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Executive Summary Birds and mice may be used to detect capon m ononade, because they are much more sensitive to the poisonous action of the gas than are men. Expenments by the Bureau of Mines show that canapes should be used in preference to mice, sparrows, or pigeons, because canapes are more sensitive to the gas. Rabbits, chickens, guinea pigs, or dogs, although useful for exploration work in mines, should be used only when birds or mice are unobtainable, and then cautiously, because of their grater resistance to carbon monoxide poisoning. Many embedments have shown that if a canary is quickly removed to good air after its collapse from breathing capon monoxide it al- w~ys recovers and can be used again arid again for exploration wo'* without danger of its becoming less sensitive. Breathing apparatus must be used where birds show sighs of distress, and for this reason birds am of great value in enabling rescue patties to use breathing apparatus to best advantage (Bunnell and Seibert, 1916~. IN177ODUC7l ION Like humans, domestic animals and fish and other wildlife are exposed to contaminants in air, soil, water, and food, and they can suffer acute and chronic health effects from such exposures. Animal sentinel systems systems in which data on animals exposed to contaminants in the environment are regularly and systematically collected and analyzed~an be used to identify potential health hazards to other animals or humans. Sentinel systems can be designed, for example, to reveal environmental contamination, to monitor contamination of the food web, or to investigate the bioavailability of contaminants from environmental media; these types of systems can be designed to facilitate assessment of human exposure to envi- ronmental contaminants. Other sentinel systems can be designed to facilitate assessment of health hazards resulting from such exposure; e.g., systems can be designed to provide early warning of human health risks or can involve 1

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2 ANIMALS AS SENTINELS deliberate placement of sentinel animals at a selected site to permit measure- ment of environmental health hazards. Some sentinel systems can be used to indicate both exposure and hazard. Animals can serve to monitor any type of environment, including homes, work places, farms, and natural aquatic or terrestrial ecosystems. They can be observed in their natural habitats or placed in work places or sites of sus- pected contamination. Purpose of He 50, The Committee on Animals as Monitors of Environmental Hazards was convened by the National Research Council's Board on Environmental Studies and Toxicology in the Commission on Life Sciences in response to a request from the Agency for Toxic Substances and Disease Registry (ATSDR). ATSDR has health-related responsibilities pertaining to hazardous waste sites and releases of chemicals. The committee was charged to review and evaluate the usefulness of animal epidemiologic studies for human risk assessment and to recommend types of data that should be collected to perform risk assess- ments for human populations. The committee reviewed many observational and experimental studies and also held a workshop to obtain information on programs that collect animal sentinel data. The committee considered the gaps in existing data that need to be addressed if animal sentinel data are to be used in human risk assessment and discussed issues of coordination be- tween programs and standardization of data collection, analysis, and reporting. The committee explored the potential use of animal sentinels in determin- ing risks to human populations posed by environmental contaminants, with special care to determine whether in situ and natural-exposure studies could supplement traditional laboratory studies or help to remove difficulties in risk assessment, such as problems in exposure assessment, and could be helpful in evaluating exposures to and effects of complex mixtures that are difficult to assess in the laboratory. Crowd Use of Animal S - inels in Risk Assess Some of the uncertainties in predicting human risk from exposure to toxic chemicals can be decreased by considering evidence of toxic effects in animal sentinels. Because clinical or epidemiologic information derived from human subjects is lacking in the case of most environmental chemicals, laboratory-

