904B92005
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MEMORANDUM
TO: Participants in the EPA Case Study
on Risk and Decision Making
RE: Purpose of the Case Study and Your Role
An analysis of risk is becoming an increasingly important
component of regulatory decision making within EPA. Even so, the
specific ways in which the concept of risk can be used in a
particular situation are not well defined. The result can be
confusion and ultimately frustration among those who must carry
out or are affected by the regulations.
The concept of risk, however, need not be overwhelming and
can provide guidance in thinking about an environmental problem.
The purpose of this workshop is to help individuals in the EPA
Regions understand the basis of risk assessment, develop a common
base of knowledge and terminology, use the concept in formulating
a site-specific decision, and help refine skills in communicating
those decisions. The workshop is not intended, however, as a
step-by-step "how to" on risk assessment. Rather, we are trying
to explain the concepts of risk assessment, risk management, and
risk communication in the context of a case study. There are
many uncertainties and issues, and often no clear "right"
answers. As you proceed through the case, you will be asked to
consider those issues. Some of the issues you normally would not
confront in your day-to-day activities, and some of the terms may
be new. But, regardless of your background, we hope you will
address those issues and develop your own conclusions. By help-
ing you understand the issues, we hope to make you more informed
consumers of information on risks and increase your understanding
of both the potential and the limitations of the concepts. In
addition, we hope to encourage discussion of the unique circum-
stances involved in developing risk assessments for the site-
specific, localized problems that confront individuals in the EPA
regional offices.
The workshop case study will focus on a hypothetical site-
specific problem that EPA regional staff might encounter in their
day-to-day work. You will have to decide what actions should be
taken at the site.
U.S. Environmental Protection Agency
Region 5, Library (PL-12J)
77 West Jackson Boulevard 1?th
Chicago, IL 60604-3590
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BACKGROUND ON THE CASE
The Company
Electrobotics was formed 15 years ago as a privately held
company. Its two owners have lived in the community for many
years. Electrobotics manufactures electronic components for the
computer industry. In the past few years, the bulk of the com-
pany's sales has been in parts for personal computers, particu-
larly the popular Bananachrome® personal computer.
Electrobotics has had a rocky history and has been close to
bankruptcy several times. However, with the recent growth in
demand for personal computers, its performance has improved.
Last year Electrobotics had revenues of $7.5 million, compared
with $1.5 million five years ago. Even so, the company was only
marginally profitable, with after-tax profits of less than
$50,000.
Electrobotics employs about 150 people and has a reputation
for treating its employees well. It has never laid off an
employee, even during difficult periods.
Location
Electrobotics is situated in a sparsely populated region. A
residential development was recently built near the facility's
western boundary, and approximately 80 people live in 20 homes
there. In addition, the town of Utopia lies a little more than
1 mile east of the facility. The area between the facility and
the town has few homes, none closer than three quarters of a mile
to.the plant's eastern boundary. There has been some discussion
about building housing on the property, but no definite plans
exist at this time. Utopia relies on ground water for its public
water system and has 40 wells in a nearby well field. The well
field supplies approximately 50,000 residents, including those in
the development west of Electrobotics. The ground water from the
Electrobotics site flows toward the public well field. Initial
indications are that any ground-water contamination from the
Electrobotics site would affect only three of the public wells.
(Figure 1 provides a schematic of the Electrobotics site and the
surrounding area.)
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Rgure 1
Site Plan
Electrobotics Property
Boundary
& "i?T-s"'* *'' f> """'• '<
Manufacturing
Plant
Equal-
ization
Lagoon
I I
Wastewater
Treatment
Plant
1.000ft.
Threatened
Water Supply
Wells
Direction of
Ground-Water Row
Residential Area
N
(Not to Scale)
Nature of the Problem
About five years ago, Electrobotics changed its production
process as it introduced a new product. The process required the
use of an industrial solvent—dinitrochickenwire (DNC). Waste-
water containing the spent solvent is stored in a flow equaliza-
tion lagoon that is part of the Electrobotics wastewater treat-
ment plant (see Figure 1). After treatment, the wastewater is
discharged to the Smith River. Electrobotics1 treatment plant
uses an activated sludge process.
EPA has classified the solvent as a hazardous waste.
Studies on the carcinogenic risks from DNC were only recently
presented and will be discussed'in more detail as you assess the
risks at the site.
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STATUTORY AND REGULATORY ISSUES
The hazardous waste regulations developed under RCRA require
that owners and operators of hazardous waste facilities, like
Electrobotics1 storage lagoon, utilize design features and con-
trol measures to prevent the leaking of hazardous waste into
ground water. Furthermore, all regulated units (a regulated
unit, such as the storage lagoon, is a facility that received
hazardous waste after July 26, 1982) are subject to monitoring
and corrective action requirements if a ground-water problem is
identified. The ground-water protection standards require the
Regional Administrator to establish in the facility permit, for
each hazardous constituent entering the ground water from a regu-
lated unit, a concentration limit beyond which degradation of
ground-water quality is not allowed. The concentration limits
determine when corrective action is required.
Three possible concentration limits can be used to establish
the ground-water protection standards:
• Background levels of the hazardous constituents
• Maximum concentration limits (MCLs) established by
regulation
• Alternate concentration limits (ACLs)
Background levels and MCLs are established in the facility permit
unless the facility owner or operator applies for an ACL. The
background level of DNC is zero, and no MCL exists for the
solvent.
In October 1985, the owners of Electrobotics submitted to
EPA, as required under the RCRA regulations, a Part B application
for an RCRA permit. This application provides the Regional
Administrator with information necessary to evaluate the safety
of the site. It generally includes:
• A description of the facility
• Chemical and physical analyses of the hazardous waste
to be handled
• Information from a hydrogeological investigation of the
site
• The potential for the public to be exposed to hazardous
wastes or hazardous constituents through releases
related to the unit, including identification of the
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potential pathways of human exposure and the magnitude
and nature of the human exposure resulting from such
releases
In addition, Electrobotics1 owners have been conducting
ground-water monitoring as required under the regulations.
The wastewater treatment system has been permitted under
EPA's National Pollution Discharge Elimination System (NPDES).
The discharge permit issued by EPA sets forth effluent quality
standards, which Electrobotics must meet if it is to discharge
the plant's wastewater to the Smith River. Under the require-
ments of the NPDES permit, conventional pollutants and indicator
parameters are monitored at the plant's outfall on a daily,
weekly, or monthly basis. These parameters include the
following:
• Biochemical oxygen demand
• Chemical oxygen demand
• Total organic carbon
• Total suspended solids
• Ammonia
• Temperature
• pH
These monitoring requirements serve to ensure the proper func-
tioning of the wastewater treatment system.
DNC is not included among the pollutants monitored in
accordance with Electrobotics1 NPDES permit. However, included
in Electrobotics1 Part B application is information on samples
taken from the plant's outfall to the Smith River and tested for
DNC.
The results presented in the Part B application and from
other sources indicate that DNC was found in the ground water
below the lagoon. The initial monitoring wells were located at
the immediate edge of the lagoon, referred to as the "point of
compliance." Additional monitoring wells have been installed to
characterize'the plume, and results indicate that it has moved to
the eastern edge of the facility boundary. In addition, DNC was
found in the air around the plant. No DNC was found in the
wastewater treatment plant effluent.
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YOUR ROLE
You, as the EPA representative responsible for the Electro-
botics site, will evaluate the available information on the risks
posed by PNC and decide whether to issue a permit and what, if
any, corrective actions should be taken at the facility.
Part I
During Part I, you wish to determine whether and to what
extent the DNC found at the Electrobotics plant endangers the
public health. Thus, you have decided to conduct a risk
assessment. Your staff has prepared a document summarizing much
of the information you will need for assessing the risks. This
document, attached as Part I, reviews the potential risks from
DNC.
The first section, which contains toxicological data on the
solvent, constitutes the hazard evaluation.
The second section of Part I contains a summary of data on
the exposure of various population groups to DNC. Several issues
arise concerning the interpretation and use of this information,
and it will be necessary for you to formulate appropriate
conclusions.
The relationship between exposure to DNC and the risk of
adverse health effects is determined by a dose-response evalua-
tion. In the third section of Part I, you must review possible
approaches to defining this relationship for the solvent. There
may be several plausible options for describing this relationship
in the region of human exposure. Normally, you would not examine
the hazard evaluation data and the dose-response information;
these results would be provided by EPA headquarters. However, in
this instance you have asked your staff to provide the material
for your review because you feel it is important to your under-
standing of the problem.
In the final section of Part I, you must present your con-
clusions regarding the human health risks posed by DNC from the
Electrobotics facility, and the uncertainties in your knowledge.
You must characterize the risks.
Part I will be completed during the first day of the
workshop.
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Part II
Once you have assessed the risks from DNC, you must decide
what actions should be required by Electrobotics' owners. You
must manage the risks. Part II of the case is currently being
prepared by your staff. It will be given to you at the end of
the first day of the workshop, when you have completed your
assessment of the risks, and will be discussed the next morning.
The new document will contain information on the options for
cleaning up the storage lagoon and ground water at the
Electrobotics site. In particular, you will have an approach
proposed by the owners of Electrobotics and alternatives
identified by your staff.
For each of the options, you will be presented with informa-
tion describing the approach, predicting the effect of the option
on the risks identified in Part I, and estimating the costs.
At each of the steps in Part I and Part II,, issues and data
will be presented and alternative conclusions listed. After
discussion, you may select the conclusion that seems most appro-
priate; if none seems appropriate you should offer your own.
Your review and evaluation will take place within a working
group of 10 to 12 people. After you discuss the issues with the
other members, your group should attempt to reach a consensus on
what action should be taken about Electrobotics1 permit applica-
tion. If you cannot reach a consensus, present the alternative
views. You should note, however, that you must ultimately decide
what cleanup actions will be required of Electrobotics' owners.
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Part I
ASSESSING THE RISKS FROM DNC
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CONTENTS
I. BACKGROUND. ON THE CHEMICAL DETECTED AT THE
ELECTROBOTICS SITE
II. HAZARD EVALUATION
III. HUMAN EXPOSURE EVALUATION
IV. DOSE-RESPONSE EVALUATION
V. RISK CHARACTERIZATION
GLOSSARY
APPENDIXES
A. Ground-Water Modeling Calculations and
Associated Assumptions
B. Human Dose Calculations and Associated
Assumptions
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I. BACKGROUND ON THE CHEMICAL DETECTED
AT THE ELECTROBOTICS SITE
Dinitrochickenwire (PNC)
• Solvent used to degrease fabricated metal parts
• Impurities: commercial product contains trace amounts
of trinitrochickenwire
• Physical state: liquid, moderate volatility
• Stability: degrades slowly in aqueous environments
• Solubility: moderately soluble in water
001
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II. HAZARD EVALUATION
Normally, you would not review information on the
hazards of specific chemicals; the results would probably be
provided to you by EPA toxicologists. But by working through
the material in this section, you will develop an understand-
ing of the nature and quality of information used by the
toxicologists. You will not become toxicologists, but we
hope you will become more informed users of the information
they provide.
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SOME PRINCIPLES FOR HAZARD EVALUATION
1. The purpose of hazard evaluation is to identify the
types of adverse health effects that may be associated
with exposure to DNC, and to characterize the quality
and strength of evidence supporting this identifica-
tion.
2. The specific hazard of concern in this review is
cancer, although systemic toxic effects will also be
discussed.
3. Epidemiological studies in exposed human populations
are generally considered the best source of information
for hazard identification. Unfortunately, they are not
available for most substances. Moreover, establishing
firm causal links between exposure and chronic human
disease (such as cancer) is very difficult.
4. Studies with experimental animals also provide useful
information for hazard identification. Such studies
can be controlled, and thus can more easily establish
causality. Results from such studies suffer from the
obvious limitation that experimental animals are not
the species of ultimate interest.
5. With one possible exception (arsenic), all known human
carcinogens are also carcinogenic in one or more
species of experimental animals. Most animal carcino-
gens have not been established as human carcinogens.
6. Biological data support the proposition that responses
in experimental animals should be mimicked in humans.
For some agents, however, species differences in
response can be substantial.
7. The specific sites of tumor formation in humans may
differ from those observed in experimental animals.
8. Data obtained by administering a substance by the same
route of exposure experienced by humans are considered
more predictive than data obtained by a different
route. If tumors form at internal body sites, however,
the route of exposure may not be important.
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II-3
In general, a varied response in experimental animals--
tumor formation or systemic effects in several species
and both sexes, at different exposure levels with
increasing response at increasing exposure, and at
multiple body sites—provides more convincing evidence
of potential human carcinogenicity or systemic damage
than does a response limited to a single species or
sex, or to body sites at which tumors or systemic
effects commonly occur in untreated animals (e.g.,
liver tumors in untreated male mice).
BACKGROUND ON PNC TOXICITY
The toxic properties of DNC were first investigated in the
1940s and 1950s. In most of these tests, small groups of experi-
mental animals were exposed to very high amounts of DNC to iden-
tify the exposure conditions that would cause death. Animals
received either a single exposure, or exposures covering only a
fraction of their lifetime.
During the 1950s and 1960s, more extensive animal toxicity
tests were conducted, although none involved DNC exposures last-
ing more than about one-sixth of a lifetime. These tests
revealed the range of doses that produced toxicity (the principal
site of toxic action was the liver) and the exposure level below
which no form of toxicity was identified.
Information available in 1970 showed that the most highly
exposed humans received a daily DNC intake several hundred times
lower than the "no-observed toxic effect" intake identified in
the animal tests. Because the liver toxicity produced by DNC was
of a type likely to occur only after a minimum threshold exposure
was exceeded, it was concluded that the most highly exposed
humans were protected from DNC toxicity by a wide safety margin.
This is discussed in more detail later.
At least until 1980, no data had been published on the
effects of DNC on exposed humans.
The Frankenstein Study
In late 1985, an article titled "Chronic Toxicity of Dini-
trochickenwire in Rats and Mice" appeared in a respected scien-
tific journal (Frankenstein, V., J. Environ. Tox.). The Franken-
stein paper presented data on the effects of lifetime exposure to
DNC in two species of rodents. These data revealed a form of
004
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II-4
toxicity—carcinogenicity—that had not been seen before. The
design of the Frankenstein experiment and the major findings are
presented in Tables 1 and 2.
Remarks on the Frankenstein Study
1. As far as can be determined from the published article, the
Frankenstein study was carefully conducted, and thera is no
reason to doubt the accuracy of the reported data.
2. DNC increased the incidence of tumors (percentage or propor-
tion of animals with tumors) in certain groups of animals.
Not all animals in a group receiving DNC developed tumors.
Tumor incidence is a measure of the risk (probability) of
tumor development. Data in Table 2 can be interpreted as in
the following example: the lifetime risk of stomach cancer
in male rats exposed by gavage to the high dose of DNC
daily, for their full lifetimes, is 0.40.
3. Rats developed spleen and liver tumors after both inhalation
and gavage exposures. Lung tumors were produced only by
inhalation, and stomach tumors only by gavage. Females of
both species showed fewer tumors than males, and mice, showed
fewer tumors than rats.
