematic survey of known human health effects
from food produced with polluted water. An assessment will be made of needed
research on this problem.
C. SCOPE: Literature will be reviewed that touches on this problem and reports
of disease reviewed. Populations exoosed to such food will be identified.
Particularly interest will be focused on food produced using recycled waste
water.
D. RESULTS: The output from this study will determine if a significant problem
exists and, if so, lead to design the need follow-up research.
E. APPROACH: In-house review of available data, with optimal funding, grants
would be provided for exploratory research.
F. SUPPORTING CONTRACTS; None
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIPS: Pesticide and radiation pollution will be considered.
I. COORDINATION: With USDA, FDA ahd Fish and Wildlife
J. UNRESOLVED POLICY ISSUES: None
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B 278
PROGRAM ELEMENT: HEALTH EFFECTS RESEARCH - WATER
PROJECT C: RESEARCH ON HUMAN HEALTH CRITERIA FOR
WATER QUALITY STANDARDS FOR FISH, SHELL-
FISH AND IRRIGATION WATER.
TASK 2. Accumulation of Contaminants by Fish and Shellfish.
A. PROGRAM JUSTIFICATION: Shellfish accumulate toxic chemicals from their
environment to such an extent that they may be unfit for human consumption.
Yet, at the same time, certain levels of trace metals are needed in the human
diet and shellfish are cited in dietary publications as good sources of certain
elements. The mercury contamination of fish is a recent example of this problem.
B. OBJECTIVES: Provide data on accumulation of contaminants from the growing
water to fish and shellfish. This will allow the translation of food limits
set to protect man to the growing water standards.
C. SCOPE: Fish and shellfish will be collected from growing waters of known
quality and contamination in the flesh determined. Accumulation studies will
be conducted by placing different species of fish and shellfish in tanks of
control quality water.
D. RESULTS: Data derived will be used as criteria in the setting of water
quality standards.
E. APPROACH: Continue in-house research at the Northwest and Gulfcoast Water
Hygiene Laboratories.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: Wet Laboratories at the NERC (Cincinnati) remote
laboratories.
H. INTERMEDIA RELATIONSHIPS: Pesticides, Radiation and Air Contaminant rain-out
and run-off.
I. COORDINATION; Close coordination will be maintained with Program Elements
310206 and 310209 that deal with fishes and other life and wildlife. There
the interest is in the accumulation of pollutants that are hazardous to fish
and wildlife and the accumulation constants will be applicable to this task.
J. UNRESOLVED POLICY ISSUES: FDA has established few limits for contaminants
in fish and shellfish.
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3 279
PROGRAM ELEMENT: HEALTH EFFECTS RESEARCH - WATER
PROJECT C: RESEARCH ON HUMAN HEALTH CRITERIA FOR
WATER QUALITY STANDARDS FOR FISH, SHELL-
FISH AND IRRIGATION WATER.
TASK 3. Toxicology of Accumulated Contaminants in Fish and Shellfish to
Test Animals.
A. PROGRAM JUSTIFICATION: Shellfish accumulate toxic chemicals from their
environment to such an extent that they may be unfit for human consumption.
Yet, at the same time, certain levels of trace metals are needed in the human
diet and shellfish are cited in dietary publications as good sources of certain
elements. The mercury contamination of fish is a recent example of this problem.
Many seafoods have high levels of trace metals but these are of the organic
form and do not exhibit the toxicity of the metallic forms.
B. OBJECTIVES: Provide data on the mammalian toxicity of accumulated con-
taminants in fish and shellfish.
C. SCOPE: Fish and shellfish that have been grown in polluted water or have
been used in accumulation studies (Task C2) will be fed to mice and rats to
test the toxicity of the accumulated contaminant.
D. RESULTS: Data derived will be used as criteria in the setting of water
quality standards.
E. APPROACH: Continue in-house research at the Northeast Water Hygiene
Laboratory.
F. SUPPORTING CONTRACT: None
G. SPECIAL FACILITIES: Wet laboratory, toxicity laboratory and animal quarters
at the NERC (Cincinnati) remote laboratory.
H. INTERMEDIA RELATIONSHIPS: The physiological availability of metals will be
determined as an adjunct to task A-ll.
I. COORDINATION; None
J. UNRESOLVED POLICY ISSUES: FDA could be expected to do this type of research
and the results used by EPA as criteria for water standards.
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B 280
PROGRAM ELEMENT: HEALTH EFFECTS RESEARCH - WATER
PROJECT C: RESEARCH ON HUMAN HEALTH CRITERIA FOR
WATER QUALITY STANDARDS FOR FISH, SHELL-
FISH AND IRRIGATION WATER.
TASK 4. Accumulation and Survival of Contaminants in Irrigated Crops.
A. PROGRAM JUSTIFICATION: Microbiological and chemicals are present in polluted
irrigation water. In some cases there is damage to the crop but the human health
effects that may result are of concern. Some research has been done on bacterio-
logical contaminants but little data is available on chemical contaminants,
especially organic chemicals.
B. OBJECTIVES: Provide data on accumulation of contaminants from irrigation
water to crops. This will allow the translation of food limits set to protect
man to the irrigation water standards.
C. SCOPE: Literature will be reviewed that touches on this problem.
D. RESULTS: The output from this study will determine if research is needed
and, if so, develop its design.
E. APPROACH: In-house review of available data with optimal funding grants
would be provided for exploratory research.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES; None
H. INTERMEDIA RELATIONSHIPS: Air pollutants have been known to concentrate in
crops'! Pesticides and radiation are two of these contaminants.
I. COORDINATION: With USDA and FDA. Close coordination will be maintained
with Program Element 310204 - Agricultural Water Uses.
J. UNRESOLVED POLICY ISSUES: FDA has authority to set limits of contaminants
in foods.
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B 281
PROGRAM ELEMENT: HEALTH EFFECTS RESEARCH - WATER
PROJECT C: RESEARCH ON HUMAN HEALTH CRITERIA FOR
WATER QUALITY STANDARDS FOR FISH, SHELL-
FISH AND IRRIGATION WATER.
TASK 5. Toxicology of Contaminants in or on Crops.
A. PROGRAM JUSTIFICATION: Microbiological and chemicals are present in polluted
irrigation water. In some cases there is damage to the crop but the human health
effects that may result are of concern. Some research has been done on bacterio-
logical contaminants but little data is available on chemical contaminants,
especially organic chemicals.
B. OBJECTIVES: Provide data on mammalian toxicity of accumulated contaminants
in meat and vegetable crops.
C. SCOPE: Literature will be reviewed that touches on this problem.
D. RESULTS: The output from this study will determine if research is needed
and, if so, develop its design.
E. APPROACH: In-house review of available data, with optimal funding, grants
would be provided for exploratory research.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES; None
H. INTERMEDIA RELATIONSHIPS; . The physiological availability of metals from
food will be determined as an adjunct to task.A-11.
I. COORDINATION; None
J. UNRESOLVED POLICY ISSUES: FDA could be expected to do this type of research
and the results used by EPA as criteria for water standards.
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OR&M
FY '73 Work Plans
TITLE: Health Effects Research - Water
RESOURCE ESTIMATE
Task
Project A
1A
2A
3A
4A Chem.
Tox.
5A
6A
7A
8A
9A
10A
11A
12A
ISA
TOTAL
Present/MY
- Health effects
drinking water
30/1.8
18/1.0
6/0.4
242.1/5.6
4.3/0.4
49.7/3.4
25/1.1
109.2/7.6
16/1.0
0/0.0
0/0.0
0/0.0
0/0.0
0/0.0
500.3/22.3
Min. Adequate/MY
research to establish
standards.
250/10
250/10
140/4
210/7
300/5
160/9
140/7
200/8
270/3
280/4
20/1
60/3
40/2
1500/8
3820/81
Optimum/MY
and support safe
1350/14
250/10
300/4
600/10
600/10
400/15
497/12
200/8
270/3
500/6 [1500]*
20/1
180/4
160/3
2250/10
7577/110
*[1500] Higher funding necessary if it is decided that EPA policy is
to promote the reuse of waste water for drinking.
oo
ro
TO
-------
OR&M
FY '73 WORK PLANS
TITLE: HEALTH EFFECTS RESEARCH - WATER
RESOURCE ESTIMATE
Task Present/MY Min. Adequate/MY Optimum/MY
Project B - Health effects research to establish and support safe recreational
extra quality standards.
