Communities and Ecosystems

Within this page - Assessing the Condition of Freshwater Ecosystems || Regional Monitoring and Environmental Assessment Program || Assessing Risks of Stressors to the Sustainability of Wildlife Populations || PFOS and Related Organic Fluorochemicals || Species and Population Extrapolation and Prediction || Toxicology and Population Biology Research || Ranking and Prioritizing Chemicals for Risk Assessments || Providing Screens and Tests for Defining Toxicity Pathways

The Division's research in this area addresses the interaction of chemical and non-chemical stressors in species- specific, media-specific, and stressor-specific results from other research areas. This research addresses fundamental relationships, processes, modes of action, and models that permit extrapolation of effects across species, geographic areas, and stressors.

This research links with applied research in Water Quality and Land: Contaminated Sites by developing means to assess the effects of multiple stressors and diagnose the causes of impairment. For ecosystems, stressors may include nutrient effects, habitat degradation, exotic / invasive species, toxic chemicals, and other perturbations. Toxic effects on species and their populations occur through overt lethality, or through impaired growth, reproduction, or development. A focus on understanding pathways of toxicity that result in adverse effects facilitates extrapolation of research results across species and chemicals.

The Division's research falls into several thematic areas captured under Multi-Year Plans of EPA's Office of Research and Development (ORD) (Ecological Research, Safe Pesticides/Safe Products, and Endocrine Disruptors), and the more recent Computational Toxicology Strategy.

Assessing the Condition of Freshwater Ecosystems:
Great Lakes and Great Rivers

Monitoring and assessment of ecosystem condition is one of the most important tools for identification of the nature and extent of environmental problems and for gaging the efficacy of resources spent on environmental protection. Monitoring and assessment research is aimed at developing scientifically-defensible and cost-effective approaches for large geographic areas and large and diverse ecosystems.

The Division's role in this research area is to develop the approaches, designs, and indicators to effectively report on the Great Lakes and on the Great Rivers of the Central Basin of the U.S. Specific goals include:

• Contribute to the scientific underpinning for adaptive management of the Great Rivers via improved biomonitoring and bioassessment;

• Develop and test designs, indicators, and general methods to be applied to Great Rivers of the U. S. Central Basin;

• Develop and test the sampling methodology and assessment designs, and evaluate biological indicators for the near shore zone of the Great Lakes;

• Contribute to the establishment of lake-wide assessment designs and indicators to report on the condition of all important biological resources across the Great Lakes.

Abstracts of Great Lakes / Great Rivers Ongoing Research Projects

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Regional Monitoring and Environmental Assessment Program (REMAP)

The Environmental Monitoring and Assessment Program (EMAP) (www.epa.gov/emap/) is a research program to develop the tools necessary to monitor and assess the status and trends of national ecological resources. Under this program, REMAP (www.epa.gov/emap/remap/) was initiated to test the applicability of the probabilistic approach to assessment to answer questions about ecological conditions at regional and local scales. Using EMAP's statistical design and indicator concepts, REMAP conducts projects at smaller geographic scales and in shorter time frames than the national EMAP program. By clicking the map above, you will see how the EPA Regions are divided. You will also be able to link to individual Regions and their projects from this map.

The objectives of REMAP are to:

• Evaluate and improve EMAP concepts for State and local use;

• Assess the applicability of EMAP indicators at differing spatial scales;

• Demonstrate the utility of EMAP for resolving issues of importance to EPA Regions and States.

Division partnerships on REMAP projects include:

www.epa.gov/emap/remap/html/three/probasmt.html

www.epa.gov/emap/remap/html/five/ecosys.html

www.epa.gov/emap/remap/html/eight/index.html

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Assessing Risks of Stressors to the Sustainability of Wildlife Populations

In assessing risks of environmental stressors to the sustainability of wildlife populations, the relationship between levels of stressors (both chemical and non-chemical) and their effects on survival and fecundity rates of wildlife species are very important, but poorly understood. Laboratory toxicity tests on a few species are used to estimate toxicity in untested wildlife species of concern under a variety of field situations. Research focuses on developing methods for integrating existing wildlife toxicity data with models for extrapolating toxicity among species. Spatially-explicit wildlife population models are used to evaluate how the spatial patterns of habitat quality and abundance affect the estimated risks of chemical stressors. Methods also address the identification and management of uncertainty in wildlife life history parameters (e.g., survival and fecundity rates, habitat use) and stressor-response relationships. Sources of uncertainty, such as natural variability and incomplete knowledge of relationships, can affect the selection of appropriate population models and the parameterization of model inputs. Research focuses on methods for determining the quality of data and types of population models needed to successfully address risk assessment questions. Modeling efforts initially center on bird populations living in agricultural systems.

