Grantee Research Project Results
Final Report: Developing Rapid Assessment Tools to Evaluate the Biological Effects of Complex and Biologically Active Chemical Mixtures
EPA Grant Number: R832741Title: Developing Rapid Assessment Tools to Evaluate the Biological Effects of Complex and Biologically Active Chemical Mixtures
Investigators: Schoenfuss, Heiko L. , Barber, Larry B. , Julius, Mathew L. , Norris, David O.
Institution: Saint Cloud State University , United States Geological Survey , University of Colorado at Boulder
EPA Project Officer: Hahn, Intaek
Project Period: November 1, 2005 through October 31, 2008 (Extended to October 31, 2009)
Project Amount: $599,640
RFA: Exposure Measurement Tools for Endocrine Disrupting Chemicals in Mixtures (2005) RFA Text | Recipients Lists
Research Category: Environmental Justice , Endocrine Disruptors , Human Health , Safer Chemicals
Objective:
This project seeks to test the hypotheses that mixtures of estrogenic compounds will have adverse effects on survival and reproduction of aquatic vertebrates that cannot solely be accounted for by the summation of individual effects. Three objectives will be completed to test the above hypothesis and develop rapid assessment biomarkers to evaluate effects of complex biologically active mixtures:
- To determine the environmentally relevant concentrations of suggested endocrine disrupting chemicals in the aquatic environment. (Phase 1 - year 1).
- To assess whether the effects of mixtures of these chemicals are more potent on aquatic wildlife than suggested by the sum of individual effects. (Phase 2A, B - second half year 1 and year 2).
- To evaluate the applicability of neurotransmitter distribution and abundance as rapid indicators of adverse health effects in exposed aquatic wildlife. (Phase 2B, 3 - second half year 2 and year 3).
Summary/Accomplishments (Outputs/Outcomes):
Phase 1 of the project, the analysis of two wastewater effluents, and Phase 2A, controlled laboratory exposure experiments have been completed for all compounds and mixtures (estrogens, alkylphenols, pharmaceuticals). The linkage of observed behavioral, anatomical and physiological endpoints to upstream neuroendocrine endpoints indicative of exposure has advanced considerably (Phase 2B). We have also conducted two field validation studies in Phase 3 of the project. Most compounds were found in higher concentrations in the Boulder treated effluent. Both effluents exhibited temporal variability creating continuously changing complex mixtures.
We have completed exposure experiments with diatoms, daphnia and fathead minnows in the St. Cloud State University Aquatic Toxicology Laboratory for all proposed classes of endocrine disrupting compounds and their mixtures. We have been working to test the hypotheses that brain adrenergic, dopaminergic and serotonergic systems are sensitive biomarkers of estrogen exposure that predict fitness outcomes. Our investigations include immunohistochemical detection of monoamine-synthesizing enzymes and detection of monoamines by HPLC. We have completed analysis of monoamine turnover in 100% of brains from single estrogen and estrogen mixture exposures. We have identified estrogen-specific responses in the brains of fathead minnows that corroborate preliminary findings from behavioral and immunohistochemical analyses. Preliminary results demonstrate that brain monoamines are sensitive to low dosages of exogenous estrogens. Monoaminergic responses appear especially sensitive to low-dose exposure to estrone. We have completed preparation of 100% of control, estrogen, and estrogen-mixture brains for immunohistochemical characterization of estrogen impacts on tyrosine hydroxylase immunoreactivity (TH-ir). Preliminary results suggest TH-ir is a sensitive early endpoint and that effects of estrone on TH-ir are distinct from estradiol, ethynylestradiol, or nonylphenol. Estrone-exposed fathead minnows have dramatically enhanced extra-hypothalamic fiber tract TH-ir. Further immunohistochemical investigations have established that this extrahypothalamic immunoreactivity is adrenergic and not dopaminergic.
Conclusions:
During the no-cost extension year 4 of this study we plan to complete the analysis of brain samples obtained from the exposed fishes to characterize the neural responses to exposure and to complete the field validation experiments.
Journal Articles on this Report : 5 Displayed | Download in RIS Format
| Other project views: | All 14 publications | 8 publications in selected types | All 8 journal articles |
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Blanksma C, Eguia B, Lott K, Lazorchak JM, Smith ME, Wratschko M, Dawson TD, Elonen C, Kahl M, Schoenfuss HL. Effects of water hardness on skeletal development and growth in juvenile fathead minnows. Aquaculture 2009;286(3-4):226-232. |
R832741 (2007) R832741 (Final) |
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Julius ML, Stepanek J, Tedrow O, Gamble C, Schoenfuss HL. Estrogen-receptor independent effects of two ubiquitous environmental estrogens on Melosira varians Agardh, a common component of the aquatic primary production community. Aquatic Toxicology 2007;85(1):19-27. |
R832741 (2007) R832741 (2008) R832741 (Final) |
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Painter MM, Buerkley MA, Julius ML, Vajda AM, Norris DO, Barber LB, Furlong ET, Schultz MM, Schoenfuss HL. Antidepressants at environmentally relevant concentrations affect predator avoidance behavior of larval fathead minnows (Pimephales promelas). Environmental Toxicology and Chemistry 2009;28(12):2677-2684. |
R832741 (Final) |
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Schoenfuss HL, Bartell SE, Bistodeau TB, Cediel RA, Grove KJ, Zintek L, Lee KE, Barber LB. Impairment of the reproductive potential of male fathead minnows by environmentally relevant exposures to 4-nonylphenolf. Aquatic Toxicology 2008;86(1):91-98. |
R832741 (2007) R832741 (2008) R832741 (Final) |
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Ye X, Schoenfuss HL, Jahns ND, Delinsky AD, Strynar MJ, Varns J, Nakayama SF, Helfant L, Lindstrom AB. Perfluorinated compounds in common carp (Cyprinus carpio) fillets from the Upper Mississippi River. Environmental International 2008;34(7):932-938. |
R832741 (2007) R832741 (2008) R832741 (Final) |
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Supplemental Keywords:
RFA, Scientific Discipline, Health, Health Risk Assessment, Endocrine Disruptors - Environmental Exposure & Risk, Microbiology, endocrine disruptors, Biochemistry, Endocrine Disruptors - Human Health, endocrine disruptor screening program, wastewater, bioavailability, EDCs, endocrine disrupting chemicals, exposure studies, chemical mixtures, rapid assessment toolProgress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.