IB 0/0.0 340/11 460/13
2B 0/0.0 100/3 500/4
3B 142/5.0 240/10 240/10
4B 36/1.7 50/3 100/3
TOTAL 178/6.7 730/27 1300/30
DO
ro
00
CO
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OR&M
FY '73 WORK PLANS
TITLE: HEALTH EFFECTS RESEARCH - WATER
RESOURCE ESTIMATE
Task Present/MY Min. Adequate/MY Optimum/MY
Project C - Health Effects Research to establish and support water quality
standards that will assure fish, shellfish and plant products that
are safe for human consumption.
1C 0/0.0 CO/3.0 180/3.0
2C 62.8/2.9 80/4.0 80/4
3C 58.6/3.3 140/7 140/7
4C 0/0.0 20/1.0 70/1
5C 0/0.0 20/1.0 70/1
TOTAL 121.4/6.2 320/16 540/16
ro
oo
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B 285
RESOURCES STATUS SUMMARY
(None Assigned)
PROGRAM ELEMENT NUMBER
Toxic Substances
PROGRAM ELEMENT TITLE
EPA FY '73 Plan
Funding Type
$ (000)
Positions
In-House
Grant
Contract
None
None
Program Element Total
None
None
T6)l/C
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B 286
A. PROGRAM ELEMENT NUMBER:
B. TITLE: Health Effects of Multimedia Toxic Substances
PREPARED BY: Douglas I. Hammer DATE: January 8, 1972
C. PROGRAM JUSTIFICATION: Environmental chemicals are constituents of
virtually everything we use. The manufacture and consumption of this
large array of chemicals creates multiple problems with waste discharge
and disposal. Chemicals safe in original form may thus undergo unde-
sirable changes during the cycle of use, disposal and return to the
environment. The upshot is that human exposure is universal, complex,
rapidly changing and often unpredictable. Chemicals which themselves
are not readily taken up by humans can interact with known air, water.
and food hazards to become more readily available and absorbed into
body tissues. Health effects resulting from these exposures are often
subtle, delayed and costly.
D. OBJECTIVE: To assess the human health effects of exposure to multi-
media toxic substances and to confirm the human safety of new and old
chemical compounds.
E. SCOPE: The work will involve clinical laboratory, toxicologic and
epidemiologic studies conducted by the Federal government, universi-
ties and private institutions.
F. RESULTS: With adequate funding, baseline data on a hazard awareness,
and the confirmation of human safety can be available by 1978.
G. APPROACH: A broad multidisciplinary approach involving all sectors
of society will be .utilized.
H. SUPPORTING CONTRACTS: A number of supporting contracts dealing
with information systems, hazard identification, exposure surveillance,
tissue monitoring and effects assessment have been discussed in other
tasks in this program element.
I. SPECIAL FACILITIES: Discussed in task statements.
J. INTERMEDIA RELATIONSHIPS: With all media and category programs.
K. COORDINATION: Coordination will be required with other ORM health
effects research program elements and with the research programs of
other agencies including DOD, NIEHS, NIOSH, NSF and AEC.
L. UNRESOLVED POLICY ISSUES: None.
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SUMMARY COMPARISON
($ Milllon/MY)
Toxic
Substances
Optimum
Minimum
Current
FY 73
16.7/203
11.2/135
FY 74
17.8/205
12.0/135
FY 75
19.1/205
12.8/140
FY 76
18.5/200
13.7/140
FY 77
18.0/190
13.5/140
CO
l\5
OO
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B 288
PROGRAM ELEMENT: Health Effects of Multimedia Toxic Substances
PROJECT A - Hazard Awareness
TASK 1. Establish a Comprehensive Environmental Information System Which Will
Include Data Relating to Toxicity, Usage and Human Exposure
A. PROGRAM JUSTIFICATION: Over 10,000 environmental chemicals including
metallic substances and synthetic organic compounds are commercially utilized
with 300 to 500 added yearly. Available information on toxicity, usage and
human exposure should be systematized to permit optimal utilization of extent
data and rapid identification of information gaps.
B. OBJECTIVE; To establish a rapid and flexible comprehensive environmental
information system which will include data relating to toxicity, usage and
human exposure effects of multimedia toxic substances.
C. SCOPE: Old and new environmental chemicals must be identified. Systems
must be developed to abstract, store and permit easy access to all available
information on these environmental chemicals. Information must be revised
and updated as new data become available.
D. RESULTS: A dynamic and useful environmental chemical information system
which can be utilized by qualified persons of both the United States and
foreign countries by 1977.
E. APPROACH; Present public and private information will be reviewed,
coordinated and systematized.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES; Storage and Retrieval apparatus and space
H. INTERMEDIA RELATIONSHIPS; Relates to all media
I. COORDINATION; With media and category programs
J. UNRESOLVED POLICY ISSUES; Relationships of the National Library of Medicine,
the Library of Congress and similar federal and non-federal institutions to the
EPA Environmental Chemical Information Center.
r
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B 289
PROGRAM ELEMENT: Health Effects of Multimedia Toxic Substances
PROJECT A - Hazard Awareness
TASK 2. Sponsor Briefings and Training Courses for Research and Development
Scientists to Foster a Free Flow of Timely Information
A. PROGRAM JUSTIFICATION: Available information regarding the health effects
of multimedia toxic substances must be disseminated to all scientists who are
responsible for research and development. This will optimize research and
planning and thus reduce the time needed to answer scientific and economic
questions.
B. OBJECTIVE: To provide a rapid flow of timely information to scientists
by means of briefings and training courses.
C. SCOPE: A broad variety of audiovisual teaching techniques will be utilized
in briefings and training courses.
D. RESULTS: Briefings, training courses, programmed texts and tapes for
self-instruction, slides and motion pictures pertaining to information on
toxic substances by 1976.
E. APPROACH; Use of all audiovisual techniques and traditional techniques
as they are appropriate.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES; Audiovisual and briefing facilities and equipment.
H. INTERMEDIA RELATIONSHIPS; All media
I. COORDINATION; With media and category programs
J. UNRESOLVED POLICY ISSUES: None
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B 290
PROGRAM ELEMENT: Health Effects of Multimedia Toxic Substances
PROJECT A - Hazard Awareness
TASK 3. Develop Rapid Relevant Standardized in vivo and in vitro Screening
Methods to Serve as Models for Industry
A. PROGRAM JUSTIFICATION: The National Center for Toxicological Research
will only be able to study four (4) major chemicals yearly. Rapid relevant
tests are necessary so industry and other laboratories can assist in screening
toxic substances.
B. OBJECTIVE; To develop rapid screening tests for toxic substances.
C. SCOPE; Several in vivo and in vitro techniques will be applied and
studied to determine optimal screening procedures for different classes of
chemicals.
D. RESULTS: Rapid standardized screening tests with protocols available to
industry by 1978.
E. APPROACH; Cell transformation in tissue monolayers; cytogenetic changes
in rodents and other species; appropriate metabolic indicators relating to
cell protein metabolism and cell growth regulators; malignant transformation
in tissue monolayers with the physical agents alone and with oncogem'c viruses
added.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: None
H. INTERMEDIA RELATIONSHIPS; All media
I. COORDINATION: With media and category programs
J. UNRESOLVED POLICY ISSUES: None
r
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B 291
PROGRAM ELEMENT: HEALTH EFFECTS OF MULTIMEDIA TOXIC SUBSTANCES
PROJECT A - HAZARD AWARENESS
TASK 4. Identify new and previously unrecognized human exposures to
toxic substances.
A. PROGRAM JUSTIFICATION: Protection of the general population from
new chemical dangers is mandatory. A fail-safe warning mechanism is
necessary and will require massive cooperative efforts between govern-
ment, universities and industry. This must be coupled to research pro-
grams to develop control technology to interrupt human exposure pathways
for toxic materials that may already be present in the environment.
B. OBJECTIVE: To develop methods of identifying new and previously
unrecognized toxic substance exposures.
C. SCOPE: Fail-safe mechanisms must be developed and coupled to re-
search programs that develop control technology to interrupt human
exposure pathways for toxic materials already present in the environment.
Special attention must be given to the routes by which toxic chemicals
may potentially contact man; these include, among others, fuel additives,
plastics, textiles, elastomers, cleaning agents and by-products from
all industrial processes and waste disposal systems.
