|
Items in cart [0] |
Questions? Call 888-624-8373 |
PAPERBACK PDF BOOK Free Resources |
||||||||||||||||
|
||||||||||||||||
|
|
|||||||||||||||
| ||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||
| Copyright © 2009. National Academy of Sciences. All rights reserved. Terms of Use and Privacy Statement |
Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 17
the Nature of
Risk Assessment
Recent criticisms of the conduct and use of risk assess-
ment by regulatory agencies have led to a wide range of
proposed remedies, including changes in regulatory stat-
utes and the development of new methods for assessing
risk. The mandate to this Committee was more limited.
Our obj ective was to examine whether alterations in
institutional arrangements of Procedures, particularly
the organizational separation of Disk assessment from
regulatory decisionrmaking and the use of uniform guide
lines for inferring risk from available scientific ~nfor-
mation, can improve federal risk assessment activities.
Before undertaking to determine whether organizational
and procedural reforms could improve the performance and
use of risk assessment in the federal government, the
Committee examined the state of risk assessment and the
regulatory environment in which it is performed. In this
chapter, we define risk assessment and differentiate it
From other elements in the regulatory process, analyze the
types of judgments made in risk assessment, and examine
its current government context. Because one chronic
health hazard, cancer, was highlighted in the Committee's
congressional mandate and has dominated public concern
about public health risks in recent years, most of our
report focuses on it. Furthermore, because activities i n
four agencies-the Environmental Protection Agency (EPA),
the Food and Drug Administration (FDA), the Occupational
Safety and Bealth Administration (OSEA), and the Consumer
Product Safety Commission (CPSC) have given rise to many
of the proposals f or changes in r isk assessment practices,
our review focuses on these four agencies. The conclu-
sions of this report, although directed primarily at risk
assessment of potential carcinogens as performed by these
17
OCR for page 18
18
four agencies, may be applicable to other federal programs
to reduce health risks.
TERMINOLOGY
Despite the fact that risk assessment }gas become a subject
that has been extensively discussed in recent years, no
standard definitions have evolved, and the same concepts
are encountered under different names. The Committee
adopted the following terminology for use in this report.
BISR ASSESS AND FISI; M~GEME:NT
We use risk assessment to mean the characterization of
the potential adverse health effects of human exposures
to environmental hazards. Risk assessments include
several elements: description of the potential adverse
health effects based on an evaluation of results of
epidemiologic, clinical, toxicologic, and env~ro~ental
research; extrapolation from those results to predict the
type and estimate the extent of health effects in humans
under given conditions of exposure; judgments as to the
number and characteristics of persons exposed at various
intensities and durations and summary judgments on the
existence and overall magnitude of the p~li~health
problem. Risk assessment also includes characterization
of the uncertainties inherent in the process of inferring
risk .
The term risk assessment is often given narrower and
broader meanings than we have adopted here. For same
observers, the term is synonymous with quantitative risk
assessment and emphasizes reliance on numerical results.
Our broader definition includes quantification, but also
includes qualitative expressions of risk. Quantitative
estimates of risk are not always feasible, and they may
be eschewed by agencies for policy reasons. Broader uses
of the term than ours also embrace analysis of perceived
risks, comparisons of risks associated with different
regulatory strategies, and occasionally analysis of the
economic and social implications of regulatory decisions--
functions that we assign to risk management.
The Committee uses the term risk management to describe
the process of evaluating alternative regulatory actions
and selecting among them. Risk management, which is car-
ried out by regulatory agencies under various legislative
OCR for page 19
19
mandates, is an agency decision-making process that
entails consideration of political, social, economic, and
engineering information with risk-related information to
develop, analyze, and compare regulatory options and to
select the appropriate regulatory response to a potential
chronic health hazard. The selection process necessarily
requires the use of value judgments on such issues as the
acceptability of risk and the reasonableness of the costs
of control.
S'~:~S IN RISK AS SESSME:NT
-
Risk assessment can be divided into four major steps:
hazard zOentif ication, dose-response assessment, exposure
assessment, and risk characterization. A risk assessment
might stop with the first step, hazard identification, if
no adverse effect is found or if an agency elects to take
regulatory action without further analysis, for reasons
of policy or statutory mandate.
Of the four steps, hazard identification is the most
easily recognized in the actions of regulatory agencies.
