Document Type : ORIGINAL RESEARCH ARTICLE

Authors

1 Department of Biological and Environmental Sciences, University of Tennessee at Chattanooga, 215 Holt Hall, 615 McCallie Avenue, Chattanooga, TN 37403, USA

2 Department of Environment and Geography, 252 Wallace, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada

Abstract

Widespread use of pharmaceuticals has resulted in mixture concentrations ranging from mg/L in effluent to µg/L concentrations in surface water. In a 2008 study, 13 pharmaceuticals, ranging in amounts from 0.0028 to 0.1757 µg/l, were identified in the Tennessee River, USA and its tributaries. In order to address the need for risk assessment of environmentally relevant pharmaceutical mixtures, Daphnia magna 21-d life cycle tests were performed on a mixture of 11 of the 13 pharmaceuticals as well as on the individual components of the mixture. Mixture exposures were based on the same initial ratios of individual compounds, up to 1000x the initial mixture concentrationsThe endpoints of mortality, time to first brood, size, and fecundity were the assessed.  The LOEC of the 11- pharmaceutical mixture was determined to be 100x greater than the measured mixture concentration detected in the Tennessee River, with the NOEC being 75x that of the measured mixture.  Single concentrations of pharmaceuticals within the mixture up to the 100x LOEC were not statistically different from control for any of the assessed endpoints.  Thus, no single pharmaceutical was deemed predominately responsible for the mixture toxicity at the concentrations tested. While mixtures of pharmaceuticals are common in many systems, based on the findings of the present study, they may not pose a significant acute or chronic hazard to aquatic invertebrates at current concentrations.