D. RESULTS: Prototype identification mechanisms to be operative by
1975 with adequate identification by 1978.
E. APPROACH; Government, university and industrial cooperation to
share research information; development of control technology to
interrupt or minimize human exposures; delineation of the routes of
contact to man; development and application of methodology to monitor
environmental media; utilization of computerized data storage and re-
trieval systems.
F. SUPPORTING CONTRACTS; None.
G. SPECIAL FACILITIES; None
H. INTERMEDIA RELATIONSHIPS: All media.
I. COORDINATION: With media and categorical programs.
J. UNRESOLVED POLICY ISSUES: Monitoring and emissions of industrial
faciTi ties'.
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8 2.P2
PROGRAM ELEMENT: HEALTH EFFECTS OF MULTIMEDIA TOXIC SUBSTANCES
PROJECT A - HAZARD AWARENESS
TASK 5. Assure that recycling and reuse of solid wastes and water does
not unduly increase human exposure to toxic substances.
A. PROGRAM JUSTIFICATION: Chemicals in our environment may be altered
or concentrated by reuse and recycling causing unexpected non-occupational
human exposures. Human pollutant burden research is the most sensitive
available index of environmental alterations due to reuse and recycling.
B. OBJECTIVE: To measure human toxic substance exposure due to reuse
and recycling by means of human, animal and plant pollutant burdens.
C. SCOPE: Human tissue burdens as well as sensitive animal and plant
sentinels will be utilized as indicators of increasing toxic substance
exposures.
D. RESULTS: A flexible, broad and practical set of pollutant burden
indicators to assess increases in human toxic substance exposure by 1977.
E. APPROACH; Human tissue burdens in living and autopsy populations
will be measured; pollutant burdens in urban flora and fauna can be
utilized as indicators of human exposure; humans, flora and fauna
around reuse and recycling point sources will be studied.
F. SUPPORTING CONTRACTS: None.
G. SPECIAL FACILITIES: None.
H. INTERMEDIA RELATIONSHIPS: All media.
I. COORDINATION: With media and category programs.
J. UNRESOLVED POLICY ISSUES: None.
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B 293
PROGRAM ELEMENT: HEALTH EFFECTS OF MULTIMEDIA TOXIC
SUBSTANCES
PROJECT B - CONFIRMATION OF HUMAN SAFETY
TASK 1. Establish a biochemical and cytological alarm system utilizing sensitive
indicators of adverse health effects in vulnerable populations.
A. PROGRAM JUSTIFICATION: Biochemical and cytological effects of a number of
environmental chemicals are already known. Our qualitative and quantitative
knowledge of pollutant effects on different organs and subcellular fractions
over exposdre-dose gradients must be enlarged. Highly vulnerable populations
would include newborns, pregnant women, the aged, patients with various
diseases and people who are genetically vulnerable. Effects of individual
toxic substances must be carefully distinguished to accurately assess their
relative toxicities. Such research would permit classification of compounds
based on their relative potential.
B. OBJECTIVE: To systematically study sensitive indices of risk; to enlarge
our knowledge of pollutant effects upon different organs and subcellular fractions
over exposure-dose gradients; to adapt sensitive biochemical and cytological
response indicators in vulnerable populations.
C. SCOPE: Laboratory research efforts will be coupled to population field testing
utilizing a full range of analytic tools and experimental systems.
D. RESULTS: With adequate finding, preliminary field testing of sensitive bio-
chemical and cytological alarm systems would be operational by 1978.
E. APPROACH: Development of biochemical and cytological assay systems for
cancer, mutagenesis and teratogenesis, improvement of present biochemical and
cytological assay systems for respiratory diseases, immune competence, reproductive
potential, endocrine performance, gastrointestinal and cardiovascular function.
More sensitive and specific assay systems will be developed. Assay systems
to discriminate among individual chemicals will be developed.
F. SUPPORTING CONTRACTOR; None.
G. SPECIAL FACILITIES: None.
H. INTERMEDIA RELATIONSHIPS: Air, Water, Pesticides, Radiation.
I. COORDINATION: With media and categorical programs.
J. UNRESOLVED POLICY ISSUES: None.
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294
PROGRAM ELEMENT: HEALTH EFFECTS OF MULTIMEDIA TOXIC SUBSTANCES
PROJECT B - Confirmation of Human Safety
TASK 2. Surveillance of specific relevant morbidity and mortality
patterns and trends in exceptionally exposed groups and the
general population.
A. PROGRAM JUSTIFICATION: Traditional epidemiologic indices have related
environmental exposure to subsequent human effects. Occupational and
paraoccupational groups are exceptionally exposed to both common and rare
metal and synthetic organic pollutants. Clinical epidemiology can use
single cases of rare or novel diseases and unusual disease clusters as
guides to the late effects of new pollutants. Morbidity and mortality
rates of diseases likely to be induced or aggravated by environmental
chemicals can also suggest environmental effects.
B. OBJECTIVE: To survey specific relevant morbidity patterns and
trends in exceptionally exposed groups and the general population which
may indicate effects of toxic substance exposure.
C. SCOPE: Both population and clinical epidemiologic techniques will
be used in assessing morbidity and mortality. Both extremely high
exposures and uncommon exposures will be sought.
D. RESULTS: Identification of high and uncommonly exposed cohorts can
be accomplished by 1976 with adequate funding. Analysis of morbidity
and mortality statistics will be begun by 1975 as will identification
of gaps in our present data collection system.
E. APPROACH: Cancers and irritative, inflammatory and degenerative
disorders of several organ systems such as the skin, respiratory tract,
pancreas, liver, kidney and genitourinary tract would be good indicators
of environmental alterations.
F. SUPPORTING CONTRACTS: None.
G. SPECIAL FACILITIES; None.
H. INTERMEDIA RELATIONSHIPS: All media.
I. COORDINATION: Hith media and categorical programs.
J. UNRESOLVED POLICY ISSUES: None.
r
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B 295
PROGRAM ELEMENT: HEALTH EFFECTS OF MULTIMEDIA TOXIC
SUBSTANCES
PROJECT B - CONFIRMATION OF HUMAN SAFETY
TASK 3. Quantitate the effects of accidental release of environmental chemicals
using mobile clinical laboratory teams, mobile exposure monitors and
intensive study of exposure victims.
A. PROGRAM JUSTIFICATION; Episode releases of environmental chemicals require a
rapid response to protect public health and environmental quality. When such
releases can be forecast as in specific testing and disposal situations, exposure
surveillance can be preplanned. Victims of accidental releases should receive
the best care and, when necessary, the closest scrutiny in clinical research
centers.
B. OBJECTIVE: To quantitate the effects of accidental releases of environmental
chemicals upon the public health and environmental quality.
C. SCOPE: Self-contained environmental monitoring and clinical research
laboratory units would be used to assess the impact of accidental exposures.
D. RESULTS; Mobile units capable of assessing human and environmental impact.
E. APPROACH; Accidental releases would be detected-through existing Federal
mechanisms. Prototype self-contained environmental monitoring and clinical
research laboratory units would be constructed and field tested. Clinical
laboratory components for evaluation of pulmonary function and cardiovascular
function are under intensive development. Advanced exposure monitoring
systems using improved data processing and telemetric techniques will be
developed.
F. SUPPORTING CONTRACTS; None.
G. SPECIAL FACILITIES; None.
H. INTERMEDIA RELATIONSHIPS; All media.
I. COORDINATION; With media and category programs.
J. UNRESOLVED POLICY ISSUES: None.
r
i
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S 296
PROGRAM ELEMENT: HEALTH EFFECTS OF MULTIMEDIA TOXIC SUBSTANCES
PROJECT B - CONFIRMATION OF HUMAN SAFETY
TASK 4. Evaluate impact on existing and pending media and categorical
standards through laboratory models using cells, organ cultures,
intact animals and human volunteers.
A. PROGRAM JUSTIFICATION; Biological models employing whole1 animals and
isolated cells have been used to study the effect of oxidants, nitrogen
dioxide and other classical air pollutants through interaction with infectious
agents. Study results were used in setting standards for these air pollutants.
These models will be employed to determine the influence of toxic chemicals
on these standards by altering the sensitivity to the previously studied
classical pollutants. Such information is necessary to determine whether
the existing or pending standards must be changed to reflect the impact
of toxic chemicals.
