title: Environmental risk assessment of paroxetine.
abstract: Paroxetine hydrochloride hemihydrate (the active ingredient in Paxil) is a pharmaceutical compound used for the treatment of depression, social anxiety disorder, obsessive compulsive disorder, panic disorder, and generalized anxiety disorder. Paroxetine (PA) is extensively metabolized in humans, with about 97% of the parent compound being excreted as metabolites through the urine and feces of patients. Therefore PA and metabolites have the potential to be discharged into wastewater treatment systems after therapeutic use. PA and its major human metabolite (PM) were investigated using studies designed to describe physical/chemical characteristics and determine their fate and effects in the aquatic environment. A significant portion of the PM entering a wastewater treatment plant would be expected to biodegrade given the higher activated sludge solids concentrations present in a typical wastewater treatment plant. The potential for direct photolysis of PM is also possible based on photolysis results for PA itself. These results provide strong support for expecting that PA and PM residuals will not persist in the aquatic environment after discharge from a wastewater treatment facility. This conclusion is also supported by the results of a USGS monitoring study, where no PM was detected in any of the samples at the 260 ng/L reporting limit. The results presented here also demonstrate the importance of understanding the human metabolism of a pharmaceutical so that the appropriate molecule(s) is used for fate and effects studies. In addition to the PA fate studies, PM was investigated using studies designed to determine potential environmental effects and a predicted no effect level (PNEC). The average measured activated sludge respiration inhibition value (EC50) for PM was 82 mg/L. The measured Microtox EC50 value was 33.0 mg/L, while the Daphnia magna EC50 value was 35.0 mg/L. The PNEC for PM was calculated to be 35.0 microg/L. Fate data were then used in a new watershed-based environmental risk assessment model, PhATE, to predict environmental concentrations (PECs). Comparison of the calculated PECs with the PNEC allows an assessment of potential environmental risk. Within the 1-99% of stream segments in the PhATE model, PEC values ranged from 0.003 to 100 ng/L. The risk assessment PEC/PNEC ratios ranged from approximately 3 x 10(-8) to approximately 3 x 10(-3), indicating a wide margin of safety, since a PEC/PNEC ratio <1 is generally considered to represent a low risk to the environment. In addition, Microtox studies carried out on PM biodegradation byproducts indicated no detectable residual toxicity. Any compounds in the environment as a result of the biodegradation of PM should be innocuous polar byproducts that should not exert any toxic effects.
authors.affiliation: Corporate Environment, Health and Safety, GlaxoSmithKline, 2200 Renaissance Boulevard, Suite 105, King of Prussia, Pennsylvania 19406, USA. virginia.l.cunningham@gsk.com
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Cunningham
authors.forename: David J C
authors.initials: DJ
authors.lastname: Constable
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hannah
mesh_terms: D000818:Animals; D001673:Biodegradation, Environmental; D003621:Daphnia; D007928:Lethal Dose 50; D017374:Paroxetine / Q000378:metabolism / Q000633:toxicity*; D010777:Photochemistry; D018570:Risk Assessment; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism / Q000633:toxicity*; D012722:Sewage / Q000382:microbiology; D014733:Vibrio; D014865:Waste Disposal, Fluid / Q000379:methods*
chemical_list: D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D012722:Sewage