4. The stomach tumors appeared at the point where DNC contacted
the stomach when introduced by stomach tube. This point is
in the rodent forestomach, an anatomical feature not present
in humans.
5. Severe irritation was observed in the areas of the rodents'
stomachs that were exposed to high doses of DNC delivered by
stomach tube. No signs of irritation were observed in low-
dose control animals. Dr. Frankenstein believes that the
stomach tumors arose as a result of the severe toxic insult
caused by the direct stomach exposure.
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II-5
Tattle 1
DESIGN OF THE FRANKENSTEIN STUDY
Species and
Rout* of Exposure
Rat, inhalation
Rat,
Mouse, gavaqa>3
Groupa
Receiving
CNC
Control
Low
High
Control
Low
High
Control
Low doaa
High
Nuaber of
Animal*
Mala Feaale Each OayJ
Amount of
ONC Received
,1
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
0
30
60
0
50
100
0
60
120
Duration of
Expoaura (weeks)2
104
104
104
104
104
104
78
78
78
of ONC par kiloqraa of the animal's body weight. The concentration
of ONC In the air in the inhalation experiment haa bean converted to a unit of
•eight ao it can be compared with the unita in the gavage study.
^Approximate Ufeapana of the aniaala tftdar laboratory eonditlona.
'Gavaga ia administration of a substance by aaana of a stoaach tuba.
Table 2
SIGNIFICANT FINDINGS FROM THE FRANKENSTEIN STUDY
Following ere the only groups in which a statistically significant exceaa
of tuaor* »aa found. Nearly 40 poaaible si tea of tumor formation Mara
examined in each sax of both apaeiaa.
Percentage of
Animla with Tuaors
(incidence rate)
Study Group
Rat, inhalation
Rat, inhalation
Rat, inhalation
Rat, gavage
Rat, gavaga
Rat, gavaga
Rat, gavaga
Sex
Male
Mala
Mala
Tumors
Found
Lung
Spleen
Liver
Control Low Ooaa High Ooaa
Mala Stomach
Female Stoaach
Mala Liver
Mala Spleen
gavaga
Mouaa, gavaga
Mala
Mala
Liver
Stomach
3
0
3
0
0
3
0
5
0
3
2
7
0
0
7
10*
30*
0
12*
40»
30«
50"
'A statistically significant exceee of tuenrs ralativa to untreated
control animals. This i»aana it ia unlikely that the difference in tumor
incidence between the treated and control aniswls ia due to chance.
Bacauaa the only difference between tha control and treated animals wae
the presence of ONC, it la likely that the excaaa tumor Incidence ia due
to this eoapound. Tuanra were found at other sites in both control and
treated aninals, but no other tumors occurred in statistically
significant axceaa.
006
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Issues to Be Considered on the Carcinoqenicity of PNC
1. How do these data conform (or not conform) to the
principles laid out on pages II-2 and II-3—particu-
larly the last principle?
2. In view of these principles, is there any reason to
conclude that DNC is not carcinogenic in rats of both
sexes (by gavage exposures) and in male mice (by
inhalation and gavage)?
3. Should the stomach tumors be considered relevant to
low-exposure risks to humans?
4. Should the data obtained by gavage treatment be
considered relevant to human exposure?
5. Is there any reason to believe that humans would not be
at risk of developing the various tumors, assuming
exposure to DNC?
6. Is there any way to determine, from the data given,
whether responses in humans are likely to be similar to
those of rats or mice? Males or females?
7. Do the data provide sufficient evidence to prove DNC
is carcinogenic in animals? Are the data too limited
or even inadequate?
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Epidemiological Data
the Frankenstein report was puolished, three DNC manu-
facturers decided to sucmit reports to EPA on their investiga-
tions into employee health. The information from these three
reports is summarized below.
Manufacturer A
Manufacturer A had been producing DNC for 45 years, but none
of the 161 employees in the mortality study had been exposed for
more than 20 years; most were exposed for 10 to 15 years. Al-
though employee exposure data were not extensive, they suggested
that past exposures were relatively high, sometimes approaching
the inhalation levels that produced an excess of tumors in
animals. (Although the concentrations of air in the workplace
approached those used in the- animal experiment, the workers were
exposed to these high levels for only a fraction of their life-
time. )
By January 1979, 35 of the 161 workers had died. No
statistically significant increase in cancers (malignant
neoplasms) of any type was noted among these workers (3 cases
observed, 3.8 expected in a population of the same size, sex, and
age). Cancers of the digestive system were elevated (2 cases
observed, 0.7 expected), but this elevation was not statistically
significant (i.e., it is not possible to say the observed
difference was not due simply to chance). The workers were also
exposed to several other chemicals, at least two of which are
known animal carcinogens.
Manufacturers B and C
Reports from Manufacturers B and C are similar to the report
of Manufacturer A. No cases of malignant neoplasms of the
stomach were reported by either manufacturer. Both manufacturers
reported slight elevations in lung cancer, but neither elevation
was statistically significant. No data on worker smoking habits
were available. Manufacturer C reported 33 deaths among 290
employees.
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Issue to Be Considered
1. Should the information from the DNC manufacturers alter
earlier conclusions about the inferences to be drawn
from the animal data? If so, how? If not, why not?
2. Are the epidemiological data sufficient evidence to
prove DNC is carcinogenic in humans? Are the data too
limited or inadequate?
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11-9
EPA's Risk Assessment Guidelines
The Office of Health and Environmental Assessment (OHEA)
within EPA's Office of Research and Development has developed
guidelines for carcinogen risk assessment. These guidelines
discuss weighing the evidence that a substance is a carcinogen
and classifying the chemical into one of five groups:
Group A—Human carcinogen
Group B—Probable human carcinogen
Group C~Possible human carcinogen
Group D—Not classified as to human carcinogenicity
Group E—Evidence of noncarcinogenicity for humans
OHEA developed an illustrative categorization of substances
based on animal and human data/ as shown in Table 3.
Table 3
ILLUSTRATIVE CATEGORIZATION OF EVIDENCE BASED ON
Animal Evidence
Hunan
Evidence
Sufficient
Limited
Inadequate
No data
No evidence
Sufficient
A
B1
82
82
82
Limited
A
B1
C
C
C
Inadequate
A
81
D
0
D
ANIMAL AND HUMAN DATA
No Data
A
31
D
D
0
No
Evidence
A
81
D
E
E
You should note that the "No Data" category means no data
are available indicating a substance is or is not carcinogenic.
"No Evidence" means, for humans/ no association was found between
exposure and increased risk: of cancer in well-conducted, well-
designed analytical epidemiologic studies. When reviewing animal
data "No Evidence" means no increased incidence of neoplasms was
found in at least two well-designed and well-conducted animal
studies of adequate power and dose in different species.
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11-10
Some Possible Conclusions
About PNC Carcinogenicity
1. DNC is a human carcinogen (Group A). There is suffi-
cient evidence from epidemiological studies to support a
causal association between DNC exposure and cancer.
2. DNC is a probab.le human carcinogen (Group B2). There is
sufficient animal evidence of carcinogenicity as demon-
strated in the increased incidence of tumors at several
sites in multiple species (rats and mice), in multiple
experiments involving different routes of administration
(inhalation, gavage), and at different dose levels.
There is inadequate evidence of carcinogenicity from
epidemiological studies.
3. DNC is a possible human carcinogen (Group C). There is
limited animal evidence of carcinogenicity because the
data obtained when DNC was administered by stomach tube
may not be relevant to any route of human exposure.
Thus, DNC resulted in increased tumors in only one
species (rat) and in one experiment involving only the
inhalation route of exposure. There is inadequate
evidence of carcinogenicity from epidemiological
studies.
4. DNC is not classifiable as to human carcinogenicity
(Group D). Because of the extreme conditions under
which tumors were produced in the animal experiments,
there is no reason to believe that DNC is a possible
human carcinogen. There is inadequate evidence of
carcinogenicity from epidemiological studies.
5. Other (formulate your own conclusion).
on
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11-11
SYSTEMIC TOXICITY OF DNC
Depending on the dose, exposure to a given chemical, such as
DNC, may result in a variety of toxic effects of which cancer is
only one. These may range from gross effects, such as death, to
more subtle biochemical, physiological, or pathological changes.
Chemicals that give rise to toxic endpoints other than cancer
(and gene mutations) are often referred to as "systemic toxi-
cants" because they affect the function of various organ systems.
It should be noted that cancer-causing chemicals commonly also
evoke other toxic effects (systemic toxicity).
So far, we have only discussed the carcinogenic properties
of DNC. But as part of the hazard identification stage of a risk
assessment, the risk assessor considers each of the toxic end-
points from all studies evaluated in assessing the risk posed by
a chemical.
A chemical such as DNC may elicit more than one toxic
effect, even in one test animal, in tests of the same or differ-
ent duration (acute, subchronic, and chronic exposure studies).
In general, the dose at which no adverse effect is demonstrated
will differ from one effect to another. For example, the highest
dose at which statistically significant increases in kidney
damage are no longer observed may differ from the highest dose at
which statistically significant increases in liver damage are no
longer observed.
Primary attention usually is given to the effect exhibiting
the lowest "no observed adverse effect level" (NOAEL), often
referred to as the critical effect. In simplest terms, an exper-
imental exposure level is selected from the critical study that
represents the level at which "no adverse effect" was demon-
strated. In our example above, if the highest NOAEL associated
with kidney damage is greater than the highest NOAEL associated
with liver damage, then liver damage is the critical endpoint for
examining systemic toxic effects of DNC. This approach is based
on the assumption that if the critical toxic effect is prevented,
then all toxic effects are prevented.
The Shakespeare Study
Only one chronic study of oral exposure to DNC was located
in the available literature. That study, conducted by
Dr. Shakespeare et al. in 1978, presented data on the effects of
exposure to DNC in rats. The design of the Shakespeare study and
the major findings are presented in the following quote from the
abstract:
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11-12
"A total of 80 rats (40 males/40 females) were exposed
to either 0 mg/kg/day, 2 mg/kg/day, 10 mg/kg/day, or
20 mg/lcg/day of DNC for two years. The method of
exposure was gavage (in water). At the 20 mg/kg/day
level of exposure, a statistically significant reduc-
tion in the rate of body weight gain and weight changes
in the kidney and liver were observed in both male and
female rats. Pigmentation of the liver and a statisti-
cally significant reduction in the rate of body weight
gain were observed in female rats exposed to at least
10 mg/kg/day of DNC. The 2 mg/kg/day level of exposure
was reported as a chronic 'no observed adverse effect
level.1"!
Remarks on the Shakespeare Study
1. As far as can be determined from the published article/ the
Shakespeare study was carefully conducted, and there is no
reason to doubt the accuracy of the reported data.
2. The Shakespeare study has been identified by your lab as th«
critical study, with liver pathology as the critical effect
or systemic toxic endpoint. That is, the primary target
organ for the systemic effects of DNC is the liver.
3. DNC increased the incidence of liv'er and kidney changes in
certain groups of animals. Not all animals in a group
receiving DNC suffered from changes in liver or kidney
weight.
^-Shakespeare, et al., "Chronic Systemic Toxicity of Dinitrochick-
enwire in Rats," Journal of Environmental Toxicology (1978).
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11-13
Issues to Be Considered on the Systemic Toxi'city of PNC
1. How do these data conform (or not conform) to the
principles laid out on pages II-l and II-2—particu-
larly the last principle?
2. In view of these principles, is there any reason to
conclude that DNC is not a systemic toxicant in rats of
both sexes?
3. Should the data obtained by gavage treatment be
considered relevant to human exposure?
4. Is there any reason to believe that humans would not be
at risk of developing liver and kidney damage if
exposed to DNC?
5. Is there any way to determine, from the data given,
whether responses in humans are likely to be similar
to those of rats?
014
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11-14
Some Possible Conclusions About the Systemic Toxicity of PNC
1. DNC is a systemic toxicant to humans. There is clear
evidence from animal studies to support a conclusion
that DNC exposure will cause kidney and liver damage in
humans.
2. It is highly likely DNC is a systemic toxicant to
humans. There is sufficient evidence of toxicity as
shown in the kidney and liver pathology found in rats
exposed to DNC at relatively low doses.
3. DNC is a potential human systemic toxicant. We have
reviewed a very limited amount of animal evidence
showing that DNC is a systemic toxicant to rats result-
ing in liver and kidney damage.
4. DNC is not classifiable as to human systemic toxicity.
The animal evidence is insufficient to make a decision
at this time.
5. Other (formulate your own conclusion)
015
-------
III. HUMAN EXPOSURE EVALUATION
SOME PRINCIPLES FOR EXPOSURE EVALUATION
1. The purpose of exposure evaluation is to identify the magni-
tude of human exposure to DNC, the frequency and duration of
that exposure, and the routes by which humans are exposed.
It may also be useful to identify the number of exposed
people along with other characteristics of the exposed popu-
lation (e.g., age, sex).
2. Exposure may be based on measurement of the amount of DNC in
various media (air, water) and knowledge of the amount of
human intake of these media per unit of time (usually per
day) under different conditions of activity.
3. Some individuals may be exposed by contact with several
media. It is important to consider total intake from all
media in such situations.
4. Because only a limited number of samples of various media
can be taken for measurement, the representativeness of
measured values of environmental contaminants is always
uncertain. If sampling is adequately planned, the degree to
which data for a given medium are representative of that
medium can usually be known.
5. Sometimes air and water concentrations of pollutants can be
estimated by mathematical models. Although some of these
models are known to be predictive in many cases, they are
not thought to be reliable in all cases.
6. Standard average values and ranges for human intake of
various media are available and are generally used, unless
data on specific agents indicate that such values are
inappropriate.
SITE DESCRIPTION
As discussed earlier, the Electrobotics Company, which manu-
factures parts for Bananachrome* personal computers, operates a
production facility. The facility employs 150 workers and
016
-------
III-2
includes a wastewater treatment plant and equalization lagoon
(surface impoundment). (The site plan is illustrated in
Figure 2.) Wastewater from the manufacturing plant operations
contains high concentrations of DNC and is periodically dis-
charged to a flow equalization lagoon, which is located within
200 feet of the western facility boundary. There are no other
potential sources of DNC releases in the surrounding area.
Adjacent to this boundary is a residential area of 20 houses in
which 80 individuals reside. Electrobotics has built an 8-foot-
high chain-link fence on the property boundary separating the
residents from the facility grounds. The area between the
Electrobotics facility and the threatened water supply wells to
the east is undeveloped and contains few residences. There has
been some discussion about building housing on the property/ but
no definite plans exist at this time. The Smith river is located
east of the facility about 1,500 feet from the facility boundary.
There are no drinking water intakes along the river, but some
recreational fishing and swimming occurs.
Figure 2
Site Plan and Points of Compliance and Exposure
Electrobotics Property
Boundary
\
[Smith River]
r~\ x
Air Monitoring
Compaance Monitoring Wells
Eastern Property Boundary
Residential Area
Wastewater
Treatment I *
Direction of
Ground-Water Row
Threatened
Water Supply
Wells
Point of Compliance
Key Characterization Wells
N
(Not to Scale)
017
-------
III-3
The equalization lagoon maintains a regular flow to an
on-sits activated sludge wastewater treatment facility. The
equalization lagoon is maintained at an average fluid depth of
10 feet and measures 10/000 square feet. The wastewater from the
treatment plant is discharged to the river in compliance with the
facility's NPDES permit.