B. OBJECTIVE: To evaluate the impact on existing and pending environmental
standards through laboratory biological models.
C. SCOPE: All feasible and practical biological models will be utilized
in interaction studied and even more sensitive models will be sought.
D- RESULTS : With adequate funding all laboratory models could be operational
by
E. APPROACH : In vivo and in vitro biological tests will be utilized including
limited human volunteer studies employing the interactions of non-invasive
infectious agents (i.e. human cold viruses).
F. SUPPORTING CONTRACTS: None.
G. SPECIAL FACILITIES: None.
H. INTERMEDIA RELATIONSHIP: Air, Water, Pesticides, Radiation.
I. COORDINATION: With media and categorical progress.
J. UNRESOLVED POLICY ISSUES: None.
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B 297
PROGRAM ELEMENT: Health Effects of Multimedia Toxic Substances
PROJECT B - Confirmation of Human Safety
TASK 5 - Biological Models to Evaluate Impact of Toxic Substances on
Important Health Effects Other than Cancer, Mutations and
Congenital Abnormalities.
A. PROGRAM JUSTIFICATION: Toxicological and clinical research studies of
the impact of toxic substances on the production or aggravation of chronic
disorders other than cancer, mutations and congenital abnormalities must
be ascertained. Additional health effects intelligence regarding the functional
integrity of erythrocytes, growth and development and neurophysiologic performance
are also required if the control of toxic substances are to be based on a solid
scientific foundation.
B. OBJECTIVE; To provide the research models and information needed for
lease social cost environmental control of multimedia toxic substances.
C. SCOPE: Included will be the necessary research and development to adapt
existing or structure new appropriate biological models.
D. RESULTS: With adequate funding it is anticipated that appropriate models
to assess the effects of toxic substances on important chronic disease
processes and other health effects will be available by 1975 and that a rapidly
responsive research effort will provide a reasonable base for important
environmental control actions involving toxic substances by 1977.
E. APPROACH; In order to determine the effect of toxic chemicals on the
various organ systems to correlate with epidemiologic patterns and further
identify a given chemical, work with models is required. Where possible,
studies directly on man are superior since extrapolations can be made directly
to naturally occurring states in human beings. However, since only relatively
mild exposure yielding completely reversible effects, such studies have only
limited application. In this program these will be limited to near ambient
levels of selected toxic chemicals and acute upper respiratory tract virus of
the common cold type or similar chemicals studied in regard to behavioral
parameters. Animal models will be employed to study the influence of the
toxicants on the development of disease known to be problems in human beings.
Existing models will be employed for acute pulmonary disease, cardiovascular
disease, liver and pancreatic disease, and various synthetic organic and
metallic compounds will be employed as modifiers as well as potential etiologic
factors. The construction of a model for chronic lung disease employing
synthetic organic compounds, and metallic compounds which might act as irritants,
depressants of cellular metabolic activity, enzyme inhibitors and the like in
interactions with meteorological and other variables. Intramural research
grants and contracts will be utilized.
F. SUPPORTING CONTRACTS: Supporting contracts with institutions or research
organizations will complement intramural research efforts. Extramural research
will comprise about 75 per cent of the total effort.
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B 298
G. SPECIAL FACILITIES: Properly instrumented clinical exposure chambers,
experimental animal exposure and holding facilities, pathology laboratory,
biochemistry capability and adequate computing facilities are necessary.
H. INTERMEDIA RELATIONSHIPS: Exist with all media and categorical programs.
I. COORDINATION: Coordination will be required with media and category programs,
with other ORM effects research and with other agencies including DOD, NIOSH,
NIEHS, other units of NIH and NSF.
J. UNRESOLVED POLICY ISSUES: None
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B 299
PROGRAM ELEMENT: Health Effects of Multimedia Toxic Substances
PROJECT B - Confirmation of Human Safety
TASK 6 - Establish Exposure Surveillance Networks for Community, Home and
Highest Level Areas
A. PROGRAM JUSTIFICATION: Existing community environmental surveillance
programs are not adequate to define man's exposure to toxic substances,
including metals and synthetic organic compounds. Present instrumentation
is often insensitive and lacks precision even though solid state sensors and
automatic electronic systems with real time data outputs and data links to
central on-line data processors can probably be developed. Environmental
protection efforts directed towards confirming human safety will require
accurate appraisal of human exposure.
B. OBJECTIVES; To provide a surveillance system for the appraisal of human
exposure to toxic substances by 1977 so that necessary health effects
research and environmental control actions can be supported.
C. SCOPE: Included is the necessary research and development effort to
produce and evaluate prototype sensors and community surveillance stations
along with the necessary data links. A demonstration network of these
stations would be established in selected communities.
D. RESULTS; With adequate funding it is anticipated-that a surveillance
network monitoring exposure in 40 communities can be established by 1978.
E. APPROACH: Pollutant classes of special interest will be specified and
appropriate solid state sensory devices developed under contract. Field
evaluation and actual deployment of the developed instrument package will
be largely an intramural operation.
F. SUPPORTING CONTRACTS; Sensor development and servicing of the resultant
surveillance network will be accomplished through contracts with industry,
institutions or research organizations.
G. SPECIAL FACILITIES; Instrument fabrication and maintenance capability,
computer processing of remote sensor signals transmitted by data phones and
interfacing population health effects studies.
H. INTERMEDIA RELATIONSHIPS; Toxic substances involve every environmental
media and category.
I. COORDINATION: In the development of suitable equipment coordination will
be maintained with air, water, pesticides and solid waste programs as well
as with other ORM health effects programs.
J. UNRESOLVED POLICY ISSUES: None
r
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B 300
PROGRAM ELEMENT: Health Effects of Multimedia Toxic Substances
PROJECT B - Confirmation of Human Safety
TASK 7. Devise and Deploy Surveillance Systems to Quantitate Personal
Exposure
A. PROGRAM JUSTIFICATION: Personal exposures to toxic substances must be
quantitated as inputs for the development and testing of population exposure
and effects models. Personal exposure surveillance must supplement community
exposure measurements. Such models will be necessary to evaluate existing
exposures to toxic substances and to predict the impact of alternate
environmental control options.
B. OBJECTIVES: To develop, test and deploy personal exposure monitors to
quantitate human exposure to toxic substances such as chlorinated aliphatic
and aromatic compounds and toxic trace elements.
C. SCOPE: Included is the necessary research and development effort to
produce and evaluate prototype personal monitoring systems along with the
necessary appraisal and data processing procedures.
D. RESULTS: With adequate funding, it is expected that personal exposure
monitors for the fifty most important toxic substances can be developed by
1977.
E. APPROACH: Pollutants of interest will be ranked in a priority order and
this listing will be reviewed for its relevance at least annually. Appropriate
unobtrusive, portable sensors will be developed under contract. Field evaluation
and actual deployment of the developed sensor packages and their coupling to
health studies will be largely an intramural activity.
F. SUPPORTING CONTRACTS; Contracts with industry, institutions or research
organizations will be utilized to develop prototype sensors.
G. SPECIAL FACILITIES: Instrument fabrication and maintenance shops and
appropriate data processing software and hardware.
H. INTERMEDIA RELATIONSHIPS; Coordination with other ORM health effects
research programs with air, pesticide and radiation programs will be required.
Interagency coordination with DOD, NIEHS and NIOSH will be necessary.
I. COORDINATION; Coordination with other OR&M health effects research programs
and with air, pesticide and radiation media and categorical programs will be
required. Interagency coordination with DOD, NIEHS and NIOSH will be necessary.
J. UNRESOLVED POLICY ISSUES: None
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B 301.
PROGRAM ELEMENT: HEALTH EFFECTS OF MULTIMEDIA TOXIC SUBSTANCES
PROJECT B - CONFIRMATION OF HUMAN SAFETY
TASK 8. Establish a national tissue bank to determine human pollutant
burdens.
A. PROGRAM JUSTIFICATION: Establishing a national tissue bank
system wilT provide a systematic predictive and bioenvironmental
flashback capability with repard to a wide variety of toxic substances.
B. OBJECTIVE: To collect tissue from appropriate populations across
the country to characterize pollutant burden profiles as a function of
age, sex, race, residence, time and exposure.
C. SCOPE: This effort includes the development of collection, storage
and analytic techniques appropriate for tissue banking procedures. Inputs
from several other tasks in the program element interface with this effort.