Keywords

Al-Ahmad, A.; Daschner, F.D.; Kummerer, K., (1999). Biodegradability of cefotiam, ciprofloxacin, meropenem, penicillin G, and sulfamethoxazole and inhibition of waste water bacteria. Arch. Environ. Contam. Toxicol., (37): 158-163 (6 pages).
American Society for Testing, M., (2002). Standard guide for conducting Daphnia magna life-cycle toxicity test (E 1193-97) In: Annual book of ASTM standards West Conshohocken PA: ATSM International, 430-447 (18 pages).
Ashton, D.; Hilton, M.; Thomas, K.V., (2004). Investigating the environmental transport of human pharmaceuticals to streams in the United Kingdom. Sci. Total Environ., (333): 167-184 (18 pages).
Brooks, B.W.; Foran, C.M.; Richards, S.M.; Weston, J.; Turner, P.K.; Stanley, J. K.; Solomon, K. R.; Slattery, M.; La Point, T.W., (2003). Aquatic ecotoxicology of fluoxetine. Toxicol. Letters, (142): 169-183 (15 pages).
Buser, H.R.; Muller, M.D.; Theobald, N., (1998). Occurrence of the pharmaceutical drug clofibric acid and the herbicide mecoprop in various Swiss lakes and in the North Sea. Environ. Sci. Technol., (32): 188-192 (5 pages).
Cahill, J. D.; Furlong, E.T.; Burkhardt, M.R.; Kolpin, D.; Anderson, L.G., (2004). Determination of pharmaceutical compounds in surface- and ground-water samples by solid-phase extraction and high-performance liquid chromatography-electrospray ionization mass spectrometry. J. Chromatogr., A (1041): 171- 180 (10 pages).
Castiglioni, S.; Bagnati, R.; Fanelli, R.; Pomati, F.; Calamari, D.; Zuccato, E., (2006). Removal of pharmaceuticals in sewage treatment plants in Italy. Environ. Sci. Technol., (40): 357-363 (7 pages).
Christensen, A.M.; Faaborg-Andersen, S.; Ingerslev, F.; Baun, A., (2007). Mixture and single-substance toxicity of selective serotonin reuptake inhibitors toward algae and crustaceans. Environ. Toxicol. Chem., (26): 85-91 (7 pages).
Cleuvers, M., (2003). Aquatic ecotoxicity of pharmaceuticals including the assessment of combination effects. Toxicol. Letters, (142): 185-194 (10 pages).
Cleuvers, M., (2008). Chronic mixture toxicity of pharmaceuticals to Daphnia - the example of non-steroidal anti-infammatory drugs. In: Pharmaceuticals in the Environment. Sources Fate Effects and Risk. Kummerer, K. ed. Berlin, Heidelberg: Springer, 277-284 (8 pages).
Conley, J. M.; Symes, S. J.; Schorr, M. S.; Richards, S.M., (2008). Spatial and temporal analysis of pharmaceutical concentrations in the upper Tennessee River basin. Chemosphere, (73): 1178-1187 (10 pages).
Cunningham, V.L., (2008). Special characteristics of pharmaceuticals related to environmental fate. In: Pharmaceuticals in the Environment. Sources Fate Effects and Risk Kummerer, K. ed. Berlin Heidelberg: Springer, 23-34 (12 pages).
Daughton, C.G.; Ternes, T.A., (1999). Pharmaceuticals and personal care products in the environment: Agents of subtle change. Environ. Health Perspect., (107): 907-938 (32 pages).
Dussault, E.B.; Balakrishnan, V. K.; Sverko, E.; Solomon, K.R.; Sibley, P. K., (2008). Toxicity of human pharmaceuticals and personal care products to benthic invertebrates. Environ. Toxicol. Chem., (27): 425-432 (8 pages).
EMEA., (2003). Note for guidance on environmental risk assessment of medicinal products for human use. CPMP/ SWP/44447/00. 
FDA., (1998). Guidance for industry-Environmental assessment of human drugs and biologics applications, Revision1. FDA ed. Rockville: FDA Center for Drug Evaluation and Research.
Fent, K.; Weston, A.A.; Caminada, D., (2006). Ecotoxicology of human pharmaceuticals. Aquat. Toxicol., (76): 122-159 (38 pages).
Ferrari, B.; Paxeus, N.; Lo Giudice, R.; Pollio, A.; Garric, J., (2003). Ecotoxicological impact of pharmaceuticals found in treated wastewaters: study of carbamazepine, clofibric acid, and diclofenac. Ecotoxicol. Environ. Saf., (56): 450-450 (1 pages).
Flaherty, C. M.; Dodson, S. I., (2005). Effects of pharmaceuticals on Daphnia survival, growth, and reproduction. Chemosphere, (61): 200-207 (8 pages).
Glassmeyer, S.T.; Furlong, E.T.; Kolpin, D.W.; Cahill, J.D.; Zaugg, S. D.; Werner, S. L.; Meyer, M.T.; Kryak, D. D., (2005). Transport of  chemical and microbial compounds from known wastewater discharges: Potential for use as indicators of human fecal contamination. Environ. Sci. Technol., (39): 5157-5169 (13 pages).
