Use of a Transgenerational Model to Evaluate Threshold Effects of Endocrine Disrupting Chemicals in Fish

EPA Grant Number: R827098
Title: Use of a Transgenerational Model to Evaluate Threshold Effects of Endocrine Disrupting Chemicals in Fish
Investigators: Foran, Christy M. , Nimrod, Alison C. , Benson, William H.
Current Investigators: Foran, Christy M. , Slattery, Marc
Institution: University of Mississippi
EPA Project Officer: Hahn, Intaek
Project Period: October 1, 1998 through September 30, 2001
Project Amount: $406,024
RFA: Exploratory Research - Environmental Biology (1998) RFA Text |  Recipients Lists
Research Category: Biology/Life Sciences , Environmental Justice , Human Health , Aquatic Ecosystems


The primary objective of the proposed research is to link whole animal reproductive impairment to alterations in morphological development and/or endocrine function following exposure to model endocrine disrupting chemicals. These model chemicals have different mechanisms of action, but will be assessed with the same endpoints to determine if there are common predictors of developmental or reproductive toxicity, or if different mechanisms induce different suites of biochemical/endocrine changes thereby providing a "fingerprint" of the mechanisms. The following hypotheses form the basis for the proposed research: (1) endocrine disrupters alter the hormonal environment during the sensitive life stages of sexual differentiation and reproduction, (2) exposure to endocrine disrupters results in altered sexual development and impaired reproduction, (3) there are several mechanisms by which chemicals function as endocrine disrupters and therefore, cellular level endocrine status may be distinguishable between chemicals, but whole animal consequences are similar, and (4) detrimental effects can be transgenerational.


To test the above hypotheses, we propose to test ethinyl estradiol, octylphenol, cadmium, atrazine and vinclozolin as model endocrine disrupting chemicals for developmental and reproductive impairment in full life-cycle, transgenerational experiments using Japanese medaka (Oryzias latipes) as the teleostean model. Fish will be exposed at different life stages (larval and sexual maturity) to determine susceptibility to endocrine imbalances. Four concentrations of each chemical will be utilized in order to detect concentration-effect responses and no effect thresholds. In addition to whole animal functional endpoints such as sex ratios and fecundity, endocrine function will be evaluated by assessing gonad morphology (histologically), vitellogenin induction, plasma hormone levels (estradiol and testosterone), pituitary function, gonadal steroidogenic capacity, hepatic P450 profiles and hepatic androgen and estrogen receptor population numbers and affinity.

Expected Results:

The major strength of the proposal lies in its approach to link individual endocrine responses to population-level effects in fish, specifically reproduction. In pursuing this goal, the proposal addresses several of EPA's designated research topics of interest including developing and validating test methods, studies on various mechanisms of action and how effects differ between them, an emphasis on the life stage of exposure as a susceptibility factor, insight into the role of hormones in sexual differentiation as well as, identification and validation of measurement endpoints indicative of population level effects. In addition to the above, the proposal addresses the unknowns associated with establishing threshold concentrations and transgenerational effects of endocrine disrupters.

Publications and Presentations:

Publications have been submitted on this project: View all 20 publications for this project

Journal Articles:

Journal Articles have been submitted on this project: View all 7 journal articles for this project

Supplemental Keywords:

water, stressors, hormone, biology, MS, Region IV., RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Toxics, Geographic Area, Environmental Chemistry, Health Risk Assessment, pesticides, State, Endocrine Disruptors - Environmental Exposure & Risk, endocrine disruptors, Risk Assessments, Biochemistry, Physical Processes, Biology, Endocrine Disruptors - Human Health, fish, predictors of reproductive toxicity, testosterone, endocrine disrupting chemicals, exposure, Japanese medaka, altered sexual development, plasma hormone levels, Mississippi (MS), atrazine, cellular level endocrine status, estrogen receptors, gonad morphology, transgenerational model, epidemiologic studies, exposure assessment, human health risk, animal reporductive impairment

Progress and Final Reports:

  • 1999 Progress Report
  • 2000 Progress Report
  • Final