During the past several years, there has been growing acknowledgement that synthetic chemicals released into the environment have disrupted teh development and/or functoin of the reproductive, endocrine, immune, and nervous systems of vertebrates. Effects of this nature have been documented for many wildlife species in the field and have also been demonstrated in laboratory studies. In several instances, exposure to endocrine-disrupting chemicals (EDCs) has led to instability or declines in wildlife populations. To address the relevance of these findings to freshwater and saltwater fishes, a group of scientists gathered in retreat at a work session at Wingspread, in Racine, Wisconsin, on 21-23 July 1995, to examine the scientific evidence and to come to some conclusions about the magnitude and scope of these effects. A multidisciplinary group of 22 scientists participated in the work session, including experts in the field of aquatic sciences, biochemistry, biometrics, chemistry, ecology, endocrinology, fisheries biology, immunology, marine sciences, pathology, pharmacology, physiology, toxicology, veterinary medicine, wildlife biology and zoology. Participants were asked to address the following questions:

1. What is the present state-of-knowledge concerning the effects of chemical exposure on fish development and reproduction?
2. What are the major gaps in this knowledge? What research is needed to answer the major questions?
3. To what extent are environmental contaminants contributing to fish population declines or impeding recovery of depleted stocks?

We are confident of the following points:

• Several classes of synthetic chemicals present in the aquatic enviornment disrupt reproduction, endocrine, immune and nervous system functions, growth, and development in fishes (e.g., polychlorinated bipheynyls [PCBs], dibenzo-p-dioxins [PCDDs], and dibenzofurans [PCDFs],dichlorodiphenyl-trichloroethate [DDT]-group chemicals, alkylphenols, and their metabolites). Some naturally occurring compounds used in industrial and agricultural processes also have this capability (e.g., heavy metals). Laboratory studies have shown that these chemicals can act directly as hormone mimics or blockers. They can also act indirectly through effects on neuroendocrine homeostasis, and they can affect immune system function.
• A wide range of effects may result from exposure to these chemicals, including anatomical malformations, functional alterations, and biochemical or molecular changes. Developing embryos and larvae are particularly sensistive to chemical exposure; however, adult fish are also affected. Depending upon the timing of exposure, irreversible effects can occur in the offspring of exposed fish which may not be immediately apparent. Because many of these chemicals eventually reach aquatic ecosystems, fish may serve as reliable sentinels of effects of chemicals in other vertebrates, including humans.
• Many fish populations in both saltwater and freshwater are presently threatened by chemicals introduced into the environment through human activities. There is a high degree of certainty that some wild fish populations have already been affected.
• The well-characterized toxic effects of PCDDs, PCDFs, and PCBs on lake trout sac larvae, the past exposure conditions, and the effects found in Lake Ontario provide compelling evidence that these chemicals probably caused reproductive or developmental damage to entire stocks of fish. In most other cases, the specific agents responsible for injury have not been definitively identified, nor has damage to reproduction and development been adequately assessed.
• Of great concern is the global distribution of many known reproductive and developmental toxicants. These deleterious agents can move through the environment, expose fishes distant from their points of release, and accumulate to high levels in some locations.
• Steps need to be taken to safeguard fish stocks from the effects of synthetic chemical exposures. The general public and many scientists are not aware of the extent to which fish species, including economically important fisheries, are presently at risk or have already been injured.

• Few multigenerational studies of wild fish populations have looked in detail at the sublethal effects caused by synthetic chemical exposure which lead to long-term functional impairment (e.g., developomental, endocrine, reproductive, neurologic, immunologic) or long-term consequences (e.g., endocrine disruption leading to reproductive failure and population decline).
• Environmental variables complicate field research linking exposure to chemicals with effects on wild fish populations. Epidemiological studies are complicated by the influence of changing climatic and geophysical forces on fish population dynamics. Additional confounding factors include impacts of human activities, such as overfishing, release of hatchery-reared fishes, habitat alterations, and the introduction of exotic species.
• Inherent characteristics of fish biology further complicate field research. For example, year class recruitment is affected by variables that are difficult to quantify; reproductive strategies vary greatly among different fish species, making interspecies comparisons difficult; little is known about normal physiological parameters for most fish species; and routine sampling and observation of specific fish populations is logistically difficult.

• More knowledge is needed of fundamental physiological processes and developmental mechanisms in fish at levels of organization from molecular and cellular to the whole organism. In particular, basic research is needed for a variety of species on sexual differentiation, ontogeny of the neuroendocrine system, hormone receptor structure and function, normal levels of circulating hormones at various life stages, and normal developmental processes.
• Better assessments of the present threat to fish stocks are needed, requiring a) detailed information on the demographics and reproductive health of fish populations where developmental or reproductive dysfunction is occurring; b) knowledge of the extent and patterns of discharge and accumulation of potential and known toxicants in aquatic ecosystems; c) ecoepidemiological studies to identify chemical exposures to demonstrate cause and effect and delineate the mechanisms of action; and e) consideratoin of the effects of the other stressors, either alone or in combination, on the toxicological action of chemicals present in the environment.
• Field and laboratory research strategies should include identification of critical times within specific life stages when organisms are most sensitive to the toxic actions of chemicals: this will require long-term multigenerational studies. The effects of chemical exposure during development must be linked to later life history characteristics (e.g., behavioral, reproductive, nutritional, immunological, and neurological), which subtly alter the organism's ability to survive and reproduce. Field studies should aslo address the long-term effects of chemical exposures on fish population and community structure.
• Field studies should quantify the tissue burdens of chemical associated with injury in standardized units of measure to facilitate coordinated laboratory research. This information will guide laboratory studies by calibrating the exposure required to produce the effects observed in the field. However, there is particular concern for non-bioaccumulative agents which are not detectable in the organism when the damage is expressed, making it difficult to establish causal relationships. Toxicological studies of these chemicals must include exposures of ova, embryos, and early life stages followed by detailed observations for effects in the mature adults and their offspring (i.e. second generation effects). It is very important that these studies incorporate the impact of maternal transfer of contaminants to the ova before spawning, mimicking the conditions in the environment.
• More basic research into the mechanisms and sites of action of known toxicants is needed. This research should include both direct and indirect effects of chemicals on specific reproductive and developmental processes, and it should identify the most sensitive endpoints and the most sensitive fish species. From this informatoin, reliable biomarkers of the effects of specific chemicals should be developed.
• In vivo and in vitro screening methods are needed to assess the potential reproductive and developmental toxicity of compounds to fishes before these chemicals are released into the environment.
• The possibility of multiple impacts of several chemicals or chemical classes should be considered, because the net effects of complex mixtures of chemicals cannot always be explained on the basis of the individual actions of known components of the mixture. Models are needed for utilizing information a) about single chemical effects to predict effects from exposures to mixtures of chemicals with a common mode of action and b) to predict effects from exposures to mixtures of chemicals with different modes of action.
• The difficulties in assessing the causes of fish population declines need to be addressed through cooperative, multidisciplinary research. Field observations of dysfunction at individual, populatoin, community and ecosystem levels should direct the course of coordinated experimental and analytical laboratory studies. The results from these coordinated field and laboratory studies on chemical exposures, effects, and dose-response can tehn be used to characterize risk and to address the causes of fish population declines.
• These activities will require long-term multidisciplinary studies by an international consortium of scientists from academia, the private sector, governmental, and nongovernmental organizations. These efforts should be supported by governments, the private sector, and an informed citizenry.

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