Ecosystem health

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Ecosystem

Health

IV. The National Animal Poison Information Network Database as a Tool for Ecological Risk Assessment’

VAL R. BEASLEY’ AND DAVID J. SCHAEFFER~ Department of Veterinary Biosciences, University of Illinois, 2001 South Lincoln Avenue. Urbana, Illinois 61801

Received August 25, I988

Toxicology is a unique discipline in human and veterinary medicine because there are orders of magnitude more toxicants available to man and animals than all known pathogenic microorganisms and parasites. The study of toxicologic responses of ecosystems to contaminants, ecoepidemiology, and the specific study of animal populations in this context, epizootiologic ecotoxicology, are concerned with identifying chemically induced causes and determining effects on and links among populations, communities, and ecosystems. Necessary activities implied by the term “epizootiologic ecotoxicology” are the systematic compilation and analysis of “health” data for ecosystem components. This concept paper describes the value and limitations ofadapting methods used by the National Animal Poison Information Network (NAPINet) for epizootiologic ecotoxicology studies. It is concluded that NAPINet methodology, as part of an innovative use of population statistics and clinical measurements, could eventually be adapted into a valuable component of a standardized approach to epizootiologic ecotoxicology. o 1989 Academic

Press. Inc.

INTRODUCTION Toxicology is a unique discipline in human and veterinary medicine. A feature that makes it challenging is that there are orders of magnitude more toxicants available to man and animals than all known pathogenic microorganisms and parasites. The study of toxicologic responses of ecosystems to contaminants has been termed “ecoepidemiology” by Coulston and Korte (Bro-Rasmussen and Lokke, 1984). Ecoepidemiological studies are concerned with describing effects, identifying causes, and determining links and pathways in disease processes affecting populations, communities, ’ This research was partially supported by the U.S. Army Construction Engineering Research Laboratory. Environmental Division. Additional support was provided by the Department of Veterinary Biosciences and by the Illinois Animal Poison Information Center. 2 To whom correspondence should be addressed. ’ This is Paper VII in this author’s “Environmental Audit” series. 63 0273-2300189 $3.00 Copyright 0 1989 by Academic Press, Inc. All rights of reprcductmn in any form resewed.

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and ecosystems. Ecoepidemiological analyses involve evaluations of many types of test systems (Sheehan, 1984; Novak et al., 1985) which are integrated with other data to provide an assessment of the expected damage to ecosystems. Four broad approaches can be used to assess the ability of toxicants to adversely affect ecosystems. First are laboratory studies using a selected exposed test organism(s) under specified conditions. Second are field studies which evaluate toxicologic effects in an organism exposed in its native environment. Third are studies which evaluate the effects of a toxicant on interacting organisms in an ecological perspective (ecotoxicology). Fourth are studies which examine the extent of contamination of similar ecosystems and correlate this with statistically reliable representations of the health of the resident populations of organisms of interest. If the organisms of greatest interest are of the animal kingdom, this type of investigation is focused on epizootiologic ecotoxicology. Necessary activities implied by the term “ecoepidemiology” are the systematic compilation and analysis of “health” data for ecosystem components in a manner similar to that used to integrate environmental and human health data in classical epidemiology studies (Gottlieb et al., 1985). This approach to data acquisition has not received much attention by ecoepidemiologists, possibly due to cost, possibly because these needs have not been identified, and most probably because the diseases of ecosystems remain largely undescribed. As a part of continuation of the development of a systematic process for designing environmental monitoring programs (Schaeffer et al., 1985; Sokolik and Schaeffer, 1986), this concept paper examines the prospects of adapting methods used by the National Animal Poison Information Network (NAPINet) for epizootiologic ecotoxicology oriented studies. CURRENT