D. RESULTS: Data from tissue bank studies will input directly to toxic
substance standard setting processes, including development of new standards
as well as reevaluating old standards.
E. APPROACH: Tissue bank specimens will be collected from free living
and autopsy populations from across the United States. Twenty geographic
regions will form the nucleus of a collection network which will even-
tually expand to more comprehensively cover the nation. Present CHESS
human pollutant burden research will form the basis for a vastly increased
program. Selected grants and contracts will complement intramural research
in this regard.
F. SUPPORTING CONTRACTS: Contracts for collection, storage and chemical
analysis of tissues will be necessary to support this task.
G. SPECIAL FACILITIES: Long term storage and analytic facilities.
H. INTERMEDIA RELATIONSHIPS: Exist with each of the media and categorical
programs.
I. COORDINATION: Coordination with other ORM health effects research
program elements and with other agencies including DOD, NIEHS, NIOSH, and
NSF will be required.
J. UNRESOLVED POLICY ISSUES: None.
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B 302
PROGRAM ELEMENT: Health Effects of Multimedia Toxic Substances
PROJECT B - Confirmation of Human Safety
TASK 9. Develop Population at Risk and Health Cost Models from Usage Patterns,
Effluent profiles, Exposure Data and Predicted Effects
A. PROGRAM JUSTIFICATION: Estimates of populations subjected to various
levels of risk and calculations of the resultant health costs will be
essential in the choice of rational environmental control options.
B. OBJECTIVE; To provide estimates of the populations exposed to relevant:
levels of fifty more important toxic substances and to estimate the accompanying
health risks, if any, by 1977.
C. SCOPE; Included is the necessary research and development effort to
calculate appropriate exposure and risk estimations utilizing inputs from the
other tasks in this program element.
D. RESULTS; With adequate support it is expected that the models developed
in this task will contribute important data to selected environmental
protection decisions by 1975 and to a broad range of decisions regarding
new and existing products and processes by 1977.
E. APPROACH; Available information will be reviewed by teams, of knowledgeable
scientists working closely with mathematicians and statisticians. Utilization
of exposure data and tissue burden data should permit reasonably accurate model
construction. Particular attention will be paid to considering pertinent
exposure covariate data. New surveillance and human pollutant burden research
data will be used to validate and refine these models. The program will be
accomplished by grants and contracts with industry, institutions and research
organizations complemented by intramural research and evaluation.
F. SUPPORTING CONTRACTS: A number of supporting contracts dealing with
information systems, hazard identification, exposure surveillance, tissue
monitoring and effects assessment have been discussed in other tasks in this
program element.
G. SPECIAL FACILITIES; Sophisticated computer facilities
H. INTERMEDIA RELATIONSHIPS: Exist with each of the media and category
programs.
I. COORDINATION: Coordination will be required with other ORM health effects
research program elements and with the research programs of other agencies
including DOD, NIEHS, NIOSH, NSF and AEC.
J. UNRESOLVED POLICY ISSUES. None
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B 303
FY '73 Work Plans
PROGRAM ELEMENT NUMBER: TITLE: Toxic Substances
WORK PLAN RECIPIENT: Director, NERC/RTP
PROGRAM ELEMENT MANAGER:
Task Present/MY
Resource Estimate
Min. Adequate/MY
Optimum/MY
PROJECT A
1A
2A
3A
4A
5A
1000/4
100/5
750/15
1250/16
750/5
3850/45
1500/6
150/7
1075/22
1825/24
1025/8
5575/67
PROJECT B
IB
2B
3B
4B
5B
6B
7B
SB
9B
1600/16
600/15
600/8
1100/15
1033/14
1380/17
1020/13
2800/24
1020/13
11153/135
2400/24
900/22
900/12
1650/23
1546/21
2070/25
1530/20
4200/36
1530/20
16726/203
...I
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B 304
RESOURCES STATUS SUMMARY
(None Assigned)
PROGRAM ELEMENT NUMBER
Health Effects of Noise
- PROGRAM ELEMENT TITLE
EPA FY '73 Plan
Funding Type
$ (000)
Positions
In-House
Grant
Contract
None
None
Program Element Total
None
None
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B 305
A. PROGRAM ELEMENT NUMBER: (Not yet assigned)
B. TITLE: Health Effects of Noise (only one project)
PREPARED BY: John F. Finklea DATE: January 8, 1972
C. PROGRAM JUSTIFICATION; Increasing ambient urban noise levels threaten
the quality of life and human health. Federal performance standards for noise
emanating from many processes and products may be established or altered in
the near future. Except for hearing loss, the needed health effects information
for these standards is inadequate. Behavioral effects are less well documented
and the full impact of noise upon stress-related disorders, including cardio-
vascular diseases, is unknown. Noise standards based solely upon hearing loss
would ignore these potentially costly health effects.
D. OBJECTIVES: To assure that risk-benefit calculations for future standards
are based upon a realistic assessment of population exposures, and to assure
that existing and proposed noise standards do not allow unacceptable behavioral
impairments and chronic disease risks in urban man.
E. SCOPE: Included are first assessment of ambient noise exposures in
typical residential communities and in known high level noise areas; second,
construction and instrumentation of suitable exposure chambers for human
volunteers and experimental animals; third, selection of appropriate
behavioral and performance indices. Both intramural and contract efforts
would be required.
F. RESULTS: With adequate funding a firm assessment of non-auditory health
impairments and realistic estimates of the magnitude of the risks of existing
and projected noise exposures would be available by 1977.
G. APPROACH: Three separate tasks are proposed. First, ambient noise
monitors distinguishing both the quality and intensity of sound will be
installed at the CHESS-CHAMP stations already located in 30 to 40 urban
residential communities. Volunteer panelists, already participating in CHESS
studies will be asked to carry miniature recorders during their daily activities.
The integrated noise exposures of housewives, children and workers can thus be
quantitated. Playback of tapes will allow identification of important noise
sources. Appropriate transducers will convert tape data into standard sound
exposure units for further computer processing. Second, rodents, primates and
other appropriate experimental animals would be exposed to noise levels relevant
to existing and projected urban noise levels. Necessary allowances for diurnal
variation would be made. Behavioral and performance tests would be administered
and chronic disease risk factors assessed. Third, anechoic chambers would be
constructed as an adjunct to the ORM CLEANS (CLjnical Evaluation and Assessment
of Noxious Substances) program. Healthy human volunteers would be subjected
to relevant noise exposures for up to ten days and the effects on behavioral
tests, performance tests and neurophysiologic indicators would be periodically
assessed. In addition the CLEVER (mobile CLjnical Environmental Epidemiologic
Research unit) would be deployed in CHESS communities where ambient and personal
noise levels were under surveillance. Residents of several areas that comprised
a dose gradient for noise exposure would be asked to volunteer for the appropriate
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B 306
behavioral, performance and neurophysiologic testing. In addition field
surveys on the sociologic impact would be carried out.
H. SUPPORTING CONTRACTS: Noise monitoring systems would be fabricated and
deployed by a contractor according to Federal protocols as would data on
personal noise exposure. Intramural clinical and toxicologic research
programs would be supplemented by appropriate contracts.
I. SPECIAL FACILITIES; Community exposure monitoring stations, equipment
maintenance and repair laboratories, data transmission, central data monitoring
and computer facilities, anechoic chambers, electroencephalograph, psychological
testing apparatus, appropriate monitoring software and hardware, the CLEVER
mobile unit, laboratory animal facilities and biochemical laboratory.
J. INTERMEDIA RELATIONSHIPS: Exist with air and water
K. COORDINATION: Coordination is required with media and category programs
and with ORM CHESS and biomedical research programs. Interagency coordination
with DOC, DOT, DOD, NSF, NBS and DHEW is also necessary.
L. UNRESOLVED POLICY ISSUES: None
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SUMMARY COMPARISON
($ million/MY)
Noise
Optimum
Minimum
Adequate
FY 73
1.5/37
1 .0/24
FY 74
3.0/72
2.0/48
FY 75
3.8/93
3.0/72
FY 76
4.0/96
4.0/96
FY 77
4.3/98
4.3/98
Current
CO
o
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B 308
PROGRAM ELEMENT: (NOISE)
PROJECT: NOISE HEALTH EFFECTS RESEARCH
TASK 1. Quantitate population chronically exposed to noise levels above
postulated irritation and hearing loss thresholds.
