|
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 121
7
Selection and Application of
Animal Sen tine! Systems
in Risk Assessment
This chapter discusses the principles that should guide the selection and appli-
cation of animal sentinel systems in risk assessment. It also discusses develop-
ments and improvements in methods that will be required if the full potential
of animal sentinel systems is to be realized.
Chapter 6 described how animal sentinel systems have been used in the
various phases of risk assessment and pointed out their advantages and disad-
vantages for each phase. Animal sentinel systems have been most useful in
general environmental monitoring, in assessing exposure of monitored organ-
isms and their consumers, in assessing bioavailability of contaminants, and in
assessing ecologic risk; in these applications, data from animal sentinels can
often be used quantitatively. Animal sentinel systems have potential value as
early warning systems for new hazards, as indicators of potential human eypo-
sure to complex mixtures or in complex environments, and as monitors of the
effectiveness of remediation measures or other environmental management
actions; in these applications, data from animal sentinels are usually used
qualitatively, but there is at least a potential for semiquantitative assessments.
Animal sentinels have more limited value as surrogates for exposed human
populations in hazard identification, dose-response assessment, and risk char-
acterization; they have rarely been used for these purposes, and to date such
applications have been entirely qualitative.
The traditional method for conducting risk assessments for humans exposed
to environmental contaminants is to measure (or calculate) the concentrations
of the contaminant in various environmental media, calculate human exposure
on the basis of rates of contact with the contaminated media, and combine the
estimates of exposure with dose-response data derived from animal studies
(NRC, 1983~. Each of those steps is subject to error and uncertainty, so that
risk estimates are often extremely rough. As discussed in Chapter 6, animal
sentinels can be used to complement the traditional approaches; if appropri-
ately used, they offer the potential for reducing some of the errors and uncer-
tainties inherent in the traditional methods.
An investigator planning an environmental assessment should always con-
121
OCR for page 122
1= ANIMALS AS SENTINELS
sider using an animal sentinel system, when it is practicable, as an adjunct to
conventional assessment procedures. Animal sentinel data are likely to be
especially useful in circumstances where the conventional procedures are most
prone to uncertainty. Those circumstances include the following:
· Accumulated chemicals—cases in which the agent under investigation is
persistent and stored in animal tissues, so a sentinel animal could serve as a
sampling and averaging device.
· Complex mixtures—cases in which humans are exposed to complex or
poorly characterized mixtures of chemicals.
· Complex exposures—cases in which humans are exposed to contaminants
at concentrations that vary widely in time or space or are exposed via multiple
routes, so total exposure is difficult to characterize.
· Uncertain biouvailabili~cases in which contaminants are present in
media from which their availability for uptake into biologic systems is difficult
to predict.
· Poorly characterized agents—cases in which humans are exposed to agents
of uncertain toxicity, pharmacokinetics, or other characteristics.
Whether an appropriate sentinel can be selected in a specific case depends
on the circumstances. Factors to consider in determining whether to use an
animal sentinel system include the following:
· Media. Humans can be exposed to a contaminant via several media,
including indoor air; animals can frequent different media and be exposed in
different ways.
· Scale of averaging. Animal sentinels average their exposure over spatial
and temporal scales that are determined by the animals' behavior (home
range) and physiology (pharmacokinetic characteristics); it might or might not
be feasible to find an animal species that averages over scales appropriate for
human risk assessment.
· Sensitivity. The animal species selected should be appropriately sensitive
to the biologic effects that are being investigated.
· Specificity. The species selected should respond reasonably specifically
to the contaminant under investigation.
· Availability. If a wild-animal species is selected, it should be reasonably
abundant and readily trapped for sampling; if no wild species is suitable, in
situ sampling should be considered.
Consideration of those factors requires communication among specialists
in several disciplines: risk assessment, environmental chemistry, toxicology,
OCR for page 123
SELECTION AND APPLICA TION OF SYSTEMS 123
ecology, and veterinary science. If a suitable sentinel species or system can
be found, several tests of practicality should be applied. Is there any previous
experience with the same animal species that would indicate that it is likely to
provide the information sought? Can the system be put into operation within
a reasonable time and with the professional resources that are available? Will
the system provide information that will supplement or complement informa-
tion provided by traditional methods of assessment? Will the system be cost-
effective in comparison with traditional methods? Will the system meet legal
requirements and animal-welfare codes? Will it provide information that win
be defensible as a basis for regulation or other risk-management activities?
As a guide to those who wish to use animal sentinel systems in risk assess-
ment, some of the advantages and disadvantages of different approaches are
summarized in Table 7-1.