USES AND PROSPECTS FOR EPIZOOTIOLOGY OF ANIMAL TOXICOSES

Fundamentals of Epidemiology and Epizootiology Epidemiology is concerned with the pattern of disease occurrence in human populations. Factors of interest in understanding the likelihood of disease processes are ( 1) host factors (sex, age, race, ethnic group, or other traits), genetic factors, individual biological characteristics (such as those relating to blood concentration of endogenous chemicals or antibodies, cellular constituents of the blood, or measurements of physiologic function); (2) environmental factors (such as socioeconomic parameters including educational background and nativity); and (3) agent factors (such as diet, exercise, drugs, toxicants, infectious microorganisms, parasites, or physical insults). An underlying requirement for a successful epidemiology study is correct diagnosis. A second essential is appropriate correlation of the data. Epidemiologists historically have relied upon two broad types of experiments. The first type (more often conducted by the nonepidemiologist) is the experimental study in which the scientist controls certain conditions and observes effects in the test population. The second type (often conducted by the epidemiologist) is the observational study in which the scientist, often without altering circumstances of the test population, attempts to learn what conditions are associated with the occurrence of a specific disease entity. There are three types of observational studies: cross-sectional, retrospective, and prospective. In both cross-sectional and retrospective studies, comparisons are made

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between a group that has the disease (the case group) and one that does not (the control); hence the term “case-control study.” It is necessary to point out that the term “case-control” also can be applied to certain prospective studies. The crosssectional study attempts to correlate the presence of a factor in the affected group at the time of the diagnosis with the occurrence of the disease. Clearly, abnormalities may be observed that are causal; however, there may also be alterations that are other manifestations of the disease process itself. The retrospective study attempts to reduce the likelihood of making such errors by correlating abnormalities detected prior to the onset of illness with the subsequent occurrence of the disease. In some instances, the distinction between cross-sectional and retrospective studies can become blurred until the disease process is sufficiently understood. The limitations of cross-sectional and retrospective studies make it desirable to conduct prospective investigations. In a prospective study, individuals bearing a particular suspected risk factor are followed over a period of time and compared with a control group to see whether they develop the disease process of concern. The control group can be a portion of the general population or, if unavoidable, figures from a previous census can be used. Epizootiology Epizootiology is the nonhuman animal equivalent of epidemiology. Historically, the primary focus of this branch of veterinary medicine has been elucidation of the etiology of a disease by comparing incidence data with information obtained using tools from various biomedical disciplines such as microbiology, biochemistry, or genetics, Often, findings are subsequently confirmed by close comparison of clinical observations with similar effects produced by the suspected agent in the laboratory. Once a disease entity is recognized and its etiology confirmed, epizootiologic tools may function in the development and evaluation of preventive procedures and, in the case of zoonotic diseases, in public health practices. Epizootiology offers methodologies which have the potential to provide direct information on the “health” of mammalian and avian populations and on the general condition of ecosystems. To a degree, the state of the art in epizootiology has developed along certain narrow channels, such as for pets, commercially important domestic animals, and certain game species including deer (Eve and Kellogg, 1977). However, the tools and principles of epizootiology have been underutilized in an effort to provide direct information on toxicant-induced ecosystem disruption. The authors, therefore, focus the discussion on two topics: ( 1) a description of the current uses and prospects for epizootiology of animal toxicoses and (2) broad and specific procedures which need to be developed to make epizootiology effective in the assessment of ecosystem effects of chemicals. Available Information

in Toxicologic

Epizootiology

Epizootiologists have correlated the incidence of specific disease processes with illdefined toxicant exposures. For example, Reif et al. (1970) and Reif and Cohen (1970) associated an increased prevalence of chronic pulmonary disease in middleaged and older dogs with exposure to the air of urban Philadelphia. In other studies (Reif and Cohen, 197 1), the incidence of respiratory tract neoplasms was related to exposure to polluted atmospheres.

