Abstract
Widespread detection of human pharmaceuticals in the environment, ranging between ng/L and mg/L levels in surface waters and effluents and ng/kg to mg/kg levels in aquatic and terrestrial organisms, has caused increased concern of potential ecological effects and hazards to aquatic species and fomented new investigations of potential effects of biosolids and effluents from wastewater treatment plants. Here, we critically review such recent research on the aquatic toxicity of human pharmaceuticals to aquatic organisms. Toxicity testing considerations are examined for differences in sensitivities among aquatic organisms and acute and chronic response thresholds. We further provide perspectives and recommendations, including integration of adverse outcome pathway approaches, during future ecotoxicological studies of human pharmaceuticals in the environment.
Keywords
- Pharmaceuticals And Personal Care Products (PPCP)
- WWTP Effluents
- Ankley
- Etidronic Acid
- Mode Of Action (MOA)
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Andersen L, Kinnberg K, Holbech H, Korsgaard B, Bjerregaard P (2004) Evaluation of a 40 day assay for testing endocrine disruptors: effects of an anti-estrogen and aromatase inhibitor on sex ratio and vitellogenin concentrations in juvenile zebrafish (Danio rerio). Fish Physiol Biochem 30:257–266
Andreozzi R, Caprio V, Ciniglia C, De Champdore M, Lo Giudice R, Marotta R, Zuccato E (2004) Antibiotics in the environment: occurrence in Italian STPs, fate, and preliminary assessment on algal toxicity of amoxicillin. Environ Sci Technol 38:6832–6838
Ankley DT, Kahl MD, Jensen KM, Hornung MW, Korte JJ, Makynen EA, Leino RL (2002) Evaluation of the aromatase inhibitor fadrozole in a short-term reproduction assay with the fathead minnow (Pimephales promelas). Toxicol Sci 67:121–130
Ankley DT, Jensen KM, Makynen EA, Kahl MD, Korte JJ, Hornung MW, Henry TR, Denny JS, Leino RL, Wilson VS, Cardon MC, Hartig PC, Gray LE (2003) Effects of the androgenic growth promoter 17-beta-trenbolone on fecundity and reproductive endocrinology of the fathead minnow. Environ Toxicol Chem 22:1350–1360
Ankley GT, Black MC, Hutchinson TH, Iguchi T (2005) A framework for assessing the hazard of pharmaceutical materials to aquatic species. In: Williams RT (ed) Human pharmaceuticals: assessing the impacts on aquatic ecosystems. SETAC, Pensacola, FL, pp 183–237
Ankley GT, Daston GP, Degitz SJ, Denslow ND, Hoke RA, Kennedy SW, Miracle AL, Perkins EJ, Snape J, Tillitt DE, Tyler CR, Versteeg D (2006) Toxicogenomics in regulatory ecotoxicology. Environ Sci Technol 40:4055–4065
Ankley GT, Brooks BW, Huggett DB, Sumpter JP (2007) Repeating history: pharmaceuticals in the environment. Environ Sci Technol 41:8211–8217
Ankley GT, Bennett RS, Erickson RJ, Hoff DJ, Horning MW, Johnson RD, Mount DR, Nichols JW, Russom CL, Schmieder PK, Serrano JA, Tietge JE, Villeneuve DL (2010) Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment. Environ Toxicol Chem 29:730–741
Anon (1993) Acute toxicity to bluegill (Lepomis macrochirus) of the test substance ketorolac tromethamine from Radian Corporation in a 96-hr static non-renewal test. AnaltiKEM Environmental Lab, Houston, USA (AnalytiKEM Test Number 01628)
Arcand-Hoy LD, Benson WH (2001) Toxic responses of the reproductive system. In: Schlenk D, Benson WH (eds) Target organ toxicity in marine and freshwater teleosts. Taylor & Francis, London
Auerbach SB, Lundberg JF, Hjorth S (1995) Differential inhibition of serotonin release by 5-HT and NA reuptake blockers after systemic administration. Neuropharmacology 34:89–96
Babich H, Borenfreund E (1987) In vitro cytotoxicity of organic pollutants to bluegill sunfish (BF-2) cells. Environ Res 42:229–237
Bach TJ, Lichtenthaler HK (1983) Inhibition by mevinolin of plant growth, sterol formation and pigment accumulation. Physiol Plant 59:50–60
Baldwin WS, Milam DL, Leblanc GA (1995) Physiological and biochemical perturbations in Daphnia magna following exposure to the model environmental estrogen diethylstilbestrol. Environ Toxicol Chem 14:945–952
Bantle JA, Burton DT, Dawson DA, Dumont JN, Finch RA, Fort DJ (1994) FETAX interlaboratory validation study: Phase II testing. Environ Toxicol Chem 13:1629–1637
Basset GJC, Quinlivam EP, Gregory JF, Hanson AD (2005) Folate synthesis and metabolism in plants and prospects for biofortification. Crop Sci 45:449–453
Belfroid A, Leonards P (1996) Effect of ethinyl oestradiol on the development of snails and amphibians. SETAC 17th Annual Meeting November 1996, Washington, DC, USA
Bell AM (2001) Effects of an endocrine disrupter on courtship and aggressive behavior of male three-spine stickleback, Gasteroseus aculeatus. Anim Behav 62:775–780
Berninger JP, Brooks BW (2010) Leveraging mammalian pharmaceutical toxicology and pharmacology data to predict chronic fish responses to pharmaceuticals. Toxicol Lett 193:69–78
Berninger JP, Du B, Connors KA, Eytcheson SA, Kolkmeier MA, Prosser KN, Valenti TW, Chambliss CK, Brooks BW (2011) Effects of the antihistamine diphenhydramine to select aquatic organisms. Environ Toxicol Chem 30:2065–2072
Bird SB, Gaspari RJ, Lee WJ, Dickson EW (2002) Diphenhydramine as a protective agent in rat model of acute, lethal organophosphate poisoning. Acad Emerg Med 9:1369–1372
Black MC, Connors DE, Rogers ED, Kwon J, Armbrust K (2009) Effects of fluoxetine and sertraline on growth and development of the African Clawed Frog (Xenopus laevis). In: Platform presentation at 30th annual Society of Environmental Toxicology and Chemistry. November 20–23
Brain RA, Cedergreen N (2008) Biomarkers in aquatic plants: selection and utility. Rev Environ Contam Toxicol 198:49–109
Brain RA, Johnson DJ, Richards SM, Sanderson H, Sibley PK, Solomon KR (2004a) Effects of 25 pharmaceutical compounds to Lemna gibba using a seven-day static-renewal test. Environ Toxicol Chem 23:371–382
Brain RA, Johnson DJ, Richards SM, Hanson ML, Sanderson H, Lam MW, Young C, Mabury SA, Sibley PK, Solomon KR (2004b) Microcosm evaluation of the effects of an eight pharmaceutical mixture to the aquatic macrophytes Lemna gibba and Myriophyllum sibricum. Aquat Toxicol 70:23–40
Brain RA, Reitsma TS, Lissemore LI, Bestari B-J, Sibley PK, Solomon KR (2006a) Herbicidal effects of statin pharmaceuticals in Lemna gibba. Environ Sci Technol 40:5116–5123
Brain RA, Sanderson H, Sibley PK, Solomon KR (2006b) Probabilistic ecological hazard assessment: evaluating pharmaceutical effects on aquatic higher plants as an example. Ecotoxicol Environ Saf 6:128–135
Brain RA, Ramirez AJ, Fulton BA, Chambliss CK, Brooks BW (2008a) Herbicidal effects of sulfamethoxazole in Lemna gibba: Using p-aminobenzoic acid as a biomarker of effect. Environ Sci Technol 42:8965–8970
Brain RA, Hanson ML, Solomon KR, Brooks BW (2008b) Aquatic plants exposed to pharmaceuticals: effects and risks. Rev Environ Contam Toxicol 192:67–115
Brambilla G, Civitareale C, Migliore L (1994) Experimental toxicity and analysis of bacitracin, flumequine and sulphadimethoxine in terrestrial and aquatic organisms as a predictive model for ecosystem damage. Qumica Analitica 13(Suppl):S73–S77
Breitholtz M, Bengtsson BE (2001) Oestrogens have no hormonal effect on the development and reproduction of the harpacticoid copepod Nitocra spinepes. Mar Pollut Bull 42:879–886