SYSTEM DESIGN
Once an animal species is found that meets the initial tests of availability,
efficacy, and practicality, the design of an appropriate system to use it should
be considered. The following design issues are important (Steele, 1975~:
· Nature of the problem. The nature and magnitude of the public-health,
veterinary, or wildlife problem for which the system is to be designed should
be clearly defined. The merits of the animal sentinel program, including its
expected sensitivity and specificity and its complementarily to other programs,
should be explicitly stated to justify implementing the proposed program.
· Objectives. Animal sentinel programs can serve a variety of purposes.
They are generally most likely to be useful if chronic low-level exposure is
suspected and human data are absent, incomplete, or inconclusive. Animal-
monitoring programs can be used in hazard identification, exposure assess-
ment, or risk characterization (see Chapter 6~. In situ monitoring programs
can enable researchers to assess bioavailability of contaminants, can provide
surrogate measures of potential human exposures, or can enable researchers
and risk managers to determine the efficacy of remediation measures taken
at sites determined to be hazardous. Animal epidemiologic studies can pro-
vide answers to specific questions about health effects of chronic low-level
exposure or long-term trends of a particular disease. The objectives of an
animal sentinel program must be formulated realistically at the outset, because
they will be bases of all other major decisions in the design and operation of
the program.
· Event and unit of observation. The exposure or event that will be under
OCR for page 124
124 ANlhL4LS AS SENTINELS
TABLE 7-1 Advantages and Disadvantages of Animal Sentinel Systems for
Risk Assessment
Characteris-
tic of System
Epidemiolog-
ic Studies in
Wildlife and
Fish
Epidemiolog-
ic Studies in
Domestic
Animals
In Situ Field
Studies
r
Availability Plentiful; Plentiful; Can select Can select
of animals diversity of limited diver- desirable desirable
species sity of spe- species species
cues
Existence of
baseline data
for disease
occurence
Limited
Yes, from
existing dis-
ease surveil-
lance systems
plus available
medical rec-
ords
Yes for labo-
ratory ani-
mals; no for
many others
Yes
Existence of Limited to a Very limited Not. NA
baseline data few existing exposure
for exposures monitoring data
programs
Knowledge Unknown Usually un- Well defined Well defined
of total pop- known, but
ulation at defined in
risk some circum-
stances
Ability to Usually none Partial; can Good; mim- Good
control for be done by ics laboratory
potentially study design setting
confounding or during
factors data analysis
Exposure
route; com-
parison with
humans
Usually dif-
ferent
Often very
. .
slm1 ar
Similar or
different,
depending on
location of
study site
Can be ma-
nipulated
OCR for page 125
SELECTION AND APPLICATION OF SYSTEMS 125
Characterize
tic of System
Epidemiolog-
ic Studies in
Wildlife and
Fish
Epidemiolog-
ic Studies in
Domestic
Animals
In Situ Field
Studies
Laboratory
Animal
Studies
Complexity Usually com- Usually cam- UsuaLly com- Can be man-
of exposures plex plex plex, but can ipulated, but
manipulate might not
doses measure hu-
man expm
sure
Latency peri- Usually Usually Usually Usually
od shorter than shorter than shorter than shorter than
for humans; for humans; for humans; for humans;
varies with varies with can select a can select
species species species for species for
short latency short latency
Interspecies
extrapolation
of results
Necessary;
physiology
and metabo-
lism of many
species often
ill-defined or
very different
from humans
Animal-wel- Usually none
fare concerns
Necessary;
physiology
and metabo-
lism of many
species often
well defined
and similar
to human
(e.g., beagle
dog)
Necessary;
can select
well-defined
species for
study, but
similarity to
humans still
questionable
Minimal to Great Great
none
Necessary,
can select
well-dehmed
species for
studier, but
similarity to
humans still
questionable
N^. = Not applicable.
surveillance must be defined precisely. The unit of observation such as the
individual, flock, herd, or population—must be specified.
· Sources of data. The most effective animal sentinel systems are those
in which data are collected by the researchers themselves according to a de-
signed protocol. In other cases, specimens or observations might be available
from farmers, veterinarians, veterinary schools, diagnostic laboratories, disease
registries, food-monitoring programs, hunters, or state and federal agencies
responsible for environmental quality, fish and wildlife monitoring, or manage-
OCR for page 126
126 ANIMALS AS SENTINELS
meet. Most of those sources of data are potentially subject to collection bias,
sample contamination, error in documentation, incomplete followup, or other
types of errors. Any program that is based on voluntary or discretionary
cooperation of sources of those kinds should take into account the likelihood
of bias and error and should seek to investigate them and minimize or assess
their effects. Even when a program is designed and conducted by research
scientists, the potential for biases and errors needs to be considered. Sam-
pling design, sample collection, analytic methods, validation, quality assurance,
and quality control are critical in animal sentinel studies (as in anv other tone
of field study).
