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About IEEA

Integrated exposure and effects analysis (IEEA) is a scientific approach that unites evaluation of the presence of the environmental contaminants and assessment of their potential effects on human and ecological health. This approach is necessary to meet the current challenges in chemistry and toxicology: an ever-growing list of chemicals present in the environment. The traditional methodology for monitoring environmental pollutants is based on separated lines of evidence: targeted chemical analysis, in which the compounds to be analyzed are pre-selected, to quantify the concentration of the contaminants in the environment, or evaluation of acute and chronic effects of the pollutants on test organisms (plants, vertebrates and invertebrates) based on classic endpoints (mortality rates, measurement of reduced growth and alterations in the reproduction rates). Considering the limitations and strengths of both chemical and biological assays to characterize the risks of chemical mixtures in the environment, an integrated analysis approach is critical. Implementation of analytical chemistry together with toxicological assays should be encouraged to assess the exposure and effects of the contaminants. The ultimate goal of this approach is to develop a transferrable toolbox to generate scientifically-sound information required to manage the chemical risk.

Analytical instruments and sample treatment techniques used in targeted chemical analysis have advanced considerably over the last 20 years, making it possible to quantify trace levels (ng/L or less) of chemicals in the environment and generating significant monitoring and occurrence data in recent years. However, many precursors, conjugates and degradation/transformation products of contaminants are known to occur in the environment. To expand the scope of chemical analysis to include those unknown derivatives, which may be responsible for bioactivity, non-targeted analysis is needed. A series of analytical techniques including chemical fractionation, chromatography, and accurate mass spectrometry are being developed on an ongoing basis. We propose here that the further use and development of toxicology and chemistry approaches should be accomplished in collaboration to yield maximum utility in meeting 21st century monitoring challenges.

International efforts to address regulation within REACH and the approach suggested in the National Academy of Sciences Toxicity in the 21st Century: A Vision and a Strategy report have culminated in the ongoing development of in vitro and alternative toxicity tests for key events or molecular initiating events in critical adverse outcome pathways, including those related to endocrine disruption, (estrogens, anti-androgen, thyroid-disruptors, etc.), oxidative stress/carcinogenesis, reproduction and development, and developmental neurotoxicity. We propose that these new assay technologies be used as part of a suite of biological approaches to characterizing environmental samples. Whole effluent toxicity (WET) testing was developed by the U.S. Environmental Protection Agency in the 1980s to measure the combined acute and chronic toxic effects of chemicals present in complex environmental samples as a way to implement the Clean Water Act; this approach is currently established in other countries, such as Canada and Korea, and being evaluated in Japan. Advantages of using WET include the use of ecologically-relevant test species and rapid characterization of whole organism effects of environmental samples. However, application of WET to environmental samples does not necessarily narrow down the mode-of-action of toxicity, which would be helpful in reducing the number of potential chemicals to be analyzed in environmental samples.

Then an extended methodology, the toxicity identification evaluation (TIE) and effects directed analysis (EDA), emerged to chemically identify responsible agents in environmental samples determined by WET and its derivative testing systems. Part of the TIE approach includes a series of physico-chemical manipulations of environmental samples, which is intended to diminish the toxicological and chemical complexity of any one sample, and hence, to facilitate the identification of sample components and the associated effects. TIE has being used successfully to characterize toxicants in sediments and effluents for decades. However, TIE focused primarily on determining the classical ecotoxicity endpoints such as mortality or altered fecundity, and was employed primarily to evaluate traditional pollutant, i.e. metals and legacy contaminants.

Updated EDA methodologies have been developed, primarily in Europe, to address the ecotoxicological problems associated with the presence of endocrine disrupting chemicals (EDCs) in the environment. Although EDCs have been studied for the past two decades, there is still much uncertainty about how to identify EDCs in bioassay, especially EDC that are not estrogenic, e,g, chemicals that act on other endocrine targets, including other receptors (androgen receptor, progesterone receptor, glucocorticoid receptor), steriodogenesis, and thyroid hormone homeostasis. Further, , the EDC concentrations that cause an observable effect in available bioassays, the consequences of the exposure to mixtures of EDCs in bioassays, and the correspondence of bioassay effects to cellular, individual, and population-level adverse outcomes represent major uncertainties in the field of toxicology as a whole.

Therefore, application of a battery of rapid assays, including high-throughput and WET methods, to identify and classify the contaminants based on their adverse outcome pathways through specific modes of action could enhance chemical analysis by informing the chemical testing strategy. A weight-of-evidence approach including chemical, toxicological and physical lines of evidence is crucial for the identification and classification of potentially toxic chemicals in the environment. Recent advances in chemical analysis and bioanalytical tools are already being applied towards this goal, but a closer collaboration between the different fields of expertise involved in the research, as well as the stakeholders who will utilize its outcomes is essential for the fast implementation of IEEA for a better chemical risk management.

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