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Effects of a Polluted Environment: Research and Development Needs (1977)

Chapter: INTRODUCTION: NEEDS FOR INFORMATION ON THE EFFECTS OF A POLLUTED ENVIRONMENT

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Suggested Citation:"INTRODUCTION: NEEDS FOR INFORMATION ON THE EFFECTS OF A POLLUTED ENVIRONMENT." National Research Council. 1977. Effects of a Polluted Environment: Research and Development Needs. Washington, DC: The National Academies Press. doi: 10.17226/18686.
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Suggested Citation:"INTRODUCTION: NEEDS FOR INFORMATION ON THE EFFECTS OF A POLLUTED ENVIRONMENT." National Research Council. 1977. Effects of a Polluted Environment: Research and Development Needs. Washington, DC: The National Academies Press. doi: 10.17226/18686.
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Suggested Citation:"INTRODUCTION: NEEDS FOR INFORMATION ON THE EFFECTS OF A POLLUTED ENVIRONMENT." National Research Council. 1977. Effects of a Polluted Environment: Research and Development Needs. Washington, DC: The National Academies Press. doi: 10.17226/18686.
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Suggested Citation:"INTRODUCTION: NEEDS FOR INFORMATION ON THE EFFECTS OF A POLLUTED ENVIRONMENT." National Research Council. 1977. Effects of a Polluted Environment: Research and Development Needs. Washington, DC: The National Academies Press. doi: 10.17226/18686.
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Suggested Citation:"INTRODUCTION: NEEDS FOR INFORMATION ON THE EFFECTS OF A POLLUTED ENVIRONMENT." National Research Council. 1977. Effects of a Polluted Environment: Research and Development Needs. Washington, DC: The National Academies Press. doi: 10.17226/18686.
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Suggested Citation:"INTRODUCTION: NEEDS FOR INFORMATION ON THE EFFECTS OF A POLLUTED ENVIRONMENT." National Research Council. 1977. Effects of a Polluted Environment: Research and Development Needs. Washington, DC: The National Academies Press. doi: 10.17226/18686.
×
Page 13
Suggested Citation:"INTRODUCTION: NEEDS FOR INFORMATION ON THE EFFECTS OF A POLLUTED ENVIRONMENT." National Research Council. 1977. Effects of a Polluted Environment: Research and Development Needs. Washington, DC: The National Academies Press. doi: 10.17226/18686.
×
Page 14
Suggested Citation:"INTRODUCTION: NEEDS FOR INFORMATION ON THE EFFECTS OF A POLLUTED ENVIRONMENT." National Research Council. 1977. Effects of a Polluted Environment: Research and Development Needs. Washington, DC: The National Academies Press. doi: 10.17226/18686.
×
Page 15
Suggested Citation:"INTRODUCTION: NEEDS FOR INFORMATION ON THE EFFECTS OF A POLLUTED ENVIRONMENT." National Research Council. 1977. Effects of a Polluted Environment: Research and Development Needs. Washington, DC: The National Academies Press. doi: 10.17226/18686.
×
Page 16
Suggested Citation:"INTRODUCTION: NEEDS FOR INFORMATION ON THE EFFECTS OF A POLLUTED ENVIRONMENT." National Research Council. 1977. Effects of a Polluted Environment: Research and Development Needs. Washington, DC: The National Academies Press. doi: 10.17226/18686.
×
Page 17
Suggested Citation:"INTRODUCTION: NEEDS FOR INFORMATION ON THE EFFECTS OF A POLLUTED ENVIRONMENT." National Research Council. 1977. Effects of a Polluted Environment: Research and Development Needs. Washington, DC: The National Academies Press. doi: 10.17226/18686.
×
Page 18
Suggested Citation:"INTRODUCTION: NEEDS FOR INFORMATION ON THE EFFECTS OF A POLLUTED ENVIRONMENT." National Research Council. 1977. Effects of a Polluted Environment: Research and Development Needs. Washington, DC: The National Academies Press. doi: 10.17226/18686.
×
Page 19
Suggested Citation:"INTRODUCTION: NEEDS FOR INFORMATION ON THE EFFECTS OF A POLLUTED ENVIRONMENT." National Research Council. 1977. Effects of a Polluted Environment: Research and Development Needs. Washington, DC: The National Academies Press. doi: 10.17226/18686.
×
Page 20
Suggested Citation:"INTRODUCTION: NEEDS FOR INFORMATION ON THE EFFECTS OF A POLLUTED ENVIRONMENT." National Research Council. 1977. Effects of a Polluted Environment: Research and Development Needs. Washington, DC: The National Academies Press. doi: 10.17226/18686.
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INTRODUCTION: MEEDS £OR ON THE EFFECTS,0? A POILUTED Many changes in the character of the environment that result from human activities can affect human health, plants, animals, biological communities and ecosystems, materials, or weather and climate, soire of these effects are beneficial, some adverse, and some of indeterminate significance. Most changes in the environment that are inimical to human health or well-being are unintended results of activities pursued to enhance that well-being. When humaji behavior, institutions, or economic pursuits must be adjusted to reduce or prevent those adverse effects, ether social objectives or strategies for achieving them may have to be modified or sacrificed. Selection of the optimal strategy for protecting cr enhancing environmental quality requires that decision makers either reconcile such competing goals, forge a compromise, or, at worst, choose one over another. Such decisions must ultimately rest on social, rather than scientific, considerations. While scientific and technical information is not in itself a sufficient basis for decisions, it is an essential prerequisite. Decisions to protect the environment require reliable scientific information en: • the physical and chemical nature of environmental pollutants; • the size, discharge characteristics, and distri- bution in space and time of sources cf substances of interest; • processes of transport, transformation, degrada- tion, and removal of contaminants within and among the various compartments of the environment; • concentrations and durations cf exposures that may be encountered by diverse receptors; • the effects of such exposures on those receptors; f - 8 -