The equalization lagoon is underlaid by a compacted natural
clay liner with a hydraulic conductivity (a measure of the rate
at which it transmits water) of 3 x 10~s cm/sec, which is
designed to provide substantial containment of the wastewater.
The uppermost geological formation beneath the site is composed
of approximately 75 feet of stratified glacial outwash, which
consists of layered sand and gravel with some silt. These
unconsolidated sediments form a productive aquifer that is a
source of potable water to the surrounding area. A well field is
located approximately 1.5 miles to the east (downgradient) of the
site and provides approximately 3 million gallons per day (mgd)
of potable water to its 50,000 customers. The well field con-
tains 40 separate wells, each pumping 75,000 gallons per day
(gpd).
The hydraulic conductivity of the aquifer has been estimated
at 40 feet per day, based on field tests in the area. However,
there may be thin continuous layers of significantly lower or
higher hydraulic conductivity within the glacial outwash. The
water table is located about 10 feet below the bottom of the
lagoon at the site. The hydraulic gradient (a measure of the
slope of the water table), based on the best available potentio-
metric head measurements, is estimated at 0.005 feet/feet toward
the community well field.
The site is located in a humid area. The wind direction is
seasonal; however, according to a wind rose from a local meteoro-
logical station (which describes wind direction and frequency),
the wind blows west across the site toward the 20 homes adjacent
to the lagoon approximately 30 percent of the time.
The owners of Electrobotics conducted analysis of the lagoon
in preparing their Part B application. The nature of the materi-
als stored in the lagoon and the meteorological and hydrogeolog-
ical conditions in the vicinity have resulted in some concern by
EPA about possible exposure of workers at the facility and resi-
dents in the vicinity to DNC via inhalation of air, as well as
possible exposure of the community via contamination of drinking
water supplies. In an attempt to respond to the regulations and
concerns of EPA staff, the owners undertook a program of air,
surface-water, and ground-water monitoring.
018
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II1-4
Measurements of concentrations of DNC on the site are
described in the next section. A ground-water monitoring program
has been undertaken to comply with regulations promulgated under
the Resource Conservation and Recovery Act (RCRA). Electrobotics
is monitoring contaminants in ground water at the downgradient
limit of the waste management unit, termed the "point of compli-
ance." The point of compliance in this case is at the eastern
limit of the berm around the lagoon. Three monitoring wells have
been installed at this point, and one well was installed upgradi-
ent (see Figure 2). This conforms to the regulatory minimum.
No DNC was found in the sample from the upgradient well. The
nearest downgradient property boundary is to the east, about
1,000 feet from the lagoon.
Because DNC has been detected at the downgradient compli-
ance-monitoring wells, a ground-water assessment has been initi-
ated, and additional monitoring wells have been constructed at
the eastern property boundary to monitor chemical concentrations.
Further downgradient, the public well field represents a point of
potential human exposure. Three of the 40 wells are located
directly downgradient of the lagoon. The relative locations of
the point of compliance, eastern regulatory boundary, and actual
point of exposure are shown in Figure 2.
AVAILABLE INFORMATION
ON DNC CONCENTRATIONS
Measurements of DNC concentrations in air along the western
site boundary, outdoors at the facility adjacent to the lagoon,
and indoors within the treatment plant have been made during a
single air-sampling program. The sampling program was conducted
for a period of one week, during which 24-hour average concentra-
tions were measured at the western property boundary, adjacent to
the equalization lagoon and within the treatment plant. During
the period of measurement/ wind was blowing generally west across
the lagoon toward the residential area. The mean, standard devi-
ation, and range of measured chemical concentrations in air are
shown in Table 4. Air measurements that were made concurrently
inside the wastewater treatment plant did not detect measurable
concentrations of the solvent. Within the treatment plant, all
treatment units are closed and vapor-controlled to limit any
fugitive air emissions.
Electrobotics1 NPDES permit requires monitoring only for
conventional pollutants and indicator parameters, so the effluent
from the treatment plant is not monitored for DNC before
019
-------
III-5
it is discharged to the Smith river. In preparing its Part B
application, however/ the owners of Electrobotics collected a
limited number of samples from the treatment facility outfall.
The results are presented in Table 4, and indicate that no DNC
was detected.
Table 4
FIELD MEASUREMENTS OF DNC CONCENTRATIONS
Detection
Medium
Air
Air
Air
Ground water
Ground Mater
Ground water
Surface water
Location
Inside treatment plant
At weatern boundary of site
On-aite
Point of compliance
Eastern property boundary
Public well field
Treatment plant outfall
iftot detected at 1 /u.g/n? for air or 1 ng/l for
^Trace concentrations below detection limit of
Level
&*«/•*]
Lug/*3]
Cug/ir>]
Cug/l]
Cug/l]
Cug/l]
Cug/l]
water.
i,ug/i.
Mean
NO*
44
188
332
BOL2
NO*
»1
i
DNC
Standard
Deviation Range
16 8-68
80 120-480
30 290-350
The ground water has been periodically sampled and tested
for DNC both at the point of compliance, the monitoring wells on
the eastern boundary/ and at the water treatment plant at the
community water system/ which draws water from the aquifer for
the municipal supply. Samples were taken at several depths as
well. The concentrations of chemicals in monitoring wells at the
point of compliance are indicated in Table 4. The concentrations
detected at the compliance point indicate contamination of the
aquifer. Trace concentrations of ONC have also been detected at
the eastern boundary in the most recent water tests/ but at con-
centrations less than the method-detection limit of 1 ug/1
(or'ppb). The municipal water supply has been tested, and no
detectable concentrations of DNC were found. However/ the
detection limit for DNC offered by available analytical methods
for ground water is 1 ug/1.
A very simple description of the area's geology and the
current status of the DNC-contaminated ground-water plume are
presented in Figure 3. Available information suggests that the
chemical plume has not yet migrated beyond the eastern property
boundary/ but without corrective action the concentrations are
expected to increase in time in this vicinity, eventually affect-
ing offsite ground water.
020
-------
III-6
Rgure 3
Site Plan
Residential Area
Electrobotlcs Property
Boundary
Smith River
Threatened
Water Supply
Wells
DNC-Contamlnated Plume
Wastewater
Treatment
Plant
Direction of
Ground-Water Row
(Not to Scale)
Geological Cross Section
Elevation
In F«et -30
300ft.
1,000ft.
Lagoon
N/
Monitoring Welle
Characterization WeN
DNC-Contamlnated Plume'
Water Supply
Well
1 The outermost contour line la believed to be the edge of the edge of the DNC-contaminated plume.
where the concentration Is below the detection limit of 1 ppb.
4 Tt'V'lS' surfac8 n«» a constant slope of 0.005 feet/feet. The apparent change In slope Is an effect
of the different horizontal scales.
021
-------
III-7
A mathematical model of the contaminant plume movement in
the aquifer has been constructed to estimate future concentra-
tions in the aquifer. A summary of the modeled environmental
concentrations in ground water is presented in Table 5. Appen-
dix A contains the calculations and the associated assumptions
that were applied in modeling these environmental concentra-
tions.
Table 5
SUMMARY OF MODELED CONCENTRATIONS OF ONC
STEADY STATE IN GROUND WATER1
Location
Eastern property boundary
Public well-field
PNC (
-------
III-8
Human exposure to contaminated soil, however, was considered
insignificant at this site because soils potentially contaminated
by ground water are located at least 10 feet below the land sur-
face. No concentrations of DNC were found in a limited set of
soil samples taken from surface soils around the lagoon. Conse-
quently, doses resulting from potential human exposure to soil
were not calculated.
In order to estimate human exposure, or dose of the consti-
tuent from each contaminated medium, certain data and assumptions
were applied. These data and assumptions relate to the extent
and frequency of human contact with these media and the degree of
absorption of chemicals for each route of exposure. When the
constituent is ingested, a certain fraction will be absorbed
through the gastrointestinal wall; when it is inhaled, a certain
fraction will be absorbed from the lungs.
The method of dose calculation depends on the route of expo-
sure. Certain standard values have been developed to estimate
contact with and intake of certain media. For drinking water,
the EPA and other scientific groups generally assume that adults
drink 2 liters of water per day. It is also generally assumed
that the average adult inhales from 20 to 23 cubic meters (m3) of
air per day. We have assumed an adult inhales 23 mVday,
although EPA risk assessments are increasingly using 20 mVday.
It should be noted, however, that the data and assumptions
required for estimation of dose from most other routes of expo-
sure are not as readily standardized.
The assumptions and calculations required to estimate DNC
dose to the 80 neighboring residents resulting from inhalation of
DNC-contaminated air are presented below to illustrate the ele-
ments of dose estimation. A complete set of calculations and
associated assumptions for the critical pathways is shown in
Appendix B.
Inhalation of DNC-Contaminated
Air by Neighooring Residents
Assumptions:
• An adult inhales 23 mVday °f air.
• Based on wind direction analysis, the duration of
exposure is 30 percent of the time on an annual average
basis.
• The body weight of an adult is 70 kg.
• The inhalation absorption factor for DNC is 0.75.
• The adult lives in the home throughout his lifetime.
023
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III-9
Calculations:
0 .044 mg
(average DNC air concentration at boundary)
23
day
x x 0.3 (percentage of time exposed)
70 kg
x 0.75 (inhalation absorption factor)
= 3.3 x 10-3 mg/kg/day
Table 6 presents a summary of all the exposure calculations
performed to estimate doses from the contaminated media to the
identified exposed population groups.
Table 6
SUMMARY OF RESULTS OF EXPOSURE CALCULATIONS
Medium
Air, neighboring residents1
Air, workers on site (outdoors)^
Ground water, point of compliance^
Ground water, eastern property boundary-5
Ground water, public well-field-*
DNC (mg/kg/day)
3.3
x 10~3
4.7 x 10-3
9.5 x 10-3
7.8 x 10-3
1.6 x 10-*
Number of
Persons
Exposed
80
150
0
0
50,000
-'•Estimated exposures from DNC in the air are based on current concentrations
in the air.
Estimated exposures at the point of compliance are based on current
concentrations of DNC at that point, although no individual is currently
exposed to those concentrations.
^Estimated exposures at the eastern property boundary will not occur for three
years, and no one currently receives their drinking water from that point.
Exposure estimates for the public well-field will not occur for about
22 years.
ECOSYSTEM EXPOSURES
The ecosystem in the ^mith river has been examined by a
biologist employed by the Electrobotics plant. The resulting
study characterizes the area upstream and downstream from the
facility. No major evidence of ecological damage was found,
024
-------
111-10
although there was some discoloration of the river around the
outfall noted when the plant switched to the use of DNC. This
discoloration has persisted.
No threatened or endangered species were found near the
Electrobitcs site. However, several threatened or endangered
species have been known to inhabit river ecosystems in the
vicinity. Fish species include the Snail Darter, Slackwater
Darter, Amber Darter, and Spotfin Chub. Terrestrial species
include the Eastern Indigo Snake. Furthermore, several of these
species are acutely sensitive to compounds similar in structure
to DNC. The data available on DNC are not adequace for estab-
lishing ambient water quality criteria for aquatic life.
As noted earlier, the effluent discharged to the Smith river
from the Electrobotics treatment plant was tested for DNC. No
DNC was detected at a detection limit of 1 /xg/1.
Remarks on Exposure Data
1. Ground water directly beneath and adjacent to the regulated
unit has been routinely sampled and analyzed for the
presence of DNC. Concentrations that have been measured
have remained relatively constant for the past two years and
indicate that DNC has leaked from the storage lagoon into
the underlying aquifer. Ground water moves toward a well
field that provides drinking water for a community of
50,000 people. DNC has not been detected in the water sup-
ply but may be present at concentrations below the current
method detection limit, which is 1 ^g/1 (ppb).
2. DNC is unstable in the environment and will decompose by
biodegradation in shallow aquifer systems. The decomposi-
tion of the chemical in aquifers has been demonstrated in
aquifer restoration programs at other sites, but the rates
of decomposition are variable and have only been quantified
in laboratory experiments. The rate of decomposition at
concentrations less than 10 ppb is uncertain.
3. Trace concentrations (less than 1 jig/I) of DNC have been
detected at the eastern facility boundary. A mathematical
model has been used to predict future concentrations of DNC
in ground water downgradient of the regulated unit. The
model prediction indicates that the chemical will migrate in
ground water and degrade at a slow rate. On the basis of
the model prediction, concentrations are expected to
increase at the eastern property boundary if no corrective
action is taken. The degradation products are not believed
to be carcinogenic.
025
-------
III-ll
4. Estimates of future concentrations of DNC in drinking water
are based on analytical predictions from a ground-watar
model. Appropriate adjustments regarding ground-water
dilution were made to estimate concentrations at the tap.
5. Estimates of current exposure in air were based on analyti-
cal results obtained from measuring the air concentrations
in the facility and at the boundary over a single seven-day
period in April 1986. Twenty-four-hour composite samples
were taken each day over the sampling period. No other air
data are available.
6. Estimates of current concentrations of DNC in treatment
plant effluent are based on analytical results from samples
taken over the same seven-day period in April 1986. Five
samples were taken during this period.
026
-------
111-12
Issues to Be Considered
1. Has Electrobotics adequately characterized the
ground-water contamination? If not, what additional
types of information would you require them to provide
and why?
2. The summary exposure data presented in Table 6 include
some current exposure estimates and some future expo-
sure estimates. Models are used to predict concentra-
tions of DNC at some point in the future/ assuming that
releases of the substance from the lagoon occur at the
current rate. Should the two types of exposure data
(current and future) be treated the same for purposes
of characterizing human risk? How should distinctions
be reported?
3. Should the ground-water concentration estimates that
are based in part on modeling of a degradation process
be used at all? How should this be decided? If
modeled concentrations are not used, how should the
analyses of chemicals that are reported as "below
detection limit" or "not detected" in the water supply
system be represented in exposure estimates?
4. Are the estimates of DNC in surface water acceptable?
What additional information would you want?
5. Is the mean concentration in the various media the
appropriate summary statistic to use to characterize
human exposure? Should the upper range or statistical
upper confidence limit be used as an alternative?
6. Are the various assumptions about human intake and
average exposure to various media valid? Should others
be substituted or added?
7. Should other routes of exposure to the various contami-
nated media have been considered?
8. Should the total exposure and risk for the regulated
unit be represented by the sum of all incremental risks
for each chemical/pathway?
027
-------
111-13
Issues to Be Considered (continued)
9. Was it appropriate to model the exposure based on an
adult population? Should other populations-at-risk
have been considered?
10. Should exposure and risk to workers at the facility be
considered in the same context as residents in the
surrounding community?
11. Do you believe DNC is affecting the ecosystem around
the Smith River?
028
-------
111-14
Some Possible Conclusions About
Human Exposure to PNC
Which of the following conclusions best characterizes
the information you have seen?