It is defined here as the process of determining whether
exposure to an agent can cause an increase in the inci-
dence of a health condition (cancer, birth defect, etc.).
It involves characterizing the nature and strength of the
evidence of causation. Although the question of whether
a substance causes cancer or other adverse health effects
is theoretically a yes-no question, there are few chemi-
cals on which the human data are definitive. Therefore,
the question is often restated in terms of effects in
laboratory animals or other test systems, e.g., Does the
agent induce cancer in test animals?. Positive answers
to such questions are typically taken as evidence that an
agent may pose a cancer risk for any exposed hens.
Information from short-term in vitro tests and on struc-
tural similarity to known chemical hazards may also be
considered.
Dose-response assessment is the process of character-
~zing the relation between the dose of an agent adminis-
tered or received and the incidence of an adverse health
effect in exposed populations and estimating the incidence
of the effect as a function of human exposure to the
agent. At takes account of inters' ty of exposure, age
pattern of exposure, and possibly other variables that
might affect response, such as sex, lifestyle, and other
modifying factors. A dose-response assessment usually
OCR for page 20
20
requires extrapolation from high to low dose and extrapo-
lation from animals to humans. A dose-response assess-
ment should describe and justify the methods of extrapola-
tion used to predict incidence and should characterize
the statistical and biologic uncertainties in these
methods.
Exposure assessment is the process of measuring or
estimating the intensity, frequency, and duration of
Herman exposures to an agent currently present in the
environment or of estimating hypothetical exposures that
might arise from the release of new chemicals into the
environment. In its most complete form, it describes the
magnitude, duration, schedule, and route of exposure; the
size, nature, and classes of the hen populations
exposed; and the uncertainties in all estimates. Exposure
assessment is often used to identify Feasible prospective
control options and to predict the effects of available
control technologies on exposure.
~~L china -~515~ is the process of estimating the
incidence of a health effect under the various colons
of human exposure described in exposure assessment.
It
is performed by combining the exposure and dose-response
assessments. The summary effects of the uncertainties in
the preceding steps are described in this step.
The relations among the four steps of risk assessment
and between risk assessment and risk management are
depicted in Figure I-1. The type of research information
needed for each step is also illustrated.
SCIENTIFIC BASIS FOR RISK ASSESSMENT
Step l. Bazard Identification
Although risk assessment as it is currently practiced by
federal agencies for the estimation of carcinogenic risk
contains several relatively new features, the scientific
basis for much of the analysis done in risk assessment is
well established. This is especially true of the first
step in the assessment process, hazard identification.
-
Four general classes of information may be used in this
step: epidemiologic data, animal-bioassay data, data on
in vitro effects, and comparisons of molecular structure.
Euidemiol ogic Data
Well-conducted epidemiologic studies that show a posz-
tive association between an agent and a disease are
OCR for page 21
21
LU
cD
z
y
u)
cD
cn
u'
y
u,
-
- o
o ~ -
~ o
c,
Q o
o
C'
C) ~
.O
E c,
CO ~
o ._
V o
_
C~ _
_ _ C3
C
o ~
_ ~,
._ _ ~
_ C
~ a~ ~
~ ~ C)
Z C'
C'
_,
~,
a~ cc
I ~ ~
_ _
, ~
_
° C2.
C) 4-C ~
{l, =5 ~-
C~ C:S
C C) ~ ~
s .3 _
C: - ~
. ~ a, c,
C) ~ ~ ~
- 1
o _
._
C~ ~
,%; ·_
._ _
C) C)
C~ C'
CZ ,~
~ _
c ~
._
C; _
2
, - _
~s
c, cc
s
_ ._
o C ~
C,
C
C~
=; C,
._ ~
C) ~
~ C)
._ ,
o
._
._
C) cn
~ o
._
V
CO
o .3
~ _
6 c~
_ ~ _
V~ C) ' ~
X cC °
~ C~ C-)
o ~ C) C C,
X '
~ ~ o~
S:
0
~S
£
S~
S:
~n
~R
m
x
~2
S~
w
o
m
~:
c:
c
LD
cn
LL
G
C)
V7
C,
C, ~
,_ -3
tl;
_
_ o
V'
o
o ._
_ _
o
_ V
J o
X (5
,=
CO _
~ o
_ _
C} ~n
~ C) ~n
_
C~
C' o
~ CC
,
o _ ~ o | ~ _ ~ o
~ o - E mE ~ ~
~1 ,= ,,l, ~ o~
OCR for page 22
22
accepted as the most convincing evidence about human risk.