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Other investigators have conducted surveys of local environments to determine the extent of contamination of fauna and/or flora with specific toxicants. Some such efforts have involved correlation of exposure data with specific disease processes. Because of their limited mobility, much work has been done to correlate toxicant exposure with residues in and effects on shellfish (NAS, 1979). Similarly, small mammals, due to their very limited ranges, can serve as a captive (exposed or control) population (Gillett et al., 1983; Cloutier et al., 1986a,b; Clulow et al., 1986; Newman and Schreiber, 1984; Wren, 1986). Consequently, concentrations in air, soil, and/or food can be compared with residues and toxic effects in the exposed animals (NAS, 1979; Kisseberth e2 al., 1984). Livestock are another example of a population with limited mobility that, therefore, can serve in monitoring a defined area. For example, calves pastured on land treated with municipal sewage sludge have experienced meningoencephalitis in association with chronic (Kradel et al., 1965) and acute (Dorn et al., 1986) lead poisoning. With regard to monitoring of populations of animals on a national scale for specific toxicoses, little information has been available until recently. Oehme (1977) described his personal experiences relative to toxicologic epizootiology. Humphreys ( 1978) reviewed the veterinary literature over a 20-year period to determine the frequency of reports on various toxicants as an index of relative importance. Osweiler ( 1983) discussed the incidence of toxicoses in a survey of American Animal Hospital Association membership and veterinary teaching hospitals involving a total of 3 128 incidents. In essentially all such reports, however, the data have been somewhat scantily reported and have been collected from multiple facilities using inconsistent criteria. Publication of the observations of veterinarians of the National Animal Poison Control Center during 1984 provided a much more detailed and uniformly collected representation of the spectrum of toxicant exposures of domestic animals in the United States (Beasley, 1986). Almost 8000 calls pertaining to small animals were assessed using computer-assisted methodology in that report. More recent data and current methods of this center are now described. COMPUTERIZED AND NONCOMPUTERIZED IN TOXICOLOGY AND TOXICOLOGIC

SYSTEMS USED EPIDEMIOLOGY

The multitude of toxicants in the environment and wide variation in the types of exposure make the use of computer-assisted databases invaluable in organizing and recalling needed information. Many types of computer-based and other resources have emerged. Computer-driven literature citation systems have been used for years to assist in reviewing the literature for scientific reports on specific compounds or groups of compounds. More specialized systems which both catalog and interpret information on given groups of toxicants include (1) the Aquatic Information Retrieval Database (AQUIRE), the Complex Effluents Toxicity Information System (CETIS), and the Chemical Profiles Information File (CHEMPROF); (2) the Toxicology Data Network (TOXNET); (3) the Chemical Manufacturers Association (CHEM-TREC) hotline; (4) the Food Animal Residue Avoidance Databank (FARAD); and (5) the Toxic Substances Control Act Test Submissions (TSCATS) database of unpublished industry-sponsored research concerning chemical effects on health and the environment (Santodonato et al,, 1987), among others. Although of

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great value in understanding toxic insult, and useful in obtaining methods to confirm diagnoses, the systems described above do little to facilitate epidemiologic or epizootiologic assessment of the frequency of or risk factors involved in a given toxicosis. New computer-based systems, the Feed Contaminant Data Sharing Program (FEEDCON) and the Veterinary Toxicology Database, have begun to address toxicologic epidemiology in more meaningful ways. These gather information on the detection of various toxicants as a result of analysis of specimens from cases of potential or suspected poisoning. Several other systems directly address toxicologic epidemiology or epizootiology by gathering information on the incidence of specific disease processes which may be toxicant related. Included are (1) the Centers for Disease Control (CDC), Center for Environmental Health; (2) the Agency for Toxic Substances and Disease Registry; (3) the Food and Drug Administration, Adverse Drug Reaction Hotlines; (4) the American Association of Poison Control Centers, National Data Collection System; (5) the Purdue Comparative Oncology Program (PCOP); (6) the Alameda and Contra Costa Counties Oncology Program; and (7) the Cancer Information System of the National Cancer Institute. In addition, several agencies (Environmental Protection Agency; Pesticide Hotline, Texas Tech University; U.S. Department of Agriculture, Residue Evaluation and Planning Division; U.S. Food and Drug Administration, Office of Consumer Affairs, Public Inquiries; U.S. Consumer Product Safety Commission) sometimes acquire information on the incidence of specific toxicoses, but epidemiologic assessment is often considered on a compound by compound, “as needed” basis. Addresses and telephone numbers for these resources are available from V.R.B. DEVELOPMENT