A. PROGRAM JUSTIFICATION: Increasing ambient urban noise levels threaten
the quality of life and human health. Federal performance standards for
noise emanating from many processes and products may be established or
altered in the near future. Except for hearing loss, the needed health
effects information for these standards is inadequate.
B. OBJECTIVE: To assure that risk-benefit calculations for future
standards are based upon a realistic assessment of population exposures.
C. SCOPE: Ambient noise levels and personal noise exposures will be
assessed in up to 30 typical urban residential areas located in CHESS
communities and in known high level geographical noise areas such as
airports, freeways, urban commuter routes and industrial complexes.
D. RESULTS: With adequate funding realistic estimates of the magnitude
of ambient and personal noise exposures will be available by 1976.
E. APPROACH: Ambient noise monitors distinguishing both the quality and
intensity of sound will be installed at the CHESS-CHAMP stations already
located in 30 to 40 urban residential communities. Volunteer panelists,
already participating in CHESS studies, will be asked to carry miniature
recorders during their daily activities. The integrated noise exposures
of housewives, children and workers can thus be quantitated. Playback of
tapes will allow identification of important noise sources. Appropriate
transducers will convert tape data into standard sound exposure units for
further computer processing.
F. SUPPORTING CONTRACTS: Noise monitoring systems would be fabricated
and deployed under contract. CHESS-CHAMP data transmission systems
established under contracts in another program element would be utilized
to allow real time noise monitoring. Data on personal noise exposure would
be collected according to Federal protocols by contractors, as in the
CHESS studies.
G. SPECIAL FACILITIES: Exposure monitoring stations, equipment main-
tenance and repair laboratories, data transmission, central data monitoring
and computer facilities. Similar facilities are necessary for the CHESS-
CHAMP program.
H. INTERMEDIA RELATIONSHIPS: Air, water.
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J B 309
I. COORDINATION: With media and category programs, with CHESS and CHESS-
CHAMP research programs of ORM with research programs in DHEW, DOD, HOT,
NBS, NSF, DOC.
J. UNRESOLVED POLICY ISSUES: None.
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PROGRAM ELEMENT: (NOISE) .'
PROJECT - NOISE-HEALTH EFFECTS RESEARCH
TASK 2. Determine the spectrum and severity of pathophysiologic effects
attributable to noise exposure through animal experimentation.
A. PROGRAM JUSTIFICATION: Hearing loss is the most obvious and best
understood consequence of chronic exposure to increased noise levels.
Behavioral effects are less well documented and the full impact of noise
upon stress-related disorders, including cardiovascular diseases, is
unknown. Noise standards based solely upon hearing loss would ignore
these potentially more costly health effects.
B- OBJECTIVE: To assure that existing and proposed noise standards do
not allow unacceptable behavioral impairments and chronic disease risks
in urban man.
C. SCOPE: Included in this task is the development of aDoropriate
exposure techniques, the selection of behavioral and performinq indices
and the execution of the required intramural and contract laboratory
research.
D. RESULTS: Hith proper funding it is expected that a more nearly
adequate health information base for noise standards will exist by 1977.
E. APPROACH: Rodents, primates and other appropriate experimental
animals v/ould be exposed to noise levels relevant to existing and
projected urban noise levels. Necessary allowances for diurnal variation
would be made. Behavioral and performance tests would be administered and
chronic disease risk factors assessed.
F. SUPPORTING CONTRACTS: A small intramural program would be buttressed by
an extensive research grant and contract effort undertaken by universities
and contract research groups.
6. SPECIAL FACILITIES: Anechoic chambers, psychological and neurophysio-
logical laboratories and testing equipment, clinical biochemistry laboratories
and experimental pathology capability.
H. INTERMEDIA RELATIONSHIPS: Air and water.
I. COORDINATION: With media and category programs and with other ORM
toxicologic research.
J. UNRESOLVED POLICY" ISSUE'S: None.
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B 311
PROJECT ELEMENT (NOISE)
PROJECT: NOISE HEALTH EFFECTS RESEARCH
Task 3. Determine the threshold of behavioral changes in humans associated
with chronic exposure to low level noise through clinical studies
of human volunteers.
A. PROGRAM JUSTIFICATION: Behavorial and neurophysiologic effects of chronic
noise exposure are important but poorly understood possibly consequences of
chronic noise exposure. Noise standards based solely on avoidance of hearing
loss would ignore these potentially more costly health effects.
B. OBJECTIVE: To assure that existing and proposed noise standards do not
allow unacceptable behavorial and neurophysiologic impairments.
C. SCOPE: Included in this task are the construction and instrumentation of
suitable exposure chambers, selection of appropriate behavorial and performance
indices and adaption of these techniques for use in field studies of urban
man.
D. RESULTS: With adequate funding a firm assessment of human health impairments
associated with noise exposures would be available by 1977.
E. APPROACH: Anechoic chambers would be constructed as an adjunct to the
ORM CLEANS (CLinical Evaluation and Assessment of_Npxious Substances) program.
Healthy human volunteers would be subjected to relevant noise exoosures for up
to ten days and .the effects on behavorial tests, performance tests and neuro-
physiologic indicators would be periodically assessed. In addition the CLEVER
(mobile CLinical Environmental Epidemiologic Research unit) would be deployed
in CHESS communities where ambient and personal noise levels were under sur-
veillance. Residents of several areas that comprised a dose gradient for noise
exposure would be asked to volunteer for the appropriate behavorial, performance
and neurophysiologic testing. In addition field surveys on the sociologic
impact would be carried out.
F. SUPPORTING CONTRACTS: Data collection according to Federal protocols would
be carried out in CHESS communities under contract as would portions of the
experimental human exposure work.
G. SPECIAL FACILITIES: Anechoic chambers, electroencephalograph, psychological
testing apparatus, appropriate monitoring software and hardware, and the CLEVER
mobile unit.
H. INTERMEDIA RELATIONSHIPS; Air and water
I. COORDINATION: Coordination will be maintained with other toxicologic,
epidemiologic and clinical research programs within EPA and with DOD, DOT, DOC,
DHEW, NSF.
J. UNRESOLVED POLICY ISSUES: None
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B 312
ORftM
FY '73 Work Plans
PROGRAM ELEMENT NUMBER: Not Assigned TITLE: NOISE
WORK PLAN RECIPIENT: Not Assigned
PROGRAM ELEMENT MANAGER: Vaun A. IJewill
Task Present/MY
Resource
Minimum Adequate/MY
Estimate
Optimum/ MY
1
2
3
Total
300/7.0
400/10.0
300/7,0
1000/24.0
450/11.0
600/15.0
450/11.0
1500/37.0
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B 313
RESOURCES STATUS SUMMARY
(None Assigned) National Center for Toxicologic Research
PROGRAM ELEMENT NUMBER PROGRAM ELEMENT TITLE
EPA FY '73 Plan
Funding Type $ (1000) Positions
In-House
Grant
Contract 4000
Program Element Total 4000
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B 314
A. PROGRAM ELEMENT NUMBER; (Not Assigned)
B. TITLE: National Center for Toxicologic Research (NCTR)
PREPARED BY: Morris Cranmer DATE: January 15, 1972
C. PROGRAM JUSTIFICATION: Toxicologic screening of new environmental chemicals
prior to release into the environment is a most economic and desirable method
to protect the public against chemical toxicants. The federal government must
provide leadership in developing standardized protocols for toxicologic screening,
evaluating the .adequacy of non-government safety tests prior to registration and use
of new environmental chemicals and developing research data that will facilitate
extrapolation. NCTR will be the federal governments only environmental health
laboratory whose mission is to serve as a watchdog and scientific leader in
evaluating the safety of new environmental chemicals.
D. OBJECTIVES; (1) To develop improved methodologies for evaluating the safety
of environmental chemicals, (2) to determine the adverse health effects resulting
from long-term, low-dose exposure to environmental chemicals, (3) to determine the
metabolic processes for chemical toxicants in animal organisms, and (4) to develop
scientific data that facilitate extrapolation from animal to man.