This evidence is, however, difficult to accumulate; often
the risk is low, the number of persons exposed is ~mall,
the latent period between exposure and disease is long,
and exposures are mined and multiple. Thus, epidemiologic
data require careful interpretation. Even if these prob-
lems are solved satisfactorily, the preponderance of
chemicals in the environment has not been studied with
epidemiologic methods, and we would not wish to release
newly produced substances only to discover years later
that they were powerful carcinogenic agents. These
limitations require reliance on less direct evidence that
a health hazard ex: sts.
AnimalBioassav Data
The most commonly available data in hazard zdentifica~
talon are those obtained from animal bioassays. The infer-
ence that results from animal experiments are applicable
to humans is fundamental to toxicologic research; this
premise underlies much of experimental biology and medi-
cine and is logically extended to the experimental obser-
vation of carcinogenic effects. Despite the apparent
validity of such inferences and their acceptability by
most cancer researchers, Mere are no doubt occasions in
which observations in animals may be of highly uncertain
relevance to humans.
Consistently positive results in the two sexes and In
several strains and species and higher inciden<:es at
higher doses constitute the best evidence of carcinogen
nici1:y. More often than not, however, such data are not
available. Instead, because of the nature of the effect
and the limits of detection of animal tests as they are
usually conducted, experimental data leading to a posz-
tive finding sometimes barely exceed a statistical thresh-
old and may involve tumor types of uncertain relation to
human carcinogenesis. Interpretation of same animal data
may therefore be d'ff icult. Notwithstanding uncertainties
associated with interpretation of she animal tests, they
have, In general, proved to be reliable indicators of car-
cinogenic properties and will continue to play a pivotal
role in efforts to identify carcinogens.
Short-Term Studies
,
Considerable experimental evidence supports the propose
sition that most chemical carcinogens are mutagens and
that many mutagens are carcinogens. As a result, a
positive response in a mutagenicity assay is supportive
OCR for page 23
23
evidence that the agent tested is likely to be carcino
genie. Such data, in the absence of a positive annoy
bioassay, are rarely, z! ever, sufficient to support a
conclusion that an agent is carcinogenic. Because short-
term tests are rapid and inexpensive, they are valuable
for screening chemicals for potential carcinogenicity and
lending additional support to observations from animal
and epidemiologic investigations.
Comparisons of Molecular Structure
Comparison of an agent's chemical or physical proper-
ties with those of known carcinogens provides some evi-
dence of potential carcinogenicity. Experimental data
support such associations for a few structural classes;
however, such studies are best used to identify potential
carcinogens for further investigation and may be useful
in priority-setting for carcinogenicity testing.
Step 2. Dose-Response Assessment
In a small nether of instances, epidemiologic data permit
a dose-response relation to be developed directly from
observations of exposure and health effects in humans.
I f epidemiologic data are available, extrapolations from
the exposures observed in the study to lower exposures
experienced by the general population are often necessary.
Such extrapolations introduce uncertainty into the esti-
mates of risk for the general population. Uncertainties
also arise because the general population includes some
people, such as children, who may be more susceptible
than people in the sample from which the epidemiologic
data were developed.
The absence of useful human data is common for most
chemicals being assessed for carcinogenic effect, and
dose-response assessment usually entails evaluating tests
that were performed on rats or mice. The tests, however,
typically have been designed for hazard identification,
rather than for determining dose-response relations.
Onder current testing practice, one group of animals is
given the highest dose that can be tolerated, a second
group is exposed at half that dose, and a control group
is not exposed.
(The use of high doses is necessary to
maximize the sensitivity of the study for determining
whether the agent being tested has carcinogenic pose::
teal.) A finding in such studies that increased exposure
leads to an increased incidence has been used primarily
OCR for page 24
24
to corroborate hazard identif ication, that is, to show
that the agent does indeed induce the adverse health
effect.
