2006 Progress Report: The Environmental Occurrence, Fate, and Ecotoxicity of Selective Serotonin Reuptake Inhibitors (SSRIs) in Aquatic Environments

EPA 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.
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, 2005 through August 31, 2006
Project Amount: $522,892
RFA: Drinking Water (2000) RFA Text |  Recipients Lists
Research Category: Drinking Water , Water Quality , Water


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. Selective serotonin reuptake inhibitors (SSRIs) are among the most commonly prescribed drugs. They are hormonally active and low concentrations have been shown to affect aquatic organisms and evidence indicates 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 pose the greatest risk to become contaminants in aquatic ecosystems and their persistence in aquatic environments. Routine sampling of a wastewater treatment plant (Starkville, Mississippi) 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 developmental effects on mosquitofish Gambusia affinis and the amphibians Xenopus laevis and Hyla chrysoscelis, will help characterize their effects on key components of aquatic ecosystems.

The primary objectives of this investigation 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 SSRIs and their major environmental metabolites to C. dubia; and (4) determine the developmental effects of chronic SSRI exposure to the mosquitofish and two amphibian species.

Progress Summary:

Environmental Monitoring

The five SSRIs (citalopram, fluoxetine, fluvoxamine, paroxotine, and sertraline) and their two degradation products (norfluoxetine and norsertraline) in water (downstream, upstream, influent, and effluent) and downstream sediment samples were monitored in environmental samples collected over an entire year, between April 2005 and March 2006. The order of detection frequency of the SSRIs (and degradation products) is as follows: sertraline (88%) > citalopram (50%) > fluoxetine (48%) > norfluoxetine (15%) > norsertraline (10%) > paroxetine = fluvoxamine (2%), and detection ranges (ng/L) were as follows: citalopram, 5.7 – 63.7; fluoxetine, 5.6 – 48.0; fluvoxamine, 3.7; paroxetine, 1.6; sertraline, 1.1 – 34.9; norfluoxetine, 3.2 – 31.7; and norsertraline, 12.5 – 61.9. As can be seen, citalopram, fluoxetine, and sertraline were the most detected SSRIs in water samples. Influent samples had the highest detection frequency of 51 percent over seven target compounds, followed by effluent of 36 percent, downstream of 20 percent, and upstream of 18 percent. For sediment samples, citalopram was detected in all samples collected ranging from 0.40-2.88 ng/g. Sertraline also was detected in many samples ranging from 0.09-0.67 ng/g, which is a lower concentration than citalopram. Fluoxetine was detected at a concentration of 1.26 ng/g in only one sample. As a result, the compounds determined to be most persistent in laboratory investigations (citalopram, fluoxetine, sertraline) were most frequently found in water and sediment environmental samples.

Toxicological Effects

For this reporting period, we conducted an additional laboratory exposure to investigate the effects of fluoxetine and sertraline on tadpole development in the African clawed frog, X. laevis. Tadpoles were exposed continuously from 1 day posthatch through metamorphosis to low concentrations of fluoxetine and sertraline (0, 0.1, 1, and 10 μg/L in FETAX solution—nominal concentrations). Exposures were conducted in glass aquaria (n = 30 tadpoles/aquaria) containing 10 L of exposure water under static renewal conditions, with a 75 percent water change every 3 days. The endpoints measured were mortality, incidence of malformations, abnormal behavior, and growth measured as dry mass at regular intervals and at metamorphosis. Developmental stages were tracked, as was the overall time to complete tail resorption (metamorphic climax). Tadpoles were sampled and frozen for evaluation of bioaccumulation, thyroid hormone levels, and corticosterone levels (ongoing), and exposure water was sampled to track actual exposure concentrations and metabolite formation. Significant reductions in dry mass at metamorphosis were observed in X. laevis exposed to fluoxetine and sertraline at 1 and 0.1 μg/L, respectively. Thus far, there are no significant differences among treatments for the other endpoints, including time to metamorphosis and malformations.

Future Activities:

Fish tissues from the chronic exposures conducted in 2003-2004 have been embedded, sectioned, and stained. Initial screening has revealed a range of developmental stages in the gonad tissues of these fish. Further histological examination will determine if external morphological indicators of delayed sexual maturity correlate with similar delays in gonad maturation.

Measurements of thyroid hormones and corticosteroids in tadpoles and metamorphs from additional fluoxetine and sertraline exposures with X. laevis currently are underway.

Journal Articles on this Report : 3 Displayed | Download in RIS Format

Other project views: All 44 publications 11 publications in selected types All 9 journal articles
Type Citation Project Document Sources
Journal Article Henry TB, Black MC. Mixture and single-substance acute toxicity of selective serotonin reuptake inhibitors in Ceriodaphnia dubia. Environmental Toxicology and Chemistry 2007;26(8):1751-1755. R829006 (2006)
R829006 (Final)
  • Abstract from PubMed
  • Journal Article Kwon J-W, Armbrust KL. Laboratory persistence and fate of fluoxetine in aquatic environments. Environmental Toxicology and Chemistry 2006;25(10):2561-2568. R829006 (2006)
    R829006 (Final)
  • Abstract from PubMed
  • Journal Article Kwon J-W, Armbrust KL. Aqueous solubility, n-octanol-water partition coefficient, and sorption of five selective serotonin reuptake inhibitors to sediments and soils. Bulletin of Environmental Contamination and Toxicology 2008;81(2):128-135. R829006 (2006)
  • Abstract from PubMed
  • Supplemental Keywords:

    pharmaceuticals, aquatic persistence, reproductive toxicity, developmental toxicity, thyroid, corticosterone,, RFA, Scientific Discipline, Waste, Water, Ecosystem Protection/Environmental Exposure & Risk, Ecology, Aquatic Ecosystems & Estuarine Research, Environmental Chemistry, Chemistry, Aquatic Ecosystem, Fate & Transport, Environmental Microbiology, Biochemistry, Ecology and Ecosystems, Drinking Water, ceriodaphnia dubia, fate and transport, pharmaceuticals, aquatic organisms, other - risk assessment, selective serotonin reuptake inhibitors (SSRIs), impact of pharmaceuticals, aquatic persistence, aquatic ecosystems, gambusia holbrooki

    Relevant Websites:

    http://www.mscl.msstate.edu Exit
    http://www.uga.edu/publichealth/ehs Exit
    http://www.clu-in.org/conf/tio/ppcp3/ Exit

    Progress and Final Reports:

    Original Abstract
  • 2002 Progress Report
  • 2003 Progress Report
  • 2004 Progress Report
  • 2005 Progress Report
  • Final Report