E. SCOPE: NCTR will operate a core program in four areas of toxicologic research:
(1) acute and subacute toxicity studies in which short duration tests will be
conducted to identify heal.th indicators and background data necessary for chronic
lifetime studies, (2) chronic toxicity studies to determine carcinogenic and other
life shortening effects of environmental chemicals, (3) teratogenic research on
chick and mammalian embryos to determine teratogenicity of environmental chemicals
and (4) mutagenic research to develop improved testing procedures for evaluating
genetic effects of environmental chemicals.
F. RESULTS: The knowledge gained from toxicologic screening of new environmental
chemicals will be of direct relevance to EPA's mission of controlling population
exposure to environmental toxicants. The adequacy of industry's own screening
programs prior to registration or marketing of new chemicals will be judged from
the point of view of protector of the public health. Needed long-term toxicity
studies, including carcinogenic and mutagenic screening, will be provided.
G. APPROACH: Toxicologic studies utilizing animal, organ and cell culture systems
will be employed following standardized and scientifically sound protocols. Dose-
response curves for carcinogenic, teratogenic, mutagenic and chronic toxicologic
endpoints will be provided.
H. SUPPORTING CONTRACTS; Contracts with industry, private research organizations
and universities are needed to supplement the core program of NCTR and to provide
supporting services such as processing of specimens for pathological and biochemical
analysis.
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n, 315
I. SPECIAL FACILITIES; Construction of special facilities is required and has
been extensively described 1n the detailed NCTR Technical Plan prepared jointly
by EPA and FDA.
J. INTERMEDIA RELATIONSHIPS: With all other health program elements in ORM and with
media and categorical offices.
K. COORDINATION; With FDA, NIEHS, NIOSH, and NCI.
L. UNRESOLVED POLICY ISSUES; None
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Not Assigned
PROGRAM ELEMENT NUMBER
FY 73
Optimum 8.0
Minimum Adequate 5.79
Current 4
SUMMARY
($ mi
FY 74
15.0
9.36
5.775
COMPARISON
llion/MY)
FY 75
20.0
15.217
8.137
National
FY 76
25.00
13.000
9.117
Center for Toxicoloqic Research
PROGRAM ELEMENT TITLE
FY 77
25.00
15.00
10.000
co
CO
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Appendix C
Operational Problems
Identified during EPA Health Effects Research
Program Planning
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C 1
The Task Force identified a number of operational problems which
ORM should consider and resolve.
First, the scope of program elements should be carefully defined.
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C 2
Option 1. Attempt to fund the entire radiostrontium study for seven
years with end of year contract funds in FY '72.
Option 2. Fund the radiostrontium project as now designed out of
operating funds each year.
Option 3. Fund the radiostrontium project as now designed and transfer
the experimental cats and the breeding stock to Pine Bluff in 1977.
Option 4. Terminate the radiostrontium exposure project and relocate
trie cat colony in a more salubrious climate.
The Task Force strongly favored Option 4, but also recommends ORM
establish a special mechanism to plan and assure support for long-term
health effects research studies.
Fourth, ORM should recognize the need to support the necessary research
to quantitate the populations exposed to a broad spectrum of pollutants
Existing efforts in air (CHESS Task BIT), radiation (Task B4), and water
(Tasks Al, B2, Cl) need additional support. Defining populations at risk
is a most important input for cost-benefit assessments of environmental
control.
Fifth, the Task Force felt better definition was needed of the scope
of acute and subacute toxicity studies to be accomplished at the Pine Bluff
facility under Phase II of the NCTR Plan.
Sixth, the Task Force recognizes the need of additional and more precise
planning of research efforts dealing with trace elements, neurophysiology and
behavior. We recommend that a group of trace metal investigators meet with
representatives of the Task Force at WERL in February 1972. Investigators
should include W. Moore of Cincinnati, Environmental Toxicology Program,
R. Tardiff of Cincinnati WSPD, R. Stanley of WERL and M. Waters, T. Hinners,
and D. temmer of RTP-DHER. A similar meeting of investigators utilizing neuro-
physiologic and behavioral endpoints should be held in Perrine in February.
Investigators should include Dr. Van Gelder, a contractor from Iowa State Uni-
versity, John Santolucito of Perrine, P. Lambert of Twinbrook, J. Knelson of
RTP, M. Gage of Cincinnati Environmental Toxicology Program and R. Bull of
Cincinnati WSPD. A similar, more general meeting to discuss toxicological
methods and interlaboratory variation in toxicologic testing was proposed.
Seventh, the Task Force found it lacked policy guidance on the importance
of research in four areas: waste waterjreuse; health''effects~rupport for fish,
shellfish and irrigation waters; radon gas exposure; sociologic and motivational
research. Thus, research tasks relating to'these areas may not be placed in
proplFperspective. There was substantial disagreement within the Task Force
on the relative importance of the radon gas exposures.
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C 3
Eighth, the Task Force identified several research tasks whose!.content '
should be closely scrutinized by ORM prior to FY '73 funding. Included are
the measurements of pesticide exposure and correlation of exposure indices
(Pesticides Health Effects Research Tasks 25 and 26), determination of impact
of environmental synergists on radiation standards (Radiation Task B6), and
radiation repair and carcinogenesis (Radiation Task B5). ORM might well
also consider funding the PCB studies of bladder cancer (Pesticides Health
Effects Research Task 13) from a program element other than pesticides.
Ninth, the Task Force recognized a real need to define those interaction
studies which deserve a high priority. Included are the effects of radiation
and ozone on lung morphology and cytogenetic abnormalities (Biomedical Task C8)»
trace metal interactions and community interactions which are well defined in
the CHESS program. More cross-media study should be devoted to designing
interaction studies.
Tenth, a consensus of the Task Force advocated the acquisition of a
multipurpose human exposure chamber facility to study the effects of air
pollutants, noise and non-ionizing radiation upon human volunteers. A small
minority expressed reservations about the appropriateness of such a facility.
Eleventh, the Task Force's estimate nf nersnnnel committed to health
effects research by the Water Supply Programs Division omitted several groups
which might properly be considered engaged in health research work. For
example, the personnel effort devoted to health staff functions and admini-
strative support which together amount to six man years were not included.
In addition, the virus research work of the Division was partitioned into
health effects and non-health effects; research components (largely virus
methodology). " The latter group, approximately 12, was not considered. The
Task Force recognized the historical roots of the virology program and its
relevance to waste water reuse problems. Retrospectively, it is also easy
to assert that a more balanced research program advocated by the Division,
but hampered because of resource limitation, is long overdue. The Task
Force also recommends that the virology programs of the Advanced Waste Treat-
ment Group and the Water Supply Programs Division be carefully coordinated.
Twelfth, the Task Force regrets that time constraints prevented personal
visits and consultation with every health effects research unit in the Agency.
The program structure and priorities presented by the Task Force should, how-
ever, serve as a useful framework for further inputs.
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C 4
PROGRAM ELEMENT: Fuel and Fuel Additive Registration
TASK 1. Fuel additive residues in exposed human populations. Development
of techniques and methods for'measuring human exposure to trace exhaust
emssions and the metabolites of fuel additive residues that accumulate in
human tissue as a result of exposure.
A. PROGRAM JUSTIFICATION: Combustion of fuels containing various types of
additives could result in the emission of compounds that might alter the
tissue burdens in exposed populations or actually interfere with crucial
enzyme systems. Methods for measuring human exposure to the anticipated
more significant additives are needed as are the determination and
quantisation of residues in humans that result from this exposure.
D. OBJECTIVES; To develop and adapt for human studies methods and techniques
for measuring exposure to trace exhaust emissions and the metabolites of
fuel additive residues (alkyl, aromatic phosphates, aromatic amines, and
trace metals) that accumulate in human tissue as a result of exposure.
* SCOPE: The Environmental Protection Agency has been given the responsibility
for registering all fuel additives used in this country and for assuring
that their use represents no increased risk to the health of individuals
exposed to exhaust emissions. Although fuel formulators or distributors
are to be required-to provide toxicity data the federal agency must
develop a cpability for validating the information received from these
sources and for predicting the types of formulations and specific
additives that are most l.ikely to produce toxic emission products.
*-i
D. RESULTS: The information obtained from these studies will provide the
federal agency with a predictive capability for assessing the kinds of
fuel additives that are most likely to result in toxic or non-toxic
emissions, and for confirming the toxicity data obtained from fuel
suppliers.