• the biological, economic, and sccial consequences of those effects; • the availability and ef fectiveress of techniques to control or reduce the level of ccntaminants in the environ- ment; and • the costs and benefits cf those control measures. Among these categories, information on effects of envi- ronmental changes is of pivotal importance for decision- making, for without knowledge of certain, likely, or pos- sible effects, there would be no impetus to take action. Furthermore, information on the nagnitude of effects must be compared with estimates of the costs cf protective measures in order to decide what action is appropriate (NRC 1975). AN APPROACH TO ASSESSING FESEARCH NEEDS ON EFFECTS Ideally, decision makers would like to know, all of the possible effects on all types of receptcrs of every poten- tial or actual change in the environment (including but not limited to introduction of contaminants), before taking regulatory action to limit or prevent such a change, since it is patently impossible to obtain information in such blanket fashion, research must concentrate instead on the development of detailed knowledge of selected specific effects of a limited nuicber of environmental agents. From that information, broad principles for evaluating the risks of changes in the environment may be deduced, to be tested and refined by subsequent research. Planning for such investigations must be well-grounded in an understanding of the nature both of effects and of research. Unless knowledge is organized into a logical framework of this kind, it is very difficult to identify insoluble problems or gaps in information, or to establish priorities for the effective allocation of limited research resources to efforts to close the gaps (Caldwell 1976). The Nature of Effects of Environmental Pollutants An effect of an environmental pollutant is expressed as a change in some receptor exposed to the pollutant. The receptors may be humans, animals, plants, and microorga- nisms; biological communities and ecosystems; natural and man-made materials; or the geophysical systems that deter- mine the weather and climate. Ir each of these categories. - 9 -

effects may appear as changes in many different tissues, organs, systems, states, or processes. Effects in organisms, for instance, may include altered enzyme activity, a tumor in the lung, or changes in behavior or reproduction. Examples of changes in ecosystems include altered ecological succession, reduced species diversity, and changes in the capacity to assindlate wastes. The approach used in this report is based not on specific pollutants or classes of environmental contami- nants, but rather on categories cf effects, as expressed in a variety of receptors, that might be produced by many different environmental contaminants or combinations of agents. The effects examined include injury to human health, damage to wildlife, vegetation, and ecological systems, corrosion of materials, and changes in climate. The order in which they are discussed does not imply relative prior- ity, and the interrelationships among effects should be recognized. Effects on wildlife or ecological processes may presage effects on human health, and the consequences to mankind of certain effects (fcr example, climatic change) may ultimately be far more serious than any direct threats to health posed by the pollutants involved. Each type of effect discussed in the report has, to a varying degree, social and economic consequences; determination of these is often a prerequisite for decision making. The distribution of effects in space and time is impor- tant. Effects may be local or global; may involve a few individuals or an entire species; may be transitory or con- tinue for centuries after the onset of environmental change; and may be reversible or cumulative and ultimately irrever- sible. A great many degrees can be identified within each of these dimensions. Patterns of susceptibility are another important aspect of effects. Sensitive subsets of varying sizes within a population cf organisms or subunits of an ecosystem may be at risk from exposures that are relatively harmless to the rest of the population or the system. In humans, for exam- ple, fetuses, infants, the aged, and people with certain diseases or special inherited or physiological conditions may be hypersensitive groups. Among other living organisms, differences in sensitivity among species may be pronounced. Some environmental contaminants can have effects that are neutral or beneficial to the receptor; for example, some trace contaminants of drinking water are also essen~ tial nutrients (NRC 1971). Other contaminants, such as chemical pesticides, can have substantial socially desir- able effects when used for their intended purposes, al- - 10 -

