Environmental Risk Assessment of Paroxetine
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- 作者：Virginia L. Cunningham ; David J. C. Constable ; and Robert E. Hannah
- 刊名：Environmental Science & Technology
- 出版年：2004
- 出版时间：June 15, 2004
- 年：2004
- 卷：38
- 期：12
- 页码：3351 - 3359
- 全文大小：142K
- 年卷期：v.38,no.12(June 15, 2004)
- ISSN：1520-5851
文摘
Paroxetine hydrochloride hemihydrate (the activeingredient in Paxil) is a pharmaceutical compound usedfor the treatment of depression, social anxiety disorder,obsessive compulsive disorder, panic disorder, andgeneralized anxiety disorder. Paroxetine (PA) is extensivelymetabolized in humans, with about 97% of the parentcompound being excreted as metabolites through the urineand feces of patients. Therefore PA and metaboliteshave the potential to be discharged into wastewatertreatment systems after therapeutic use. PA and its majorhuman metabolite (PM) were investigated using studiesdesigned to describe physical/chemical characteristics anddetermine their fate and effects in the aquatic environment.A significant portion of the PM entering a wastewatertreatment plant would be expected to biodegrade giventhe higher activated sludge solids concentrations presentin a typical wastewater treatment plant. The potentialfor direct photolysis of PM is also possible based on photolysisresults for PA itself. These results provide strong supportfor expecting that PA and PM residuals will not persistin the aquatic environment after discharge from a wastewatertreatment facility. This conclusion is also supported bythe results of a USGS monitoring study, where no PM wasdetected in any of the samples at the 260 ng/L reportinglimit. The results presented here also demonstrate theimportance of understanding the human metabolism of apharmaceutical so that the appropriate molecule(s) is usedfor fate and effects studies. In addition to the PA fatestudies, PM was investigated using studies designed todetermine potential environmental effects and a predictedno effect level (PNEC). The average measured activatedsludge 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. ThePNEC for PM was calculated to be 35.0 
g/L. Fate data werethen used in a new watershed-based environmental riskassessment model, PhATE, to predict environmentalconcentrations (PECs). Comparison of the calculated PECswith the PNEC allows an assessment of potentialenvironmental risk. Within the 1-99% of stream segmentsin the PhATE model, PEC values ranged from 0.003 to100 ng/L. The risk assessment PEC/PNEC ratios rangedfrom ~3 × 10-8 to ~3 × 10-3, indicating a wide marginof safety, since a PEC/PNEC ratio < 1 is generally consideredto represent a low risk to the environment. In addition,Microtox studies carried out on PM biodegradationbyproducts indicated no detectable residual toxicity. Anycompounds in the environment as a result of thebiodegradation of PM should be innocuous polar byproductsthat should not exert any toxic effects.
g/L. Fate data werethen used in a new watershed-based environmental riskassessment model, PhATE, to predict environmentalconcentrations (PECs). Comparison of the calculated PECswith the PNEC allows an assessment of potentialenvironmental risk. Within the 1-99% of stream segmentsin the PhATE model, PEC values ranged from 0.003 to100 ng/L. The risk assessment PEC/PNEC ratios rangedfrom ~3 × 10-8 to ~3 × 10-3, indicating a wide marginof safety, since a PEC/PNEC ratio < 1 is generally consideredto represent a low risk to the environment. In addition,Microtox studies carried out on PM biodegradationbyproducts indicated no detectable residual toxicity. Anycompounds in the environment as a result of thebiodegradation of PM should be innocuous polar byproductsthat should not exert any toxic effects.