Abstracts of Wildlife Populations Ongoing Research Projects

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PFOS and Related Organic Fluorochemicals

A host of fluorinated surfactants increasingly are being used for a variety of applications. Concern for the potential toxicological risk of these types of chemicals had been minimal until recent documentation of the extensive distribution in both humans and wildlife of perfluorooctanesulfonate (PFOS), the primary degradation product of a commonly-used class of sulfonyl-based fluorochemicals originally manufactured by industry. There is some information, primarily from rodent studies, concerning the potential developmental, reproductive, and systemic toxicity of PFOS. It appears that aspects of early development are quite sensitive to the effects of PFOS. However, comparatively little is known about its toxicity in wildlife. This is of particular concern given the relatively high concentrations of PFOS that have been reported in mammals, birds, and fish from locations throughout the world. Exacerbating this lack of information is the fact that the actual toxic mode/mechanism of action (MOA) of PFOS is unknown, so extrapolation of effects from rodent studies to wildlife of concern is uncertain. Further complicating assessment of the ecological risk of fluorinated chemicals in general and PFOS, in particular, are their unique physico-chemical properties. For example, historically-used models, developed primarily for nonionic organic chemicals, are of limited utility with respect to predicting the distribution and effects of these chemicals either in the environment, or within individual animals. In addition, existing test methods with aquatic species may not suffice for evaluating fluorinated chemicals in terms of traditional approaches for chemical delivery.

The overall objective of the studies associated with this research area is to develop techniques to assess the ecological risk of fluorinated organic chemicals, initially utilizing perfluorooctanesulfonate (PFOS) and related products as prototypical representatives of this class of compounds. This work would complement ongoing and planned studies with PFOS conducted in the Reproductive Toxicology Division (RTD) (www.epa.gov/nheerl/rtd/) of NHEERL. A critical aspect of the research conducted at our Division is identification of biological models (species, life stages, endpoints) that effectively reflect both conditions of the greatest sensitivity to PFOS, and result in data of utility for predicting population-level effects. This work examines reproduction and development in a small fish model(s) (fathead minnow, medaka, zebrafish) and development in amphibians (Xenopus, native North American ranids). Toxicology studies are conducted with careful attention to dosimetry issues (uptake, metabolism, distribution) to enhance development of credible exposure approaches, as well as support derivation of models suitable for extrapolation across species. Characterization of dosimetry under controlled conditions is complemented with hypothesis-driven analyses of key environmental samples to facilitate extrapolation from the laboratory to the field. We also attempt to gain insights as to toxic MOA of PFOS through the use of DNA microarrays currently under development for amphibians. An understanding of MOA would not only enhance extrapolation of effects across species, but could directly support the development of in vivo endpoints and/or in vitro systems that could be utilized to obtain data for structure-activity relationship (SAR) models suitable for hazard identification.

Abstracts of Emerging Hazards Ongoing Research Projects

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Species and Population Extrapolation and Prediction

The need to extrapolate data from tested species to a limited number of untested species occurs in the context of ecological risk assessment. Often, ecological risk assessors are charged with protecting a large number of species, with a focus on identifying those species at highest risk. In ecological risk assessment, laboratory and field data are used to evaluate stressor-response relationships and define the relationships between assessment and measurement endpoints. The effects assessment is evaluated in the context of likely exposure scenarios. Typically, EPA is not able to test all chemicals, species, and life stages of interest under ecologically-realistic conditions or durations to detect subtle toxic effects.

The Division's ECOTOX database (www.epa.gov/ecotox/) provides researchers with a cost-effective means of locating high quality ecological effects data for a wide range of terrestrial and aquatic receptors. The primary source of data presented in ECOTOX is the peer-reviewed literature, with test results identified through comprehensive searches of the open literature, and manual data abstraction and data entry of relevant results into the database. The comprehensive nature of the collection itself in relation to species and chemical coverage, and the encoding of all relevant test conditions and results presented by the author make the database amenable for use in ranking and prioritization exercises as well as for modeling purposes.

To advance species extrapolations in ecological risk assessments, we employ an approach founded in the logic of physiologically-based toxicokinetic (PB/TK) models. The principal benefit of PB/TK models is that they yield estimates of the chemical time-course in specific target tissues. In addition, because they are based on biological attributes of the organism, PB-TK models are uniquely suited for extrapolation of toxicokinetic information among species. Over the last decade, research conducted by Division scientists has led to the development of PB/TK models for several species of fish exposed to organic chemicals in water or in the diet. Increasingly, research on PB/TK models for fish is focused on compounds that undergo metabolic biotransformation. In both fish and mammals, metabolism can either reduce toxicity by eliminating the parent compound or increase toxicity by activating the parent substance to a more toxic derivative. Division efforts are directed toward measuring metabolic products in vivo using microdialysis sampling methods in order to compare in vivo metabolic rate and capacity parameters with similar parameters determined using in vitro systems. An additional focus of modeling efforts at the Division is development of models for selected wildlife species within a larger effort to improve population-level risk assessments for piscivorus birds.