The testing of chemicals at high doses has been
challenged by soree scientists who argue that metabolism
of chemicals differs at high and low doses; i.e., high
doses may overwhelm normal detoxification mechanists and
provide results that would not occur at the lower doses
to which humans are exposed. An additional factor that
is often raised to challenge the validity of animal data
to indicate effects in man is tha. metabolic differences
among animal species should be considered when animal
test results are analyzed. Metabolic differences can
have important effects on the validity of extrapolating
from animals to man if, for exile, the actual carcinoma
gen is a metabol~te of the administered chemical and the
animals tested differ markedly from horns in their prom
auction of that metabolite. A related point is that the
actual dose of carcinogen reaching the affected tissue or
organ is usually not known; thus, dose~response informal
tion, of necessity, is based on administered dose and not
tissue dose. Although data of these types would certainly
improve the basis for extrapolating from high to low doses
and from one species to another, they are difficult to
acquire and often unavailable.
Regulators are interested in doses to which humans
might be exposed, and such doses usually are much lower
than those administered in animal studies. Therefore,
dose-response assessment often requires extrapolating an
expected response curve over a wide range of doses from
one or two actual data points. In addition, differences
in size and metabolic rates between man and laboratory
animals require that doses used experimentally be con
versed to reflect these differences.
Low-Dose Extrapolation
One may extrapolate to low doses by fitting a mathemat-
ical model to animal dose-response data and using the
model to predict risks at lower doses corresponding to
those experienced by humans. At present, the true shape
of the dose-response curve at doses several orders of
magnitude below the observation range cannot be deter-
mined experimentally. Even the largest study on record--
the EDGE study involving 24,000 animals--was designed
only to measure the dose corresponding to a 1% increase
in tumor incidence. However, regul atory agencies are
often concerned about much lower risks (1 in 100,000 to 1
OCR for page 25
25
in 1,000). Several methods have been developed to extrap-
olate from high doses to low doses that would correspond
to risk of such magnitudes. A difficulty with low-dose
extrapolation is that a number of the extrapolation
methods f it the data f rom animal experiments reasonably
well, and it is impossible to distinguish their validity
on the basis of goodness of fit. (From a mathematical
point of view, distinguishing among these models on the
basis of their fit with experimental data would require
an extremely large experiment; from a practical point of
view, it is probably impossible). As Figure 7-2 shows,
the dose-response curves derived with different models to
d iverge below the experimental doses and may diverge sub-
stantially In the dose range of interest to regulators.
Thus, low-dose extrapolation must be more than a curve-
f itting exercise, and considerations of biological plau-
sibility must be taken into account.
Although the five models shown in Figure I-2 may fit
experimental data equally well, they are not equally
plausible biologically. Most persons in the field would
agree that the supralinear model can be disregarded,
because it is very difficult to conceive of a biologic
mechanism that would give rise to this type of low dose
response. The threshold model is based on the assumption
that, below a particular dose (the .threshold. dose of.a
given carcinogen) there is no adverse effect. This con-
cept is plausible, but not now confirmable. The EDb1
study showed an apparent threshold for bladder cancers
caused by 2-acetylaminofluorene; when the data were
repotted on a scale giving greater resolution IOTA,
1981), the number of bladder tumors consistently ins
creased with dose, even at the lowest doses, and no
threshold was detected. Another aspect of the debate
over thresholds for inducing carcinogenic effects Is the
argument that agents that act through genotoxic mecha-
nisms are not likely to have a threshold, whereas agents
whose effects are mediated by epigenetic mechanisms are
possibly more likely to have a threshold. The latter
argument is also currently open to scientific challenge.
Finally, apparent thresholds observable in animal b~o-
assays cannot be equated with thresholds for entire
populations. Even if a threshold exists for individuals,
a single threshold would probably not be applicable to
the whole population.
Animal-to-Buman Dose Extrapolation
In extrapolating from animals to humans, the doses
used in bioassays must be adjusted to allow for differ-
OCR for page 26
26
lo-2
10-4
-
~s
-
C~
A
~ 10 6
6
cr:
X
Lo
10-8
/
/Subl Sneer ~ I
10 lo | 1
0.01
i'
Supralinear '~7
I ~
/
0.1
Sublinear I |
Threshold I
1
1.0 10.0
DOSE (,uglweek)
FIGURE I-2 Results of alternative extrapolation models
for the same experimental data. UNCLE: Dose-response
functions were developed (Crump, in press) for data from
a benzopyrene carcinogenesis experiment with mice
conducted by Lee and O'Neill (1971).
