Presentation Abstract

Overview of ORD’s Aquatic Toxicology Research on Endocrine-Active Chemicals
Joseph E. Tietge
National Health and Environmental Effects Research Laboratory, Office of Research and Development,
U.S. Environmental Protection Agency,
Duluth, MN

Office of Research and Development laboratories are engaged in a variety of research projects with aquatic organisms that are relevant to the assessment of pharmaceuticals in the environment, specifically as they pertain to endocrine pathways. The broad objectives of these projects are to assess effects of chemicals on endocrine pathways in fish and amphibian species in laboratory studies and to evaluate exposure to endocrine-active chemicals in the environment using field studies.

There are three major approaches being used to reach these objectives. In the first approach, two short-term screening assays are being developed to identify chemicals that affect hormone (i.e., estrogen, androgen, and thyroid hormone) regulation and function using a variety of organismal, biochemical, and histological endpoints. One such assay utilizes the fathead minnow (Pimephales promelas) in a 21-day protocol to evaluate the effect of test chemicals on estrogen and androgen pathways, as determined by reproductive success, circulating sex steroid concentrations, gonadal histology, secondary sexual characteristics, and other biochemical endpoints. The basic protocol for this assay is complete, and validation studies are currently underway. The other screening assay utilizes the metamorphic phase of the African clawed frog (Xenopus laevis) in a 14-to-21-day assay to evaluate the effects of test chemicals on thyroid function. Metamorphosis is a thyroid hormone-dependent event, and perturbations of normal thyroid hormone homeostasis alter developmental rate as well as thyroid histology. This screening assay also is in the process of validation. In the second approach, partial and full life cycle tests are being developed to evaluate the effect of chemicals on reproductive and developmental endpoints in a fish, the Japanese medaka (Oryzias latipes), and in an amphibian (Xenopus tropicalis). The intent of this research is to determine if endocrine-disrupting chemicals result in transgenerational effects that are not detected in the preceding short-term screening assays. Furthermore, these tests, when fully developed and validated, may be used to better understand population level effects. In the third approach, selected endpoints that were developed in both the screening and testing protocols are being used in field studies wherein naive fish are exposed to surface water discharges, such as effluents emanating from confined animal feeding operations and municipal wastewater treatment plants. These studies demonstrate that androgenic and estrogenic activities can be detected in surface water discharges using well-defined methods. Taken together, these projects have advanced the basic understanding of endocrine disruption in aquatic organisms, help to meet Agency screening and testing requirements mandated through the Food Quality Protection and Safe Drinking Water Acts, and provide the Agency with tools to assess potential endocrine disruption in aquatic species in the environment.

Future activities will focus on the use of genomic, proteomic, and metabonomic endpoints in endocrine-disruption research. The objectives of applying these endpoints are to improve the diagnostic capabilities of the assays, abbreviate the screening assays by using early responding endpoints that are related to later outcomes, provide data that will aid in predictive modeling of endocrine disruption, and establish a molecular basis for interspecies extrapolation.

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