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EXECUTIVE SUMMARY 3 animal testing data usually are a principal component of the basis for risk assessments. Animals outside the laboratory can yield information at each step in risk assessment- risk characterization, hazard identification, dose-response assess- ment, and exposure assessment. Under appropriate conditions, the use of domestic and wild animals can help to reveal the presence of unknown chemi- cal contaminants in the environment before they cause harm to humans or to help identify the amount of exposure to known chemical contaminants. Do- mestic and wild animals share the human environment and are in the human food web, so sentinel systems can help to identify acute and chronic health hazards caused by contaminants in air, soil, water, and food. The potential of animal sentinels to provide early warnings of chemical exposures is enhanced by the tendency of animals in many cases to respond more quickly than hu- mans who are similarly exposed (i.e., decreased latency) and to respond at a lower dose (increased susceptibility). A suitable animal sentinel species for risk assessment is one that is exposed to chemical contaminants in habitats that are shared with humans or are comparable with human habitats and concentrations. A suitable sentinel species should be capable of responding to chemical insults that are manifest- ed by a broad spectrum of pathologic conditions, including behavioral and reproductive dysfunctions, immunologic and biochemical perturbations, and anatomic changes as varied as birth defects and cancers. No animal species used for risk assessment can be expected to respond in exactly the same ways as humans. This necessitates an understanding of the toxic properties or mechanisms of the chemicals in question, of the physiology of the animal species tested and of humans, and of the potential for human exposures. Three main types of methodologic approaches for animal sentinel programs and studies are described in this report: Descnptive epiden~iolog~ci studies of animal populations estimate the frequency and pattern of disease and evaluate associations with environmental exposures by such techniques as spatial mapping. Clusters of unusual health events, such as a new disease or an epidemic, might suggest environmental exposures. Animals are tested for environmental chemicals to describe the prevalence of exposure in populations and to evaluate cumulative doses of persistent compounds. 1The committee chose to use the term epidemiology rather than epizootiology, because the basic approaches and methodology are the same; it also chose to use the term epidemics rather than epizootics.

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4 ANIA~1LS AS SENTINELS Analytic epidemiologic studies test hypotheses regarding environmental exposures and estimate risks using controlled-observation study designs, as in humans. In an in situ study, animals are taken to a site where contamination is suspected (e.g., a hazardous-waste site), and then, under controlled conditions in the natural environment, monitored for bioaccumulation and health effects. Animal sentinel systems often are particularly well suited for monitoring the complex array of environmental insults to human health and for assessing the health of delicately balanced ecosystems. Three primary strengths are noteworthy: Many animals share environments with humans, often consuming the same foods and water from the sources, breathing the same air, and experi- encing similar stresses imposed by technologic advances and human conflicts. Animals and humans respond to many toxic agents in analogous ways, often developing similar environmentally induced diseases by the same patho- genetic mechanisms. Animals often develop environmentally induced pathologic conditions more rapidly than humans, because they have shorter lifespans. CONCEPTS AND DEFIN177ONS Before an animal sentinel system is chosen, several characteristics must be selected, including species, kind of exposure, length of exposure, and the way in which effects of exposure will be measured. Charactenstics of Animal Ser''inel Systems Species The committee identified the following attributes as being important in selecting animals sentinel species: A sentinel should have a measurable response (ideally including accumu- lation of tissue residues) to the agent or class of agents in question. A sentinel should have a territory or home range that overlaps the area to be monitored. A sentinel species should be easily enumerated and captured.

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EXECUTIVE SUMMARY 5 A sentinel species must have sufficient population size and density to permit enumeration. In some situations, the most desirable species might not be present in the study area. Deliberate placement of a sentinel species in the area might then be appropriate. In some circumstances, animals might have to be caged or penned and special attention paid to prevent dispersal and to facilitate reloca- tion. Exposure Sources Sources of toxic substances that can be monitored with sentinel animals include soil, air, plants, water, and human habitats. A sentinel species should have a close association with the source of interest. Some examples noted by the committee are: Soil small digging animals, such as earthworms, soil insects, gophers, moles, mice, and voles can be used. The National Contaminants Biomoni- toring Program uses starlings to monitor soil contaminants, because starlings feed on soil invertebrates and range over wide areas. Air Any above-ground animals can be suitable for monitoring air pollu- tion, especially if they are large or mobile enough to be free of filtering vege- tation. Honey bees are excellent monitors of air pollution, and other flying insects might be equally suitable. However, it is difficult to monitor air for contamination with sentinel animals, because many routes of exposure must be taken into account. Plants Herbivorous animals are useful as sentinels of plant contamina- tion. The species used should depend on whether specific plants are of inter- est or whether many plants are to be considered. Water Wholly aquatic organisms are the best monitors of water pollu- tion. In situ bioassays with caged fish have been used for many years to detect the presence of toxic chemicals in lakes and streams. Bivalves, such as mussels and oysters, accumulate many chemicals to concentrations much higher than those in the ambient water. Terrestrial animals that use water as a source of food or as habitat, such as gulls, ospreys, seals and some reptiles and amphibians, also can be used to monitor water pollution. Human homesDomestic animals, such as cats and dogs, can be used to monitor contamination in human homes. Companion animals often are more exposed than their owners to soil, house dust, and airborne particles, and cats are exposed differently to airborne contaminants, such as lead, be-