Breton R, Boxall A (2003) Pharmaceuticals and personal care products in the environment: regulatory drivers and research needs. QSAR Comb Sci 22:399–409
Bringmann G, Kuhn R (1982) Ergebnisse der Schadwirkung wassergefahrdender Stoffe gegen Daphnia magna in einem weiterentwickelten standardisierten Testverfahren. Z Wasser Abwasser Forsch 15(1):1–6
Bringolf RB, Heltsley RM, Newton TJ, Eads CB, Fraley SJ, Shea D, Cope WG (2010) Environmental occurrence and reproductive effects of the pharmaceutical fluoxetine in native freshwater mussels. Environ Toxicol Chem 29:1311–1318
Brooks BW, Foran CM, Richards SM, Weston J, Turner PK, Stanley JK, Solomon KR, Slattery M, La Point TW (2003a) Aquatic ecotoxicology of fluoxetine. Toxicol Lett 142:169–183
Brooks BW, Turner PK, Stanley JK, Weston JJ, Glidewell EA, Foran CM, Slattery M, La Point TW, Huggett DB (2003b) Waterborne and sediment toxicity of fluoxetine to select organisms. Chemosphere 52:135–142
Brooks BW, Richards SM, Weston J, Turner PK, Stanley JK, La Point TW, Brain R, Glidewell EA, Massengale ARD, Smith W, Blank CL, Solomon KR, Slattery M, Foran CM (2005) Aquatic ecotoxicology of fluoxetine: a review of recent research. In: Dietrich D, Webb S, Petry T (eds) Hot spot pollutants: pharmaceuticals in the environment. Academic/Elsevier, London, UK, pp 165–187
Brooks BW, Riley TM, Taylor RD (2006) Water quality of effluent-dominated stream ecosystems: ecotoxicological, hydrological, and management considerations. Hydrobiologia 556:365–379
Brooks BW, Ankley GT, Hobson JF, Lazorchak JM, Meyerhoff RD, Solomon KR (2008) Assessing the aquatic hazards of veterinary medicines. In: Crane M, Boxall A, Barrett K (Eds) Veterinary medicines in the environment. CRC/SETAC Press. pp 97–128
Brooks BW, Huggett DB, Boxall ABA (2009a) Pharmaceuticals and personal care products: research needs for the next decade. Environ Toxicol Chem 28:2469–2472
Brooks BW, Huggett DB, Brain RA, Ankley GT (2009b) Risk assessment considerations for veterinary medicines in aquatic systems. In: Henderson K, Coats J (eds) Veterinary pharmaceuticals in the environment. American Chemical Society, Washington DC, pp 205–223
Brown JN, Paxeus N, Forlin L, Larsson DGJ (2007) Variations in bioconcentration of human pharmaceuticals from sewage effluents into fish blood plasma. Environ Toxicol Pharmacol 24:267–274
Bruschweiler BJ, Wurgler FE, Fent K (1995) Cytotoxicity in vitro of organotin compounds to fish hepatoma cells PLHC-1 (Poeciliopsis lucida). Aquat Toxicol 32:143–160
Burton GA, Chapman PM, Smith EP (2002) Weight-of-evidence approaches for assessing ecosystem impairment. Human Ecol Risk Assess 8:1657–1673
Buttgereit F, Burmester GR, Simon LS (2001) Gastrointestinal toxic side effects of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2-specific inhibitors. Am J Med 110:13–19
Calleja MC, Personne G, Geladi P (1994) Comparative acute toxicity of the first 50 multicentre evaluation of in vitro cytotoxicity chemicals to aquatic non-vertebrates. Arch Environ Contam Toxicol 26:69–78
Caminada D, Escher C, Fent K (2006) Cytotoxicity of pharmaceuticals found in aquatic systems: comparison of PLHC-1 and RTG-2 fish cell lines. Aquat Toxicol 79:114–123
Carlsson G, Orn S, Larsson DGJ (2009) Effluent from bulk drug production is toxic to aquatic vertebrates. Environ Toxicol Chem 28:2656–2662
Chapman PM, McDonald BG, Lawrence GS (2002) Weight-of-evidence issues and frameworks for sediment quality (and other) assessments. Human Ecol Risk Assess 8:1489–1515
Christensen AM, 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
Chu S, Metcalfe CD (2007) Analysis of paroxetine, fluoxetine and norfluoxetine in fish tissues using pressurized liquid extraction, mixed mode solid phase extraction cleanup and liquid chromatography-tandem mass spectrometry. J Chromatogr A 1163:112–118
Clements S, Schreck CB (2007) Chronic administration of fluoxetine alter locomotor behavior, but does not potentiate the locomoter stimulating effects of CRH in juvenile Chinook salmon (Onchorhynchus tshawytscha). Comp Biochem Physiol A Mol Integr Physiol 147(1):43–49
Cleuvers M (2003) Aquatic ecotoxicity of pharmaceuticals including the assessment of combination effects. Toxicol Lett 142:185–194
Cleuvers M (2004) Mixture toxicity of the anti-inflammatory drugs diclofenac, ibuprofen, naproxen, and acetylsalicylic acid. Ecotoxicol Environ Saf 59:309–315
Cleuvers M (2005) Initial risk assessment for three β-blockers found in the aquatic environment. Chemosphere 59:199–205
Clotfelter ED, O’Hare EP, McNitt MM, Carpenter RE, Summers CH (2007) Serotonin decreases aggression via 5-HT1A receptors in the fighting fish Betta splendens. Pharmacol Biochem Behav 87(2):222–231
Clubbs RL, Brooks BW (2007) Daphnia magna responses to a vertebrate estrogen receptor agonist and an antagonist: a multigenerational study. Ecotoxicol Environ Saf 67:385–398
Coats JR, Metcalf RL, Lu P-Y, Brown DO, Williams JF, Hansen LG (1976) Model ecosystem evaluation of the environmental impacts of the veterinary drugs phenothiazine, sulfametazine, clopidol and diethylstibestrol. Environ Health Perspect 1:167–197
Collinge J, Pycock CJ, Taberner PV (1983) Studies on the interaction between cerebral 5-hydroxytryptamine and gamma-aminobutyric acid in the mode of action of diazepam in the rat. Br J Pharmacol 79:637–643
Conners DE, Rogers ED, Armbrust KL, Kwon J-W, Black MC (2009) Growth and development of tadpoles (Xenopus laevis) exposed to selective serotonin reuptake inhibitors, fluoxetine and sertraline, throughout metamorphosis. Environ Toxicol Chem 28:2671–2676
Corcoran J, Winter MJ, Tyler CR (2010) Pharmaceuticals in the aquatic environment: a critical review of the evidence for health effects in fish. Crit Rev Toxicol 40:287–304
Crane M, Watts C, Boucard T (2006) Chronic aquatic environmental risks from exposure to human pharmaceuticals. Sci Total Environ 367:23–41
Crespi EJ, Denver RJ (2004) Ontogeny of corticotrophin-releasing factor effects on locomotion and foraging in the Western spadefoot toad (Spea hammondii). Horm Behav 46:399–410
Cunningham VL, Constable DJC, Hannah RE (2004) Environmental risk assessment of paroxetine. Environ Sci Technol 38:3351–3359
Cunningham VL, Buzby M, Hutchinson T, Mastrocco F, Parke N, Roden N (2006) Effects of human pharmaceuticals on aquatic life: next steps. Environ Sci Technol 40:3457–3462
Czech P, Weber K, Dietrich DR (2001) Effects of endocrine modulating substances on reproduction in the hermaphroditic snail Lymnaea stagnalis L. Aquat Toxicol 53:103–114
Dahl U, Gorokhova E, Breitholtz M (2006) Application of growth-related sublethal endpoints in ecotoxicological assessments using a harpacticoid copepod. Aquat Toxicol 77:433–438
Daston GP, Gooch JW, Breslin WJ, Shuey DL, Nikiforov AI, Ficao TA, Gorsuch JW (1997) Environmental estorgens and reproductive health: a discussion of the human and environmental data. Reprod Toxicol 11:465–481
Daughton CG (2002) Environmental stewardship and drugs as pollutants. Lancet 360:1035–1036
Daughton CG, Brooks BW (2011) Active pharmaceuticals ingredients and aquatic organisms. In: Environmental contaminants in wildlife: interpreting tissue concentrations, 2nd edn. Meador J, Beyer N (eds) Taylor and Francis, pp 281–341
Daughton CG, Ternes TA (1999) Pharmaceuticals and personal care products in the environment: agents of subtle change? Environ Health Perspect 107:907–938