OCR for page 27
27
ences in size and metabolic rates. Several methods cur-
rently are used for this adjustment and assume that animal
and human risks are equivalent when doses are measured as
milligrams per kilogram per day, as milligrams per square
meter of body surface area, as parts per million in air,
diet, or water, or as milligrams per kilogram per life-
time. Although some methods for conversion are used more
frequently than others, a scientific basis for choosing
one over the other is not established.
S ten 3. Exposure Assessment
The f ~ rst task of an exposure assessment is the determiner
tion of the concentration of the chemical to which humans
are exposed. This may be known from direct measurement,
but more typically exposure data are incomplete and must
be estimated. Models f or estimating exposure can be com-
plex, even in the case of structured activity, as occurs
in the workplace. Exposure measurements made on a small
group (e.g., workers in a particular industrial firm) are
often applied to other segments of the worker population.
Exposure assessment in an occupational setting consists
primarily of estimation of long-term airborne exposures in
the workplace. However, because an agent may be present
at various concentrations in diverse occupational set-
tings, a census of exposures is difficult and costly to
conduct. In the community environment, the ambient con-
centrations of chemicals to which people may be exposed
can be estimated from emission rates only if the transport
and conversion processes are known. Alternative eng~neer-
~ng control options require different estimates of the
reduction in exposure that may be achieved. For new chew
icals with no measurement data at all, rough estimations
of exposure are necessary. Some chemical agents are of
concern because they are present in foods or may be am
sorbed when a consumer product is used. Asses rents of
exposure to such agents are complicated by variations in
diet and personal habits among different groups in the
population. Even when the amount of an agent in a food
can be measured, differences in food storage practices,
food preparation, and dietary frequency often lead to a
wide variation in the amount of the agent that individual s
ingest. Patterns of use affect exposure to many consumer
products; for example, a solvent whose vapor is poten-
tially toxic may be used outdoors or it may be used in a
small, poorly ventilated room, where the concentration of
vapor in the air is much higher.
OCR for page 40
40
determine whether regulatory action is warranted, risk
assessment serves at least two major functions in regular
tory decisions: first, it provides an initial assessment
of risks, and, if the risk is judged to be important
enough to warrant regulatory action, it is used to evalu-
ate the effects of different regulatory options on expo-
sure. In addition, it may be used to set priorities for
regulatory consideration and for further toxicity testing.
These varied functions place different requirements on
risk assessors, and a single risk assessment method may
not be sufficient. A risk assessment to establish testing
priorities may appropriately incorporate many worst-case
assumptions if there are data gaps, because research
should be directed at substances with the most crucial
gaps; but such assumptions may be inappropriate for
analyzing regulatory controls, particularly If the regal
later must ensure that controls do not place undue strains
on the economy. In establishing regulatory priorities,
Me same inference options should be chosen for all chem~-
cals, because the main point of the analysis is to make
useful Disk comparisons so that agency resources will be
used rationally. Bowever, this approach, which may be
reasonable for priority-setting, may have to yield to
more sophisticated and detailed scientific arguments when
a substance's cnmmercia1 life is at stake and the agency's
decision may be challenged in court. Furthermore, the
available resources and the resulting analytic care
devoted to a risk assessment for deciding regulatory
policy are likely to be much greater for analyzing
control actions for a single substance than for setting
priorities.
THE AGENCIES TEAT BEGUL~TE
The approach to risk assessment varies considerably among
the four federal agencies. Differences stem pr~r~ly
from variations in agency structure and differences in
statutory mandates and their interpretation.
Organizational Arrangements
The Food and Drug Administration (FDA) is a component of
the Department of Bealth and Buman Services, whose
Secretary is the formal statutory delegate of the powers
exercised by FDA. FDA is headed by a single official,
OCR for page 41
41
the Commissioner of Food and Drugs, who is appointed by
and serves at the pleasure of the Secretary of the Depart-
ment of Health and Baton Services. It is organized in
product-related bureaus, each of which employs its own
scientists, technicians, compliance off icers, and adminis-
trators. FDA has a long (75-year) and strong scientific
tradition. According to a recent Office of Technology
Assessment summary, FDA had taken or proposed action on
24 potential carcinogens by 1981.
Like FDA, the Environmental Protection Agency (EPA) is
headed by a single official, but EPA's Administrator is
appointed by the President subject to Senate confirmation.