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6 ANIMALS AS SENTINELS cause they lick their coats regularly. Felines in urban zoos have been good indicators of lead contamination. Duration of Exposure A monitoring study can last minutes, months, or years, depending on the questions asked and the end points measured. The likely duration will influ- ence the choice of sentinel species. Some factors to be considered are wheth- er the study will look for acute toxicity or long-term exposure, whether biolog- ic fluids or tissues can be collected, and whether life spans and reproductive capacity of sentinels are suitable. Measures of Effect An animal-sentinel system can be used to monitor concentrations of pollut- ants and their distribution in the environment much as strategically placed mechanical devices can. However, the advantage of using a biologic system is that it affords the opportunity to couple measures of exposure with a variety of subclinical or clinical effects. It therefore can yield a better evaluation of hazard to humans or to the animal population itself than can be obtained with inanimate sampling devices. Once an animal (or a human) has been exposed to a toxic chemical, a series or set of biologic events often can be detected. If an animal is to func- tion as a sentinel, biologic responses must be observed soon after exposure. Therefore, changes in ordinarily measured biologic characteristics, such as the hematologic profile and serum chemical values, probably are more generally useful end points than are reproductive characteristics, mutagenesis, teratogen- esis, or neoplasia. Structural changes generally are easier to measure than functional changes, but both can provide important information after exposure. Animals can respond to pollutant effects in many ways, with several mea- surable end points. They can be monitored for subcellular changes (e.g., abduct formation on DNA and hemoglobin molecules), cellular changes that can result in tumorigenesis, physiologic changes, organ-system malfunctions, and the presence of chemical residues in tissues. Such chemical and cellular monitoring can be useful for assessing relatively short-term toxic effects or for extrapolation to human health. Population dynamics of fish and other wildlife species can be monitored to obtain measures of effects of environmental pollution. It is necessary to have some knowledge of the natural history of a species (e.g., the 10-year cycles of

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EXECUTIVE SUMMARY 7 snowshoe hares) and of biologic disease agents that could affect its population dynamics. Population studies of this kind are often prolonged, expensive, and difficult to conduct. Moreover, populations of wild animals are influenced by many interacting natural factors that are difficult to control, as well as by the contaminants that are under investigation. Reference Populations Epidemiologic research and disease surveillance require knowledge of the population at risk and of the number of cases of disease for calculating inci- dence and rates. In human populations, those are generally determined through a census or a special survey in a defined geographic area. Effective use of pet animals as sentinels of environmental health hazards requires simi- lar information. Once the population at risk is defined, it can provide the basis for calculating incidence and risk. Census data on livestock and poultry are collected in the Agriculture Cen- sus, and census data are available on some species of fish and other wildlife. Numbers of game fish and other wildlife are estimated annually by state con- servation agencies and the U.S. Fish and Wildlife Service. The Christmas bird count, breeding-bird census, and winter-bird population study are long-stand- ing wildlife censuses. Their results are available to the public and to research- ers in various publications. But the pet-animal population has not been clear- ly defined. Estimates often are achieved through the marketing surveys of dog and cat food sales, but those data are suspect, in part because it is believed that some animal-food products are consumed by humans. Pet census data would be useful in the establishment of a large national pet population data base, which would represent the population at risk for calcula lions of disease incidence or prevalence; the data would potentially enable correlations of disease or exposure patterns between pet and owner popula- tions (through retrospective veterinary epidemiology of pets counted by the census) and allow for prospective prediction of human risk. Objectives of Monitoru~gAnirr~ Sentinels Among the many objectives of monitoring animals sentinels are data collec- tion to estimate human health risks, identify contamination of the food chain, determine environmental contamination, and identify adverse effects on ani- mals themselves.