1. None of the exposure estimates is adequate for use in
risk assessment. Given the currently available data,
the risk assessment should describe exposure in quali-
tative terms only. No quantitative risk assessment
should be developed until better information is
available.
2. The exposure estimates presented in Table 6 for drink-
ing water and air are reliable and can be used for risk
assessment. However, no risks should be assessed until
more detailed data are obtained from other pathways of
exposure, such as showering or ingestion of contami-
nated soils.
3. The exposure estimates presented in Table 6 and based
on field measurements are reliable and can be used for
assessing risks. The exposure estimates based on
modeling, however, are too uncertain to be used to
assess the risks.
4. Although the exposure estimates in Table 6 are based on
different data and assumptions, they are all adequate
and sufficient for assessing risks. The risk manager
should be made aware of the uncertainties in each of
the data sets, but a quantitative risk assessment
should be developed.
5. In addition to Conclusion 2, it should be noted that
all the exposures from various media should be added
for those people exposed to all sources of DNC.
6. Other (formulate your own).
029
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IV. DOSE-RESPONSE EVALUATION
Normally, you would not be involved in reviewing dose- '
response information; the results generally would be pro-
vided to you. As discussed before, however, we hope that by
having you evaluate this information and address the key
issues here, you will be able to better use the dose-
response information you will receive.
We have given you the EPA approach to evaluating dose-
response relationships. In addition, we have identified
alternative approaches so that you develop an understanding
of how others may perceive the issue.
030
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IV-2
DOSE-RESPONSE EVALUATION FOR
CARCINOGENICITY: THE GENERAL
PROBLEM AND PRINCIPLES GUIDING
APPROACHES TO ITS SOLUTION
Because of the relative complexity of dose-response evalua-
tion, the following discussion is substituted for a statement of
key principles.
Animal data showing that DNC is carcinogenic were obtained
in the high-exposure region of the dose-response curve. Thus,
animal exposures were in the 30-to-300-unit range (see Table 1),
and these produced measurable risks in the range of 10 to 50 per-
cent (see Table 2). Predictions of human exposure, as discussed
in Section III, are at much lower levels. What can be said about
risks in the range of human exposure?
At least three general approaches to this problem have been
proposed by various experts.
Approach 1
Based on general theories of how carcinogens act to produce
cancer (largely derived from experimental studies and epidemi-
ological data), all finite exposure levels will produce a finite
risk. The magnitude of the risk will decline as the magnitude of
exposure declines (clear even in the animal data).1
If the quantitative relationship between exposure and risk
were known for all exposures, the risks to rodents exposed at
very low levels could be predicted from the measured exposure-
risk data. The risks to humans could be predicted at these very
low levels if the relationship between rodent and human suscepti-
bilities were known. Although these relationships cannot be
known with accuracy, a plausible upper limit on human risk can be
predicted with sufficient accuracy to be used as a guide to mak-
ing risk decisions. Actual human risk is not likely to exceed
the upper limit, and it may be less. This is the approach
generally adopted by EPA in evaluating the risk associated with
low-level exposure to carcinogens.
iThese two sentences are the proper formulation of the "no-
threshold" concept. It does not mean that all finite exposures
will cause cancer; rather, it means that all finite exposures
will increase the probability (risk) that cancer will occur.
031
-------
IV-3
Approach 2
The quantitative relationships between high-exposure and
low-exposure risks in rodents and between rodent and human risk
are not known with sufficient reliability to be used in risk
assessment. Moreover, there is no reliable theory on which one
can conclude with assurance that low-level human exposure (i.e.,
exposure below the range producing detectable risks) poses any
risk at all. As with other toxic effects, carcinogenicity will
not be initiated within an individual until a minimum threshold
of exposure is exceeded. In such circumstances, the only reason-
able course is to report the magnitude of the margin-of-exposure
(MOE) by which humans are protected. MOE is the maximum amount
of exposure producing no measurable tumorigenic response in ani-
mals divided by the actual amount of human exposure. MOE gives
the risk manager adequate information on which to decide whether
exposures must be reduced or eliminated to provide human protec-
tion. A relatively large MOE is desirable because it is likely
that the threshold for the entire human population is lower than
that observed in small groups of experimental animals. This
approach is generally applied when evaluating the potential risk
of most noncarcinogenic effects.
Approach 3
Although there is adequate theory and some evidence to per-
mit the conclusion that humans are at finite risk at all finite
exposure levels, there is insufficient knowledge to allow predic-
tion of the risks in quantitative terms. The risk assessor
should simply attempt to describe risks qualitatively, perhaps
coupling this description with some information on the potency of
the compound and the magnitude of human exposure. This type of
presentation is adequate for the risk manager, who should not be
concerned with the quantitative magnitude of risk in any case.
Each of these views, and perhaps others as well, has some
merit. The first approach is now used by most federal public
health and regulatory agencies, including EPA. These agencies
emphasize that the predicted numerical risks are not known to be
accurate, but because of the nature of the models used to predict
them, they are likely to be upper-bound estimates of human risk.
An upper-bound estimate is one that is not likely to be lower
than the true risk and is likely to exceed the true risk (which
could be zero).
032
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IV-4
For this exercise, we will estimate low-exposure risks using
the model currently used by EPA. A model is a mathematical for-
mula that describes the relationships between various measures.
Two models are needed to predict low-exposure risks:
• A high to low exposure extrapolation model is needed to
predict low-exposure risks to rodents from the measured
high-exposure, high-risk data (see Table 2). EPA
currently uses a "linearized multistage model" for this
purpose. This model is based on general (not chemical-
specific) , widely held theories on the biological pro-
cesses underlying carcinogenesis. Application of the
model to the rodent exposure risk data produces an
estimate of the lifetime risk for each unit of exposure
in the low-exposure region. This is called the unit
cancer risk. The linearized model is used to ensure
that the unit cancer risk is an upper-bound estimate of
risk.
• An interspecies extrapolation model is used to extra-
polate from rodent unit risks to human unit risks. EPA
assumes that rodents and humans are at equal risk at
the same exposure measured in milligrams of carcinogen
per square meter of body surface area per day. Inter-
species extrapolation models are commonly called
"scaling factors" because they are used to scale doses
between species.
EPA's selection of these models is based on the agency's
view that they are the best supported for purposes of deriving an
upper-bound estimate of risk. Alternative models are available
for both these forms of extrapolation, and several are equally
plausible. In most cases, but not always, use of plausible
alternative models will yield lower estimates of risk than those
predicted by the two described here. Differences can sometimes
be very large/ but are generally relatively small when the models
are limited to those that are linear at low exposures.
Further discussions of various models and their plausibility
can be found in the handout "Principles of Risk Assessment: A
Nontechnical Review."
APPROACH TAKEN FOR THIS EXERCISE
In this exercise we determine the upper-bound estimate of
unit cancer risks predicted for DNC using the models currently
preferred by EPA. The effect of using alternative, plausible
033
-------
IV-5
models is also described, as are the animal.data that pertain to
the second or third approaches described above for dose-response
evaluation (i.e., the MOE or qualitative approaches).
Estimates of Upper-Bound,
Lifetime Slope Factors
Using Current EPA Models
Application of the EPA models for high-to-low-dose and
interspecies extrapolation to the measured animal cancer data for
DNC (Table 2) yields the results shown in Table 7. The result of
such extrapolations is the slope factor. In this exercise, one
unit of exposure is equal to one milligram (mg) of the carcinogen
per kilogram (kg) body weight of the animal (or human) per day
throughout the lifetime of the animal (or human). Thus, if the
slope factor for DNC is 0.0897 (8.97 x 10~2), the risk of
developing cancer from 1 mg/kg/day of lifetime exposure to DNC is
3.97 x 10-2 (a probability of about 9 in 100, or 1 in 10).
Table 7
UPPER-BOUND ESTIMATES ON LIFETIME SLOPE FACTORS
PREDICTED BY APPLYING EPA'S PREFERRED MODELS
TO DNC TUMOR DATA
(based on Table 2)
Species. Sex Route of Exposure Tumor Site
Rat, male Inhalation Lung
Rat, male Inhalation Spleen
Rat, male Inhalation Liver
Rat, male Gavage Stomach
Rat, female Gavage Stomach
Rat, male Gavage Liver
Rat, male Gavage Spleen
Mouse, male Gavage Liver
Mouse, male Gavage Stomach
Slope Factor
(potency)
0.0186
0.0126
0.0168
0.0054
0.0054
0.0120
0.0228
0.0897
0.0096
(1.86xlO-2)
(1.26xlO-2)
(1.68x10-2)
(5.4xlO-3)
(5.4xlO-3)
(1.2x10-2)
(2.28x10-2)
(8.97x10-2)
(9.6xlO-3)
*Risk for an average daily lifetime exposure of one unit. Units are
the same as those used earlier for describing the animal exposure
(Table 1), such that one unit s one milligram per kilogram body weight
per day. Risk is obtained from the slope factor by multiplying the
latter by the actual number of units of human exposure. For a given
exposure, the higher the slope factor, the higher the risk.
034
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IV-6
This relationship is presented graphically in Figure 4. The
horizontal axis is the dose of DNC measured in mg/kg/day. The
vertical axis is the response and is a probability.
Figure 4
Dose-Response Relationship for DNC
.0897
(slope Factor)
1 DOM
(mg/kg/day)
To obtain the risk from other levels of exposure, the slope
factor is multiplied by the number of units of exposure. The
assumption is that at low doses the relationship between dose and
response is linear. Thus/ if a person were exposed to 0.003
units of DNC throughout his lifetime (0.003 mg/kg/day), the risk
would be 0.003 units times 0.0897/unit, or 0.00027 (2.7 x 10~4),
a probability of 2.7 cases arising in 10,000 individuals exposed
at this level. The greater the slope of the line the more potent
the carcinogen.
Estimates of Lifetime Slope
Factors Using Other Models
Application of other models for high-to-low-dose extrapola-
tion yields slope factors equal to or slightly lower than (less
than fivefold) those in Table 7, as long as the other models
incorporate the concept that risk increases in direct proportion
to exposure in the low-exposure region (linear models). Use of
the most plausible alternative interspecies extrapolation model
(that generally used by FDA) yields slope factors sixfold (for
rats) and thirteenfold (for mice) lower than those predicted in
Table 7. Thus, alternative models predict slope factors about 30
to 65 times lower than those predicted using the EPA models.
035
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IV-7
Adoption of certain nonlinear models for high-to-low-dose
extrapolation predicts risks about 1,000 to 10,000 times lower
than those predicted by use of the EPA model. The nonlinear
models are not used by agencies charged with protecting human
health, but cannot be rejected on purely scientific grounds.
Carcinogenic Dose-Response
Evaluation not Involving
Formal Extrapolation
For those who believe formal extrapolation beyond the
measurable dose-response data should not be performed, it is
important to identify the exposures at which DNC produces tumors
and those at which no tumor excess is found (the "no observed
adverse effect level" or NOAEL). Table 8 identifies NOAELs from
data on DNC in Table 2. This is not the approach generally
applied by EPA for carcinogenic substances.
Table 8
CARCINOGENIC NO-OBSERVED ADVERSE EFFECT LEVELS
(NOAELs) FOR CHRONIC EXPOSURE TO DNC1
(based on Table 2)
Study Group Sex Tumor NOAEL
Rat, inhalation Male Lung JO
Rat, inhalation Male Spleen 30
Rat, inhalation Male Liver 30
Rat, gavage Male Stomach 50
Rat, gavage Female Stomach SO
Rat, gavage Male Liver 50
Rat, gavage Male Spleen None found
Mouse, gavage Male Liver None found
Mouse, gavage Male Stomach 60
1Unita are identical to those in Tables 1 and 2.
"None found" means that a measurable excess of
tumors was found at both levels of exposure used
in the experiment.
036
-------
IV-8
Issues to Be Considered
1. If explicit estimates of slope factors are made, should
only EPA's currently preferred models be used? Should
the results of applying other models also be displayed?
2. Which species/sex/tumor site data from Table 7 should
be used for slope factor assessment? All, shown
individually as in Table 7? Only the data set yielding
the highest slope factor? A sum of all? Other?
3. Should the DNC stomach tumor data set be rejected
because there is no exact anatomical counterpart in
humans?
4. How should the uncertainties in use of models be
described?
5. Are the observed NOAELs true "no-effect" levels? Could
they simply reflect the fact that in experiments with
relatively small numbers of animals, the failure to
observe a statistically significant increase of tumors
is an artifact of the experimental design, and not a
true absence of biological effect? How should this
uncertainty, if it is real, be taken into account?
6. EPA has adopted the first approach, using slope factors,
to extrapolate from the high doses used in the animal
studies to the low doses at which humans are exposed.
How might you respond to someone who argues for one of
the other approaches?
037
-------
IV-9
Some Possible Conclusions About
Carcinogenic Dose-Response Evaluation
Which of the following conclusions best characterizes
the information you have seen?
1. The slope factors listed in Table 7 are true upper-
bound estimates. The true slope factor is not likely
to exceed those listed, may be lower, and could be
zero.
2. The same as the first conclusion, but add: The use of
alternative, plausible models yields slope factors
about 10 to 100 times lower than those in Table 7.
3. Slope factors should be reported for all plausible
models, and the full range of estimates should be
reported without bias.
4. There is no justification for calculating and reporting
slope factors. What is critical for understanding the
public health importance of low-level exposure to DNC
is the margin of exposure (MOE). Estimation of the MOE
is based on the NOAELs for its carcinogenic effects;
these figures are reported in Table 8.
5. Neither slope factors nor NOAELs are reliable indi-
cators of human risk, and neither should be considered
for risk assessment. Dose-response relations for the
human population are not known for DNC; risk should be
described in qualitative terms only.
6. Other (formulate your own conclusion).
038
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IV-10
DOSE-RESPONSE EVALUATION FOR
CHRONIC SYSTEMIC HEALTH EFFECTS;
THE GENERAL PROBLEM AND PRINCIPLES
GUIDING APPROACHES TO ITS SOLUTION
As discussed earlier, "systemic" effects are toxic effects
other than carcinogenicity or mutagenicity, such as liver or
kidney damage, induced by a chemical. The EPA's approach to
assessing the risks associated with systemic toxicity is
different from that for assessing the risks associated with
carcinogenicity. This is because different mechanisms of action
are thought to be involved in the two cases. In the case of
carcinogens, the EPA assumes that a small number of molecular
events can evoke changes in a single cell that can lead to
uncontrolled cellular proliferation. This is the basis for the
no-threshold approach discussed for carcinogenicity in the
previous section. The assumption for carcinogens is that there
is essentially no level of exposure for such a chemical that does
not pose a small, but finite, probability of generating a
carcinogenic response. In the case of systemic toxicity,
mechanisms must be overcome before the toxic endpoint is
manifested. For example, a large number of cells could be
performing the same or similar function, and the population must
be significantly depleted before the effect is seen.
Generally, based on our understanding of the mechanisms of
action, systemic toxicity is treated as if there is an identifi-
able exposure threshold (both for the individual and for the
population), below which effects are not observable. The thres-
hold concept is important in the regulatory context. The indi-
vidual threshold hypothesis holds that a range of exposures from
zero to some finite value can be tolerated by an individual with
essentially no chance of expression of the toxic effect.
