2002 Progress Report: The Environmental Occurrence, Fate, and Ecotoxicity of Selective Serotonin Reuptake Inhibitors (SSRIs) in Aquatic EnvironmentsEPA Grant Number: R829006
Title: The Environmental Occurrence, Fate, and Ecotoxicity of Selective Serotonin Reuptake Inhibitors (SSRIs) in Aquatic Environments
Investigators: Black, Marsha C. , Armbrust, Kevin L. , Henry, Theodore B. , Kwon, Jeong-Wook
Current Investigators: Black, Marsha C. , Armbrust, Kevin L.
Institution: University of Georgia , Mississippi State University - Main Campus
Current Institution: University of Georgia
EPA Project Officer: Page, Angela
Project Period: September 1, 2001 through August 31, 2004 (Extended to April 30, 2007)
Project Period Covered by this Report: September 1, 2001 through August 31, 2002
Project Amount: $522,892
RFA: Drinking Water (2000) RFA Text | Recipients Lists
Research Category: Drinking Water , Water Quality , Water
The objectives of this research project are to: (1) determine the environmental fate of Prozac (fluoxetine), Luvox (fluvoxamine), Paxil (paroxetine), Zoloft (sertraline), and Celexa (citalopram) in laboratory studies similar to those used for pesticide registration; (2) determine their occurrence in raw wastewater, treated effluent, and downstream receiving waters; (3) determine the acute and chronic toxicity of the five selective serotonin reuptake inhibitors (SSRIs) and their major environmental metabolites to Ceriodaphnia dubia; and (4) determine the reproductive effects of chronic SSRI exposure to the mosquitofish, Gambusia holbrooki.
Pharmaceutical chemicals can enter aquatic environments after their prescribed use and lead to negative effects on aquatic organisms. For most pharmaceutical chemicals, the environmental fate and ecotoxicological characteristics are unknown. Of particular concern are drugs that are hormonally active because disruption of physiological processes in aquatic organisms can occur at low environmental concentrations. SSRIs are among the most commonly prescribed drugs. They are hormonally active, low concentrations have been shown to affect aquatic organisms, and evidence indicates that they can be present in effluents from wastewater treatment plants. This project will characterize the occurrence, environmental fate, and ecotoxicity of five SSRI drugs (Fluoxetine, Fluvoxamine, Paroxetine, Citalopram, and Sertraline) and their relevant metabolites. Investigations on the environmental chemistry of these five compounds will be used to identify the specific compounds that are more likely to become contaminants in aquatic ecosystems and environments. Routine sampling of a wastewater treatment plant (Peachtree City, GA), combined with market information on the numbers of prescriptions for specific SSRIs, will be used to gauge the potential environmental exposure of specific compounds. Acute and chronic toxicity testing with Ceriodaphnia dubia, followed by determination of long-term reproductive effects on mosquitofish, will help characterize their effects on key components of aquatic ecosystems.
During our investigation, we conducted analyses of SSRI chemicals extracted from tablets as their salts showed high-water solubilities and octanol-water partition coefficients (Kows). Solubilities ranged from 3,022-15,460 mg/L, and Kows ranged from 1.12-1.39. Fluoxetine was relatively resistant to hydrolysis and photolysis at all pH ranges, and degradation generally was less than 10 percent over a 10-day period. Due to the very low degradation rate, degradation products were not detected. For Paroxetine, degradation by hydrolysis could not be detected; however, Paroxetine was completely degraded within 4 days after exposure to simulated sunlight. The photolysis of Paroxetine was accelerated by increasing pH. Two degradation products were detected. Degradation product I was not stable and the highest concentrations occurred at 12-18 hours of treatment at all pH values. Degradation product II increased through the 7-day experiment and appeared resistant to further photodegradation. The UV spectra of the two degradation products of Paroxetine were consistent with their measured photostability.
Results of our tests with Ceriodaphnia dubia have determined the range of concentrations that lead to acute and chronic toxicity. Acute toxicity (48-hour LC50) was between 0.1 and 5 mg/L for all compounds. Sertraline was most toxic, followed by Fluoxetine, Fluvoxamine, Paroxetine, and Citalopram in order of decreasing toxicity. At SSRI concentrations that were not lethal to C. dubia, reproduction was reduced during 7-day chronic tests. Further refinement and confirmation of the acute and chronic toxicity of the five SSRIs are underway. From experiments with C. dubia, two SSRIs have been selected for use in chronic exposure experiments with mosquitofish. Initial experiments with mosquitofish larvae indicate that acute toxicity of Fluoxetine occurs at similar concentrations as observed for C. dubia.
Future activities include experiments determining the physicochemical properties of the five SSRIs and fate characterization for all compounds (to be completed during Year 2). All acute and chronic toxicity tests with C. dubia should be completed during Year 2, and the mesocosm exposures with mosquitofish should be completed in Year 3. Current work with mosquitofish is focused on identifying exposure concentrations to be used in the long-term mesocosm studies. Identification of SSRI compounds in wastewater effluents, coupled with acute and chronic toxicity determinations, will be conducted along with concomitant surveys of SSRI drugs prescribed in Peachtree City. These data will be analyzed in an attempt to correlate the amounts of SSRI drugs prescribed with their appearance in wastewaters.