Grung, M.; Kallqvist, T.; Sakshaug, S.; Skurtveit, S.; Thomas, K.V., (2008). Environmental assessment of Norwegian priority pharmaceuticals based on the EMEA guideline. Ecotoxicol. Environ. Saf., (71): 328-340 (13 pages).
Halling-Sorensen, B.; Lutzhoft, H. C. H.; Andersen, H. R.; Ingerslev, F., (2000). Environmental risk assessment of antibiotics: comparison of mecillinam, trimethoprim and ciprofloxacin. J. Antimicrobial Chemotherapy, (46): 53-58 (6 pages).
Han, G. H.; Hur, H. G.; Kim, S. D., (2006). Ecotoxicological risk of pharmaceuticals from wastewater treatment plants in Korea: Occurrence and toxicity to Daphnia magna. Environ. Toxicol. Chem., (25): 265-271 (7 pages).
Henry, T. B.; Kwon, J. W.; Armbrust, K. L.; Black, M. C., (2004). Acute and chronic toxicity of five selective serotonin reuptake inhibitors in Ceriodaphnia dubia. Environ. Toxicol. Chem., (23): 2229-2233 (5 pages).
Henschel, K. P.; Wenzel, A.; Diedrich, M.; Fliedner, A., (1997). Environmental hazard assessment of pharmaceuticals. Regul.Toxicol. and Pharmacol., (25): 220-225 (6 pages).
Isidori, M.; Lavorgna, M.; Nardelli, A.; Pascarella, L.; Parrella, A., (2005). Toxic and genotoxic evaluation of six antibiotics on nontarget organisms. Sci. Total Environ., (346): 87-98 (12 pages).
Kaiser Family, F., (2011). 50 state comparison: retail prescription drugs filled at pharmacies (per capita). In: http://www.statehealthfacts.org/, p. 50 state comparison: retail prescription drugs filled at pharmacies (per capita).
Kim, Y.; Choi, K.; Jung, J. Y.; Park, S.; Kim, P. G.; Park, J., (2007). Aquatic toxicity of acetaminophen, carbamazepine, cimetidine, diltiazem and six major sulfonamides, and their potential ecological risks in Korea. Environ. Int., (33): 370-375 (6 pages).
Kolpin, D. W.; Furlong, E. T.; Meyer, M. T.; Thurman, E. M.; Zaugg, S. D.; Barber, L. B.; Buxton, H. T., (2002). Pharmaceuticals, hormones, and other organic wastewater contaminants in US streams, 1999-2000: A national reconnaissance. Environ. Sci. Technol., (36): 1202-1211 (10 pages).
Kuhn, R.; Pattard, M.; Pernak, K. D.; Winter, A., (1989). Results of the harmful effects of water pollutants to daphnia-magna in the 21 day reproduction test. Water Res., (23): 501-510 (10 pages).
Kummerer, K., (2001). Drugs in the environment: emission of drugs, diagnostic aids and disinfectants into wastewater by hospitals in relation to other sources - a review. Chemosphere, (45): 957-969 (13 pages).
Lee, H. B.; Peart, T. E.; Svoboda, M. L.; Backus, S., (2009). Occurrence and fate of rosuvastatin, rosuvastatin lactone, and atorvastatin in Canadian sewage and surface water samples. Chemosphere, (77): 1285-1291 (7 pages).
Lopes, C.; Charles, S.; Vollat, B.; Garric, J., (2009). Toxicity of ivermectin on cladocerans: comparison of toxic effects on Daphnia and Ceriodaphnia species. Environ. Toxicol. Chem., (28): 2160-2166 (7 pages).
Lurling, M.; Sargant, E.; Roessink, I., (2006). Life-history consequences for Daphnia pulex exposed to pharmaceutical carbamazepine. Environ. Toxicol., (21): 172-180 (9 pages).
Metcalfe, C.D.; Miao, X.S.; Koenig, B.G.; Struger, J., (2003). Distribution of acidic and neutral drugs in surface waters near sewage treatment plants in the lower Great Lakes, Canada. Environ. Toxicol. Chem., (22): 2881-2889 (9 pages).
Minagh, E.; Hernan, R.; O’Rourke, K.; Lyng, F. M.; Davoren, M., (2009). Aquatic ecotoxicity of the selective serotonin reuptake inhibitor sertraline hydrochloride in a battery of freshwater test species. Ecotoxicol. Environ. Saf., (72): 434-440 (7 pages).
Olmstead, A.; LeBlanc, G., (2005). Toxicity assessment of environmentally relevant pollutant mixtures using a heuristic model. Integrated Environmental Assessment and Management, (1): 114-122 (9 pages).
Park, S.; Choi, K., (2008). Hazard assessment of commonly used agricultural antibiotics on aquatic ecosystems. Ecotoxicol., (17): 526-538 (13 pages).
Pery, A. R. R.; Gust, M.; Vollat, B.; Mons, R.; Ramil, M.; Fink, G.; Ternes, T.; Garric, J., (2008). Fluoxetine effects assessment on the life cycle of aquatic invertebrates. Chemosphere, (73): 300-304 (5 pages).
Phillips, M.M.; Dinglasan-Panlilio, M.J.A.; Mabury, S.A.; Solomon, K. R.; Sibley, P. K., (2010). Chronic toxicity of fluorotelomer acids to Daphnia magna and Chironomus dilutus. Environ. Toxicol. Chem., (29): 1123-1131 (9 pages).