Also like FDA, EPA resembles a confederation of relatively
discrete programs that are coordinated and overseen by a
central management. The agency was established in 1970,
but many of its programs (e.g., air and water pollution
control and pesticide regulation) predate its formation
and previously were housed in and administered by other
departments. Other programs, such as those for toxic
substances and hazardous waste, are rather new. EPA's
research, policy evaluation, and, until recently, enforce-
ment efforts were separated organizationally from the
program offices that write regulations. EPA has had the
widest experience with regulating carcinogens; as of
1981, it had acted on 56 chemicals in its clean~water
program, 29 in its clean~air program, 18 in its pesticide
program, and two in its drinking-water program.
The Occupational Safety and Bealth Administration
(OS=) is part of the Department of Labor. The agency' s
head Is an Assistant Secretary of Labor, who requires
Senate confirmation. Although Fl)A and EPA derive their
scientific support largely from their own full-time
employees, until the late 1970s OSEA relied on other
agencies, primarily the National Institute of Occupant
tional Safety and Bealth, an agency of the Department of
Health and Human Services. This division reflects a
conscious congressional choice in 1970 to place ache
health experts on whom OSEA was expected to rely in an
outside environment believed more congenial to scientific
inquiry and less vulnerable to political influence. As
of 1981, 18 potential carcinogens had been acted on by
OSEA.
The Consumer Product Safety Commission (CPSC) enforces
five statutes, including the Consumer Product Safety Act
and the Federal Hazardous Substances Act. Both empower
CPSC to regulate unreasonable risks of injury from prod-
ucts used by consumers in the home, in schools, or in
OCR for page 42
42
recreation. The much smaller CPSC differs sharply from
the other three agencies in two important respects: it
does not have a single administrative head, but instead
is governed by five Commissioners, who can make major
regulatory decisions only by majority vote; and the
Comm' ssioners are appointed for f ixed terms by the
President with Senate confirmation. Before 1981, CPSC
had acted on five potential carcinogens.
The four agencies have attempted to coordinate risk
assessment activities in the past, most notably through
the Interagency Regulatory Liaison Group (DOG), which
formed a work group on risk assessment to develop a guides
line for assessing carcinogenic risks. Assisted by scien-
tists from the National Cancer Institute and the National
Institute for Environmental Health Sciences, it examined
the various approaches used by the four agencies to evalu-
ate evidence of carcinogenicity and to assess risk. The
IRLG (1979a,b) then integrated and incorporated these
evaluative procedures into a document, "Scientific Bases
for Identification of Potential Carcinogens and Esteem
tion of Risks, which described the basis for evaluation
or carcinogenic hazards identified through epidemiologic
and experimental studies and the methods used for quanti-
tat~ve estimation of carcinogenic risk.
Requlatorv Statutes*
Examination of the statutes that the four agencies admit
ister reveals important differences in the standards that
govern their decisions. The Office of Technology Assess-
ment has summarized {Table I-2) statutes that pertain to
the regulation of carcinogenic chemicals. In particular,
the statutes accord different weights to such criteria as
risk, costs of control, and technical feasibility. In
addition, different modes of regulation vary in their
capacity to generate the scientific data necessary to
perform comprehensive risk assessments.
Several laws require agencies to balance regulatory
costs and benefits. Examples of balancing provisions are
found in the Safe Drinking Water Act; the Federal Insecti-
cide, Fungicide, and Rodenticide Act; the Toxic Substances
*This discussion draws heavily on the Office of Techr
nology Assessment report, Technologies for Determining
Cancer Risks from the Environment, }981.
OCR for page 43
43
Control Act; and the section on fuel additives in the
Clean Air Ace. Under such provisions, a risk assessment
can be used to express the nature and extent of public-
health benef its to be attained through regulation.
Some regulatory programs involve the establishment of
technology-based exposure controls. This approach is
Followed, for example, in portions of the clean-water
program and the part of the hazardous-wastes program that
deals with waste incineration standards. In such pro-
grams, ~ risk assessment may be used to show the human
exposure that corresponds to a specific degree of risk or
to calculate the risk remaining after control technologies
are put in place.