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8 ANIMALS AS SENTINELS Advantages and Lirnito~r~s of Al 5~1 Systems Most sentinel animals have shorter lifespans than humans. Thus, diseases that have long latency periods and are most likely to occur late in the lifetime of an organism will manifest themselves in sentinel animals in fewer years than in humans. In addition, sentinel animals might be more susceptible to agents to which they and humans are exposed. Multifactorial Causality Disease usually results from a series of highly complex events involving multiple, heterogeneous environmental insults occurring over a broad range of individual susceptibilities. The impact of these events can be appreciated best by studying population effects under natural conditions over time. Herein lies the strength of epidemiologic methods: If vigorously applied, they can bring us closer to understanding complex interactions and provide a clearer biologic picture. Many environmentally caused diseases in humans are recognized to be multifactorial. Identification of the contribution of each specific factor might be less important than determination of the effect of reducing exposure to all factors simultaneously, in recognition of their usually occurring together. The primary goal of an animal sentinel system is to identify harmful chemicals or chemical mixtures In the environment before they might otherwise be detected through human epidemiologic studies or toxicologic studies in laboratory animals. Once identified, exposures could be minimized until methods can be devised to determine specific etiologic agents. Animal sentinel systems them- selves are not the answer to the latter problem, but might provide additional valuable time in which to search for the answer. Measurement of Exposure and Extrapolation to Humans Animals have been used in exposure assessments as surrogates for humans. Where humans are exposed to contaminants in complex environments (e.g., in the home or in the work place), it can be difficult to estimate exposures by the conventional procedure of measuring ambient concentrations of the con- taminants and calculating intakes of the contaminated media. One approach to solving the problem is to use surrogate monitors animals exposed in the

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EXECUTIVE SUMMARY 9 same environments; blood or tissues of the animals can be taken for analysis and provide an integrated measure of exposure. If the animals' contact with the contaminated media is sufficiently similar to that of humans, the animals' exposure might provide a reasonable indirect measure of the humans' expo- sure. Animals differ from humans in metabolism and pharmacokinetics, so ani- mals and humans will differ in the relationships between exposure and tissue concentrations. However, these differences can be adjusted with modeling techniques based on direct findings in two or more species. Animal bioassays, whether conducted in the laboratory or in the field, have several recognized disadvantages and limitations for risk assessment. The most notable disadvantage is that quantitative extrapolation of e~osure-relat- ed and dose-related effects to humans is at best uncertain. But animal bio- assays might be more predictive of human experience than are short-term in vitro tests, and the use of multiple animal species might provide important comparative information. FOOD ANlAL4lSAS SENT7NEI5 Food animals are exposed to infectious agents and to a multitude of envi- ronmental contaminants that can accumulate in their bodies. Food animals can seine as sentinels of environmental health hazards, in that identification of infectious or foreign substances in a food animal is a signal of potential biologic or chemical contamination of the a~umal's environment, of other animals and humans that share the animal's environment, and of humans that ingest the animals and animal products. Although food animals biodegrade most chemicals and toxins in their diets, certain toxic chemicals are taken up in the tissues of food animals. For example, after accumulating in forage plants, a chemical can accumulate further in beef cattle that eat the plants. The result of serial bioaccumulation, particularly of some chlorinated hydro- carbon pesticides, is the potential for greater exposure of animals at the top of the food chainincluding humansthan of animals lower in the food chain. Because food animals are part of the food chain, they are monitored for biologic or chemical contaminants in numerous programs. All the programs can generate descriptive epidemiologic studiesdata usually are collected on animals that are not intentionally exposed to biologic or chemical contami- nants. Among the several agencies that monitor foods for purity in the Unit- ed States are the Food Safety and Inspection Service (FSIS) of the U.S. De- partment of Agriculture (USDA), the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS), and state