though pollution may be an inevitable result of such use. We recognize the importance of information on such bene-r ficial effects, in that all of the consequences of a given environmental change must be evaluated by decision makers. Nevertheless, the primary thrust of environmental regula- tion is to protect against adverse effects, and our concern in this report must therefore be almost exclusively with these. Causative Factors Most research on the effects of environmental pollu- tants has fccused on individual chemicals or physical agents (for example, noise, heat, particles). Agents have been tested singly, or at most in combinations of two or three, with other conditions controlled as part of the experimental design. In the environment, however, innumerable pollutants may be present simultaneously, intermittently, or sequen- tially; and factors such as temperature, light, moisture, and physiological and ecological states and processes are likely tc vary a great deal. Pollutants and these other factors may interact in additive, antagonistic, or synergis- tic ways to produce the observed effects. It is essential that both researchers and decision makers recognize and take into account the complexity of causative processes. Mechanisms It is important to know not cnly what effects occur in response to exposure to a polluted environment, but alsc how they occur. For organisms and fcr ecosystems, information is needed on the biochemical, physiological, and pharmaco- logical mechanisms of uptake, translocation, accumulation, storage, biochemical transformation, and removal or excre- tion of pollutants, and on mecharisms of toxic action and response. The need includes information on the mechanisms of interactions among agents that may occur at any stage in this sequence. Information on mechanisms can clarify cause- effect relationships, and may provide a basis for predic- tion, prevention, or treatment of effects. The study of mechanisms is particularly important in cases in which environmental agents undergo transformations. Some chemical reactions in the environment and metabolic processes in many organisms can degrade and detoxify con- taminants (for example, see discussion in NRC 1977). In other cases, chemical or biological processes may produce substances that are far more toxic than the original mate- rial (for instance, see Wood et al. 1968, Hall 1971). Greater understanding of these processes is an important need. - 11 -

Cose-Response Relationships is the amount cf a substance in the environment to which a receptor is exposed, summed over time. The magni- tude and timing of exposures, of the appearance of effects, and cf recovery when exposure ceases are important dose- response parameters. A.cute effects occur in minutes to hours, and §ubac.u£e effects in days to weeks, in response to exposures~tc relatively high concentrations of agents. £hroj;ic effects, in contrast, appear only after extended periods, sometimes approaching the lifetime of the organ- ism. Chronic effects may result from long-term, low-level exposure, or may be due to short-term, larger doses, but appear only long after exposure to causative agents has ended. Probably the greatest current needs for additional information about effects of environmental contaminants involve chronic effects (Congressional Research service 1975). Many environmental agents reach receptors by more than one route, and at different rates by each pathway. For example, humans may be exposed tc a given toxic substance in air, drinking water, food, Pharmaceuticals, and in occu- pational environments. It is important (though difficult) to be aware of and account for all such exposures and their contributions to total dose. Some contaminants accumulate in living tissues, making the cumulative dose over time significant even at extremely low levels of exposure, or at infrequent but high exposures. A critical and controversial issue is whether a no- effect level or threshold of toxicity exists for a given effect of an environmental agent, and, if it does exist, whether such a level car be identified^ For some biochemi- cal and pharmacological phenomena, such as the action of analgesic drugs, the existence of a no-effect level is generally accepted; in other cases, however, such as car- cinogenesis, the concept is vigorously debated (Eingham and Falk 1969; Kotin 1976; anonymous 1976). In most testing systems, some level of exposure can be identified at which there is no detectfd adverse effect. This fact may be due to one or more of the following considerations: (a) sample size — effects may occur at all exposure levels, but with such a lew frequency at the levels tested that their detec- tion would be .statistically significant only with a much larger population of exposed organisms; (b) measurement techniques — effects may be present, but not detected by the particular testing procedures available; (c) biologi- cal defenses — excretion, detoxification, DNA repair, or other mechanisms may enable the organism or system to cope with a low level of exposure. - 12 -

