Chemical Toxicity Distributions as a Novel Approach to Assess the Sensitivities of Common In Vivo and In Vitro Assays of Environmental Estrogenicity: A Case Study with ParabensEPA Grant Number: F07E60219
Title: Chemical Toxicity Distributions as a Novel Approach to Assess the Sensitivities of Common In Vivo and In Vitro Assays of Environmental Estrogenicity: A Case Study with Parabens
Investigators: Dobbins, Laura L.
Institution: Baylor University
EPA Project Officer: Zambrana, Jose
Project Period: September 1, 2007 through September 1, 2009
RFA: GRO Fellowships for Graduate Environmental Study (2007) RFA Text | Recipients Lists
Research Category: Ecological Assessment , Academic Fellowships , Fellowship - Ecotoxicology
Parabens represent a class of antimicrobial agents present in thousands of food, pharmaceutical and cosmetic products. Select parabens are known to reach aquatic systems through wastewater discharges. Whereas the potential aquatic hazards of parabens have been relatively understudied, these compounds also appear to possess estrogenic properties to fish. In this study, chemical toxicity distributions (CTDs), a probabilistic ecological hazard assessment approach for evaluating groups of compounds with limited environmental exposure data, will be employed to assess the relative sensitivities of common in vivo and in vitro assays of estrogen agonist activity. A group of six parabens and their common metabolite p-hydroxybenzoic acid will be evaluated using standardized toxicity assays and biomarkers of estrogenicity using in vivo and in vitro models. CTDs will further be employed to develop a novel aquatic hazard assessment of parabens for fish.
Acute and chronic toxicity of six parabens and p-hydroxybenzoic acid will be assessed using standard EPA protocols with Daphnia magna and Pimephales promelas. To evaluate estrogenicity of these compounds, adult male P. promelas studies will be performed with vitellogenin (VTG) induction utilized as a biomarker of estrogenicity. Paraben estrogen agonist activity will also be determined in vitro by VTG induction in hepatocyte cell cultures.
It is anticipated that parabens will elicit dose-dependent responses in both in vivo and in vitro models. Subsequently, this research project will: 1. identify the relative sensitivity of the most common in vitro and in vivo assays for estrogen agonist activity to freshwater fish; 2. broaden the knowledge of aquatic hazards of parabens found in wastewater discharges; and 3. evaluate the usefulness of CTDs in risk assessment of compounds that have limited environmental exposure data.