.__, ~ ~r~
· Characterization of the system. It is important in system design to su~m-
marize the characteristics of the species or system that is to be used. If a
wild-animal species is to be used as a sentinel, its behavior, ecology, physiolo-
gy, and population should be characterized, to determine what the system is
likely to measure (e.g., to establish spatial and temporal scales of averaging).
If important species-specific or site-specific information is missing, the system
should be designed to obtain this information. If a domestic-animal species
is to be used, characteristics of its population (e.g., breeds, age structure, diet,
nutrition, and morbidity patterns) need to be established, either at the outset
or as part of the investigation.
· Selection of controls. Many types of program (e.g., case-control epidemi-
ologic studies) require selection of appropriate control populations. General-
ly, control populations will need to be established in uncontaminated (or less
contaminated) areas. Selection of appropriate control locations and popula-
tions requires careful and often complex, multidimensional comparisons of
sample locations and populations, to minimize the potential for confounding
and bias.
· Characteristics of the program. The program can be either active or
passive; the first requires a deliberate effort to collect new information, and
the second uses data generated without solicitation or intervention. Data
collection can be continuous or intermittent and for long or short periods. A
decision must be made whether an entire population will be tested (as for
some livestock diseases) or samples will be selected—and if so, how.
IMPr CEMENTATION
Once a system is designed, its implementation and operation raise addition-
al issues:
· Professional and institutional issues. Effective operation of an animal
OCR for page 127
SELECTION AND APPLICATION OF SYSTEMS ID
sentinel system requires effective cooperation by professionals in several disci-
plines; in this regard, animal sentinel systems are more complex than other
systems used in risk assessment. Provision should be made from the outset for
regular communication, program integration, and peer review. Many prod
grams will require cooperation among institutions in unusual combina-
tions—e.g., military installations with veterinary schools and hazardous-waste
facilities with wildlife research institutions. Special efforts might be needed
to overcome institutional barriers and problems in communication.
· Long-term continuity. Some programs are designed to be conducted over
a long term (e.g., the National Contaminants Biomonitoring Program (NCBP)
and other programs designed to monitor long-term consequences of remedial
activities). Such programs require long-term institutional commitment, includ-
ing stable funding and provision for storage of data and archived specimens.
They also require long-term stability of methods or measures to ensure long-
term comparability of data (e.g., intercalibration of results when analytic
methods are changed). In practice, long-term continuity has been very diffi-
cult to achieve in the programs reviewed for this report.
· Mechanisms of recording, coding' and storing data. Forms used for re-
cording information should be easy to use. To be useful for analysis and
interpretation, chemical and biologic data must be codable with widely accept-
ed and standardized nomenclature. Temporal and geographic data should be
integrated, where possible, into geographic information systems (GISs).
A wide variety of applications can benefit from the use of GIS technology.
One of the more common applications of GIS technology relevant to the use
of animals as sentinels is in resource management, specifically in defining
wildlife habitat. Placement of food, water sources, and terrestrial components
in prescribed forms and relationships establishes the habitat for a particular
wildlife species. For example, a habitat change in the use of a specific area
in Georgia by a colony of wood storks was determined (Hodgson et al., 1988~.
A more focused potential application would result in the juxtaposition of data
on animals (individuals or populations), distribution of toxicant sources and
concentrations, occurrence of adverse health effects, and a multitude of relat-
ed geographic and nongeographic data. Thematic maps can be produced that
outline, for example, the relationship between high concentrations of a partic-
ular pollutant and the incidence of a specific effect in a sentinel animal. The
distribution and density of the human population at risk, the infrastructure,
health facilities, water supply, etc., could be overlaid on the graphic displays.
Data should be stored in data bases that are accessible to users who wish
to link them with other data bases or to use data for other purposes.
Many of the advantages of GISs for the study of environmental conditions
are obvious. The storage of large amounts of data in a logically retrievable
OCR for page 128
128 ANIMALS AS SENTINELS
form that retains their geographic integrity is the central theme underlying the
current surge of interest in this rapidly evolving technology. The use of com-
puter hardware and software to process widely disparate data interactively
almost in real time yields insight into issues and processes that were hard to
study because of lack of understanding, time, or trained staff. Decisions can
be made on the basis of a hierarchy of deliberately structured algorithms, and
the data sets can readily be updated to allow temporal and geographic rela-
tionships to be examined more closely than is possible with conventional
techniques. Models, statistical algorithms, and graphics can be incorporated
into this analytic scheme. The trend toward greater use of GIS technology
will continue as computer hardware and software improve, GIS technology
develops, and our understanding of the complexity of environmental issues
increases. For it to be effectively integrated into programs that use animals
as sentinels, a substantial commitment must be made to identify uses of the
data generated, to complement consistent systems and data management, and
to incorporate existing data bases and networks into the system.