Abstracts of Species Extrapolation Ongoing Research Projects

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Toxicology and Population Biology Research to Improve Predictions of the Effects of Chemicals on Population Dynamics in Fish and Birds

Initial toxicology tests with fish were short-term (< 96h) exposures where lethality was the primary endpoint. As culturing and testing experience increased, scientists realized the importance of chronic exposures and sublethal endpoints. Fish tests became longer and more sophisticated. Such full- and multi- generational life cycle tests are resource-intensive and challenging to conduct routinely. Progressively more abbreviated assays have been developed that focus on early survival and development for regulatory purposes and risk assessment, but such assays have limited ability to assess effects on reproduction. Because most ecological risk assessments are focused on effects at the population level, the lack of estimates of fecundity from standard tests represents an important uncertainty with regard to prediction of recruitment.

In addition to supporting the needs of EPA's Office of Prevention, Pesticides and Toxic Substances (OPPTS) with respect to screening / testing for endocrine disruption effects, the Division has been involved in several efforts focused on assessing and diagnosing potential endocrine disrupting chemical (EDC) - associated impacts in the field. In conjunction with collaborators from a number of other laboratories in government and academia, the Division has been involved in identifying chemicals responsible for estrogenic and androgenic effects, respectively, in municipal and pulp and paper mill effluents. The Division has taken a variety of approaches including the use of the short-term fathead minnow reproduction assay to examine the potential effects of chemicals associated with sources of EDCs. An objective is to use controlled studies with contaminated effluent and/or single chemicals to provide baseline information that can be linked to field exposure data to make predictions of the status of fish populations in the field.

Complementary research to understand the consequences of toxic chemical exposures on wildlife population dynamics is aimed at toxicity test methods that define ecologically-meaningful dose-response relationships for important effects endpoints. There is need to improve population-level risk assessments. An objective is to provide a framework for improving interspecies extrapolation of toxicity effects in the context of advancing probabilistic risk assessments.

Abstracts of Toxicology / Population Biology Ongoing Research Projects

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Ranking and Prioritizing Chemicals for Risk Assessments

The EPA Office of Prevention, Pesticides and Toxic Substances (OPPTS) must implement a variety of regulations aimed at reducing the risk of adverse effects on human health and the environment from chemical exposures, including the Toxic Substances Control Act (TSCA), Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and the Food Quality Protection Act (FQPA). This has required the development of test guidelines for implementation of the directives within these Acts, and risk assessment methods for evaluating data submitted under the Acts. Although there is still a need for targeted test development, there is a broader need to develop a more efficient risk assessment paradigm that ensures the Agency's limited assessment and testing resources are focused on those chemicals and toxic endpoints with the greatest potential to cause adverse outcomes. Through requirements of the above Acts and TSCA's Pre-Manufacture Notification (PMN), thousands of new and existing industrial organic chemicals per year must be assessed for acute and chronic human health and ecological effects. Optimistic estimates predict that new information may be forthcoming on as many as 2,800 chemicals, out of a pool of approximately 10,000 chemicals, with variable amounts of data available across toxic endpoints of concern. There is a striking data scarcity for the majority of 2,500 PMN new chemicals submitted for review under TSCA each year. Any available information on analogous structures previously reviewed or information available in toxicological databases for similar chemicals is incorporated into the assessments made by each panel of highly skilled risk assessors. The lack of test data forces a heavy reliance on experience and expert judgement of the risk assessors. Quantitative structure-activity relationships (QSAR) are being used by the Agency to predict some endpoints, such as acute aquatic toxicity and bioconcentration potential. However, models are largely absent for prediction of chronic and sub-chronic toxicity endpoints.

Regardless of the amount of data available or the time frame under which risk management decisions must be made, a more efficient risk assessment paradigm, with an associated improvement in computational and biological models, is required. This focuses limited testing and assessment resources on those chemicals and toxic endpoints most likely to cause adverse outcomes. A new integrated and versatile Agency paradigm would include computational ranking and prioritization models, combined with in vitro assays, that could trigger in vivo screening tests. These would be comprehensive and efficient in vivo assays for evaluating adverse effects at critical life stages invoked as required, based on identification of the greatest uncertainties impeding risk management decisions.