OF THE NATIONAL ANIMAL INFORMATION NETWORK

POISON

The Animal Poison Control Center was established at the University of Illinois College of Veterinary Medicine in 1978, as a 24-hr-a-day, 365-days-a-year toxicology consultation service for veterinarians, animal owners, and others. Initially intended to serve the needs of Illinois, its name was eventually changed to the National Animal Poison Control Center since it had become a national concern through its position as the most readily accessible provider of such information. Recently, the center was renamed the Illinois Animal Poison Information Center (IAPIC) to emphasize its regional role as it becomes the hub of the National Animal Poison Information Network (NAPINet). NAPINet has begun with the activity of a second regional center at the College of Veterinary Medicine, University of Georgia, and tentative agreements with other Colleges of Veterinary Medicine. All regional centers will submit case call data in the same form as IAPIC for computer-assisted epizootiologic assessment. OPERATIONS ANIMAL

OF THE NAPINet AND POISON INFORMATlON

THE ILLINOlS CENTER

At least annually, center personnel review its methods of gathering data and modify procedures to improve epizootiologic usefulness and reliability. The NAPINet data bank most closely resembles the American Association of Poison Control Centers,

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National Data Collection System, but much more detailed information is obtained by NAPINet, particularly in diagnostic and clinical assessment categories. In the NAPINet database, an idea of the reliability of the information on the animals’ condition can be gleaned from the caller designation: greatest with veterinarians, generally reliable with veterinary technicians, somewhat less reliable with owners, often least reliable with other parties. The number of toxicants available to animals makes the correct association of toxicant with effect difficult. Exposure must actually occur (not just be possible); the degree of exposure must be sufficient to induce the observed toxic effect; the manifestations must be compatible with the toxic potential of the agent; the time to onset and duration of action must be appropriate; and a more likely alternate explanation for the clinical signs must not be identifiable. For each NAPINet case the following data are collected and stored: date and time of call, caller data (name, location, and phone numbers), animal data (species, breed, sex, age, weight, and numbers of animals at risk, affected, treated, and dead), exposure data (route, location, source, intent, and time of exposure), agent data (trade name(s), generic name(s), NAPINet-designated agent class and type of formulation, manufacturer), clinical manifestation data (clinical sign(s) and lesions by body system affected, estimates of severity), and call assessment (assurance that exposure occurred, assurance of degree of exposure, appropriateness of time factors for the toxicant involved, and overall assessment). When an overall assessment is made, the case is categorized as (1) a toxicosis (everything fits); (2) a suspected toxicosis (everything fits but some data are unavailable); (3) a doubtful association between the agent and the problem (something does not fit and another diagnosis is more likely); (4) an exposure only (there are no clinical signs); (5) an information call (there is no exposure); (6) a residue concern; or (7) other (fits none of the above; usually there is no relationship to toxicology). The Illinois center received 14,150 nationwide calls in 1985 and approximately 22,000 calls in 1986. In 1986, veterinary facilities and owners were responsible for 45 and 42% of the calls, respectively. Calls involving dogs, cats, horses, cattle, birds, and humans comprised 59, 19,4.6, 5.4,2.2, and 2.9% of the total, respectively. Animals at risk included 26,08 1 cattle, 12,40 1 birds, 13,788 pigs, 6003 dogs, 1840 sheep, 1443 horses, and 2097 cats. Private homes and yards were the site of exposure in 72% of the calls. Ingestions were the most common route of exposure, followed by a combination of routes, dermal, injection, inhalation, and ocular. The general class “insecticides” accounted for 15.3% of all cases. Rodenticides, somewhat overrepresented (due to the presence of the IAPIC phone number on rodenticide labels), were even higher in number of calls at 17.3%. These classes were followed by plants at 14.4%, human medicines at 13.0%, household products at 6%, veterinary medicines at 5.7%, miscellaneous chemicals at 4.4%, construction products at 3.8%, nutritional agents at 3.3%, herbicides at 2.8%, petroleum and derivatives at 1.9%, biotoxins at 1.7%, and metals at 1.5%. With the exception of rodenticides, more than 25% of the calls in each of the above-listed classes and over 25% of avicide and molluscicide calls tend to be assessed as either a toxicosis or suspected toxicosis. In human medicine, it is possible to obtain morbidity and especially mortality data (via death certificates) for a wide range of diseases. By comparing morbidity with census data, one can derive attack rates. To derive an epizootiologic attack rate, it is necessary to assessthe numbers of animals affected versus numbers at risk. In veterinary medicine, however, toxicant-related diseases are generally not “reportable”; therefore, the numerator is hard to obtain. In addition, the number of animals at risk