· Characteristics of intended report. Reporting of methods, validation, and
early results of current animal sentinel systems is important for the further
development of such systems. As programs are implemented and begin to
yield useful results, the results should be reported regularly to interested
parties to ensure the maintenance of individual and institutional commitments
to long-term programs. Important considerations are how often and to whom
reports will be distributed. Typically, enthusiasm for monitoring diminishes
as the interval between reports increases. Some reports should contain inter-
pretative summaries of key findings; some need not.
· Quality assurance. Periodic assessment of a monitoring program is
important to determine whether it is achieving its stated objectives and at
what cost. A method for program evaluation and the frequency of evaluation
should be established when a program is instituted.
VALIDATION
Many of the animal sentinel systems discussed in this report are exploratory
or experimental, in the sense that each type of system has been used only
once or a few times. Before any of these systems can be used on a wide scale
as an element in exposure assessment, hazard assessment, or risk characteriza-
tion (see Chapter 6), it will require an extensive process of validation. In this
context, validation of a system includes the following elements:
· Charactenzation of the systen'. What are the characteristics of the spe-
OCR for page 129
SELECTIONAND APPLICATION OF SYSTEMS 129
cies selected for the system? What are the characteristics of the end point
selected for measurement? How variable is the end point, and how do the
variations depend on such factors as age, sex, strain, environmental conditions,
and other contaminants?
· Replicabili~. Does the system yield replicable results? Are the results
similar in replicate groups within a study? Between studies? Between labora-
tories? Are the results stable over time?
· Sensitivity. Is the system responsive to the contaminant under investiga-
tion? Does it respond at environmentally relevant concentrations? What is
the form of the dose-response relationship?
· Specipci~. Does the system respond only to one or a few agents, or
does it respond similarly to a variety of contaminants or environmental stress-
es?
· Predictive value. Are the results useful in predicting human exposure or
human effects? Can the results be correlated with direct observations in
humans? If a study yields information on the sentinels' exposure, are the
sentinels exposed in ways similar to those of humans? If not, are the differ-
ences predictable? Is the bioavailability of contaminants from environmental
media similar in the animals and humans? If the study yields information on
biologic effects, is there reason to expect that humans will respond in ways
similar to those of the sentinels?
Except for some systems that have been designed to monitor exposure (e.g.,
the NCBP), no animal sentinel systems have been fully validated, in the sense
that all five elements has been considered. If the potential value of any other
animal sentinel system is to be realized, it must be subjected to a thorough
program of validation. The lack of a systematic program of validation is
probably the most important obstacle to the wider use of animal sentinel
systems in risk assessment and risk management.
PROGRAlLf INTEGRATION
Many existing programs have been designed for specific purposes, and the
resulting data have been used sparingly. In some cases, different programs
collect data on the same contaminants and in the same areas but are poorly
integrated. For example, programs in several federal agencies measure or-
ganochlorines in fish. If those programs could be better integrated, each
could tap a larger data base and could become more cost-effective. State
departments of natural resources, federal laboratories, and universities already
field questions from the public bringing in material for inspection. State
OCR for page 130
130 ANIMALS AS SENTINELS
departments and law enforcement agencies obtain a wide range of material
year-round from road kills, poaching, and similar events. In addition, tag-
return programs in fisheries have been well supported.
A second way in which program integration could yield more efficient use
of resources is the use of specimens for multiple purposes. Many animal
specimens are collected for single purposes and discarded after single analy-
ses. For example, the National Animal Health Monitoring System and Market
Cattle Identification programs collect and analyze tissue and blood, respective-
ly, from market cattle. The programs handle large numbers of documented
specimens that could be useful for other purposes; analysis of subsets of the
specimens for organochlorines or other contaminants could provide a new and
efficient way to assess human exposure to these contaminants. Another way
to extend the value of existing programs is by archiving or banking specimen
material from monitoring programs for analysis when new contaminants are
discovered or new analytic methods developed.
A third desirable form of program integration is the integration of data
from animal sentinel programs with data from traditional environmental sam-
pling. Animal sentinel data could become more valuable if they could be
correlated with environmental data, such as measurements of ambient concen-
trations of the same contaminants. Such correlations could improve not only
the utility of each type of data, but also the basis for modeling of environmen-
tal transport and exposure assessment.
The committee is aware of the technical and institutional obstacles to
program integration of the types mentioned here. However, much of the
information now collected in animal sentinel programs is underused. Even
modest efforts to extend and integrate existing programs could lead to a sum
stantial improvement in applications.
Representative terms from entire chapter:
epidemiologic studies