David A, Pancharata K (2009) Developmental anomalies induced by a non-selective COX inhibitor (ibuprofen) in zebrafish (Danio rerio). Environ Toxicol Pharmacol 27:390–395
De Lange HJ, Noordoven W, Murk AJ, Lurling M, Peeters ETHM (2006) Behavioural responses of Gammarus pulex (Crustacea, Amphipoda) to low concentrations of pharmaceuticals. Aquat Toxicol 78:209–216
De Liguoro M, Fioreto B, Poltronieri C, Gallina G (2009) The toxicity of sulfamethazine to Daphnia magna and its additivity to other veterinary sulfonamides and trimethoprim. Chemosphere 75:1519–1524
De Young DJ, Bantle JA, Hull MA, Burks SL (1996) Differences in the sensitivity to developmental toxicants as seen in Xenopus and Pimephales embryos. Bull Environ Contam Toxicol 56:143–150
DellaGreca M, Iesce MR, Isidori M, Nardelli A, Previtera L, Rubino M (2007) Phototransformation products of tamoxifen by sunlight in water. Toxicity of the drug and its derivatives on aquatic organisms. Chemosphere 67:1933–1939
DeLorenzo ME, Fleming J (2008) Individual and mixture effects of selected pharmaceuticals and personal care products on the marine phytoplankton species Dunaliella tertiolecta. Arch Environ Contam Toxicol 54:203–210
Denver RJ (1997) Proximate mechanisms of phenotypic plasticity in amphibian metamorphosis. Am Zool 37:172–184
Di Delupis GD, Macri A, Civitareale C, Migliore L (1992) Antibiotics of zootechnical use: effects of acute high and low dose contamination on Daphnia magna Straus. Aquat Toxicol 22:53–60
Dinchuk JE, Car BD, Focht RJ, Johnston JJ, Jaffee BD, Covington MB, Contel NR, Eng VM, Collins RJ, Czerniak PM, Gorry SA, Trzaskos JM (1995) Renal abnormalities and an altered inflammatory response in mice lacking cyclooxygenase II. Nature 378:406–409
Disch A, Hemmerlin A, Bach TJ, Rohmer M (1998) Mevalonate-derived isopentyl diphosphate is the biosynthetic precursor of ubiquinone prenyl side chain in tobacco BY-2 cells. Biochem J 331:615–621
Dobbins LL, Brain RA, Brooks BW (2008) Comparison of the sensitivities of common in vitro and in vivo assays of estrogenic activity: application of chemical toxicity distributions. Environ Toxicol Chem 27:2608–2616
Dobbins LL, Usenko S, Brain RA, Brooks BW (2009) Probabilistic ecological hazard assessment of parabens using Daphnia magna and Pimephales promelas. Environ Toxicol Chem 28:2744–2753
Dorne JLCM, Ragas AMJ, Frampton GK, Spurgeon DS, Lewis DF (2007) Trends in human risk assessment of pharmaceuticals. Anal Bioanal Chem 387:1167–1172
Dussault EB, Balakrishnan VK, Sverko E, Solomon KR, Sibley PK (2008) Toxicity of human pharmaceuticals and personal care products to benthic invertebrates. Environ Toxicol Chem 27:425–432
Dzialowski EM, Turner PK, Brooks BW (2006) Physiological and reproductive effects of beta adrenergic receptor antagonists in Daphnia magna. Arch Environ Contam Toxicol 50:503–510
Eguchi K, Nagase H, Ozawa M, Endoh YS, Goto K, Hirata K, Miyamoto K, Yoshimura H (2004) Evaluation of antimicrobial agents for veterinary use in the ecotoxicity test using microalgae. Chemosphere 57:1733–1738
Elvers KT, Wright SJL (1995) Antibacterial activity of the anti-inflammatory compounds ibuprofen. Lett Appl Microbiol 20:82–84
Emblidge JP, DeLorenzo ME (2006) Preliminary risk assessment of the lipid-regulating pharmaceutical clofibric acid, for three estuarine species. Environ Res 100:216–226
EMEA (1998) Note for guidance: environmental risk assessment of veterinary medicinal products other than GMO-containing and immunological products. EMEA, London (EMEA/CVMP/055/96)
EMEA (2005) Note for guidance on environmental risk assessment of medicinal products for human use, CMPC/SWP/4447/draft. The European Agency for the Evaluation of Medicinal Products (EMEA), London
EMEA (2006) Guideline on the environmental risk assessment of medicinal products for human use, EMEA/CHMP/4447/00. The European Agency for evaluation of medicinal products, London
Eravci M, Pinna G, Meinhold H, Baumgartner A (2000) Effects of pharmacological and nonpharmacological treatments of thyroid hormone metabolism and concentrations in rat brain. Endocrinology 141:1027–1040
Escher BI, Hermens JLM (2002) Modes of action in ecotoxicology: their role in body burdens, species sensitivity, QSARs, and mixture effects. Environ Sci Technol 36:4201–4217
Escher BI, Bramaz N, Eggen RIL, Richter M (2005) In vitro assessment of modes of toxic action of pharmaceuticals in aquatic life. Environ Sci Technol 39:3090–3100
European Union (2001) White Paper; Strategy for a future chemicals policy. COM 2001. Brussels
Faxon DP, Halperin JL, Creager MA, Gavras H, Schick EC, Ryan TJ (1981) Angiotensin inhibition in severe heart failure: acute central and limb hemodynamic effects of captopril with observations on sustained oral therapy. Am Heart J 101:548–556
FDA (1996) Retrospective review of ecotoxicity data submitted in environmental assessments. US Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Rockville, MD
FDA (1998) Evidence for industry for the submission of an environmental in human drug applications and supplements. US Food and Drug Administration, Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research, Rockville, MD
Fent K, Weston AA, Caminada D (2006) Ecotoxicology of human pharmaceuticals. Aquat Toxicol 76:122–159
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 55:359–370
Ferrari B, Mons R, Vollat B, Frayse B, Paxeus N, Lo Guidice R, Pollio A, Garric J (2004) Environmental risk assessment of six pharmaceuticals: are the current environmental risk assessment procedures sufficient for the protection of the aquatic environment? Environ Toxicol Chem 23:1344–1354
Fick J, Lindberg RH, Parkkonen J, Arvidsson B, Tysklind M, Larsson DGJ (2010) Therapeutic levels of levonorgestrel detected in blood plasma of fish: results from screening rainbow trout exposed to treated sewage effluents. Environ Sci Technol 44:2661–2666
Flippin JL, Huggett D, Foran CM (2007) Changes in the timing of reproduction following chronic exposure to ibuprofen in Japanese medaka (Oryzias latipes). Aquat Toxicol 81:73–83
Fong PP, Huminski PT, D’Urso LM (1998) Induction and potentiation of parturition in fingernail clams (Sphaerium striatinum) by selective serotonin re-uptake inhibitors (SSRIs). J Exp Zool 280:260–264
Foran CM, Weston J, Slattery M, Brooks BW, Huggett DB (2004) Reproductive assessment of Japanese medaka (Oryzias latipes) following a four-week fluoxetine (SSRI) exposure. Arch Environ Contam Toxicol 46:511–517
Foster HR, Burton GA, Basu N, Werner EE (2010) Chronic exposure to fluoxetine (Prozac) causes developmental delays in Rana pipiens larvae. Environ Toxicol Chem 29(12):2845–2850
Fraker SL, Smith GR (2004) Direct and indirect effects of ecologically relevant concentrations of organic wastewater contaminants on Rana pipiens tadpoles. Environ Toxicol 19:250–256
Fujioka Y (2002) Effetcs of hormone treatments and temperature on sex-reversal of Nigorobuna Carassius carassius grandoculis. Fish Sci 68:889–893
Fulton BA, Brain RA, Usenko S, Back JA, King RS, Brooks BW (2009) Influence of N and P concentrations and ratios on Lemna gibba growth responses to triclosan in laboratory and stream mesocosm experiments. Environ Toxicol Chem 28:2610–2621
Fulton BA, Brain RA, Usenko S, Back JA, Brooks BW (2010) Exploring Lemna gibba thresholds to nutrient and chemical stressors: differential effects of triclosan on internal stoichiometry and nitrate uptake across a N:P gradient. Environ Toxicol Chem 29:2363–2370