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in a given population (the denominator) can be difficult to estimate in the absence of detailed census figures as exist for humans. However, since the NAPINet obtains data on the specific herds or groups of animals at risk, the attack rate for that particular problem can be estimated. With regard to epidemiologic assessment, it is essential to recognize that the functions of a poison information center provide no opportunity to monitor a paired unexposed group. A disadvantage of an individual medical or veterinary practitioner reporting observed diseases without monitoring a control population is that initial observations of the frequency of any disease may cause the investigator to conclude incorrectly that an epidemic is occurring simply because the subsample observed is not representative of the population or the nonepidemic frequency is underestimated. The likelihood of incorrect estimation of nonepidemic frequency can, however, be reduced by monitoring the occurrence of disease in a large population or by closely monitoring the population over a prolonged period of time (years). At present, IAPIC, to a degree, continuously monitors toxicologic disease in the entire population of domestic animals in the United States. Since, in the process of history gathering, the IAPIC staff obtains information about the animals prior to exposure and records the time intervals between exposure and onset of adverse effects, the resultant data resemble those of retrospective studies. For agents new to or expanding in the environment, however, exposure of the population has just begun. Thus, because of the continuous nature of the monitoring process, the data take on the nature of a prospective study for the population at risk.

PROBLEMS WITH EPIZOOTIOLOGY-RELATED

REGARD TO DATABASES

The principal problem with most currently available data on spontaneous poisoning of animals is that there is not enough collected. In addition, inadequate attention has been given to alternative explanations for the observed illness. In the few surveys conducted by veterinary groups, assessment has been made by a wide range of veterinarians with differing levels of expertise, with differing criteria for diagnosis. Surveys conducted by diagnostic laboratories depend on submission of feed or dead animals for most of the specimens and, therefore, toxicoses that cause less severe illnesses, those involving agents for which there are no methods for analytical confirmation, and those that involve species of lesser economic importance are inadequately represented. NAPINet methods have circumvented at least some of these problems. They have evolved so that, using structural criteria, most NAPINet calls would be assessed similarly by any of the responding toxicologists/trainees. There are, however, other concerns. The primary limitation of the NAPINet data bank is inadequate financial resources to provide staff (1) to receive more calls thereby obtaining more data, (2) for callbacks to confirm that the diagnosis did not change, and (3) to determine the outcome of the recommended therapy. Toxicoses producing acute effects overshadow those with chronic effects. In addition, veterinarians are likely to call for the more difficult cases and, once familiar with how to deal with a given toxicosis, are unlikely to consult with NAPINet when subsequent incidents of the same type are encountered.

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Assessment of IAPIC data acquired over a period of years has demonstrated that some products being used in the home are causing far more problems than others. For example, the organophosphorus insecticide most often associated with toxicoses in cats is chlorpyrifos, despite the fact that no pesticides approved for intentional spraying, “dipping,” or dusting on this species contain this generic compound. Because of the numbers of calls, IAPIC has repeatedly documented the occurrence of several, previously poorly recognized toxicoses in small animals such as those due to piperazine (anthelmintic), pennyroyal oil (insecticide), and ornamental fig trees (Ficus). Similarly, abortion in swine due to exposure to topical diesel oil has been encountered on several occasions. In addition, some products have been shown to be particularly hazardous to the exposed animals. For example, IAPIC data confirm that toxicoses due to scirriloside- and methomyl-based pesticides are more often lethal than those due to commercially available pindone and propoxur formulations. The continuous nature of the data collection enables IAPIC to detect sensitively the emergence of new problem formulations into the market place. In this prospective mode, IAPIC data are used to assessthe comparative frequency of problems associated with various formulations of pesticides and medications for use on or around animals. For example, new rodenticides based on vitamin D3 are causing a far greater problem than that predicted by the manufacturers. Similarly, the initial use of a new anthelmintic drug (ivermectin) in horses was rapidly recognized as a problem of major proportions in certain breeds of dogs (collies, Shetland sheepdogs, and related breeds), even though there were relatively few such exposures (that occurred almost exclusively at the hands of ill-informed owners). A large number of recent inquiries have involved a reasonably consistent pattern of clinical signs of toxicosis after exposure to a new fenvalerate/DEET-based insecticide-repellent for use on small animals. Apparently, the manufacturer’s extrapolations from laboratory animals had incorrectly predicted that cats and dogs would be unlikely to be affected adversely by this formulation. ADAPTING ANIMALS