Richards, S. M.; Cole, S. E., (2006). A toxicity and hazard assessment of fourteen pharmaceuticals to Xenopus laevis larvae. Ecotoxicol., (15): 647-656 (10 pages).
Robinson, A. A.; Belden, J. B.; Lydy, M. J., (2005). Toxicity of fluoroquinolone antibiotics to aquatic organisms. Environ. Toxicol. Chem., (24): 423-430 (8 pages).
Sadezky, A.; Loffler, D.; Schlusener, M.; Roig, B.; Ternes, T., (2010). Real situation: occurrence of the main investigated PPs in water bodies. In: Pharmaceuticals in the environment. Roig, B. ed. London: IWA Publishing, 31-40 (10 pages).
Sanderson, H.; Johnson, D. J.; Reitsma, T.; Brain, R. A.; Wilson, C. J.; Solomon, K. R., (2004). Ranking and prioritization of environmental risks of pharmaceuticals in surface waters. Regul. Toxicol. Pharmacol., (39): 158-183(26 pages).
Sanderson, H., Johnson, D. J., Wilson, C. J., Brain, R. A., Solomon, K. R., (2003) Probabilistic hazard assessment of environmentally occurring pharmaceuticals toxicity to fish, daphnids and algae by ECOSAR screening. Toxicol. Letters, (144): 383-395 (13 pages).
SAS. Institute Inc. (2008). SAS Version 9.2. Cary, North Carolina. 
Schloss, P., Williams, D.C., (1998) The serotonin transporter: A primary target for antidepressant drugs. J. Psychopharmacol., (12): 115-121 (7 pages).
Solomon, K., Brock, T., De Zwart, D., Dyer, S., Posthuma, L., Richards, S.; Sanderson, H.; Sibley, P.; Van den Brink, P., (2008). Conclusions. In: Extrapolation practice for ecotoxicological effect characterization of chemicals New York: CRC press, 257-267 (11 pages).
Stanley, J. K.; Ramirez, A. J.; Chambliss, C. K.; Brooks, B. W., (2007). Enantiospecific sublethal effects of the antidepressant fluoxetine to a model aquatic vertebrate and invertebrate. Chemosphere, (69): 9-16 (8 pages).
Stuer-Lauridsen, F.; Birkved, M.; Hansen, L. P.; Lutzhoft, H. C. H.; Halling-Sorensen, B., (2000). Environmental risk assessment of human pharmaceuticals in Denmark after normal therapeutic use. Chemosphere, (41): 1509-1509 (1 pages).
Ternes, T. A.; Andersen, H.; Gilberg, D.; Bonerz, M., (2002). Determination of estrogens in sludge and sediments by liquid extraction and GC/MS/MS. Anal. Chem., (74): 3498-3504 (7 pages).
Thomas, K.V.; Hilton, M. J., (2004). The occurrence of selected human pharmaceutical compounds in UK estuaries. Mar. Pollut. Bull., (49): 436-444 (9 pages).
Vieno, N.; Tuhkanen, T.; Kronberg, L., (2007). Elimination of pharmaceuticals in sewage treatment plants in Finland. Water Res., (41): 1001-1012 (12 pages).
Yamashita, N.; Yasojima, M.; Nakada, N.; Miyajima, K.; Komori, K.; Suzuki, Y.; Tanaka, H., (2006). Effects of antibacterial agents, levofloxacin and clarithromycin, on aquatic organisms. Water Sci. Technol., (53): 65-72 (8 pages).
Al-Ahmad, A.; Daschner, F.D.; Kummerer, K., (1999). Biodegradability of cefotiam, ciprofloxacin, meropenem, penicillin G, and sulfamethoxazole and inhibition of waste water bacteria.. Archives Environ. Contam. Toxicol.. 37 (2), 158-163

Letters to Editor

GJESM Journal welcomes letters to the editor for the post-publication discussions and corrections which allows debate post publication on its site, through the Letters to Editor. Letters pertaining to manuscript published in GJESM should be sent to the editorial office of GJESM within three months of either online publication or before printed publication, except for critiques of original research. Following points are to be considering before sending the letters (comments) to the editor.

[1] Letters that include statements of statistics, facts, research, or theories should include appropriate references, although more than three are discouraged.
[2] Letters that are personal attacks on an author rather than thoughtful criticism of the author’s ideas will not be considered for publication.
[3] Letters can be no more than 300 words in length.
[4] Letter writers should include a statement at the beginning of the letter stating that it is being submitted either for publication or not.
[5] Anonymous letters will not be considered.
[6] Letter writers must include their city and state of residence or work.
[7] Letters will be edited for clarity and length.

CAPTCHA Image