Furr BJA, Tucker H (1996) The preclinical development of bicalutamide: pharmacodynamics and mechanism of action. Urology 47:13–25
Gaworecki KM, Klaine SJ (2008) Behavioral and biochemical responses of hybrid striped bass during and after fluoxetine exposure. Aquat Toxicol 88:207–213
Gledhill WE, Feijtel TCJ (1992) Environmental properties and safety assessment of organic phosphonates used for detergent and water treatment. In: de Oude NT (ed) Detergents. Handbook of environmental chemistry. Springer, New York, pp 261–285
Gould GG, Brooks BW, Frazer A (2007) [3H] Citalopram binding to serotonin transporter sites in minnow brains. Basic Clin Pharmacol Toxicol 101:203–210
Gravel A, Wilson JM, Pedro DFN, Vijayan MM (2009) Non-steroidal anti-inflammatory drugs disturb the osmoregulatory, metabolic and cortisol responses associated with seawater exposure in rainbow trout. Comp Biochem Physiol C 149:481–490
Grisolia CK (2002) A comparison between mouse and fish micronucleus test using cyclophosphamide, mitomycin C and various pesticides. Mutat Res 518:145–150
Grung M, Kallqvist T, Sakshaug S, Skurtveit S, Thomas KV (2008) Environmental assessment of Norwegian priority pharmaceuticals based on the EMEA guideline. Ecotoxicol Environ Saf 71:328–340
Guler Y, Ford AT (2010) Anti-depressants make amphipods see the light. Aquat Toxicol 99:397–404
Gyllenhammar I, Holm L, Eklund R, Berg C (2009) Reproductive toxicity in Xenopus tropicalis after developmental exposure to environmental concentrations of ethynylestradiol. Aquat Toxicol 91:171–178
Haider S, Baqri SSR (2000) β-Adrenoceptor antagonists reinitiate meiotic maturation in Clarias batrachu oocytes. Comp Biochem Physiol A 126:517–525
Halling-Sorensen B (2000) Algal toxicity of antibacterial agents used in intensive farming. Chemosphere 40:731–739
Halling-Sorensen B, Nielsen SN, Lanzky PF, Ingerster F, Lutzhoff HCH, Jorgensen SE (1998) Occurrence, fate and effects of pharmaceutical substances in the environment-a review. Chemosphere 36:357–393
Han GH, Hur HG, Kim SD (2006) Ecotoxicological risk of pharmaceuticals from wastewater treatment plants in Korea: occurrence and toxicity to Daphnia magna. Environ Toxicol Chem 25:265–271
Harrass MC, Kindig AC, Taub FB (1985) Responses of blue-green and green algae to streptomycin in unialgal and paired culture. Aquat Toxicol 6:1–11
Hasselberg L, Grosvik B-E, Goksoyr A, Celander MC (2005) Interactions between xenoestrogens and ketoconazole on hepatic CYP1A and CYP3A in juvenile Atlantic cod (Gadhus mortiua). Comp Hepatol 4:2
Heath RJ, Rubin JR, Holland DR, Zhang E, Snow ME, Rock CO (1999) Mechanisms of triclosan inhibition of bacterial fatty acid synthesis. J Biol Chem 274:11110–11114
Heckmann LH, Callaghan A, Hooper HL, Connon R, Hutchinson TH, Mound SJ, Sibley RM (2007) Chronic toxicity of ibuprofen to Daphnia magna: effects on life history traits and population dynamics. Toxicol Lett 172:137–145
Heddle JA, Cimino MC, Hayashi M, Romagna MD, Shelby JD, Vanparys P, MacGregor JT (1991) Micronuclei as an index of cytogenetic damage: past, present, and future. Environ Mol Mutagen 18:277–291
Hegelund T, Ottoson K, Radinger M, Tomberg P, Celander MC (2004) Effects of the antifungal imidazole ketoconazole on CYP1A and CYP3A in rainbow trout and killifish. Environ Toxicol Chem 23:1326–1334
Henry TB, Black MC (2008) Acute and chronic toxicity of fluoxetine (selective serotonin reuptake inhibitor) in western mosquito fish. Arch Environ Contam Toxicol 54:325–330
Henry TB, Kwon JW, Armbrust KL, Black MC (2004) Acute and chronic toxicity of five selective serotonin reuptake inhibitors in Ceriodaphnia dubia. Environ Toxicol Chem 23:2229–2233
Henschel KP, Wenzel A, Diederich M, Fliedner A (1997) Environmental hazard assessment of pharmaceuticals. Regul Toxicol Pharmacol 25:220–225
Hernando MD, Mezcua M, Fernandez-Alba AR, Barcelo D (2006) Environmental risk assessment of pharmaceutical residues in wastewater effluents, surface waters and sediments. Talanta 69:334–342
Higniite C, Azarnoff DL (1977) Drugs and drug metabolites as environmental contaminants: chlorophenoxyisobutyrate and salicylic acid in sewage water effluent. Life Sci 20:337–341
Hinz B, Cheremina O, Brune K (2008) Acetaminophen (paracetamol) is a selective cyclooxygenase-2 inhibitor in man. FASEB J 22:383–390
Hoeger B, Kollner B, Dietrich DR, Hitzfeld B (2005) Water-borne diclofenac affects kidney and gill integrity and selected immune parameters in brown trout (Salmo trutta f. fario). Aquat Toxicol 75:53–64
Hogan NS, Duarte P, Wade MG, Lean DRS, Trudeau VL (2008) Estrogenic exposure affects metamorphosis and alters sex ratios in the northern leopard frog (Rana pipiens): identifying critically vulnerable periods of development. Gen Comp Endocrinol 156:515–523
Holten Lutzhoft HC, Halling-Sorensen B, Jorgensen SE (1999) Algal testing of antibiotics applied in Danish fish farming. Arch Environ Contam Toxicol 36:1–6
Huet M-C (2000) OECD activity on endocrine disrupters test guidelines development. Ecotoxicology 9:77–94
Huggett DB, Brooks BW, Peterson B, Foran CM, Schlenk D (2002) Toxicity of select beta adrenergic receptor-blocking pharmaceuticals (B-blockers) on aquatic organisms. Arch Environ Contam Toxicol 43:229–235
Huggett DB, Cook JC, Ericson JF, Williams RT (2003) A theoretical model for utilizing mammalian pharmacology and safety data to prioritize potential impacts of human pharmaceuticals to fish. Hum Ecol Risk Assess 9:1789–1799
Hughes JS (1973) Acute toxicity of thirty chemicals to striped bass (Marone saxatilis). In: Presented at the Western Association of State Game and Fish Commissioners in Salt Lake City, Utah
Hutchinson TH (2002) Reproductive and developmental effects of endocrine disruptors in invertebrates: in vitro and in vivo approaches. Toxicol Lett 131:75–81
Hutchinson TH, Yokota H, Hagino S, Ozato K (2003) Development of fish tests for endocrine disruptors. Pure Appl Chem 75:2343–2353
Hutchinson TH, Ankley GT, Segner H, Tyler CR (2006) Screening and testing for endocrine disruption in fish – Biomarker as “signposts”, not “traffic lights”, in risk assessment. Environ Health Perspect 114:106–114
Isidori M, Lavorgna M, Nardelli A, Parrella A, Previtera L, Rubino M (2005a) Ecotoxicity of naproxen and its phototransformation products. Sci Total Environ 348:93–101
Isidori M, Lavorgna M, Nardelli A, Pascarelli L, Parrella A (2005b) Toxic and genotoxic evaluation of six antibiotics on non-target organisms. Sci Total Environ 346:87–98
Isidori M, Nardelli A, Pascarella L, Rubino M, Parrella A (2007) Toxic and genotoxic impact of fibrates and their photoproducts on non-target organism. Environ Int 33:635–641
Jobling S, Sheahan D, Osborne JA, Matthiessen P, Sumpter JP (1996) Inhibition of testicular growth in rainbow trout (Oncorhynchus mykiss) exposed to estrogenic alkylphenolic chemicals. Environ Toxicol Chem 15:194–202
Johnson SK (1976) Twenty-four hour toxicity tests of six chemicals to mysis larvae of Penaeus setiferus. Texas A & M University Extension, Disease Laboratory (Publication No. FDDL-S8)
Johnson DJ, Sanderson H, Brain RA, Wilson CJ, Solomon KR (2007) Toxicity and hazard of selective serotonin reuptake inhibitor antidepressants fluoxetine, fluvoxamine, and sertraline to algae. Ecotoxicol Environ Saf 67:128–139
Jones OA, Voulvoulis N, Lester JN (2002) Aquatic environmental assessment of the top 25 English prescription pharmaceuticals. Water Res 36:5013–5022