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10 ANIMALS AS SENTINELS government agencies. Those agencies conduct tests for contaminantsinfec- tious agents, pesticides, and tome chemicalsin and on plant and animal food products. COALPANION~LVA15AS SENT~NEI5 Companion animals have been used as surrogates for humans in exposure assessments. Where humans are exposed to contaminants in complex environ- ments (e.g., in the home or in the work place), it can be difficult to estimate their exposure with conventional procedures of measuring ambient concentra- tions of the contaminants and calculating their intakes from the contaminated media. One approach to solving the problem is to use animals exposed in the same environments as surrogate monitors; tissues of the animals are taken for analysis and used to provide an integrated measure of the animals' exposure. If the animals' contact with the contaminated media is sufficiently similar to that of the humans, the animals' exposure might provide a reasonable indi- rect measure of the humans' exposure. Most examples of such animal senti- ne! systems involve the use of domestic or companion animals. Blood and other tissues of companion animals often are sampled, e.g., at surgery or after euthanasia. Most pet animals have short lives relative to humans, and their tissues can be sampled when they die. Pet animals occupy some of the same environments as their owners and are expected to be ex- posed in broadly similar ways. However, exposures of pets are not identical with those of their owners; among other differences, animals usually have greater contact with soil, house dust, and floor surfaces than do humans, and they are more likely to ingest contaminants when cleaning or grooming them- selves. FISH AND 077IER WlIJ9LIFEAS SEN77NELS Environmental pollutants have had substantial impacts on fish and wildlife populations. Probably the best-known example is the response of wildlife populations to the rise and fall of the use of persistent organochlorine pesti- cides and industrial chemicals (e.g., DDT and PCBs). The literature is replete with reports documenting the presence of residues of environmental contami- nants in the tissues of fish, shellfish, and wildlife. Many studies were intended to investigate the suitability of using wildlife as sentinels of environmental hazards to humans. Large volumes of literature are available on the use of wild animals in surveillance programs for arboviruses and zoonotic diseases.

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EXE:CUTI~E SUMMARY 11 The use of fish, shellfish, and other wildlife species in coordinated environ- mental monitoring programs can be a valuable, cost-effective mechanism for assessing the bioavailability of environmental contaminants. The few pro- grams that have been in place for a long time (e.g., Mussel Watch and the National Contaminant Biomonitoring Program) have been able to differentiate areas of high pollution and have shown substantial reduction in contaminant loads after restriction of the use of particular chemicals. Those programs have the advantage of using animals that are in direct contact with an environ- ment in question. They have been successful at providing information both about the state of the habitat and ecologic consequences to the species them- selves and about potential human-health risks. In addition, fish, shellfish, and wildlife are part of the human food chain and thus are sources of contamina- tion in themselves. Therefore, monitoring free-ranging animals is important in food-safety concerns as well. The study of cancer in fish and amphibians not only yields new insights into the origins of human cancers, but also provides numerous other benefits, because these animals serve as sentinels of environmental contaminants and as models for studying neoplasia and basic mechanisms in oncology. Despite the obvious advantages of monitoring animals that live in an env~- ronment in question, substantial difficulties are associated with designing and executing such monitoring programs. Techniques for analyzing chemical residues in tissues from a wide variety of species are more difficult, less devel- oped, and less standardized than similar techniques for less-complex matrices (e.g., the water column). Logistically, it often is difficult and expensive to sample appropriate species, particularly those whose populations have been reduced by exposure to hazardous substances. An~mal-welfare issues are important and can pose substantial obstacles in any monitoring programs that involve large vertebrate species. Consequently, most of the current monitoring programs have been restricted to fish and shellfish. ANIMAL SENT7MEI5 IN RISK ASSESSMENT The assessment of risk due to environmental contaminants depends, to a large extent, on scientific data. When such data are incomplete, as is often the case, assumptions based on scientific judgments are made to calculate potential exposures and effects. Specifically, when direct observations of the effects of environmental contaminants on human or environmental health are incomplete or missing, assumptions must be made to estimate the risks. Those assumptions often are imprecise or speculative, so estimates of risks are highly uncertain. In some cases, the use of animal sentinels can reduce uncer-