Reference Doses
To evaluate systemic effects, the EPA has developed the
concept of a reference dose (RfD). The RfD is an estimate, with
an uncertainty spanning perhaps an order of magnitude or greater,
of a daily exposure to the human population (including sensitive
subpopulations) that is likely to be without an appreciable risk
of deleterious systemic effects during a lifetime.
The RfD is derived from the_NOAEIr^aentified during the „
hazard evaluation stage_jQf—the risk assessment. In particular, l^
the NOAEL^-is redujeedoy consistent application of uncertainty
factors «OTsJ)--that reflect various types of data and a modifying v
factor (|MFT)that is based on professional judgment of the entire
chemicalVdatabase. That is:
RfD - NOAEL/(UF X MF)
039
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IV-11
The uncertainty factors account for such considerations as
the variation in sensitivity among the members of the human popu-
lation, the uncertainty in extrapolating animal data to the case
of humans, the uncertainty in extrapolating from data obtained in
a study that is of less-than-lifetime exposure, and the uncer-
tainty in using data where a NOAEL was not identified. Each
level of uncertainty usually adds a factor of ten. Thus, if the
RfD for DNC was to be based on the animal study conducted by
Dr. Shakespeare, we would have two factors of ten or an uncer-
tainty factor of 10 x 10 * 100. The first factor of ten accounts
for sensitivity among the members of the human population, and
the second factor of ten is based on the extrapolation from
animal data to the case of humans. The Shakespeare study was a
chronic study and a NOAEL was identified, hence no other factors
apply.
The modifying factor is greater than zero and less than or
equal to ten, and reflects qualitative professional judgments
about scientific uncertainties not covered under the standard
uncertainty factors. These include such considerations as the
completeness of the overall database and the number of species
and animals, tested. The usual modifying factor is one.
The concept of an RfD is presented graphically in Figure 5.
Figure 5
Reference Dose
Critical Effects
Response
NOAEL Dose
(mg/kg/day)
The RfD is useful as a reference point for gauging the
potential effects of various doses. Usually, doses less than the
RfD are not likely to be.associated with any systemic health
risks and are therefore less likely to be of regulatory concern.
However, as the frequency of exposure exceeding the RfD
increases, and as the size of the excess increases, the probabil-
ity increases that adverse effects may be observed in a human
population. Nonetheless, a clear conclusion cannot be categor-
ically drawn that all doses above the RfD are unacceptable.
040
-------
IV-12
An alterantive measure that is sometimes useful is the mar-
gin of exposure (MOE) discussed earlier, which is the magnitude
by which the NOAEL of the critical toxic effect exceeds the esti-
mated exposure/ or:
MOE
NOAEL for Critical Effect
Human Dose
A summary of the reference dose information for DNC is
presented in Table 9.
Table 9
REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
SUMMARY TABLE
Experimental
Critical Effect Doses* (F_
Liver and kidney pathology 2 mgAg/day (NQAEL) 100
Rat oral chronic study 10 mgAg/day (LOAEL)
Shakespeare et al. (1978)
RfD
2 x 10-2
mgAg/day
*0oae conversion factors and assumptions: none.
041
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IV-13
Issues to Be Considered
On the Reference Dose for PNC
1.. Is the observed NOAEL from the Shakespeare study a true
"no-effect" level? Could it simply reflect the fact
that in experiments with relatively small numbers of
animals, the failure to observe a statistically signif-
icant increase of systemic effects is an artifact of
the experimental design, and not a true absence of
biological effect?
2. Do you think the reference dose approach adequately
accounts for the uncertainties associated with NOAELs?
3. Is the information presented in Table 9 an adequate
description of the RfD? What, if any, additional
information would you like to see?
4. The RfD for DNC is based on oral ingestion of DNC by
rats. Is it appropriate to use this RfD when evaluat-
ing the potential health risks to residents near the
Electrobotics plant who are exposed to DNC through the
air?
5. Should systemic health effects from exposure to DNC or
carcinogenic effects be of greater concern? Why? Do
we have enough information at this time to decide?
6. Are the RfD and unit cancer risks reliable indicators
of human risk? Should they be used to conduct quanti-
tative risk assessments, or should risks be described
only in qualitative terms?
042
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IV-14
Some Possible Conclus-ions About
Systemic Toxicity Evaluation
Which of the following conclusions best characterizes
the information you have seen?
1. The RfD listed in Table 9, and the NOAJ3L from which it
is derived, are sufficient to determine the systemic
risks associated with exposure to ONC.
2. There is no justification for calculating RfDs. The
uncertainty and modifying factors create an artificial
sense of precision in an area involving tremendous
uncertainty. Risks from systemic toxicants should be
described in qualitative terms only.
3. Other (formulate your own conclusion).
043
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V. RISK CHARACTERIZATION
PURPOSE
In the last step of risk assessment, the information col-
lected and analyzed in the first three steps is integrated to
characterize the excess risk to humans. In line with the alter-
native approaches for describing dose-response relationships, at
least four approaches to this step can be taken:
1. Provide an explicit numerical estimate of excess lifetime
cancer risk for each population group by multiplying the
slope factor times the number of units of exposure
experienced by each group:
Excess lifetime = (slope factor) x (units of exposure)
risk
In this equation, excess risk is unitless—it is a probabil-
ity.
2. Compare the exposure experienced by each group with the
RfD.
3. Estimate the margin of exposure (MOE) for each group by
dividing the NOAEL from the critical study used to estimate
the RfD by the exposure experienced by that group.
4. Describe risks qualitatively for each population group.
Risk characterization would normally include some combina-
tion of all four approaches, along with a description of their
relative merits.
It is also essential that the statistical and biological
uncertainties in estimating the extent of health effects be
described in this step.
Tables 10, 11, and 12 present the excess lifetime cancer
risks for each population group using data from Tables 6 and 7.
These risks are based on the highest slope factor for DNC. If
other slope factors from Table 7 had been used, excess cancer
risks would be somewhat lower. And if slope factors derived from
other dose response models had been used, the excess risks shown
in Tables 10, 11, and 12 would be 10 to 100 times lower. The
risks in Tables 10, 11, and 12 are thought to be upper-bound
lifetime risks.
044
-------
V-2
Tables 10, 11, and 12 also report the RfD and MOE for
systemic health effects for each group. The MOE is not an
expression of risk, but the ratio of the NOAEL identified in the
Shakespeare study to the measured or modeled human exposure.
T»ble 10
UPPER-BOUND ESTIMATES OF EXCESS LIFETIME HUMAN RISK AND
MARGINS OF EXPOSURE FROM EXPOSURE TO DNC
BASED ON POTENTIAL CONTAMINATION
AT THE PUBLIC WELL-FIELD
General
Population
(49.770)
Current excess individual cancer risk from air1
Potential excess individual cancer risk from water,
assuming exposure at the public Hell-field
22 years hence1
Total exceaa individual cancer risk2
Upper-bound estimate of excess cancer
cases over a lifetime3
Exposure (ao/kg/day)4
MOE*
Nearby
Residents
180)
3 x 10-*
0.7
1.6 x 10-4
12,500
0.02
3.5 x 10-3
580
Workers
(150)
4 x 10-*
0.07
4.9 x 10-J
410
^Excess individual cancer risk obtained by Multiplying the highest slope factor from Table 7 (0.0897 for
DNC) by the unite of exposure from Table 6.
2Total excess individual cancer risk obtained by adding excess individual cancer risks from air and water
exposures.
'obtained by multiplying total individual excess cancer risk by the estimated number of people exposed.
^Exposures for nearby residents and workers are baaed on current air exposures and estimates of future
exposures from drinking water obtained fro* the public well-field.
5MOE for DNC obtained by dividing the NOAEL (2 mg/kg/day) from Table 9 by the appropriate DNC air and
water exposures from Table 6. If the MOE is less than 100, the exposure exceeds the RfD. The RfD is
0.002 mg/kg/day.
045
-------
V-3
Table 11
UPPER-SOUND ESTIMATES OF EXCESS LIFETIME HUMAN RISK AND
MARGINS OF EXPOSURE FROM EXPOSURE TO DNC
BASED ON POTENTIAL CONTAMINATION
AT THE EASTERN PROPERTY BOUNDARY
General
Population
(49.770)
Current excess individual cancer risk from air'1
Potential excess individual cancer risk from
water, assuming all drinking water is obtained
at the eastern property boundary1
Total excess individual cancer risk?
Upper-bound estimate of excess cancer
cases over a lifetime3
Exposure (ma/kg/day)4
MOE5
Nearby
Residents
(80)
3 x 10-4
35
7.8 x 10-'
260
0.08
1.1 x 10-z
180
Workers
(150)
4 x 10-4
0.2
1.3 x 10-2
160
^Excess individual cancer risk obtained by multiplying the highest slope factor from Table 7
(0.0897 for DNC) by the units of exposure from Table 6.
2Total excess individual cancer risk obtained by adding excess individual cancer risks from air
end water exposures.
'Obtained by multiplying total individual excess cancer risk by the estimated number of people
exposed.
^Exposures for nearby residents and workers are based on current air exposures and estimates of
future expoeures from drinking water, assuming it is obtained at the eastern property boundary.
5MOE for DNC obtained by dividing the NOAEL (2 mg/kg/day) from Table 9 by the appropriate DNC air
and water exposures from Table 6. If the MOE is less than 100, the exposure exceeds the RfD.
Table 12
UPPER-BOUND ESTIMATES OF EXCESS LIFETIME HUMAN RISK AND
MARGINS OF EXPOSURE FROM EXPOSURE TO DNC
BASED ON CONTAMINATION AT
THE POINT OF COMPLIANCE
Current excess individual cancer risk from air1
Potential excess individual cancer risk from
water, assuming all drinking water is obtained at
the point of compliance1
Total excess individual cancer risk2
Upper-bound estimate of excess cancer
cases over a lifetime'
Exposure (mg/kg/day)4
General
Population
(49.770)
42
9.5 x 10-3
210
Nearby
Residents
(80)
3 x 10-*
0.09
1.3 x 10-2
156
Workers
(150)
4 X 10-4
9 x 10-4
1 x 10-3
0.2
1.4 x 10-2
141
^Excess individual cancer risk obtained by multiplying the highest slope factor from Table 7 (0.0897 for
DNC) by the units of exposure from Table 6.
2Total excess individual cancer riak obtained by adding excess individual cancer risks from air and water
exposures.
^Obtained by multiplying total individual excess cancer risk by the estimated number of people exposed.
'Exposures for nearby residents and workers are based on current air exposures and estimates of future
exposures from drinking water, assuming it is obtained at the point of compliance.
5MOE for DNC obtained by dividing the NOAEL (2 mg/kg/day) from Table 9 by the appropriate DNC air and
water exposures from Table 6. If the .MOE is less than 100, the exposure exceeds the RfO.
046
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V-4
Issues to Be Considered
1. Are the results reported in Tables 10, 11, or 12 an adequate
characterization of DNC risks? What else should be added?
2. Risks are presented at three points: the point of compliance,
the eastern property boundary, and the public well field. What
are the advantages and disadvantages of using each? Which one
do you feel best represents the risks?
3. Should risks derived using other slope factors reported in
Table 7 and slope factors obtained using alternative models
also be discussed? How would you present these uncertainties?
4. The risks, MOE, and number of cases reported in Tables 10, 11,
and 12 depend on the assumption that the number of people
exposed and their level of exposure will remain constant over a
lifetime. Is this a plausible assumption? Can alternative
assumptions be used?
5. Is it important to distinguish routes of exposure? Should
slope factors obtained from the gavage data be used for popula-
tion groups exposed by inhalation? Should gavage data be used
at all?
6. Is it appropriate to estimate the number of cancer cases by
multiplying risk times population size? Which is more impor-
tant—risk to an individual, or risk to a population?
7. Do you believe that animal data obtained from continuous, life-
time exposure should not be used to characterize the risk of
people exposed by certain routes intermittently, for a rela-
tively small fraction of their lifetime?
8. Is the RfD exceeded by any of the exposure levels? How do the
risks from cancer compare with the risks from systemic health
effects? Are they comparable?
9. How would you characterize the risks to the ecosystem? Would
concern about ecosystem damages ever take precedence over
concern about risks to human health?
047
-------
V-5
Some Possible Conclusions
About PNC
Which of the following best characterizes the informa-
tion you have seen?
1. Upper-bound excess cancer risks to humans exposed to
DNC are those reported in Tables 10, 11, and 12.
Although risks obtained from the use of other models
are lower, the risks could be as high as those reported
in the table. The risk of systemic health effects are
properly represented by the RfD and MOE.
Same as Conclusion 1, except restrict estimates of
excess risks for inhalation exposure to slope factors
estimated from inhalation data, and restrict risks for
ingestion to gavage data.
3. The excess cancer risks shown in Tables 10, 11, and 12
as well as those obtained from all other plausible
models and all the various tumor site data should be
reported, and all estimates should be given equal
weight. Such a presentation affords the decision maker
a view of the uncertainty in the estimated risks. In
addition, a detailed discussion of the RfD should be
provided.
4. Upper-bound estimates of excess lifetime cancer risks
to humans are those reported in Tables 10, 11, and 12.
Use of all other animal data sets and alternative
cancer risk models used by some other agencies would
result in prediction of lower cancer risks, perhaps up
to 65 times lower. These risks are conditional on the
assumption that DNC is a probable human carcinogen,
based on observations of carcinogenicity in two
species of experimental animals. Uncertainties in the
exposure and population estimates are those described
in the Exposure Assessment section.
5. DNC is a probable human carcinogen, based on observa-
tions of carcinogenicity in two animal species.
Exposures needed to produce animal carcinogenicity are
many times higher than those to which humans are
exposed. The margins of exposure by which humans are
protected from systemic health effects are shown in
Tables 10, 11, and 12.
04S
-------
V-6
Some Possible Conclusions
About PNC (continued)
6. DNC is a probable human carcinogen, based on observa-
tions of carcinogenicity in two species of experimental
animals. Humans are exposed to DNC through air and
water. In general, large numbers of people will oe
exposed continuously to very low levels of DNC in
drinking water, and a few groups are exposed to rela-
tively high levels in air, some continuously, others
intermittently. The individual cancer risk in the
general (larger) population is probably low, and this
translates to a very small number of cancer cases. The
individual risk to nearby residents is moderate, and
this also translates to a small number «1) of excess
cancer cases. The individual risk to workers at the
plant is slightly higher than that of nearby residents,
although because of the relatively small number of
workers, this again translates to less than one excess
cancer case expected in this group. In addition,
potential exposures to all groups are below the RfD,
indicating no significant risks of systemic health
effects from DNC exposure.
7. Other? Some combination of the others?
049
-------
Comparative Risks
An obvious question associated with the quantitative results
presented in the risk characterization is, "are these big numbers
or small numbers?" To help you think about this question, we
have provided a list of some commonplace risks.