Jørgensen SE, Halling-Sørensen B (2000) Drugs in the environment. Chemosphere 40:691–699
Jos A, Repetto G, Rios JC, Hazen N, Molero ML, del Peso A, Salguero M, Fernandez-Freire P, Perez-Martin JM, Camen A (2003) Ecotoxicological evaluation of carbamezapine using six different model systems with eighteen endpoints. Toxicol In Vitro 17:525–532
Kang IJ, Yokota H, Oshima Y, Tsuruda Y, Yamaguchi T, Maeda M, Imada N, Tadokoro H, Honjo T (2002) Effects of 17β-estradiol on the reproduction of Japanese medaka (Oryzias latipes). Chemosphere 47:71–80
Key PB, Hoguet J, Reed LA, Chung KW, Fulton MH (2008) Effects of the statin antihyperlipidemic agent simvastatin on grass shrimp, Palaemonetes pugio. Environ Toxicol 23:153–160
Kidd KA, Blanchfield PJ, Mills KH, Palance VP, Evans RE, Lazorchak JM, Flick RM (2007) Collapse of a fish population after exposure to a synthetic estrogen. Proc Natl Acad Sci USA 104:8897–8901
Kim Y, Choi K, Jung J, 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. Eniviron Int 33:370–375
Kim J-W, Ishibashi H, Yamauchi R, Ichikawa N, Takao Y, Hirano M, Koga M, Arizono K (2009) Acute toxicity of pharmaceutical and personal care products on freshwater crustacean (Thamnocephalus platyurus) and fish (Oryzias latipes). J Toxicol Sci 34:227–232
Kim J, Park J, Kin PG, Lee C, Choi K, Choi K (2010) Implications of global environmental changes on chemical toxicity-effect of water temperature, pH, and ultraviolet B irradiation on acute toxicity of several pharmaceuticals in Daphnia magna. Ecotoxicology 19:662–669
Kirkegaard C, Faber J (1998) The role of thyroid hormones in depression. Eur J Endocrinol 138:1–9
Kirpichnikov D, McFarlane S, Sowers JR (2002) Metformin: an update. Ann Intern Med 137:25–33
Knoll/BASF (1995) Pharmaceutical safety data sheet ibuprofen (Issue/Revision 06/04/94). Knoll Pharmaceuticals, Nottingham, UK
Kollros JJ (1961) Mechanisms of amphibian metamorphosis: hormones. Am Zool 1:107–114
Kopf W (1995) Wirkung endokriner Stoffe in Biotest mit Wasserorganismen. Vortag bei der 50. Fachtagung des Bay. LA fur Wasserwirtschaft: Stoffe mit endokriner. Wirkung im Wasser
Kreke N, Dietrich DR (2008) Physiological endpoints for potential SSRI interactions in fish. Crit Rev Toxicol 37:215–247
Kuhn R, Pattard M, Pernak KD, Winter A (1989) Results of the harmful effects of selected water pollutants (anilines, phenols, aliphatic compounds) to Daphnia magna. Wat Res 23:495–499
Küster A, Alder AC, Escher BI, Duis K, Fenner K, Garric J, Hutchinson TH, Lapen DR, Pery A, Rombke J, Snape J, Ternes T, Topp E, Wehrhan A, Knacker T (2010) Environmental risk assessment of human pharmaceuticals in the European Union: a case study with the β-blocker atenolol. Integr Environ Assess Manag 6(Suppl 1):514–523
Kwon JW, Armbrust KL, Vidal-Dorsch D, Bay SM (2009) Determination of 17α-ethynylestradiol, carbamazepine, diazepam, simvastatin, and oxybenzone in fish livers. J AOAC Int 92:359–369
Laird BD, Brain RA, Johnson DJ, Wilson CJ, Sanderson H, Solomon KR (2007) Toxicity and hazard of a mixture of SSRIs to zooplankton communities evaluated in aquatic microcosms. Chemosphere 69(6):949–954
Lange R, Dietrich D (2002) Environmental risk assessment of pharmaceutical drug substances – conceptual considerations. Toxicol Lett 131:97–104
Lange R, Hutchinson TH, Croudace CP, Siegmund F, Schweinfurth H, Hampe P, Panter GH, Sumpter JP (2001) Effects of the synthetic estrogen 17 alpha-ethinylestradiol on the life cycle of the fathead minnow (Pimephales promelas). Environ Toxicol Chem 20:1216–1227
Lange IG, Daxenberger A, Schiffer B, Witters H, Ibarreta D, Meyer HHD (2002) Sex hormones originating from different livestock production systems: fate and potential endocrine disrupting activity in the environment. Anal Chim Acta 473:27–37
Lanzky PF, Halling-Sorenson B (1997) The toxic effects of the antibiotic metronidazole on aquatic organisms. Chemosphere 35:2553–2561
Larkin P, Folmar LC, Hemmer MJ, Poston A, Denslow ND (2003) Expression profiling of estrogenic compounds using a sheepshead minnow cDNA macroarray. Environ Health Perspect 111:839–846
Larsson DGJ, Hyllner SJ, Haux C (1994) Induction of vittelline envelope proteins by estradiol-17β in 10 teleost species. Gen Comp Endocrinol 96:445–450
Larsson DGJ, Adolfsson-Erici M, Parkkonen J, Pettersson M, Berg AH, Olsson P-E, Forlin L (1999) Ethinylestradiol-an undesired fish contraceptive? Aquat Toxicol 45:91–97
Laufs U, Liao JK (1998) Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by RhoGTPase. J Biol Chem 273:24266–24271
Laville N, Ait-Aissa S, Gomez E, Casellas M, Porcher JM (2004) Effects of human pharmaceuticals on cytotoxicity, EROD activity and ROS production in fish hepatocytes. Toxicology 196:41–55
Lawrence JR, Swehone GDW, Wassenaar CI, Neu TF (2005) Effects of selected pharmaceuticals on riverine biofilm communities. Can J Microbiol 51:655–669
LeBlanc GA, Campbell PM, den Besten P, Brown RP, Chang ES, Coats JR, deFur PL, Dhadialla T, Edwards J, Riddiford LM, Simpson MG, Snell TW, Thorndyke M, Matsumura F (1999) The endocrinology of invertebrates. In: deFur PL, Crane M, Ingersoll CG, Tattersfield L (eds) Endocrine disruption in invertebrates: endocrinology, testing, and assessment. SETAC Press, Pensacola, FL
Li Z, Li P, Randak T (2010) Ecotoxicological effects of short-term exposure to a human pharmaceutical verapamil in juvenile rainbow trout (Oncorhynchus mykiss). Comp Biochem Physiol C 152:385–391
Li Z, Zlabek V, Velisek J, Grabic R, Machova J, Kolarova J, Li P, Randak T (2011) Acute toxicity of carbamazepine to juvenile rainbow trout (Oncorhynchus mykiss): effects on antioxidant responses, hematological parameters and hepatic EROD. Ecotoxicol Environ Saf 74:319–327
Lichtenthaler HK, Schwender J, Disch A, Rohmer M (1997a) Biosynthesis of isoprenoids in higher plant chloroplasts proceeds via a mevalonate-independent pathway. FEBS Lett 400:271–274
Lichtenthaler HK, Rohmer M, Schwender J (1997b) Two independent biochemical pathways for isopentyl diphosphate and isoprenoid biosynthesis in higher plants. Physiol Plant 101:643–652
Liebig M, Fernandez AA, Blübaum-Gronau E, Boxall A, Brinke M, Carbonell G, Egeler P, Fenner K, Fernandez C, Fink G, Garric J, Halling-Sørensen B, Knacker T, Krogh KA, Küster A, Löffler D, Cots MA, Pope L, Prasse C, Römbke J, Rönnefahrt I, Schneider MK, Schweitzer N, Tarazona JV, Ternes TA, Traunspurger W, Wehrhan A, Duis K (2010) Environmental risk assessment of ivermectin: a case study. Integr Environ Assess Manag 6:567–587
Lilius H, Isomaa B, Holmstrom T (1994) A comparison of the toxicity of 50 reference chemicals to freshly isolated rainbow trout hepatocytes and Daphnia magna. Aquat Toxicol 30:47–60
Lin AY-C, Yu T-H, Lateef SK (2009) Removal of pharmaceuticals in secondary wastewater treatment processes in Taiwan. J Hazard Mater. doi:10.1016/j.Jhazmat.2009.01.108
Lister A, Regan C, Van Zwol J, Van Der Kraak G (2009) Inhibition of egg production in zebrafish by fluoxetine and municipal effluents: a mechanistic evaluation. Aquat Toxicol 95:320–329
Long ER, Chapman PM (1985) A sediment quality triad-measures of sediment contamination, toxicity and infaunal community composition in Puget Sound. Mar Environ Poll 16:405–415
Lundholm CE (1997) DDE-induced eggshell thinning in birds: effects of p, p′-DDE on the calcium and prostaglandin metabolism of the eggshell gland. Comp Biol Physiol 118C:113–128