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12 ANIMALS AS SENTINELS tainties by providing data on animals exposed in parallel to the humans whose risks are to be determined. The animal data can help risk assessors to make more accurate exposure estimates. Animal sentinels, like humans, are exposed to complex and variable mix- tures of chemicals and other environmental agents. However, the characteris- tics of animal sentinel studies offer important advantages over laboratory animal studies, in which animals are usually exposed to high, constant doses of a single chemical substance that is under investigation. Thus, the use of animal sentinels constitutes an approach to identifying hazards and estimating risks in circumstances similar to those in which actual human exposures occur, and can complement or provide an alternative to traditional chemical toxicity testing through standardized laboratory studies. Data obtained in studies of animal sentinels also can lead to insights into human health by stimulating epidemiologic studies of humans exposed to agents that might not have been previously identified as potentially hazardous. Such data can be used to identify diseases related to chemicals in the environ- ment. Systematic collection of such data in disease registries can help to identify unusual clusters of deaths, cases of disease, or cancers in defied populations and geographic areas. Collection of comparable information (i.e., exposures, toxicoses, and environmentally caused diseases) for humans and animals likely will improve understanding of diseases in humans, provide clues to etiology that cannot be evaluated in laboratory animals, and provide a basis for evaluating the validity of sentinel data. Although risk assessment might not be the end use to which those data are applied, data collected through animal sentinel programs can provide some of the ancillary information neces- sary for risk assessment. SELEC~ON~ PEON OF ANIMAL SENTINEL SYSTEMS mr RISK ASSESSMENT An investigator planning an environmental assessment should always con- 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, including assessing accumulated chemicals, complex mixtures, complex exposures, uncertain bioavailability, and poorly character- ized agents. Factors to consider in determining whether to use an animal sentinel sys- tem include consideration of the media, scale of averaging, sensitivity, specif~c-

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EXECUTIVE SUMMARY 13 ity, and species availability. Consideration of these factors will require com- munication among specialists in many disciplines, such as risk assessment, environmental chemistry, toxicology, ecology, and veterinary science. Once an animal species is found that meets the initial tests of availability, efficacy, and practicality, design issues are important. Areas that must be addressed include the nature of the problem, the objectives of the study, the definition of the event and unit of observation, characterization of the system, sources of data, selection of controls, and characteristics of the program. The operation and implementation of the system raises further issues of profes- sional and institutional cooperation, long-term continuity, mechanisms of recording, coding and storing data, characteristics of the intended report, and quality assurance. Before any system can be used on a wide scale as an element in exposure assessment, hazard assessment, or risk characterization, it requires an exten- sive validation process, including the following steps: characterization of the system, replicability, sensitivity, specificity, and predictive value. 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 manage- ment. 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. If those programs could be better integrated, each could tap a larger data base and could become more cost-effective. Program integration could yield efficient use of resources if specimens for multiple purposes or archiving specimen material from monitoring programs for analysis when new contaminants are discovered or improved analytic methods are developed. Another form of program coordination is to integrate data from animal senti- nel programs with data from traditional environmental sampling. Resulting correlations could improve not only the utility of each type of data, but also the basis for modeling of environmental transport and for exposure assess- ment. The committee is aware of the technical and institutional obstacles to program integration; however, much information now collected in animal sentinel programs is underused, and even modest efforts toward integration would lead to great improvement in applications. CONCLUSIONS AND RECOMMENDATIONS Data collected from laboratory animals that are experimentally exposed to