NAPINet METHODS FOR USE IN MONITORING FERAL FOR ADVERSE EFFECTS OF TOXICANT EXPOSURE

In order to assessthe effects of toxicants under conditions of existing rates of environmental contamination, it would be possible to place (temporarily) caged laboratory animals in the field during times of exposure and monitor them for effects. While worthwhile data might be obtained in some situations, the results would not represent the exposure of the feral animals because of differences in food and water, inability of caged animals to seek shelter in burrows, marked genetic differences, and numerous other factors. A principal lesson of recent work (e.g., Schaeffer et al., 1987) is that, for epizootiologic ecotoxicology studies to be valid, the sample size must be adequate and the background incidence of disease in the ecosystem must be quantified. The ecology of potentially affected sites must be studied in some depth to provide a baseline for detection of ecosystem parameters expected to be altered by the agents under study (Schaeffer and Herricks, in preparation). Generally, a site currently exposed needs to be compared with an unexposed reference site(s) and, when possible, graduated

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exposures can be defined by moving away from a known point source (Kisseberth et al., 1984). Due to seasonal and annual fluctuations in an ecosystem’s community composition, a minimum 2-year monitoring program is needed at the exposed and reference sites for many studies. Regardless of the approach used, most studies need to extend for a time long enough to indicate that a steady state has begun to develop. Until some evidence of an equilibrium is observed at a given level of exposure, and the factors responsible for arrival at this steady state are recognized, there will be no way of predicting the long-range effects of exposure. Clearly, field work is essential since laboratory studies cannot accurately represent the different strains, species, habitats, and ecosystem interactions of feral animals. Conversely, field studies must be carefully designed and conducted, and the data assessed with extreme care, to ensure that meaningful epizootiologic data will be derived to permit sound judgment as to appropriate long-term land uses. Response Parameters To minimize experimental error and therefore lessen the sample sizes that must be monitored, data from the environment and from animals at the exposed and reference sites must be collected and recorded using tightly standardized criteria. For species of lower density at the test site, repeated trapping and nonstressful testing may be necessary. Repeated observations of such animals followed by a rapid return to freedom often tend to result in a steady reduction in evidence of stress on each subsequent capture date. If repeated trapping is used, therefore, the number of repetitions among the test and control populations must be similar. Also, if repeated observations of the same animals must be made, the animals should be disturbed only minimally in the process of data collection (i.e., weighing, infrequent bleeding) and the means of data analysis must account for the repeated observations. Morbidity and mortality records should be kept on the exposed population indicating the actual diagnosis. For each animal, a careful assessment of the compatibility of all abnormalities with exposure to the ecosystem insult versus alternative etiologies must be made. Lesions, if they occur, are a very useful endpoint and a sample of exposed animals from a currently used, heavily exposed area should be examined grossly and histologically in a preliminary study to determine what changes are to be anticipated. Subsequently, in formal studies when similar lesions are observed, less highly exposed animals should be evaluated to determine whether dose/response relationships can be used in support of cause/effect associations. IAPIC criteria derived to assure that an assessment is based on sound judgment (adequate exposure, consistency of response in the affected population, effects compatible with the properties of the toxicant, appropriate time factors) could be used to ensure the quality of the data being entered. Computer programs developed by the IAPIC staff which compile clinical sign data by systems affected and agent involved could be adapted to include lesions in vital organs, changes in fecundity, teratogenesis, or other responses to enable recognition of previously unidentified associations for subsequent study (and possible confirmation) in the laboratory. Epizootiologic criteria (e.g., species, ages, sexes, locations, and attack rates) could be used to identify practices and other risk factors that have led to a problem of toxicosis in the exposed animals. For one to recognize subtle functional changes (which sometimes may have marked effects beyond the study), the animal population might also be monitored