Tibia
2
SOME COMMONPLACE RISKS
(eaan values with
Action
Motor vehicle accident (total)
Motor vahicla accident (pedeatrian only)
Ham accidents
Electrocution
Air pollution, aaatam United Statea
Cigaratta seeking, one pack par day
Sea- level background radiation (except radon)
All eancara
Tour tablaapoona peanut butter par day
Drinking Mater with EPA liait of chlorofora
Drinking water with EPA limit of trichlonathylene
Alcohol, light drinker
Police killed in line of duty (total)
Police killed in line of duty (by felona)
Frequent flying profeaaor
Mountaineering (Mountaineers)
Sources Baaed on annual risks presented by Wilson and
uncertainty)
Lifetime Risk Uncertainty
1.7 x UP2
2.9 x ID'3
7.7 x IDT3
3.7 x 10-*
1.4 x Itr2
2.5 x ID-1
1.4 x ID-3
2 x 10-1
6 x HT*
4 x ID'5
i x ur7
i x ur3
1.5 x 10-2
9.1 x ur3
4 x 10-3
4 x 10~2
Crouch, Science.
105
105
55
55
Factor of 20 downward only
Factor of 3
Factor of 3
105
Factor of 3
Factor of 10
Factor of 10
Factor of 10
205
105
505
505
April 17, 1987.
Which, if any of these, are relevant to the situation at
Electrobotics? Why?
050
-------
GLOSSARY
Acceptable daily intake (ADI). Estimate of the largest amount
of chemical to which a person can be exposed daily that is not
anticipated to result in adverse effects (usually expressed in
mg/kg/day).
Carcinogen. A substance that increases the risk of cancer.
Control animals. Animals that receive identical treatment as
test animals, except exposure to DNC, for the purpose of observ-
ing the natural or background rate of cancer in that type of
animal.
Dose. Measurement of the amount received by the subject, whether
human or animal.
Dose-response evaluation. A component of risk assessment that
describes the quantitative relationship between the amount of
exposure to a substance and the extent of toxic injury or
disease.
Dose-response relationship. The quantitative relationship
between the amount of exposure to a substance and the extent of
toxic injury produced.
Epidemiological study. Study of human populations to identify
causes of disease. Such studies often compare the health status
of a group of persons who have been exposed to a suspect agent
with that of a comparable unexposed group.
Exposure. To be accessible to the influence of a chemical or
chemical action.
Extrapolation. The estimation of a value beyond the known range
on the basis of certain variables within the known range, from
which the estimated value is assumed to follow.
Gavaqe. Type of exposure in which a substance is administered to
an animal through a stomach tube.
Hazard evaluation. A component of risk assessment that involves
gathering and evaluating data on the types of health injury or
disease (e.g., cancer) that may be produced by a chemical and on
the conditions of exposure under which injury or disease is
produced.
051
-------
High-to-low-dose extrapolation. The process of predicting low-
exposure risks to rodents from the measured high-exposure,
high-risk data.
Human exposure evaluation. A component of risk assessment that
involves describing the nature and size of the population exposed
to a substance and the magnitude and duration of exposure. The
evaluation could concern past exposures, current exposures, or
anticipated exposures.
Human health risk. The likelihood (or probability) that a given
exposure or series of exposures may have or will damage the
health of individuals experiencing the exposures.
Incidence of tumors. Percentage of animals with tumors.
Interspecies extrapolation model. Model used to extrapolate from
results observed in laboratory animals to humans.
Linearized multistage model. Derivation of the multistage model,
where the data are assumed to be linear at low doses.
Margin of exposure (MOE). Maximum amount of exposure producing
no measurable adverse effect in animals (or studied humans)
divided by the actual amount of human exposure in a population.
Previously this was called the margin of safety.
Microgram (ug). One-millionth of a gram (1 H9 • 3.5 x 10"8 oz. =
0.000000035 oz.).
Milligram (mg). One-thousandth of a gram (1 mg « 3.5 x 10~5 oz.
- 0.000035 oz.).
Modifying factor. An uncertainty factor, greater than zero and
less than or equal to ten inclusive; its magnitude reflects
professional judgment regarding aspects of the data used for the
assessment; e.g., the number of species tested and the complete-
ness of the overall database.
Multistage model. Mathematical model based on the multistage
theory of the carcinogenic process, which yields risk estimates
either equal to or less than the one-hit model.
Neoplasm. An abnormal growth of tissue, as a tumor.
No observed adverse effect level (NOAEL). The highest experi-
mental dose at which there was no statistically or biologically
significant increase in a toxicologically significant endpoint.
052
-------
One-hit model. Mathematical model based on the biol oa i<\Hl theory
that a single "hit" of some minimum critical amount of a carcino-
gen at a cellular target—namely DNA—can initiate an irrevers-
ible series of events, eventually leading to a tumor.
Potency. Amount of material necessary to produce a given level
of a deleterious effect.
ppb. Parts per billion.
ppm. Parts per million.
Reference dose (RfD). An estimate (with uncertainty spanning
perhaps an order of magnitude or greater) of the daily exposure
to the human population (including sensitive subpopulations) that
is likely to be without appreciable risk of deleterious effects
during a lifetime. The RfD is appropriately expressed in units
of mg/kg/day.
Risk. Probability of injury, disease, or death under specific
circumstances.
Risk assessment. The scientific activity of evaluating the toxic
properties of a chemical and the conditions of human exposure to
it both to ascertain the likelihood that exposed humans will be
adversely affected, and to characterize the nature of the effects
they may experience.
Risk characterization. Final component of risk assessment that
involves integration of the data and analysis involved in hazard
evaluation', dose-response evaluation, and human exposure evalua-
tion to determine the likelihood that humans will experience any
of the various forms of toxicity associated with a substance.
Risk management. Decisions about whether an assessed risk is
sufficiently high to present a public health concern and about
the appropriate means for control of a risk judged to be
significant.
Route of exposure. Method by which the chemical is introduced
into the biological organism.
Safe. Condition of exposure under which there is a "practical
certainty" that no harm will result in exposed individuals.
Scientifically plausible. An approach or concept having substan-
tial scientific support but without complete empirical
verification.
053
-------
Slope factor. The increased likelihood of an individual
developing cancer from exposure to one unit of a substance over a
lifetime (exposure measured as mg of the substance per kg of body
weight per day—mg/kg/day).
Statistically significant. The difference in tumor incidence
between the treated and control animals that is probably' not due
to chance.
Systemic effects. Effects observed at sites distant from the
entry point of a chemical due to its absorption and distribution
into the body.
Threshold dose. The dose that has to be exceeded to produce a
toxic response.
Total dose. Sum of doses received by all routes of exposure.
Uncertainty factor. Factors used in operationally deriving the
RfD from experimental data. These factors are intended to
account for (a) the variation in sensitivity among the members of
the human population; (b) the uncertainty in extrapolating animal
data to the case of humans; (c) the uncertainty in extrapolating
from data obtained in a study that is of less-than-lifetime
exposure; and (d) the uncertainty in using LOAEL data rather than
NOAEL data. Usually these factors are set equal to ten. See
Table 1.
Unit cancer risk. The increased likelihood of an individual
developing cancer from exposure to one unit of a substance over a
lifetime (exposure measured as concentration in a particular
media)
Upper-bound estimate. Estimate not likely to be lower than the
true risk.
054
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Appendix A
GROUND-WATER MODELING CALCULATIONS
AND ASSOCIATED ASSUMPTIONS
Predicted Concentration of PNC
in Ground Water at Eastern Property
Boundary and Public Well Field
• Concentration in lagoon: 30 ppm (mg/1 )
• Concentration measured at compliance point: 332 ppo
• Half-life of DNC in aquifer: 10 years * 3/650 days
— Degradation rate of DNC » 0.693/half-lif e
» 1.9 x 10~4 day'1
Distance from source to property boundary: 1,000 feet
• Travel time (T) from the source to property boundary:
[distance traveled] x [effective porosity]
T - -
[hydraulic conductivity] x [hydraulic gradient]
1,000ft x 0.2
1,000 days
40 feet/day x 0.005
• Steady-state concentration at property boundary:
[332 ppb] x exp [(-1.9 x 1Q-4 day"1) x 1,000 days]
» 275 ppo
• Distance from source to public well field:
1.5 miles • 8,000 feet
055
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A-2
• Travel time from the source to three threatened wells:
8,000 x 0.2
40 feet/day x 0.005
8,000 days
• Steady-state concentration at the three threatened
wells:
[332 ppb] x exp [(-1.9 x 10~4 day-1) x 8,000 days]
» 73 ppb
• Steady-state concentration at actual point of exposure
(drinking water supply):
The three threatened wells provide 7.5 percent of total
drinking water supply; therefore, the concentration at
the actual point of exposure (the drinking water
supply):
0.075 x 73 ppb * 5.5 ppb
058
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Appendix B
HUMAN DOSE CALCULATIONS AND ASSOCIATED ASSUMPTIONS
Inhalation of PNC-Contaminated
Air by Neighboring Residents'
Assumptions:
• An adult inhales 23 m3/day of air.
• Based on wind direction analysis, the duration of
exposure is 30 percent of time on an annual average
basis.
• The body weight of an adult is 70 kg.
• The inhalation absorption factor for DNC is 0.75.
• The adult lives in the home throughout his lifetime.
Calculations:
0.044 mg
(average DNC air concentration at boundary)
x 0.3 (human intake factor)
x 0.75 (inhalation absorption factor)
» 3.3 x 10~3 mg/kg/day
Inhalation of DNC-Contaminated
Air by Worker's
Assumptions:
• An adult inhales 23 m^/day of air.
• The body weight of an adult is 70 kg.
• The inhalation absorption factor for DNC is 0.75.
057
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B-2
• The duration of exposure is 40 hours/week for a 30-yea:
work period, or 10.2 percent of an average lifetime.
Calculations:
0.188 mg
m
3
(average DNC air concentration on-site)
23 ra3 1
x x x 0.102 (human intake factor)
day 70 kg
x 0.75 (inhalation absorption factor)
- 4.7 x 10-3 mg/kg/day
058
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B-3
Inqestion of DNC-Contaminated
Drinking Water at Point of Compliance
Calculations:
3.32 x 10-1 mg
(measured DNC concentration in ground
liter water at point of compliance)
2 liters 1
x x (human intake factor)
day 70 kg
x 1 (ingestion absorption factor)
- 9.5 x 10-3 mg/kg/day
Ingestion of DNC-Contaminated
Drinking Water at Eastern
Property Boundary
Assumptions:
• An adult consumes 2 liters of water per day.
• The body weight of an adult is 70 kg.
• Absorption is 100 percent.
• The water is consumed throughout the adult's lifetime,
Calculations:
0.275 mg
(predicted DNC concentration in ground water
liter at eastern property boundary)
2 liters 1
x x (human intake factor)
day 70 kg
x 1 (ingestion absorption factor)
» 7.8 x 10*3 mg/kg/day
059
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B-4
Ingestion of PNC-Contaminated
Drinking Water at Public Well Field
Calculations:
5.5 x 10"3 mg
(predicted DNC concentration in ground
™ . . . * 1 * * • * 9 \
liter water at public-well field)
2 liters 1
x i x (human intake factor)
day 70 kg
x 1 (ingestion absorption factor)
* 1.6 x 10~4 mg/kg/day
060
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Part II
MANAGING THE RISKS FROM DNC
AT THE ELECTROBOTICS SITE
-------
CONTENTS
I. INTRODUCTION
II. REGULATORY BACKGROUND
III. OPTIONS
Overview
Economic Impact of Options
Changes in Risk
IV. CONCLUSIONS
-------
I. INTRODUCTION
You have just finished analyzing the potential risks from
DNC at the Electrobotics facility. Your working group must now
decide what actions you will require of Electrobotics' owners to
deal with the situation.
Your staff has reviewed several possible approaches to
managing the risks. The first option was proposed by the owners
of the facility; the other four were developed by your staff.
This document briefly summarizes each option/ presents its costs
and economic impacts/ and describes how it alters the risks at
the Electrobotics site. In addition, Appendix A describes the
hazardous waste treatment technologies available for use at the
site.
After reviewing this information/ you and your group must
choose one of these approaches or develop an alternative of your
own. Your choice will be incorporated into a first draft of the
permit. Your recommendation is expected at the end of this
meeting.
061
-------
II. REGULATORY BACKGROUND
As discussed earlier, RCRA regulations require that hazard-
ous waste facilities (such as Electrobotics1 storage lagoon) be
designed and operated in a manner that will prevent the leaking
of hazardous waste into ground water. The regulations also
require ground-water monitoring and corrective action if a prob-
lem is identified.
RCRA's ground-water protection standards require the
Regional Administrator to establish in the facility permit a DNC
concentration limit, beyond which degradation of ground-water
quality is not allowed. The concentration limit determines when
corrective action is required and is set at the point of com-
pliance, immediately east of the storage lagoon.
Three possible concentration limits can be used to establish
the ground-water protection standard:
• Background level of the hazardous constituent
• Maximum concentration limit (MCL) established by
regulation
• Alternate concentration limit (ACL)
The background level and MCL are established in the facility
permit unless the facility owner or operator applies for an ACL.
In this case, the background level of DNC is zero, and no MCL
exists for the solvent. An ACL may be available to Electro-
botics1 owners if they can demonstrate that the DNC will not pose
a substantial present or potential hazard to human health or the
environment.
To continue operating the lagoon, the regulations also
require that Electrobotics1 owners retrofit the lagoon to ensure
no DNC leaches into the ground water. The owners of
Electrobotics have proposed retrofitting the lagoon, which would
require them to:
• Pump out the free liquids from the lagoon
• Excavate the contaminated soil
• Install "minimum technology" to ensure no DNC leaches
into the ground water. In this case the owners would
install a double liner under the lagoon.
062
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II-2
An alternative to retrofitting the lagoon is to close it and
install an above-ground storage tank. Existing regulations allow
the owners to close the lagoon in one of two ways. They must
either remove the hazardous waste and waste residues (clean
close) or retain the waste and manage the lagoon as a land
disposal unit.
The owners have been advised that, because of existing
ground-water contamination, it is probably not possible to meet
the standards for clean closure and terminate responsibility for
hazardous waste management in the near future. As a result, your
staff has developed a closure option based on the owners managing
the lagoon as a land disposal unit and installing an above-ground
tank. To comply with regulations for this option, the owners
must:
• Eliminate the free liquids from the lagoon either by
removing them from the impoundment or by solidifying
them
• Stabilize the remaining waste and waste residues to
support a final cover
• Install a final cover to minimize future infiltration
into the lagoon
• Perform post-closure care and ground-water monitoring
You must now decide whether the facility's retrofitting plan
is adequate and what actions to require of the owners to clean up
both the lagoon and the associated ground-water contamination
problem. You will not try to specify the particular concentra-
tion limits for the ground-water protection standard. You must
only recommend the specific actions required at the site. You
may accept the proposal from the owners, pick one of the options
presented by your staff, or develop an alternative that you feel
is more appropriate. Implicit in your decision, however, is the
concentration limit.
063
-------
III. OPTIONS
OVERVIEW
You must now evaluate five possible approaches to addressing
the problem at the Electrobotics plant. The first is the
proposal from the owners which involves retrofitting the lagoon.