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14 ANIMALS AS SENTINELS potentially hazardous chemicals and from animals exposed to chemical con- taminants In their natural habitats form a vital part of the risk assessment process for human and environmental health. Domestic and wild animals can be used to identify and monitor a wide range of environmental hazards to human health and ecosystems. The committee noted that many current ani- mal-monitoring systems could, with relatively minor modifications, be made suitable for use in the process of risk assessment of many environmental contaminants. These would complement the more traditional rodent models by adding species diversity and a method to evaluate natural and often com- plex exposures. The committee concludes that various factors have contributed to the un- deruse and lack of synthesis of data from animal sentinel systems: The data collected by most animal sentinel systems have not been stan- dardized, and data-collection programs themselves have been poorly coordi- nated and lack specific and realistic objectives. Basic information on the biology, behavior, and similar characteristics of many potentially useful species of sentinel animals is insufficient. The predictive value of animal sentinel data for human health usually has not been evaluated sufficiently. The predictive value for human health of any data obtained from ani- mals has inherent uncertainties, because it is difficult to extrapolate them to humans. The concept and methods of risk assessment have generally not received sufficient attention in training programs in veterinary epidemiology, toxicology, pathology, and environmental health. Perhaps most important, the committee concludes that communication vital to development, refinement, and implementation of animal sentinel programs is lacking. Input from relevant government agencies, industry, and academic institutions will be required, if animals sentinel programs are to be more use- fully developed and operated. The committee offers the following recommendations for the use of animal sentinels in risk assessment: Animal diseases that can serve as sentinel events to identify environ- mental health hazards for humans or to indicate insults to an ecosystem should be legally reportable to appropriate state or federal health agencies. When reporting systems are established for environmental diseases of animals in a defined geographic area, appropriate efforts should be made to

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EXECUTIVE SUMMARY 15 compare the frequency and pattern of these diseases with those of co~Te- sponding diseases in humans, and it should be determined whether animals can provide early warning of health hazards to humans. The pet population in the United States should be estimated either with statistical sampling or through incorporation of a few pertinent animal- ownership questions into the census of the human population. Food-animal and wildlife populations should continue to be determined with a variety of methods by the U.S. Department of Agriculture- and the Fish and Wildlife Service, respectively, and by other appropriate agencies. Existing animal sentinel systems should be coordinated on regional and national scales to avoid duplication of effort and maximize use of resources, and standardization of methods and approaches should be encouraged. Computer equipment, software, nomenclature, coding, data collection, and quality control should be standardized to facilitate coordination and collaboration in animal exposure and disease record systems, and such systems should be used for fish and wildlife species, as well as for compan- ion animals and livestock. Geographic information system (GIS) technology should be used whenever appropriate. Increased emphasis should be given to research into development of comlative relationships that reduce the uncertainty in animal to human extrapolations and how animals sentinels should be used in the risk-assess- ment process. Support for academic courses and graduate programs in epidemiology at colleges of veterinary medicine and colleges of biologic sciences should increase, and emphasis should be placed on the development of methods for the use of animal exposure and disease data in human and environmental health risk assessment. The committee believes that implementation of these recommendations will greatly enhance and improve human risk assessment. STRUCTURE OF THE REPORT Chapter 2 explains and illustrates the definitions and concepts used in the report. The characteristics of animal sentinel systemsspecies, exposure

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16 ANIMALS AS SENTINELS media, temporal and spatial considerations, and measures of effect are dis- cussed. The objectives of animal sentinel systems for identification of environ- mental contamination, food-chain contamination, and adverse human and animal health effects are outlined. The uses of animal sentinel systems in epidemiologic and in situ studies are characterized. The chapter also discuss- es the advantages and limitations of such systems, e.g., with respect to prob- lems in extrapolation to humans and suitability for evaluating chemical mix- tures and multifactorial exposures. Chapters 3, 4, and 5 describe applications of sentinel studies in food ani- mals, companion animals, and fish and wildlife. Programs that already use animal systems for environmental monitoring and hazard identification are described, as well as programs with potential applicability. Observational studies including outbreak investigations, analytic epidemiologic investiga- tions, and in situ studies are reviewed and illustrated for the populations of food animals, companion animals, and fish and wildlife. The use of animal sentinel systems specifically in risk assessment is consid- ered in Chapters 6 and 7, which focus on selection and application of animal sentinels for components of qualitative and quantitative risk assessment. As requested in the committee's task, some discussion of application of animal sentinel data to geographic information systems methods is included. The committee's conclusions and recommendations for the use of animal sentinel systems are presented in Chapter 8.

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Animals as Sentinels of Environmental Health Hazards

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