Metabolic Androgenization of Invertebrates by Endocrine-Disrupting ChemicalsEPA Grant Number: R826129
Title: Metabolic Androgenization of Invertebrates by Endocrine-Disrupting Chemicals
Investigators: LeBlanc, Gerald A.
Institution: North Carolina State University
EPA Project Officer: Klieforth, Barbara I
Project Period: October 1, 1997 through September 30, 2000 (Extended to September 30, 2002)
Project Amount: $406,155
RFA: Endocrine Disruptors (1997) RFA Text | Recipients Lists
Research Category: Economics and Decision Sciences , Health , Safer Chemicals , Endocrine Disruptors
Growing concern over the ability of xenobiotics to interfere with normal endocrine function has prompted extensive investigation into the endocrine-disrupting effects of chemicals in vertebrates. While invertebrates constitute over 95% of the known animal species, and maintain invaluable societal and ecological roles, little is known of the susceptibility of these organisms to endocrine-disruption. Preliminary studies in our laboratory have indicated that some environmental chemicals have the ability to alter hormone metabolism in invertebrates resulting in elevated levels of androgens (chemically-induced metabolic androgenization). The purpose of the proposed study is to definitively characterize the phenomenon of metabolic androgenization and elucidate the putative relationships among chemical exposure, metabolic androgenization, and toxicological consequences such as pseudohermaphrodism, developmental abnormalities, and reproductive impairment.
The first objective of the study will be to definitively characterize chemically-induced metabolic androgenization in a commonly used invertebrate toxicity test organism, the water flea (Daphnia magna) and an invertebrate species that has suffered significant environmental endocrine disruption, the mud snail (Nassarius obsoletus). This species has been shown to experience pseudohermaphrodism (imposex) due to environmental exposure to tributyltin. The ability of the chemicals, tributyltin, propiconazole, and 4-nonylphenol, to induce metabolic androgenization in the two species will be characterized. These chemicals were chosen because they are known or suspected to cause environmental endocrine disruption, and all have been shown in preliminary experiments to cause metabolic androgenization. Once the ability of these chemicals to androgenize the invertebrates has been characterized, experiments will be undertaken to evaluate possible endocrine-related toxicity associated with the chemicals. Included will be effects of the chemicals on endogenous androgen levels, development of secondary sex characteristic, imposex, parthenogenic reproduction, nutrient transfer to eggs, and sexual reproduction (Objective 2). Objective 3 will focus upon establishing causality between chemically-induced metabolic androgenization and the toxicological effects documented during the execution of Objective 2. This will be accomplished by exposing daphnids and snails to both androgenic and nonandrogenic steroids and evaluating whether androgen exposure mimics the toxicity caused by exposure to the endocrine-disrupting chemicals. Finally, the use of metabolic androgenization as a biomarker of endocrine disruption in invertebrates will be explored and validated (Objective 4).
Results from this program will provide a definitive evaluation of the susceptibility of invertebrates to endocrine disruption via perturbations in hormone homeostasis and will identify biomarkers of endocrine-related toxicity that could be routinely incorporated into standard laboratory and field toxicity evaluations.