There are four alternative options that have been developed by
your staff.
Proposal
The owners of Electrobotics have proposed retrofitting the
lagoon. To accomplish this the owners would have to pump out the
liquids from the lagoon, excavate any contaminated soil, and
install a double liner under the lagoon to stop any leaching of
DNC from the lagoon into the ground water. The type of liner to
be used has been effective at test sites, although it is general-
ly recognized that there is always the possibility that the liner
will fail at some point.
The owners have proposed a limited retrofitting program
which does not include any treatment of the current contamination
of the ground water. They feel the current contamination of the
ground water does not pose a substantial present or potential
hazard to human health or the environment.
Alternative Control Options
The four options reviewed by your staff are described below.
All four involve closing the lagoon and managing it as a land
disposal unit. In addition, all four would require the owners of
Electrobotics to install a new above-ground tank. The first
involves installing a cap over the lagoon. The second option
involves installing the cap and pumping and treating the contami-
nated ground water. The third option, which is somewhat more
expensive, contains the elements of the first two options as well
as the construction of a slurry wall around part of the lagoon.
The last option requires the owners to excavate the material
under and around the lagoon and pump and treat the contaminated
ground water.
064
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III-2
Option 1: Cap
This option requires the installation of a cap over the
lagoon, which directly affects the lagoon but does not deal with
the current ground-water contamination.
Scope
• De-water the lagoon and excavate any accumulated
sludges, which requires removing any free liquids and
managing them as hazardous waste
• Solidify any remaining sludges and refill the lagoon
with clean fill
• Install a multimedia cap over the lagoon to prevent
infiltration
• Maintain the cap and conduct post-closure monitoring
and care
Uncertainties
• Long-term integrity of the cap and its effectiveness
in preventing infiltration
• Continued source strength of chemicals/ in or near the
saturated zone, that are released by ground-water
through-flow beneath the cap
• Extent of long-term monitoring and general
post-closure care
Option 2; Cap/Pump and Treat
This option includes the cap described in Option 1 plus
pumping and treating the contaminated ground-water plume with a
carbon adsorption system.
Scope
The scope includes the items described for Option 1. In
addition, the owners would have to:
• Conduct an additional hydrogeological study
065
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III-3
• Install extraction wells and treat the ground water by
carbon adsorption
Uncertainties
The same uncertainties as in Option 1 exist, with two
additions:
• Length of time for operating the treatment system
• Effectiveness of ground-water extraction system in
removing contaminated ground water
Option 3; Cap with Slurry
Wall/Pump and Treat
Scope
This option is similar to Options 1 and 2 in that the lagoon
would be capped in the same manner and the ground-water contami-
nation corrected through pumping and a carbon adsorption
treatment system. However, Option 3 would also include
installation of a soil-bentonite slurry wall at the perimeter of
the lagoon to prevent ground-water through-flow and further limit
the movement of DNC from the saturated zone beneath the lagoon
into the ground water.
Uncertainties
The same uncertainties as in Options 1 and 2 exist, with one
addition:
• Long-term integrity of the slurry wall as a method of
isolating both the contamination and the potential for
future releases of DNC into ground water
Option 4; Excavation/Pump and Treat
Option 4 comes closest to completely eliminating any traces
of DNC from the Electrobotics facility and the surrounding area.
The current ground-water contamination would be corrected by
pumping the ground water and treating it with a carbon adsorption
system. In addition, the source of contamination would be
controlled by excavating the soil around and under the lagoon.
066
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III-4
Scope
• De-water the lagoon and excavate any accumulated
sludges and liner material
• Test the underlying soil for chemical contamination
and remove soil to the water table if DNC
concentrations are above ground-water contamination
levels
• Refill the excavation with clean fill and stabilize it
with grass or other cover material
• Conduct an additional hydrogeological study
• Install extraction wells and treat ground water by
carbon adsorption
• Conduct long-term monitoring and general post-closure
care
Uncertainties
• Length of time for operating the treatment system
• Effectiveness of ground-water extraction system in
removing contaminated ground-water plume
067
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III-5
Issues to Be Considered
1. What are the key components of each option, and how do
the options differ?
2. What is the nature of the uncertainties associated
with each option? Which ones are most critical?
3. Which aspects of each option do you find most
troublesome?
4. Are there other options that you think the Regional
Administrator should consider?
068
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III-6
ECONOMIC IMPACT OF OPTIONS
Adopting any one of the options discussed above would
require cash expenditures by Electrobotics. A summary of the
costs for each option is presented in Table 1.
Table 1
COSTS OF CONTROL OPTIONS FOR THE ELECTROBOTICS PLANT
Proposal
Retrofit
Option 1
Cap and Associated Costs
Option 2
Cap and Associated Costs
Pump and Treat System
Total
Option 3
Cap and Associated Costs
Slurry Wall
Pump and Treat System
Total
Option 4
Excavation and Associated Costs
Pump and Treat System
Total
Present Value of Costs1
$ 450,000
$ 600,000
$ 600,000
290,000
$ 890,000
$ 600,000
500,000
220,000
$1,320,000
$2,400,000
220,000
$2,620,000
Annualized Costs'
(costs per year)
$ 48,000
$ 64,000
$ 64,000
31,000
$ 95,000
$ 64,000
53,000
24,000
$141,000
$255,000
24,000
$279,000
Mime sequence of costs is discounted at 10 percent.
^Present value of costs is annualized at a 10 percent interest rate over
30 years.
069
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III-7
Electrobotics has a turbulent history and has been close to
bankruptcy several times. Its recent performance, however, has
improved, with revenues increasing from $1.5 million in 1980 to
$7.5 million in 1986. Even so, the company was only marginally
profitable in 1986, with after-tax profits of less than $50,000.
We do not have a good forecast of 1987 revenues, although the
computer industry as a whole has been performing poorly.
Electrobotics1 owners feel they can, with great difficulty,
pay the costs of their proposed retrofitting program and costs
estimated for Option 1. They are adamant, however, that
implementing Options 2, 3, or 4 would force them to declare
bankruptcy; these three options would result in annual costs
substantially greater than the company's 1986 after-tax profits.
If Electrobotics goes out of business, its 150 employees
would have to find new jobs. This would worsen an already diffi-
cult situation in the town of Utopia, whose unemployment rate is
among the highest in the country. In addition, Electrobotics has
paid significant property taxes—about $120,000 in 1986—to the
town.
Finally, if the Electrobotics facility were closed because
of bankruptcy, it would have to be considered for addition to the
National Priority List for cleanup as a Superfund site.
070
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III-8
Issues About Economic Impacts
to Be Considered
1. How accurate are the cost and economic impact estimates?
How does the accuracy of the cost estimates compare with
the risk estimates?
2. What additional information would you want? Are any key
elements missing?
3. Is it appropriate to consider such factors as costs of
the control options and economic impacts in deciding
what will be required of Electrobotics1 owners? Are any
of the impacts large enough to rule out a particular
option?
4. If economic considerations are to play a part in the
decision making, should the focus be on the dollar costs
of each option or on the impact of the option on the
continuing viability of Electrobotics and the potential
loss of jobs?
071
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III-9
CHANGES IN RISK
Adopting the proposal or any of the alternative options
identified above would reduce individual exposure to DNC and
hence reduce the risk. However, the options do not reduce the
risk to the same degree or with the same certainty. In addition,
it is difficult to predict the changes in risk by predicting the
reduction in concentrations resulting from the adoption of each
option. Even so, your staff and the engineers hired by
Electrobotics1 owners have estimated the reduction in the DNC
concentrations in the ground water and air, and the reduction in
risk for each option.
A program of retrofitting the lagoon would reduce the risks
associated with contaminated ground water. No more DNC would
leach into the aquifer (assuming the double liner under the
lagoon does not leak). The upper-bound estimates of excess
lifetime risks for an individual receiving drinking water from
the Eastern property boundary after the retrofitting program are
presented in Table 2:
The retrofitting program will not eliminate the air risk
associated with the lagoon. As a result, the risks to workers
and nearby residents are higher than for the general population.
The ground-water risks confronting the general population are
estimated using an average concentration of DNC in the
ground water over the next 70 years, assuming the retrofitting
has been completed.
The upper-bound estimates of excess lifetime human risk for
an exposed individual after implementation of one of the
alternative control options are also presented in Table 2.
072
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111-10
Table 2
UPPER-BOUND ESTIMATES OF EXCESS LIFETIME HUMAN
RISK UNDER ALTERNATIVE CONTROL OPTIONS1
Individual Risks-3
Proposal
(Retrofit)
General Population
Nearby Residents
Workers
Alternative
Control Options2
1. Cap
2. Cap/Pump and Treat
3. Cap/Slurry Wall/
Pump and Treat
4. Excavate/Pump
and Treat •
Eastern Property
Boundary
1 x 10"5
3 x ID"4
4 x 10~4
1 x 10-5
1 x ID'6
2 x 10~7
1 x 10~7
Public Well
Field
2 x 10-7
2 x iQ-8
4 x ID-9
2 x 10~9
iRisks are obtained by multiplying the highest slope factor
estimate from Table 7 of Part I (0.0897 for ONC) by the
estimated units of exposure after each option has been
implemented.
2A11 four alternative control options eliminate any air risks
from the lagoon. The remaining risks are attributable to the
risks from DNC remaining in the ground water after completion
of the control option. As a result, the risks remaining after
implementation of an option are the same for the general
population, nearby residents, and workers.
3The individual risks at the Eastern property boundary and the
public well field are based on estimated average
concentrations in the ground water at these points over the
next 70 years. Your engineers have estimated that control
options will reduce the concentrations of DNC in the ground
water, and the associated risks, by 98 percent. Current risks
at the Eastern property boundary and the public well field are
zero.
The upper-bound estimates of excess cancer cases over a
lifetime after implementing the retrofitting program or one of
the alternative options are presented in Table 3:
073
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III-ll
Table 3
UPPER-BOUND ESTIMATES OF EXCESS CANCER CASES
OVER A LIFETIME UNDER ALTERNATIVE CLOSURE
AND CORRECTIVE ACTION OPTIONS1
(Cases based on drinking water consumption at
• the Eastern property boundary2)
Proposal
(Retrofit)
. Alternative
Control Options*
1. Cap
2. Cap/Pump and Treat
3. Cap/Slurry Wall/Pump
and Treat
4. Excavate/Pump and
Treat
Workers
(150)
0.06
Nearby
Residents
(80)
0.02
0.0015 0.0008
0.0015 0.00008
0.00003 0.000016
0.000015 0.000008
General
Population
(50.000)
0.5
0.5
0.05
0.01
0.005
Total
0.6
0.5
0.05
0.01
0.005
Reduction in
Upper-Bound
Estimates
of Excess
Cancer Cases
34.54
34.62
35.07
35.11
35.12
estimates of excess cancer cases are obtained by multiplying the excess lifetime risk by
the estimated number of people exposed.
2The cases are estimated assuming exposure at the Eastern property boundary. Estimated cases
assuming exposure at the public well field would be significantly lower.
'All four alternative options eliminate any air risks from the lagoon. The estimated excess
cancer cases for each option are attributable to the DNC remaining in the ground water after
completion of the control option.
Electrobotics1 owners are concerned about the air risks
after reviewing the material prepared for their Part B applica-
tion. In response, they have discussed installing a floating
synthetic cover over the lagoon to control the air emissions in
the short run. This would address some of the risks during the
period of negotiation of the permit requirements. The cover
would cost $10,000.
074
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111-12
Remarks on Risks
1. The proposed approach, retrofitting, would not eliminate the
air risks. All four of the alternative options would
eliminate the risks from the air route of exposure.
2. Engineers working for Electrobotics' owners have argued that
it is technically impossible to completely eliminate DNC from
the contaminated ground-water plume. Your staff generally
agrees that it is probably not possible to remove all traces
of DNC, but feels that the risks could be reduced beyond the
most stringent option (Option 4) with an extended pump and
treat system. Extended pump and treat would involve increas-
ing the length of time a pump and treat system is operated.
3. It is difficult to forecast the effectiveness of the
retrofitting program, or any closure and corrective action
option.
4. The four alternative options will eliminate volatilization of
DNC from the lagoon. Some members of your staff have
speculated that this could potentially increase the concen-
tration of DNC in the wastewater sent to the wastewater
treatment plant, which in turn could lead to concentrations
of DNC in the treatment plant effluent.
075
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111-13
Issues About Changes in Risk
1. Risk to an individual is:
Excess
Lifetime = (slope factor) x (Units of Exposure)
Risk
The allowable units of exposure for a given excess
lifetime risk can thus be estimated as follows:
Units of Excess Lifetime Cancer Risk
Exposure = Slope Factor
If the excess lifetime cancer risk at the point of
compliance is 1 x 10~6, what is the associated DNC
exposure?
2. What effect would installing the synthetic cover over
t'he lagoon have on the risks from DNC, assuming the
cover eliminated the air risks? What percentage of the
estimated current excess cancer.cases would be
eliminated?
3. What are the key uncertainties associated with estimates
of risk'under each option? What additional information
would you want on the effect of each option on the
risk?
4. In light of the major uncertainties in the risk esti-
mates, is it valid to compare the different options in
terms of risk or reduction in risk?
5. Is it at all appropriate to consider the risk assessment
results and the associated estimates of the changes in
risk when evaluating possible options? Is a less
quantitative and more qualitative approach preferred?
6. Should you balance the increased costs of Options 1, 2,
3, and 4 against the associated benefits (as measured by
increased reductions in risk)?
7. What other approaches might be more appropriate?
076
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IV. CONCLUSIONS
At this point/ you and your working group should decide what
actions you will require of Electrobotics1 owners. You have
information on a number of options, including the one proposed by
the owners. You may accept the owners' proposal, choose one of
the alternative options, or develop an alternative you feel is
more appropriate. In addition, you may attach any caveats,
qualifications, or modifications you wish. At the end of this
meeting, you will present your results.
What do you recommend?
077
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APPENDIX A
Overview of Hazardous Waste Treatment
Technologies Available for Use at the
Electrobptics Site
Capping
Installation of a Slurry Wall
Ground-Water Extraction/Injection
Carbon Adsorption
In-situ Biological Treatment
078
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A-2
CAPPING
After the lagoon has been dewatered and refilled with clean
fill, it must be covered with a secure cap to prevent water
infiltration, which could leach DNC from the fixed sludges in the
fill. The primary steps in cap construction are layering imper-
meable material over the landfill, revegetation, and regrading
the site.
Impermeable cover material for landfills can be clay, syn-
thetic membranes or liners, or a combination of clay and syn-
thetics. Hazardous waste landfills are usually capped with a
sandwich of clay/ synthetic liners, and topsoil for vegetation.
According to the National Center for Ground Water Research's
State-of-the-Art of Aquifer Restoration, synthetic materials
(such as bituminous or Portland cement concrete barriers) or
synthetic membranes (alone or in conjunction with clay barriers)
may be preferable to soil-based systems when protecting high-risk
wastes. After the chosen impermeable material has been placed on
the site, the area should be covered with topsoil, seeded, and
regraded.