The Nature cf Research on Effects of Environmental Pollutants Effects of environmental polluticn, and especially chronic effects of low-level exposures, may be expressed so subtly or obscurely that they are difficult to detect and measure, and conclusive proof of causation may be all but impossible, even after damage has been done. We be- lieve that in many cases it is not acceptable to postpone decisions until such proof is available, especially when the only truly convincing evidence would be the occurrence of, for example, serious damage to human health or a major change in climate. Action must instead be taken to pre- vent adverse effects, using presumptive evidence and valid scientific estimates of the nature, magnitude, and proba- bility of the effects. For instance, the risks to human health inherent in long-term exposure to low levels of toxic substances have been estimated from studies of the effects cf higher doses of the same substances on laboratory animals (e.g., Hoel 1976). Similarly, the responses of some plants and animals with well understood physiological processes to measured exposures to pollutants in the laboratory have been used to model possible responses of other organisms to the same pollutants in the ambient environment. Reliance on indirect evidence of this sort, however, introduces additional uncertainties into the assessment of risks. The underlying biological principles that might sup- port the validity of some such extrapolations may not yet be known. For example, there is not yet an accepted theoreti- cal basis for a gu£D£i£gtive transfer of data on carcinc- genicity from one species to another, e.g., from rodents to humans, although most empirical results support a qualita- tive extrapolation. Some sophisticated statistical tech- niques have been developed for estimating the magnitude of risks to huitans of very low-level exposures, using data on far higher exposures in animals or humans; but in many cases the biological models that must be assumed in making such estimates have not been (and may never be) verified (Hoel et al. 1975). Similarly, there is not yet any reliable way to translate data on effects of a pollutant under controlled laboratory conditions into estimates of the effects that the same pollutant might have in intermittent exposures, in the presence of other pollutants, and with numerous other uncon- trolled variables in the ambient environment. Data on the effects of a given pollutant can sometimes be used to pre- dict effects of chemically similar compounds; however, knowledge of the relationship between structure and biolog- ical activity is still too incomplete to make this approach widely applicable, and some erroneous conclusions might be reached if structure-activity correlations were relied upon as the chief basis for assessments (Van Cuuren et al. 1972). - 13 -

Some circumstances cf environmental exposures or char- acteristics of the causative process make it quite diffi- cult to design studies that reliably link effects to their causes. In many cases, an entire population of humans, plants, or animals is exposed to a potentially toxic sub- stance, making it impossible to use a ccmparable unexposed segment of the population as a control group. Instead, the population must be examined over time, cr comparisons niade with groups elsewhere that have not been exposed to the agent. Introducing such geographic or temporal differences into the comparison introduces additional variables (for instance, other environmental factors and changes in the population itself) for which there is often no control. In other cases, the appearance of effects nay be long delayed. For example, some developmental abnormalities may not be expressed until relatively late in the life of an organism (Coyle et al, 1976, Spyker 1976) ; some kinds of human can- cers have latent periods of 20 years or more (Bingham et al. 1976); and some mutations, because of their recessive nature, may be observed only in later generations. The limits cf Research There are many questions about the effects of environ- mental pollutants that science can pose, but cannot answer. Some questions, such as the extrapolation of estimates of risks of cancer discussed above, may be inherently unanswer- able, or Kay need to await the development of additional fundamental knowledge. Others may be theoretically answer- able, but impractical to address because of the cost, time, and effort required. For example, it has been estimated that a study to determine experimentally whether genetic effects of radiation in mice are linearly related to doses at exposures that would increase the natural incidence of mutations by 0.5 percent, with statistically significant results at a confidence level of 95 percent, would require eight billion mice (Weinberg 1975). In many cases, therefore, prcof of effects of environ- mental changes may not be attainable through experimental research. Decisions will of necessity have to be based on extrapolation and statistical assessments of risk. In the face of continuing and unresolvable major gaps in funda- mental knowledge, research on some problems may offer little promise of producing meaningful answers. Such questions must be identified, so that necessary social decisions may be made on the strength of whatever i§ known, and other (nonscientific) considerations (KPC 1975).