Macri A, Sbardella E (1984) Toxicological evaluation of nitrofurazone and furazolidone on Selenaslrum capricornurum, Daphnia magna and Musca domes rica. Ecotoxicol Environ Saf 8:115–105
Majewski AR, Blanchfield PJ, Wautier PK (2002) Waterborne 17alfa-ethynylestradiol affects aggressive behavior of male fathead minnows (Pimephales promelas) under artificial spawning conditions. Water Qual Res J Can 37:697–710
Manocha S, Venkataraman S (2000) Pharmacological and histopathological evaluation of ulcer formation and end organ toxicity by NSAIDS with concurrent ranitidine treatment in aged rats. In: Presentation at sixth Internet World Congress for Biomedical Science
Manuell A, Beligni MV, Yamaguchi K, Mayfield SP (2004) Regulation of chloroplast translation: interactions of RNA elements, RNA-binding proteins and the plastid ribosome. Biochem Soc Trans 23:601–605
Marking L, Howe GE, Crowther JR (1988) Toxicity of erythromycin, oxytetracycline and tetracycline administered to Lake Trout in water baths, by injection or by feeding. The Progressive Fish-Culturist 50:197–201
Marques CR, Abrantes N, Goncaes F (2004) Life-history traits of standard and autochthonous cladocerans: II. Acute and chronic effects of acetylsalicylic acid metabolites. Environ Toxicol 19:527–540
Martinovic D, Hogarth WT, Jones RE, Sorensen PW (2007) Environmental estrogens suppress hormones, behavior, and reproductive fitness in male fathead minnows. Environ Toxicol Chem 26:271–278
Masuda S, Deguchi Y, Masuda Y, Watanabe T, Nukaya H, Terao Y, Takamura T, Wakabayashi K, Kinae N (2004) Genotoxicity of 2-[2-(acetylamino)-4-[bis(2-hydroxyethyl)amino]-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2 H-benzotriazole (PBTA-6) and 4-amino-3,3′-dichloro-5,4′-dinitro-biphenyl (ADDB) in goldfish (Carassius auratus) using the micronucleus test and the comet assay. Mutat Res 560:33–40
McFadden GI, Roos DS (1999) Apicomplexan plastids as drug targets. Trends Microbiol 7:328–333
McMurry LM, Oethinger M, Levy SB (1998) Triclosan targets lipid synthesis. Nature 394:531–532
Meguid MM, Fetissov SO, Varma M, Sato T, Zhang L, Laviano A, Rossi-Fanelli F (2000) Hypothalamic dopamine and serotonin in the regulation of food intake. Nutrition 16:843–857
Mehinto AC, Hill EM, Tyler CR (2010) Uptake and biological effects of environmentally relevant concentrations of the nonsteroidal anti-inflammatory pharmaceutical diclofenac in rainbow trout (Oncorhynchus mykiss). Environ Sci Technol 44:2176–2182
Meinertz JR, Schreier M, Bernardy JA, Franz JL (2010) Chronic toxicity of diphenhydramine hydrochloride and erythromycin thiocyanate to daphnia, Daphnia magna, in a continuous exposure test system. Bull Environ Contam Toxicol 85:447–451
Mennigen JA, Sassine J, Trudeau VL, Moon TW (2010a) Waterborne fluoxetine disrupts feeding and energy metabolism in the goldfish Carassius auratus. Aquat Toxicol 100:128–137
Mennigen JA, Lado WE, Zamora JM, Duarte-Guterman P, Langlois VS, Metcalfe CD, Chang JP, Moon TW, Trudeau VL (2010b) Waterborne fluozetine disrupts the reproductive axis in sexually mature male goldfish, Carassius auratus. Aquat Toxicol 100:354–364
Mennigen JA, Stroud P, Zamora JM, Moon TW, Trudeau VL (2011) Pharmaceuticals as neuroendocrine disruptors: lessons learned from fish on Prozac. J Toxicol Environ Health, Part B 14:387–412
Miller DH, Jensen KM, Villeneuve DL, Kahl MD, Makynen EA, Durhan EJ, Ankley GT (2007) Linkage of biochemical responses to population-level effects: a case study with vitellogenin in the fathead minnow (Pimephales promelas). Environ Toxicol Chem 26:521–527
Mimeault C, Woodhouse AJ, Miao XS, Metcalfe CD, Moon TW, Trudeau VL (2005) The human lipid regulator, gemfibrozi bioconcentrates and reduces testosterone in the goldfish, Carassius auratus. Aquat Toxicol 73:44–54
Minagh E, Hernan R, O’Rourke K, Lyng FM, 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
Mitchelmore CL, Chipman JK (1998a) Detection of DNA strand breaks in Brown trout (Salmo trutta) hepatocytes and blood cells using the single cell gel electrophoresis (comet) assay. Aquat Toxicol 41:161–182
Mitchelmore CL, Chipman JK (1998b) DNA strand breakage in aquatic organisms and the potential value of the comet assay in environmental monitoring. Mutat Res 399:135–147
Mitchelmore CL, Birmelin C, Livingstone DR, Chipman JK (1997) Polycyclic and nitro-aromatic compounds produce DNA strand breakage in Brown trout (Salmo trutta) and mussel (Mytilus edulis L.) cells. Mutagenesis 12:101
Monteiro SC, Boxall ABA (2010) Occurrence and fate of human pharmaceuticals in the environment. Rev Environ Contam Toxicol 202:53–154
Moore MT, Greenway SL, Farris JL, Guerra B (2008) Assessing caffeine as an emerging environmental concern using conventional approaches. Arch Environ Contam Toxicol 54:31–35
Mu X, LeBlanc GA (2002) Developmental toxicity of testosterone in the crustacean Daphnia magna involves anti-ecdysteroidal activity. Gen Comp Endocrinol 129:127–133
Nakamura Y, Yamamoto H, Sekizawa J, Kondo T, Hirai N, Tatarazako N (2008) The effects of pH on fluoxetine in Japanese medaka (Oryzias latipes): acute toxicity in fish larvae and bioaccumulation in juvenile fish. Chemosphere 70:865–873
Nassef M, Matsumoto S, Seki M, Khalil F, Kang IJ, Shimasaki Y, Oshima Y, Honjo T (2010) Acute effects of ticlosan, diclofenac and carbamazepine on feeding performance of Japanese medaka fish (Oryzias latipes). Chemosphere 80:1095–1100
Nation JL (2002) Insect physiology and biochemistry. CRC Press, Boca Raton
Nayler WG, Poole-Wilson CH (1981) Calcium antagonists: definition and mode of action. Basic Res Cardiol 76:1–15
Nentwing G (2007) Effects of pharmaceuticals on aquatic invertebrates. Part II: the antidepressant drug fluoxetine. Arch Environ Contam Toxicol 52:163–170
Nentwing G, Oetken M, Oehlmann J (2004) Effects of pharmaceuticals on aquatic invertebrates – the example of carbamazepine and clofibric acid. In: Kummerer K (ed) Pharmaceuticals in the environment: sources, fate, effects and risks, 2nd edn. Springer, Berlin, Germany, pp 195–208
Neuman NF, Galvez F (2002) DNA microarrays and toxicogenomics: applications for ecotoxicology? Biotechnol Adv 20:391–419
Nickerson JG, Gugan SG, Drouin G, Moon TW (2001) A putative β2-adrenoceptor from the rainbow trout (Oncorhyncus mykiss). Molecular characterixation and pharmacology. Eur J Biochem 268:6465–6472
Nie X, Gu J, Lu J, Pan W, Yang Y (2009) Effects of norfloxacin and butylated hydroxyanisole on the freshwater microalga Scenedesmus obliquus. Ecotoxicology 18:677–684
Oakes KD, Coors A, Escher BI, Fenner K, Garric J, Gust M, Knacker T, Küster A, Kussatz C, Metcalfe CD, Monteiro S, Moon TW, Mennigen JA, Parrott J, Péry ARR, Ramil M, Roennefahrt I, Tarazona JV, Sánchez-Argüello P, Ternes TA, Trudeau VL, Boucard T, Van Der Kraak GJ, Servos MR (2010) Environmental risk assessment for the serotonin re-uptake inhibitor fluoxetine: case study using the European risk assessment framework. Integr Environ Assess Manag 6(Suppl 1):524–539
Oaks JL, Gilbert M, Virani MZ, Watson RT, Meteyer CU, Rideout BA, Shivaprasad HL, Ahmed S, Chaudhry MJI, Arshad M, Mahmood S, Ali A, Khan AA (2004) Diclofenac residues as the cause of vulture population decline in Pakistan. Nature 427:630–633
OECD (1999) Detailed review paper: appraisal of test methods for sex-hormone disrupting chemicals. OECD Environmental Health and Safety Publication No. 21