Landfill caps, seemingly a good infiltration prevention
measure, actually are subject to a number of problems. The
problem that often appears first is erosion, which is exacerbated
by the cap's impermeability function. (Rain hits the cap and,
not being absorbed, carries off the maximum amount of soil.)
Regrading techniques, such as terracing the topsoil and creating
lined waterways and storage basins, help minimize this problem.
Establishing vegetation early will also help control erosion by
decreasing rain and wind impact on the cap. Grass should be
planted first for a quick cover, and then shrubs and trees should
be cultivated.
Other factors that affect clay caps in particular are
changes in the fill, such as settling and freeze-thaw/wet-dry
cycles, which can cause cracks. In the Midwest, these cracks can
reach three to six feet, below commonly practiced cap and cover
depths. Plants growing in the cracks can widen them further, as
can burrowing animals. In addition, large plant tap roots can
increase water infiltration in the cap. Cracks are most likely
to form in systems where the clay has been combined with some
other agents (e.g., lime, Portland cement, fly ash) to increase
impermeability, because the clay and other mixture components do
not settle at the same rate.
079
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Synthetic membranes, on the other hand, can be affected by
tearing if they are flexible and cracking if they are rigid,
especially if differential settlement occurs in the fill.
Installation of a smooth sand buffer can reduce the chance of
flexible-liner puncture during cap construction. Concrete
barriers are subject to both cracking and deterioration,
especially in sulfate-rich environments. However, cracks in
rigid membranes can be cleaned and sealed (most often with tar)
fairly easily, giving rigid membranes an advantage over the
flexible variety in the long run.
There is no foolproof method for sealing off a landfill.
Therefore, all literature sources stress good initial planning
and long-term management as the primary factors in maintaining
the integrity of a landfill cap.
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INSTALLATION OF A SLURRY WALL
Option 2 calls for the installation of a slurry wall at the
lagoon's perimeter to prevent further movement of DNC by
restricting ground-water movement under the contaminant source.
A slurry wall is a civil engineering technique previously used
primarily in construction; its recent use in Superfund sites has
made it more popular with hazardous waste landfill operators. By
far the most common slurry wall construction method is the trench
method.
The first step in building a slurry wall using the trench
method is digging a channel in the selected area. (Choosing
where to place the wall requires study of the site and ground-
water characteristics.) Excavation techniques include the
backhoe method/ which is good for shallow depths/ and the
dragline method/ which is used for trenches that will be
30 meters or more deep. As the trench is dug/ a slurry of 4 to
7 percent bentonite clay is recirculated through to support the
channel walls and form a more impermeable soil structure.
Bentonite is popular because it swells when wet and so restricts
the flow of water through it. Digging usually proceeds a short
way into the clay or bedrock underlying the aquifer.
Once the trench has reached the desired depth/ it is solidi-
fied in one of two ways: backfilling with a mixture of bentonite
and the excavated solid (the soil-bentonite/ or S-B, method)/ or
letting it solidify by itself by mixing cement with the original
slurry (the cement-bentonite/ or C-B/ method). Choosing a soli-
dification technique requires examination of the pros and cons of
each. With the C-B method/ there is no worry, over availability
of quality soil for backfilling/ the cement sets quickly/ and the
trench can be constructed in sections. This method is also
better for limited-access areas. The S-B method is cheaper
(lower materials costs) and generally less permeable than the
C-B, but it is not as strong as the C-B and requires continuous
trenching in one direction. S-B trenches are used more often,
primarily because of their low cost and low permeability.
Possible problems from slurry walls include inadequate con-
struction and stress/strain forces, which can cause structural
damage. Acids and sulfates in ground water can seriously degrade
C-B trenches, and the permeability of S-B trenches can increase
in the presence of certain organics, calcium, magnesium, heavy
metals, and solutions of high ionic strength. Even if the walls
do not degrade appreciably, some leakage through slurry walls
081
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is inevitable; permeability ranges from less than 1x10-8 cm/sec
for an S-B trench to over 1x10-5 cm/sec for a C-B trench. A more
complete list of the advantages and disadvantages of slurry walls
is provided in Table 1.
Table 1
ADVANTAGES/DISADVANTAGES OF SLURRY TRENCHES
Advantages
1. Construction methods are
simple.1
2. Adjacent areas are not affected
by ground-water drawdown.1
3. Bentonite (mineral) will not
deteriorate with age.1
4. leachate-resistant bentonites
are available.1
5. Maintenance requirements are
low.1
6. Risks from pump breakdowns or
power failures are eliminated.2
7. Headers and other above-ground
obstructions are eliminated.2
Disadvantages1
1. Shipping bentonite from the
West is costly.
2. Some construction procedures
are patented and require a
license.
3. In rocky ground, overexcava-
tion is necessary because of
boulders.
4. Bentonite deteriorates when
exposed to high-ionic-strength
leachates.
1Tolroan, et al., "Guidance Manual for Minimizing Pollution from
Waste Disposal Sites," 1978.
2Ryan, "Slurry Cut-off Walls: Methods and Applications," 1980.
Source: National Center for Ground Water Research, State-of-the-Art of
Aquifer Restoration. 1984.
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A-6
GROUND-WATER EXTRACTION/INJECTION
To treat the contaminated ground water/ extraction and/or
injection wells must be dug. Carbon adsorption requires extrac-
tion wells; in-situ biodegradation requires both extraction and
injection wells. The same basic sequence of steps is used to
install either well type. The first step, drilling the hole, can
be accomplished by one of several methods, depending on the site
characteristics and economics. Next, casings and liners are
installed, annular spaces are grouted and sealed, and well
screens and other fittings are put into place. Finally, above-
ground facilities (pump houses, etc.) are built.
Some information (e.g., plume size, aquifer characteristics)
is necessary before the wells can be constructed. The depth
within the aquifer to which each of the wells is drilled is a
function of the plume location, which can stretch through the
entire aquifer or remain close to the upper boundary. Hydro-
geologists can determine plume dimensions as well as plume
movement and the hydrogeological characteristics of the aquifer.
Within the injection and extraction categories, two types of
well systems currently are in use. The first, well point
systems, consists of a number of closely spaced, shallow wells
that are connected to a main pipe, or "header." If water is
being extracted, this header leads to a central suction lift
pump, which draws the water to the surface. (Injection wells
require a different type of pump to force water from the surface
to the aquifer.) The main constraint on extraction well point
operation is the suction pump, which cannot raise water more than
25 feet. Since the aquifer under Electrobotics is 20 feet below
the surface, deeper wells may be needed. The second type of well
system, deep well, can be used at greater depths than the well
point system. Unlike well point, in which pumping is done for
groups of wells, in the deep well system each well is individu-
ally pumped.
After the wells are sunk in the path of the plume and pump-
ing starts, a number of things happen in the aquifer. As water
is removed from the "zone of influence" around the well, the
water level decreases, causing a change in aquifer flow patterns,
or "drawdown" (see Figure 1). Wells are designed so that this
drawdown intersects the plume. As water is pumped to the
surface, plume movement away from the source stops and eventually
reverses itself. The rate of extraction must be monitored care-
fully, as it is fairly easy to pump a well dry if pumping is done
too fast. For injection wells, essentially the reverse happens:
083
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A-7
water is pumped into the aquifer, and the water table rises,
especially around the point of injection. This pushes the plume
forward and increases the rate of ground-water flow.
Figura 1
Ground-Uaear Pattarna dua to Extraction Wall*
Extraction
Wall
Original Wacar
1 Tabla
Hydraulic
40 ft./day
Hoe drawn eo acala.
084
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A-8
CARBON ADSORPTION
As reported in the March 1986 edition of Pollution Engineer-
ing, biological methods are usually the chosen treatment for
industrial and municipal waste waters, but "the low concentra-
tions found in ground water . . . make air stripping and carbon
adsorption the most widely used ground water treatment methods."
The primary constraint on carbon adsorption is the concentration
of the hazardous constituents. The concentration must be less
than 1 percent for removal to be effective; at this level the ICF
RCRA Risk-Cost Analysis Model estimates the efficiency of the
process to be 99 percent (i.e., 99 percent of the contaminants in
the influent are tied up in the carbon after treatment). Since
DNC concentrations in the ground water are well below 1 percent/
carbon adsorption should work well in removing the contaminants
from the ground water.
In carbon adsorption, activated carbon granules remove the
organic contaminants from the waste water by attracting and hold-
ing the constituents onto their surface. Figures 2 and 3 display
two slightly different treatment trains for this option. The
train selected depends on the amount of carbon used per day: For
amounts exceeding 400 pounds per day, it is more economical to
recycle the carbon; otherwise, the carbon is placed into con-
tainers and disposed of.
The basic treatment steps outlined in Figures 2 and 3 are
the same. Contaminated ground water flows from the storage tank
into a prefilter. The prefilter removes excess suspended solids,
oil, and grease, which can interfere with the adsorption process
by clogging the surface of the carbon particles. After this
pretreatment, the waste is directed to the activated carbon tank,
where the organics are transferred to the carbon granules. The
ICF model has determined that the average carbon adsorption
capacity is 5 pounds of organics per 100 pounds of carbon;
however, this value can vary with the compound being adsorped.
(Adsorptivity increases with decreasing solubility.)
As mentioned above, the exhausted carbon is then recycled,
or regenerated if over 400 pounds are used per day. (The ICF
model estimates that only 90 percent of exhausted carbon can be
regenerated; the remaining 10 percent must be made up with fresh
carbon.) Regeneration can be performed using heat, steam, or
solvents. Thermal regeneration, the most common method, destroys
the organics on the carbon but leaves a low-concentration, gas-
eous emissions stream. Figure 3 depicts the equipment necessary
for regeneration (two storage tanks for spent and regenerated
085
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A-9
carbon and a multiple-hearth furnace). The furnace should
destroy most of the organics. (The ICF assumes 99.993 percent;
the remaining 0.007 percent will appear in the emissions
stream.)
Contaminant releases during the adsorption process can occur
through air releases from the furnace as well as from discharge
of the treated effluent, which contains approximately 1 percent
of the original amount of organics. In addition, contaminants
are discharged into the air from vessel failures and/or spills
(estimated in the ICF report to occur at a rate of 0.000013
releases per year) and to a lesser degree from pumps, valves, and
flanges.
086
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A-10
Figure 2
CARBON ADSORPTION FLOW DIAGRAM
(carbon consumption leu than 400 pounds per day)
Split
Volatilization
WaMaStoraea
Tank
H Multi-Media L^^f(
"""** II
Puattlva
(Granular Aattoatad
CarMfl Column*
Souraa: Th« BCBA
Inc. Marcn 1SW4.
•fflu«m
r»ttinn
from V
Figure 3
CARBON ADSORPTION FLOW DIAGRAM
(carbon consumption greater than 400 pounds per day)
•put
Tank
Multl-M«l«
Carbon Column*
Multtpta Haarth
r>umae*/Cafl>on
•ffhj«nt
087
KWi-Co*cAnalviteMod*
ICP Inc.. Maren 19*4.
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A-ll
IN-SITU BIOLOGICAL TREATMENT
Another method of contaminant treatment advanced by Super-
fund is in-situ biodegradation, in which the waste is biodegraded
in the aquifer by indigenous or added microorganisms to produce
carbon dioxide, water, various intermediates, and new cell bio-
mass. The two main techniques used are modifying the environment
to enhance microbial activity and altering the microbial popula-
tion by seeding with microorganisms that have already been
acclimated to the pollutants to be degraded. Environmental
modification is currently the more popular and more effective
technique.
Enhancing the indigenous microbial population involves the
addition of nutrients and/or dissolved oxygen. A number of steps
are involved. First, the extent of ground-water contamination,
site hydrogeology, and other characteristics is examined.
Various environmental factors control biodegradation, including
pH, temperature, oxidation-reduction potential, salinity, avail-
ability of nutrients, dissolved oxygen level, and concentration
of contaminants. Next, researchers must determine whether native
microorganisms will degrade the spill. If biodegradation is
possible, researchers must then find the nutrient/dissolved oxy-
gen levels that will yield maximum cell growth over a set time
period at ground-water temperature. Possible nutrient choices
are nitrogen, phosphorus, and inorganic salts such as ammonium
sulfate, magnesium sulfate, sodium carbonate, ferrous sulfate,
and calcium chloride. Nutrients are added at concentrations of
0.005 percent to 0.02 percent by weight; this can result in tons
of nutrients being added before treatment is complete.
Once the optimal nutrient/dissolved oxygen levels have been
calculated, the well system for injecting the nutrients and
oxygen and recirculating them in the aquifer is designed and
constructed. Extraction wells are used to draw water for recir-
culation out of the aquifer, while injection wells are used to
force the nutrients, oxygen, and drawn water into the aquifer.
Recycling contaminated water for mixing purposes is recommended,
as it eliminates problems of waste disposal and permits recircu-
lation of unused nutrients. Wells should be placed at the begin-
ning of the plume so that the nutrients move with the ground
water through the contaminated zone.
After the equipment has been set up, the nutrients and
oxygen are added. Nutrients can be supplied using either a batch
or a continuous process. Generally, the batch process has
yielded better results and is more economical. Oxygen is added
by forcing air through the wells with diffusers. The advantages
and disadvantages of microbial enhancement are listed in
Table 2.
088
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A-12
Table 2
ADVANTAGES/DISADVANTAGES OF IN-SITU BIODEGRADATION
BY MICR08IAL ENHANCEMENT
Advantages
1. Useful for removing low levels
of organic compounds that are
"difficult to remove by other
means.
2. Environmentally sound (no waste
products, uses indigenous
microorganisms).
3. Fast, safe, and generally
economical.
4. Treatment moves with the
contaminant plume.
5. Good for short-term treatment.
Disadvantages
1. Does not degrade some
organics.
2. Introduction of nutrients could
adversely affect nearby surface
water.
3. Residues left in ground water
may cause taste and/or odor
problems.
4. May be slower than physical
recovery methods under certain
conditions (e.g., high
pollutant concentrations).
5. Could be expensive if long-term
oxygen/nutrient injection is
necessary or if equipment
maintenance costs are high.
6. Long-term effects are not
known.
7. Bacteria can plug soil and
decrease circulation.
Source: National Center for Ground Water Research, State-of-the-Art of
Aquifer Restoration. 1984.
The second technique, adding microorganisms that have been
acclimated to the pollutants/ is not yet completely successful
but has good potential for the future. In this procedure,
researchers test a variety of microbes to determine which will
best degrade the contaminants. The chosen microbes are used
instead of (or in addition to) the indigenous population. It is
also possible to genetically alter microorganisms to get strains
that will work even better; this, however, is still in the
experimental stage.
089
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A-13
Since in-situ biodegradation is so new, there is little
information on its efficiency. According to the National Center
for Ground Water Research's State-of-the-Art of Aquifer Restora-
tion, in-situ biodegradation of organic solvents has been "fairly
effective." More research still needs to be done, but this tech-
nology has been used with positive results in the past and holds
great promise for the future.
090
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U.S. Environmental Protection Agency
Region 5, Library (PL-12J)
77 West Jackson Boulevard 13th n
Chicago, IL 60604-3590 '°0r
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