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with a neurophysiology/neurobehavioral battery. Neurobehavioral criteria suggested include grip strength assessment, open field monitoring, figure-8 maze monitoring, and startle response followed by startle response after accommodation to a “warning” signal. The latter is believed to be related to “learning ability.” Other parameters may include auditory, visual, and somatosensory evoked potential monitoring. Removal of a subsample of the exposed population to the laboratory and comparison with an age/sex paired sample from the unexposed population could reveal functional changes in physiology and/or behavior that, in the wild, could lead to increased susceptibility to predation, failure to obtain food when supplies dwindle, failure to court or breed successfully, or failure to care for the young. CONCLUSIONS For the development of an epizootiologic ecotoxicology study to be successful, the toxicant exposure and ecosystem dynamics must be well characterized. If aerial exposure is involved, engineers with expertise in airflow patterns and inhalation toxicologists able to characterize particle size distributions and mass concentrations of toxicants are needed to estimate the inhalation exposure. An approximation of total exposure requires sampling of soil, water, food plants, air, and animal tissues. Analytical toxicologists are essential in these efforts. Test criteria should be developed based on a careful preliminary study. Studies require integrated efforts by ecologists and wildlife biologists to monitor changes in interacting variables, e.g., animal and plant densities, feeding habits, animal movements, and others. Trapping by wildlife biologists must reflect the population in a representative fashion. In addition, a team of veterinarians specializing in toxicology, pathology, clinical pathology, and systems of interest (e.g., neurology, cardiology, and internal medicine) must identify abnormalities induced by the toxicant or its effects on other components of the ecosystem. Such responses then become endpoints of interest. Innovative use of population statistics with evaluation of a subsample for lesions, fecundity, terata, alterations in clinical pathologic and pathologic measures, and neurophysiologic and neurobehavioral measures could eventually evolve into a semistandardized approach to epidemiologic epizootiology. Each investigation will still need to be tailored to the toxicant, the species affected, and the nature of primary and secondary manifestations which are induced. REFERENCES BEASLEY, V. R. (1986). Prevalence of poisonings in small animals. In Chemical and Physical Disorders (G. D. Osweiler, Ed.), in Current Veterinary Therapy, Vol. IX, Small Animal Practice (R. W. Kirk, Ed.), pp. 120- 128. Saunders, Philadelphia. BREITSCHWERDT, E. G., ARMSTRONG, P. J.. ROBINETTE, C. L., DILLMAN, R. C., KARL, M. L., AND LOWRY, E. C. (1985). Three cases of acute zinc toxicosis in dogs. Vet. Hum. Toxicol. 28, 109-l 17. BRO-RASMUSSEN, F., AND LOKKE. H. ( 1984). Ecoepidemiology-A casuistic discipline describing ecological disturbances and damages in relation to their specific causes: Exemplified by chlorinated phenols and chlorophenoxy acids. Regul. Toxicol. Pharmacol. 4,39 l-399. CLOUTIER, N. R., CLULOW, F. V., LIM, T. P., AND DAVI?. N. K. (1986a). Transfer coefficient of226Ra from vegetation to meadow voles, Microtuspennsylvanicus, on U mill tailings. Health Phys. 50,775-780. CLOUTIER, N. R., CLULOW, F. V., LIM, T. P., AND DA!&, N. K. (1986b). Metal (Cu, Ni, Fe. Co, Zn, Pb) and Ra-226 levels in tissues of meadow voles Microtus pennsylvanicus living on nickel and uranium mine tailings in Ontario, Canada: Site, sex, age and season effects with calculation of average skeletal radiation dose. Environ. Pollut. Ser. A. 41,295-3 14. CLULOW, F. V., CLOUTIER, N. R., DAVY, AND LIM, T. P. (1986). Radium-226 concentrations in faeces of

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