Orn S, Holbech H, Madsen TH, Norrgren L, Petersen GI (2003) Gonad development and vitellogenin production in zebrafish (Danio rerio) exposed to ethinylestradiol and methyltestosterone. Aquat Toxicol 65:397–411
Owen SF, Giltrow E, Huggett DB, Hutchinson TH, Saye J, Winter MJ, Sumpter JP (2007) Comparitive physiology, pharmacology and toxicology of β-blockers: mammals versus fish. Aquat Toxicol 82:145–162
Painter MM, Buerkley MA, Julius ML, Vajda AM, Norris DO, Barber LB, Furlong ET, Schultz MM, Schoenfuss HL (2009) Antidepressants at environmentally relevant concentrations affect predator avoidance behavior of larval fathead minnows (Pimephales promelas). Environ Toxicol Chem 28:2677–2684
Panter GH, Thompson RS, Beresford N, Sumpter JP (1999) Transformation of a non-oestrogenic steroid metabolite to an oestrogenically active substance by minimal bacterial activity. Chemosphere 38(15):3579–3596
Panter GH, Hutchinson TH, Hurd KS, Sherren A, Stanley RD, Tyler CR (2004) Successful detection of (anti-)androgenic and aromatase inhibitors in pre-spawning adult fathead minnows (Pimephales promelas) using easily measured end points of sexual development. Aquat Toxicol 70:11–21
Parrott JL, Blunt BR (2005) Life-cycle exposure of fathead minnows (Pimephales promelas) to an ethinylestradiol concentration below 1 ng/L reduces egg fertilization success and demasculinize males. Environ Toxicol 20:131–141
Parrott JL, Bennie DT (2009) Life-cycle exposure of fathead minnows to a mixture of six common pharmaceuticals and triclosan. J Toxicol Environ Health A 72:633–641
Pascoe D, Karntanut W, Muller CT (2003) Do pharmaceuticals affect freshwater invertebrates? A study with the cnidarians Hydra vulgaris. Chemosphere 51:521–528
Pawlowski S, van Aerle R, Tyler CR, Braunbeck T (2004) Effects of 17α-ethinylestradiol in a fathead minnow (Pimephales promelas) gonadal recrudescence assay. Ecotoxicol Environ Saf 57:330–345
Perreault HA, Semsar K, Godwin J (2003) Fluoxetine treatment decreases territorial aggression in a coral reef fish. Physiol Behav 79(4–5):719–724
Pery ARR, 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
Pomati F, Netting AG, Calomari D, Neilan BA (2004) Effects of erythromycin, tetracycline and ibuprofen on the growth of Synechocystis sp. and Leman minor. Aquat Toxicol 67:387–396
Pounds N, Maclean S, Webley M, Pascoe D, Hutchinson T (2008) Acute and chronic effects of ibuprofen in the mollusk Planorbis carnatus (Gastropoda: Planorbidae). Ecotoxicol Environ Saf 70:47–52
Powers DA (1989) Fish as model systems. Science 246:352–358
Pro J, Ortiz JA, Bolocs S, Fernandez C, Carbonell G, Tarazona JV (2003) Effect assessment of antimicrobial pharmaceuticals on the aquatic plant Lemna minor. Bull Environ Contam Toxicol 70:290–295
Purdom CE, Hardiman PA, Bye VJ, Eno NC, Tyler CR, Sumpter JP (1994) Estrogenic effects of effluents from sewage treatment works. Chem Ecol 8:275–285
Quinn B, Gagne F, Blaise C (2008) An investigation into the acute and chronic toxicity of eleven pharmaceuticals (and their solvents) found in wastewater effluent on the cnidarians, Hydra attenuate. Sci Total Environ 389:306–314
Ralph S, Petras M, Pandrangi R, Vrzoc M (1996) Alkaline single cell gel (comet) assay and genotoxicity monitoring using two species of tadpoles. Environ Mol Mutagen 28:112–120
Ramirez AJ, Mottaleb MA, Brooks BW, Chambliss CK (2007) Analysis of pharmaceuticals in fish using liquid chromatography-tandem mass spectrometry. Anal Chem 79:3155–3163
Ramirez AJ, Brain RA, Usenko S, Mottaleb MA, O’Donnell JG, Stahl LL, Wethen JB, Snyder BD, Pitt JL, Perez-Hurtado P, Dobbins LL, Brooks BW, Chambliss CK (2009) Occurrence of pharmaceuticals and personal care products in fish: results of a national pilot study in the United States. Environ Toxicol Chem 28:2587–2597
Rand GM (ed) (1995) Fundamentals of aquatic toxicology, 2nd edn. Taylor and Francis, Philadelphia, PA
Revai T, Harmos G (1999) Nephrotic syndrome and acute interstitial nephritis associated with the use of diclofenac. Wien Klin Wochenschr 111:523–524
Richards SM, Cole SE (2006) A toxicity and hazard assessment of fourteen pharmaceutical compounds to Xnopus laevis larvae. Ecotoxicology 15:647–656
Robinson AA, Belden JB, Lydy MJ (2005) Toxicity of fluoroquinolone antibiotics to aquatic organisms. Environ Toxicol Chem 24:423–430
Rodriguez C, Chellman K, Gomez S, Marple L (1992) Environmental assessment report pursuant to 21 CFR 25.31(a) submitted to the US FDA in support of the New Drug Application (NDA) for naproxen for over-the-counter use. Hamilton Pharmaceuticals Limited, Puerto Rico
Rosal R, Rodea-Palomares I, Boltes K, Fernandez-Pinas F, Leganes F, Gonzalo S, Pere A (2010) Ecotoxicity assessment of lipid regulators in water and biologically treated wastewater using three aquatic organisms. Environ Sci Pollut Res Int 17:135–144
Runnalls TJ, Hala DN, Sumpter JP (2007) Preliminary studies into the effects of the human pharmaceutical clofibric acid on sperm parameters in adult fathead minnow. Aquat Toxicol 84:111–118
Russom CL, Bradbury SP, Broderius SJ, Hammermeister DE, Drummond RA (1997) Predicting modes of toxic action from chemical structure: acute toxicity in the fathead minnow (Pimephales promelas). Environ Toxicol Chem 16:948–967
Saito H, Sudo M, Shigeoka T, Yamauchi F (1991) In vitro cytotoxicity of chlorophenols to goldfish GF-Scale (GFS) cells an quantitative structure-activity relationships. Environ Toxicol Chem 10:235–241
Sanderson H, Thomsen M (2007) Ecotoxicological quantitative structure activity relationships for pharmaceuticals. Bull Environ Contam Toxicol 79:331–335
Sanderson H, Thomsen M (2009) Comparative analysis of pharmaceuticals versus industrial chemicals acute aquatic toxicity classification according to the United Nations classification system for chemicals: assessment of the (Q)SAR predictability of pharmaceuticals acute aquatic toxicity and their predominant acute toxic mode-of-action. Toxicol Lett 187:84–93
Sanderson H, Johnson DJ, Wilson CJ, Brain RA, Solomon KR (2003) Probabilistic hazard assessment of environmentally occurring pharmaceuticals toxicity to fish, daphnids and algae by ECOSAR screening. Toxicol Lett 144:383–395
Sanderson H, Johnson DJ, Reitsma T, Brain RA, Wilson CJ, Solomon KR (2004) Ranking and prioritization of environmental risks of pharmaceuticals in surface waters. Regul Toxicol Pharmacol 39:158–183
Sanofi (1996) Tiludronate disodium material safety data sheet. SR 41319B. Sanofi Research
Santos L, Araujo AN, Fachini A, Pena A, Delerue-Matos C, Montenegro MC (2010) Ecotoxicological aspects related to the presence of pharmaceuticals in the aquatic environment. J Hazard Mater 175:45–95
Sanyal AK, Roy D, Chowdhury B, Banerjee AB (1993) Ibuprofen, a unique anti-inflammatory compound with antifungal activity against dermatophytes. Lett Appl Microbiol 17:109–111
Schena M, Shalon D, Davis RW, Brown PO (1995) Quantitative monitoring of gene expression patterns with a complimentary DNA microarray. Science 270:467–470
Schmidt W, O’Rourke K, Hernan R, Quinn B (2011) Effects of pharmaceuticals gemfibrozil and diclofenac on the marine mussle (Mytilus spp.) and their comparison with standardized toxicity tests. Mar Pollut Bull 62:1389–1395