E- APPROACH: Initially analytical and sampling techniques must be devised
and developed to enable the accurate measurement of fuel additive
residues in body fluids as well as inspired and expired air. These
techniques and methods will be utilized in feasibility tests involving
traffic policemen, garage attendants, or other individuals heavily exposed
to exhaust emissions. Whenever necessary to provide supporting data,
suitable laboratory studies will be undertaken.
! SUPPORTING CONTRACTS; This work will be assigned to contractors selected
after advertising and careful review of capabilities. Detailed protocols
will be developed in-house and provided to the contractor selected.
Frequent reviews of progress will be made to assure that work is advancing
in line with the protocol.
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C 5
u- SPECIAL FACILITIES: None unless it becomes advisable to conduct these
studies as part of our in-house effort in which case special exhaust
generating and exposure facilities would become necessary.
H. INTERMEDIA RELATIONSHIPS: Anticipate relationships with other EPA
offices on effects of pollution research.
1. COORDINATION: Liaison with FDA, NIOSH, NIEHS.
J. UNRESOLVED POLICY ISSUES: None
BUDGET
($1000)
Present/MY Minimal Adequate/MY Optimal/MY
Contract 105/1.0 190/1.0 300/2.0
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C 6
PROGRAM ELEMENT: Fuel and Fuel Additive Registration
TASK 2. Toxicolony of fuel additives emissions.
A. PROGRAM JUSTIFICATION: Pursuant to directives by Administrator EPA for
registration-regulation of fuel additives, orotocols are to be developed for
the evaluation of biological effect in relation to exposure from fuel additives
and/or their combustion products. Although fuel additive manufacturers are
reguested to provide toxicity data, the federal agency must have capability to-
confirm these studies and develop methods for assuring that no increased risks
ensue from additive use in man.
B- OBJECTIVES: To develop methods for the assessment of exposure to fuel
additives and/or their combustion products and the determination of biological
effects as a result of exposure to these chemicals in order that meaningful
human monitoring can be undertaken.
c- SCOPE: Minimal adequate funding would permit only limited confirmation of
selected additives. Ootimal funding would permit a capability of comprehensive
review of the fuel additive data with supnlemented animal studies to evaluate
their environmental imoact.
D- RESULTS: These studies will provide methods and techniques applicable for
the assessment of human exposure to fuel additives and/or their combustion
products. They will also provide information necessary for a more realistic
hazards evaluation and the selection of fuel additives with minimal environment
and toxicological impact.
E. APPROACH: Current "state of the art" methods and techniques will be evaluated
to determine their feasibility and sensitivity to detect adverse biological effects.
Animal models will be exposed to labeled additives to determine their biological
fate and the "critical" tissue sites.
F. SUPPORTING CONTRACTS: Contractors will select after advertising and careful review
of capabilities.A smaller in-house effort will be continued to develop protocol and
to monitor contractor performance.
G. SPECIAL FACILITIES: Special exhaust generating and exposure facilities and
instrumentation is available in-house in NERC-Cincinnati.
H. INTERMEDIA RELATIONSHIPS: Anticipate relationships with other EPA offices on
effects of pollution research.
I. COORDINATION: Liason with FDA, NIOSH, NIEHS.
J. UNRESOLVED POLICY ISSUES: Unknown
dUDGiiT fiil OuO)
Present/MY Minimal Adequate/MY Optimal/MY
Contract " 0/0 190/1.0 300/2.0
In-house 0/0 85/1.0 100/2.0
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C 7
PROGRAM ELEMENT: STANDARDIZATION OF INSTRUMENTATION
AND ANALYTICAL METHOD
TASK 1. Biochemistry Control Program.
A. JUSTIFICATION: in order to insure uniformity and high quality
of performance, it is necessary to implement a quality control
program for biochemical testing in the Community Studies
Pesticides Project. This control program will augment the
value of the Community Studies Pesticide Project by increasing
accuracy and precision and minimizing inter- and intra-
laboratory variation.
B. OBJECTIVE: «rne purpose of the program is to implement and
supervise the biochemical quality control program for the
Community Studies Pesticide Project.
SCOPE:
The program will .consist of inter- and intra-laboratory
control samples. Laboratories will be required to report
acceptable values for intra-laboratory control before they will
be authorized to participate in biochemical testing for the
Community Studies Pesticide Project.
D. RESULTS: inter- and intra-laboratory results will be analyzed
and correlated for all participating laboratories.
E APPROACH'
Known and unknown control sera for glucose/ urea
nitrogen, cholesterol, uric acid, protein, albumin, phosphorus
and creatinine will be provided for each participating
laboratory.
F. SUPPORTING CONTRACTS: None
G. SPECIAL FACILITIES: Biochemistry laboratory
H. INTERMEDIA RELATIONSHIPS: With and and water programs.
I. COORDINATION: With 14 Community Studies Laboratories of Office of Pesticides
Program.
J. UNRESOLVED POLICY ISSUES: None
BUDGET ($1000)
Present/!1Y Minimal Adeguate/MY Optimal/MY
In-House 50/2 50/2 50/2
Contract 0/0 50/0 50/0
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C 8
PROGRAM ELEMENT: STANDARDIZATION OF INSTRUMENTATION
AND ANALYTICAL METHODS
TASK 2. Inter-laboratory analytical reference service for biological samples.
A. PROGRAM JUSTIFICATION: Biological tissues including body organs and body fluids,
accumulate toxic compounds contained in the environment and can reach concentration
levels hazardous to body health. It is necessary that accurate measurements of
toxic compounds in tissues be made for proper appraisal of the extent of the hazard.
Because measurement values can and often do vary considerably from one laboratory
to another, even for the same procedure, it becomes important to establish reliable
duplicable and accurate techniques which can be monitored by a reference laboratory
in close cooperation with other laboratories using one or more of identical procedures,
B. OBJECTIVE: To establish an expertise for the analyses of biological specimens
for toxic compounds such as metals and their metabolites that will serve to maintain
a "quality control" of measurements among the laboratories faced with similar
requirements of analyses; namely, those laboratories in government service.
C. SCOPE: Biological tissue samples from experimentally exposed animals and
deceased humans will be treated according to the latest most reliable procedures.
In addition, body fluids will be similarly examined from both human and animal
subjects. Such methods will be identified by their wide application and their
established accuracy of determination of compounds of immediate and potential
concern. A continuous monitoring of the literature and also communications
with various laboratories will be maintained to keep abreast of additional
accurate and sensitive new procedures and to test these procedures for adoption
as standard methods. Samples containing known amounts of compounds added to
the tissues will be supplied to the cooperating laboratories to test the
accuracy of application of procedures under their own laboratory conditions.
D- RESULTS: The procedures confirmed to be the most accurate for the compounds
under consideration, used by a staff of established, competent analysts, will
be used to maintain "quality control" of measurements through cooperative efforts
with the various laboratories. Such cooperative work should lead to an increasing
improvement in expertise that will be accepted over an expanding field of
laboratories.
E- APPROACH: Initially, the trace metals of immediate concern as toxic substances
in animal tissues will be considered. Also, organic comoounds such as pesticides
and components in cosmetic formulations (e.g., hexachlorophene) and in food
(e.g., diethylstilbestrol) will be considered. Known methods of analyses will
be used, and tested for imorovement in accuracy and/or expeditious handling.
These methods will be checked out with other laboratories for duplicable and
accurate results. Our laboratory will serve as the center for the group of
cooperating laboratories to obtain and maintain a consistency of analytical
competence.
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C 9
F. SUPPORTING CONTRACTS: Not identified as yet.
G. SPECIAL FACILITIES: To develop the expertise that would be acceptable for
reference service by other laboratories, the best and latest equipment for
analyses required. Faster service and more accurate concentration values are
obtained by use of such instruments and techniques as X-ray fluorescence
spectrophotometry, plasma jet atomic absorption spectrochemistry, etc.
H. INTERMEDIA RELATIONSHIPS: The analytical procedures have application to
analyses of atmospheric, water, food, solid waste and radioactive samples.
! COORDINATION: Cooperation of the various laboratories confronted with the
same analytical measurements is the key to the application of the suggested
reference service.
J- UNRESOLVED POLICY ISSUES: A canvassing of laboratories for their interest
and need of such a reference center should indicate the priority of the service.
LEVELS OF ACTIVITY ($1000)
PRESENT MINIMUM ADEQUATE OPTIMUM
Funding: 0 80 300K
Man Years: 0 4 15
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