Some statutes mandate control techniques to reduce
risks to zero whenever hazard is affirmed. Such tech-
niques include outright bans of products, as envisioned
in the Delaney clause in the Federal Food, Doug, and
Cosmetic Act. In addition, if the concept of a threshold
below which carcinogens pose no risk is not accepted,
strict interpretations of ample margin of safety language
in federal clean-air and clean-water legislation would
require that exposures to carcinogenic pollutants be
reduced to zero. The role of risk assessment in cases
where mandatory control techniques must reduce risks to
zero may be simply to affirm that a hazard exists.
m e difference between programs that involve premarket-
inn approval of substances and programs that operate
through post hoc mechanisms, such as environmental em~s-
sion limits, may have an important influence over the
quality of risk assessments. The most important effect
of this difference may lie in the fact that premarketing
approval programs (such as those for pesticides, for new
human drugs, and for new food additives empower an agency
to require the submission of sufficient data for a compre-
hens~ve risk assessment, whereas other programs tend to
leave agencies to fend for themselves in the acquisition
of necessary data.
There can be little question that differing statutory
standards for decision affect the weight that agencies
accord risk assessments. Like differences in the mode of
regulation, they probably have affected the rigor and
scope of many assessments. If risk is but one of several
criteria that a regulator must consider or if data are
expensive to obtain, it would not be surprising if an
agency devoted less effort to risk assessment. However,
the Committee has not discovered differences in existing
statutes that should impede the adoption of uniform,
OCR for page 44
OCR for page 47
OCR for page 48
OCR for page 49
OCR for page 50
Representative terms from entire chapter:
regulatory decisions
~4
~,
O !
;
1
V
5~
o
1
1
O '
1 o.,
-
CO
C)
G
~ 1
c !
C C .
_ _,
o {e
1
C5 C5:
~1
i
~ 1
~ 1 ~ i
s~t I C
° I o '
W ~ ~ G
~ C
_ O
C~ ,
~ o I
O
C CL
C:~- j
o
~,
1 1
81
S
V
~t
~ !
-
t8 ~
i
o 1
o~
C)
C)
o
c
-
o
G t
CD
~D
~j
O j=~ =80
~ 1 1
C~
t
~ 1
~,
1
~:
p
oo
-
o
c
CO
oo
-
-
~o
o
o
-
-
ee c
C C
_ _
C C
{S C~
~ CC
C: {D
-
-
x
o
-
-
CS
1
oo
o .=
C C)
tD a~ c
~ ~c E
D _
°o co C
~D ~n
O
o
z
-
C
C
E
-
o
=..
::)
_ ~>
C o ~s
o ~ c.'
G C O ~
a~< - 0
o _ Ce O
'C,~^
~ C I,
.o
:D
O ~
O _
_ .
O
C
C
a'G~
u, c c
~ o o
mD
~ - 0
"c ~ ~ ~ E
(cD o G C) D
O C° a~ c: _
Z 0 o 0 c,,
_ o _ O
G 0 _
c
E
-
~D
-
o
z
-
0
D
~D
-
C 0
O C,
45
0 ~ 0 .~ 8 ~ ~ ~ ~ ~ ~ · ~ e ~ °
== O ~ ~ 3 ~ E E c ~ ~ ~ ~ ~ ~ E c ~
0 0 c
c c
_ 0 ~ ~
_ ct ° ~ >
0 ~ _ cO _
_ .= E~ a:
c ~ C vl ~ °
_ c ~ 0 ~ c
c ~ c . c
D _ ~D G 3
o' Q D ~ C C
' o ' C:' o ~ ~ C _ C) :^
C tD C,~ o _ c~ ~ C D O _
~ O. ~ ~G E~ ~ ° · > E ~ z
.. ~..'g.'~-s. '., 566.~ ~'2!~.:2.-~0
o G _ `, ~ c, ~ C
~ ~D C~ ~ ~ <~
47
~ ~ v ' ~ ° co ~ 5 E E C|
.. | ~
tr c,'° !3
=- `, E
,C 2' - . ~
al ~ a
0 C' O ~
C,~ 0
OD^i~- ~
~ 2 c
~ D as ! ~
~ ~ O
ID as ~ O
O lC ID · C
_ ~ O - cat of as ~ 0 ~
~ o ~ 2 ~ ~ '_ ' ° ~ ', C
!.-2~.l§.~.--~ I..- il~ls~r=~ ail - ~
'-a E hi, e< 0 c
48
government-wide risk assessment guidelines. Indeed, it
is not satisfied that there are legal bases for inter-
agency differences in the performaw e--as distinct from
the use--of risk assessment for chronic health hazards.