An innovative program, entitled Computational Toxicology (CT), was initiated by ORD to develop chemical prioritization and screening methods based upon QSAR and rapid screens to streamline and focus existing tiered testing approaches. This results in a reduction of the number of chemicals requiring extensive testing in animals, and refinement of the use of the higher-tiered testing to ensure that maximum information is gained for the resources invested. The proposed CT program seeks to integrate sophisticated, modern computing (e.g., QSAR) with advances in molecular biology (e.g., genomics/proteomics/metabonomics) to provide a potentially viable alternative to the traditional, animal-intensive approaches, and greatly advance the application of toxicology in Agency risk assessments. In essence, this approach focuses on the "starting" point for chemical testing (i.e., the determination as to whether testing will be required for a given chemical). The successful development and appropriate application of CT tools greatly reduces the probability that testing will be conducted on "low risk" chemicals, thus reducing the numbers of tests conducted and animals used.

As proof-of-concept of the CT approach, the Division is developing methods for the immediate priority-setting issues facing OPPTS in evaluating endocrine disruptors as mandated by the Food Quality Protection Act. The approach, developed in consultation with OPPTS, will provide, in the near-term, additional predictive, computer-based structure-activity models and in vitro assays that will identify those compounds most likely to disrupt endocrine systems (endocrine disrupting chemical, EDCs). In the longer-term, the ORD-wide research efforts will refine existing in vivo assays to increase the amount of diagnostic information gained for the invested resources by eliminating redundancies among these assays and reducing the number of animals needed.

The Division has a rich history of developing mechanistically-based QSARs for prediction of acute and chronic toxicity and bioconcentration potential of industrial chemicals. Building on this expertise, the objectives of Division research are to develop mechanistically-based QSARs, in conjunction with in vitro bioassay methods that can be used to efficiently gather empirical information; and to predict the toxicological potential of large numbers of chemicals in an efficient and credible manner for additional adverse effect endpoints. Essential to the application of predictive models for ranking and prioritizing chemicals for further testing is an understanding of the linkage between the endpoint predicted in a QSAR (e.g., in vitro receptor binding, enzyme inhibition, etc) and the endpoint of concern in a risk assessment (e.g., impaired reproduction, development, neurotoxicity, etc). These linkages across multiple levels of biological organization of toxicological effects, from the key initiating event to the resultant individual or population level adverse effect, can be termed "toxicity pathways." Division research is aimed at developing toxicity pathway-specific QSARs. The in vitro or in vivo assays used to elucidate pathways of chemical toxicity incorporate markers diagnostic of specific toxicity pathways, allowing groups of "similar-acting chemicals" to be identified by the type of toxicity they initiate. Subsequently, the development of pathway-specific QSARs allows one to identify whether or not a an untested chemical is likely to produce each characterized type of toxicity.

Abstracts of Ranking / Prioritization Ongoing Research Projects

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Providing Screens and Tests for Defining Toxicity Pathways Triggered by Industrial Chemicals, Pesticides, and Water Contaminants

The large number of chemicals in use in commerce, industry, and agriculture makes it impractical to develop comprehensive toxicological data for each chemical risk assessment. As a consequence, after chemicals have been prioritized for assessments, the Agency needs to screen chemicals for potential adverse effects to complete the hazard identification/problem formulation phases so that limited risk assessment resources can be applied in an efficient manner. Screening represents an early tier in the assessment process which utilizes relatively low cost tests that yield data indicative of a specific toxicity pathway. However, with such tests, uncertainty remains as to the probability of an adverse outcome and/or the potency estimate needed for a quantitative dose-response evaluation. Chemicals judged as positive in the screening process may be selected to advance to higher tiers of a risk assessment that generally require more elaborate and expensive testing, but reduce the level of uncertainty associated with the toxicological outcomes.

In this regard, several fish and amphibian in vivo bioassays have been developed to characterize chemicals' toxic potential after initial ranking and prioritization with SAR/QSAR models and/or in vitro evaluations. Three screening bioassays are presented below that enable OPPTS and the Office of Water (OW) to screen chemicals and acquire additional information necessary to determine which compounds require further, usually more costly and time-consuming, testing. The fathead minnow short-term reproduction and the amphibian thyroid mechanistic assays allow OPPTS to evaluate chemical potential to disrupt endogenous endocrine systems. Each of these assays is also being evaluated for its diagnostic capabilities. Specifically, additional diagnostic tests done in conjunction with the fathead minnow assay are being assessed for their ability to distinguish estrogen pathway-mediated toxicity from that of androgen pathway-mediated toxicity. The gene profiles, proteomics, and biochemical endpoints, measured during the amphibian assay, along with histological and apical developmental endpoints, are being assessed for their ability to discriminate thyroid axis toxicity pathways. The medaka multi-endpoint bioassay is being evaluated by OW and ORD for its ability to detect adverse effects of chemicals in water at concentrations below which current mammalian models can efficiently and effectively be tested. The medaka multi-endpoint is also being considered by OPPTS and ORD for its potential to provide value-added reproduction and development endpoints as part of, or in place of, a multi-generation testing scheme.

Abstracts of Screening / Testing Ongoing Research Projects

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