Research on the Economic Impacts of Pollution like our knowledge of the biological measurement of effects, our current ability to assign economic values to effects is characterized by significant gaps in available information and limitations in existing theory. Economics can provide a mechanism for comparing the values of some otherwise noncomparable entities, through the use of market prices and substitute measures. However, subjective value judgments must be made if dollar values are to be assigned to such outcomes as risk to human life or the survival cf bald eagles. Determination cf the full social impact of a change in the environment requires consideration of costs in labor, energy, loss cf amenities, depletion or destruc- tion of natural resources, and other indirect but signifi- cant consequences. Environmental economists can use available models to infer values for some -effects and can produce estimates, however crude, of the costs of pollution. The reliability of such estimates is limited by scientific uncertainties iji the prediction of effects, as well as by the difficulty of obtaining data in the form required by economic models. Improved economic measurements of effects depend, therefore, not only on advances in economic research and in data col- lection, but also on improvements in krcwledge of the nature of adverse effects of exposures to envircnmental pollutants and cf the likelihood of their occurrence. The Multidisciplinary Approach The study of the effects of environmental pollutants is a complex undertaking requirirg the coordinated partici- pation of many scientific and technical disciplines. For example, evaluation of the role cf toxic environmental agents in diseases of humans or animals depends cn contri- butions from epidemiology, pathology, pharmacology, toxi- cology, clinical medicine, and other specialties. Research programs that facilitate the interaction of workers in sev- eral disciplines on interrelated aspects of a problem, beginning with the posing of research questions, have shown considerable promise for producing information of great value. Quality of Research Results In order to make the information that is available to decision makers current, reliable, and credible, research must be based on sound scientific principles and methods, must ask relevant and critical questions, and should draw - 15 -

as much as possible upon the best scientific talent of the country. The objectivity of research is also very impor- tant. Unfortunately, many research investigations are designed to prove a point or to gather informaticn to sup- port only one side of a controversial issue. Such work is often conducted by interested parties in adversary situa- tions, and its credibility is consequently suspect. Despite obvious potential biases, however, the quality cf some such research may be high, and the results extremely valuable. To increase public confidence in the quality and integrity of the research used for decision making, peer review and similar safeguards against potential bias should be used extensively in gathering and evaluating information (NRC 1975). PRINCIPLES FOR ESTAELISHING RESEARCH PRIORITIES Research resources are finite and irust therefore be applied to areas that offer substantial opportunities tc produce results of the greatest value for decision making. This need applies particularly tc the limited research budgets of regulatory agencies such as EFA. Eecause of the subjective component inevitable in any ranking of the relative importance cf research topics, the criteria used should be stated explicitly. The considera- tions that follow are ones we have used; others might use them, with their own emphasis, fcr setting research priori- ties. Some of these criteria might be given greater weight than others, but they are not listed specifically in order cf relative importance. The panel agreed unanimously that research resources should be applied to the study of important effects, but we could find no completely objective definition of importance. The importance of effects may be proportional to all or some of the following variables: • the magnitude of impacts experienced by individual human beings, animals, plants, other organisms, inanimate materials, or ecosystems affected by changes in the environment; • the numbers of people, animals, plants, and sc forth, so affected; • the amounts of energy, food, natural resources, ecological processes, or other amenities that may be made unavailable (or available) because cf changed environmental quality; - 16 -

• the economic value of benefits or camages, or the costs or benefits to individuals or society of living with the effects; • the geographical extent of effectjs; • the time qver which effects may be felt; / • whether effects are reversible or irreversible. Additional criteria beyond tre importance of effects include: • the social and economic corsequences of regulatory action (or inaction); • the immediacy of either the consequences of environ- mental change or the need to begin research; • the extent to which identified information gaps influence regulatory decisions (for example, see North and Merkhofer 1975). • the magnitude of information gaps; (this intuitive criterion may be misleading, if lack of information is due to a dearth of basic principles to guide research or if the topic fails to meet the ether criteria stated here;) • the existence of adequate basic knowledge, methodolo- gies, and theoretical constructs to make research feasible; • the resolvability of questions with a practical amount of resources and time; • the availability of capable trained personnel, appro- priate facilities, a source of funding, a favorable research environment, and so forth; • the breadth of applicability of results. Popular interest in certain problems and resulting political pressures may drive research in the direction of seeking information on specific effects, regardless of whether other criteria are met. Conversely, research that meets all previous criteria may rot seem justified to an appropriations committee, a bureaucracy, or the Office of Management and Budget. While political decision makers have a legitimate role to play in the definition of priori- ties, continual shifts cf attention to new "pollutants of - 17

the month" can create an unstable atrrosphere that rrakes it difficult to maintain the continuity of research. The criteria spelled out here are intended to be applied to research programs that are undertaken by, or in support cf, agencies responsible for protection cf the environment. Investigation of fundamental prirciples in all areas of bio- logical and environmental sciences is a necessity as well; in fact, it is difficult to distinguish some of the needs identified here from "basic" research. Many kinds of work on effects of pollutants will depend on the continued sup- port of basic, ncntargeted research if they are to be feasible. - 18 -