CONCLUSIONS
On the basis of a review of the nature and the policy
context of risk assessment, the Committee has drawn the
following general conclusions:
1. Risk assessment is only one aspect of the process
of regulatory control of hazardous substances,, 24~3ctc~`
-
~marov~ments in risk assessment
to eliminate controversy over federal risk management
decisions.
Restrictive regulation nas seemed onerc~u:~ rev Can "-
turers, distributors, and users of products judged useful
and valuable; conversely, inaction and delay with respect
to regulatory proceedings have appeared callous and
irresponsible to others.
.
These dissatisfactions have
been manifested in many ways, including criticizer of risk
assessment processes. The Committee believes that much
of this criticism is inappropriately directed and gives
rise to an unrealistic expectation that modifying risk
assessment procedures will result in regulatory decisions
more acceptable to the critics. Certainly risk assessment
can and should be Improved, with salutary effects on the
appropriateness of regulatory decisions. However, risk
management, although it uses risk assessment, is driven
by political, social, and economic forces, and regulatory
decisions will continue to arouse controversy and
conflict.
2. }lis}c assessment is an analytic process that is
firmly based on scientific considerations, but it also
requires iudsments to be made when the available informal
tion is incomplete.
both scientist`: no! P~ilE[~YLi4~Ya~CL
Jon ris}c assessment is that the
information on which decisions must be based is usually
inadequate. Because the decisions cannot wait, the gaps
in information must be bridged by inference and belief,
and these cannot be evaluated in the some way as facts.
Improving the quality and comprehensiveness of knowledge
is by far the most effective way to Improve risk assess-
49
meet, but some limitations are inherent and unresolvab, e,
and inferences will always be required. Although we
conclude that the mixing of science and policy in risk
assessment cannot be eliminated, we believe that most of
the intrusions of policy can be identified and that a
major contribution to the integrity of the risk assess-
ment process would be the development of a procedure to
ensure that the judgments made in risk assessments, and
the underlying rationale for such judgments, are made
explicit.
3. Two kinds of policy can potentially affect risk
assessment: that which is inherent in the assessment
Process itself and that which Governs the selection of
regulatory options. The lay i
should not be allowed to control the former, risk
assessment Policv.
Risk management policy, by its very nature, must entail
value judgments related to public perceptions of risk and
to information on risks, benefits, and costs of control
strategies for each substance considered for regulation.
Such information varies from substance to substance, so
the judgments made in risk management must be case-
specific. If such case-specific considerations as a
substance's economic importance, which are appropriate to
risk management, influence the judgments made in ye risk
assessment process, the integrity of the risk assessment
process will be seriously undermined. Even the perception
that risk management considerations are influencing the
conduct of risk assessment in an important way will cause
the assessment and regulatory decisions based on them to
lack credibility.
4 . Risk assessment suf ~
of a mechanism for addressing generic issues in isolation
,
from specific risk management decisions.
spent has progressed
in recent years, there is currently no mechanism for st
ulating and monitoring advances on generic questions in
relevant scientific fields or for the timely disseminar
tion of such information to risk assessors.
REFERENCES
Cramp, R. S. In press. Issues related to carcinogenic
risk assessment from animal bioassay data. Paper
50
presented May 1981 at the International School of
Technological Risk Assessment, a NATO Advanced Study
Institute, Erice, Italy.
IRLG (interagency Regulatory Liaison Group), Work Group
on Risk Assessment. 1979a. Scientific }cases for
identification of potential carcinogens and estimation
of risks. Fed. Reg. 44 :39858.
IREG (Interagency Regulatory Liaison Group), Work Group
on Risk Assessment. 1919b. Scientific bases for
identification of potential carcinogens and estimation
of risks. 3. Natl. Cancer Inst. 63 :242.
Lee, P. N., and J. A. O'~eill. 1971. The effect both of
time and dose applied on tumor incidence rate In
benzopyrene skin painting experiments. Brit. J.
Cancer 25: 759-770 .
National Academy of Sciences. 1981. The Health Effects
of Nitrate, Nitrite, and N=Nitroso Compounds.
Washington, I).C.: National Academy Press. 544 pp.
OTA tOffice of Technology Assessment). 1981. Assessment
of the Technologies for Determining Cancer Risks from
the Environment. 240 pp.