B£f£££££££ Anonymous (1976) International Symposium on Threshold Doses in Chemical Carcinogenesis. Heidelberg, 1976. Oncology 33(2) :49-100. (Entire Issue) Eingham, E. and H. Falk (1969) Ervircnmertal carcinc- genesis. Threshold concentrations of carcinogens and co-carcinogens. Archives of Environmental Health 19:779-783. Eingham, E., R.W. Niemeier, and J.E. Reid (1976) Multiple factors in carcinogenesis. Symposium on Occupational Carcinogenesis. Annals of the New York Academy of Sciences 271:13-21. Caldwell, L.K. (1976) Ar agenda fcr research. Pages 89-109, Research to Anticipate Environmental Impacts of Changing Pesource Usage. Proceedings cf a Symposium. Menlo Park, Calif.: Stanford Research Institute. Congressional Research Service (1975) Effects of Chronic Exposure to Low-Level Pollutants in the Environment. Eackground document for Hearings presented before the Subcommittee on the Environment and the Atmosphere, Committee on Science and Technology, U.S. Congress, House of Representatives. Washingtcn, B.C.: U.S. Gcverrment Printing Office. Coyle* I,, M.J. Wayner, and G. Singer (1976) Behavioral teratogenesis: a critical evaluation. Pharmacology, Biochemistry and Behavior 4:191-200. Hall, R.J. (1971) The distribution of organic fluorine in some toxic tropical plants. New Phytclogy 71:855-871. Heel, D.G. (1976) Statistical extrapolation methods for estimating risks frcm animal data. Symposium on Cccupational Carcinogenesis. Annals cf the New York Academy of Sciences 271:418-420. - 19 -

Heel, D«G., D.W. Gaylor, R.L. Kirshstein, U. saffiotti, and M.A. Schneiderman (1975) Estimation of risks of irreversible delayed toxicity. Jourral of Toxicology and Environmental Health 1:133-151. Kotin, P. (1976) Dose response relationships and threshold concepts. Symposium on Occupaticnal Carcinogenesis. Annals of the New York Academy of Sciences 271:22-28. National Research Council (1974) Geochemistry and the Environment. Volume 1. The Relation cf Selected Trace Elements to Health and Disease. Subcommittee on the Geochemical Environment in Felation to Health and Disease, U.S. National Committee for Geochemistry, Division cf Earth Sciences, Assembly of Mathematical and Physical Sciences. Washington, C.C.: National Academy cf Sciences. National Pesearch Council (1975) Decision Making for Regu- lating Chemicals in the Environment. Environmental Studies Board, commission on Natural Resources. Washington, D.C.: National Academy of Sciences. Naticnal Research Council (1977) The Fates of Pollutants: Research and Development Needs. A Report of the Panel on Fates of Pollutants to the Ervironmental Research Assessment Committee. Environmental Studies Eoard, Commission on Natural Resources. Washington, D.C.: National Academy cf sciences. North, D.K. and M.w. Merkhofer (1975) Analysis of alterna- tive emissions ccntrol strategies. Pages 540-711, Air Quality and stationary source Emission Ccntrol. Feport prepared by the Commission on Natural Resources cf the National Research Council for the committee on Public Works, U.S. Congress, senate. Serial No. 94-a, 94th Congress, 1st Session. Spyker, J.M. (1976) Assessing the impact of low level chemicals on development: behavioral and latent effects. Pages 161-190, Behavioral Pharmacology: The Current Status, edited by B. Weiss and V.G. Laties. Kew York: Plenum Press. Van Duuren, B.L, L.C. Katz, E.M. Goldschmidt, K. Frenkel, and A. Sivik (1972) Carcinogenicity cf halo-ethers. II. Structure-activity relationships of analogues of bis(chloromethyl)ether. Jourral of the National Cancer Institute 48:1431-1439. - 20 -

Weinberg, A.M. (1975) Testimony. Pages 174-184, the Costs and Effects of Chronic Exposure to Low-Level Pollutants in the Environment, Hearings before the Subcommittee on the Environment and the Atmosphere, Committee on Science and Technology, U.S. Congress, House. 94th Congress, 1st Session. Wood, J.M., F.S. Kennedy, and C.G. Fosen (1968) The synthe- sis of methylmercury compounds by methanogenic bacteria. Nature 220:173-175." - 21 -

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