Schmitt H, Bouchard T, Garric J, Jensen J, Parrott J, Pery A, Rombke J, Straub JO, Hutchinson TH, Sanchez-Arguello P, Wennmalm A, Duis K (2010) Recommendations on the environmental risk assessment of pharmaceuticals: effect characterization. Integr Environ Assess Manag 6(Suppl 1):588–602
Schnell S, Bols NC, Barata C, Porte C (2009) Single and combined toxicity of pharmaceuticals and personal care products (PPCPs) on the rainbow trout liver cell line RTL-W1. Aquat Toxicol 93:244–252
Schulte-Oehlmann U, Oetken M, Bachmann J, Oehlmann J (2004) Effects of ethinyloestradiol and methyltestosterone in prosobranch snails. In: Kummerer K (ed) Pharmaceuticals in the environment: sources, fate, effects and risks, 2nd edn. Springer, Berlin, Germany, pp 233–247
Schultz MM, Furlong ET, Kolpin DW, Werner SL, Schoenfuss HL, Barber LB, Blazer VS, Norris DO, Vajda AM (2010) Antidepressant pharmaceuticals in two U.S. effluent-impacted streams: occurrence and fate in water and sediment, and selective uptake in fish neural tissue. Environ Sci Technol 44:1918–1925
Schwaiger J, Ferling H, Mallow U, Wintermayr H, Negele RD (2004) Toxic effects of the non-steroidal anti-inflammatory drug diclofenac. Part I: histopathological alterations and bioaccumulation in rainbow trout. Aquat Toxicol 68:141–150
Schweinfurth H, Lange R, Schneider PW (1996) Environmental risk assessment in the pharmaceutical industry. In: Presentation at the 3 rd Eurolab Symposium: testing and analysis for industrial competitiveness and sustainability. Berlin, Germany
Segner H, Caroll K, Fenske M, Janssen CR, Maack G, Pascoe D, Schäfers C, Vendenbergh GF, Watts M, Wenzel A (2003a) Identification of endocrine disrupting effects in aquatic vertebrates and invertebrates: report from the European IDEA project. Ecotoxicol Environ Saf 54:302–314
Segner H, Navas JM, Schäfers C, Wenzel A (2003b) Potencies of estrogenic compounds in in vitro screening assays and in life cycle tests with zebrafish in vivo. Ecotoxicol Environ Saf 54:315–322
Seki M, Yokota H, Matsubara H, Tsuruda Y, Maeda M, Tadokoro H, Kobayashi K (2002) Effect of ethinylestradiol on the reproduction and induction of vitellogenin and testis-ova in medaka (Oryzias latipes). Environ Toxicol Chem 21:1692–1698
Semsar K, Perreault HA, Godwin J (2004) Fluoxetine-treated male wrasses exhibit low AVT expression. Brain Res 1029(2):141–147
Sheahan DA, Bucke D, Matthiessen P, Sumpter JP, Kirby MF, Neall P, Waldock M (1994) The effects of low levels of 17α-ethinylestradiol upon plasma vitellogenin levels in male and female rainbow trout, Oncorhynchus mykiss, held at two acclimation temperatures. In: Müller R, Lloyd R (eds) Sublethal and chronic effects of pollutants on freshwater fish. Blackwell, Oxford, UK, pp 99–112
Singh NP, McCoy MT, Tice RR, Schneider EL (1998) A simple technique for quantification of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191
Smith GR, Burgett AA (2005) Effects of three organic wastewater contaminants on American toad, Bufo americanus, tadpoles. Ecotoxicology 14:477–482
Sole M, Shaw JP, Frickers PE, Readman JW, Hutchinson TH (2010) Effects on feeding rate and biomarker responses of marine mussels experimentally exposure to propranolol and acetaminophen. Anal Bioanal Chem 396:649–656
Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart J-C (1998) Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation 98:2088–2093
Stanley JK, Brooks BW (2009) Perspectives on ecological risk assessment of chiral compounds. Integr Environ Assess Manag 5:364–373
Stanley JK, Ramirez AJ, Mottaleb M, Chambliss CK, Brooks BW (2006) Enantio-specific toxicity of the β-blocker propranolol to Daphnia magna and Pimephales promelas. Environ Toxicol Chem 25:1780–1786
Stanley JK, Ramirez AJ, Chambliss CK, Brooks BW (2007) Enantiospecific sublethal effects of the antidepressant fluoxetine to a model aquatic vertebrate and invertebrate. Chemosphere 69:9–16
Stuer-Lauridsen F, Birkved M, Hansen LP, Lutzhoft HC, Halling-Sorensen B (2000) Environmental risk assessment of human pharmaceuticals in Denmark after normal therapeutic use. Chemosphere 40:783–793
Sumpter JP, Jobling S (1995) Vitellogenesis as a biomarker for estrogenic contamination of the aquatic environment. Environ Health Perspect 103(Suppl 7):173–178
Sweetman SC (ed) (2002) Martindale: the complete drug reference, 33rd edn. Pharmaceutical, London
Ternes T, Jos A, Siegrist H (2004) Scrutinizing pharmaceutical and personal care products in wastewater treatment. Environ Sci Technol 38:393–399
Thompson RJ, Mosig G (1985) An ATP-dependant supercoiling topoisomerase of Chlamydomonas reinhardtii affects accumulation of specific chloroplast transcripts. Nucleic Acids Res 13:873–891
Tooby TE, Hursey PA, Alabaster JS (1975) The acute toxicity of 102 pesticides and miscellaneous substances to fish. Chem Ind 611975:523–526
Triebskorn R, Casper H, Heyda A, Eikemper R, Kohler H-R, Schwaiger J (2004) Toxic effects of the non-steroidal anti-inflammatory drug diclofenac. Part II. Cytological effects in liver, kidney, gills, and intestine of rainbow trout (Oncorhynchus mykiss). Aquat Toxicol 68:176–183
Triebskorn R, Casper H, Scheil V, Schwaiger J (2007) Ultrastructural effects of pharmaceuticals (carbamezapine, clofibric acid, metoprolol, diclofenac) in rainbow trout (Oncorhynchus mykiss) and common carp (Cyprinus carpio). Anal Bioanal Chem 387:1405–1416
Ullman U, Svedmyr N (1988) Salmeterol, a new long acting inhaled beta2 adrenoreceptor agonist: comparison with salbutamol in adult asthmatic patients. Thorax 43:674–678
United States Environmental Protection Agency (1994) Policy for the development of effluent limitations in National Pollutant Discharge Elimination System (NPDES) permits to control whole effluent toxicity for the protection of aquatic life. EPA833-B-94-002. Office of Water, Washington, DC
United States Environmental Protection Agency (2000) Method guidance and recommendations for whole effluent toxicity (WET) testing (40 CFR Part 136). EPA/821/B-00-004. Office of Water, Office of Science and Technology. Washington DC
United States Environmental Protection Agency (2002a) Methods for measuring the acute toxicity of effluents and receiving waters to freshwater and marine organisms. EPA 821/R-02/012, 5th edn. Office of Science and Technology, Washington, DC
United States Environmental Protection Agency (2002b) Short-term methods for estimating the chronic toxicity of effluents and receiving waters to freshwater organisms. EPA 821/R-02-013, 4th edn. Office of Science and Technology, Washington, DC
United States Environmental Protection Agency (2002c) Short-term methods for estimating the chronic toxicity of effluents and receiving waters to marine and estuarine organisms, 3rd edn. Office of Science and Technology, Washington DC
Valenti TW, Perez Hurtado P, Chambliss CK, Brooks BW (2009) Aquatic toxicity of sertraline to Pimephales promelas at environmentally relevant surface water pH. Environ Toxicol Chem 28:2685–2694
Valenti TW, Taylor JT, Back JA, King RS, Brooks BW (2011) Influence of drought and total phosphorus on diel pH in wadeable streams: implications for ecological risk assessment of ionizable contaminants. Integr Environ Assess Manag 7:636–647
Valenti TV, Gould GG, Berninger JP, Connors KA, Keele NB, Prosser KN, Brooks BW (2012) Human therapeutic plasma levels of the selective serotonin reuptake inhibitor (SSRI) sertraline decrease serotonin reuptake transporter binding and shelter seeking behavior in adult male fathead minnows. Environ Sci Technol 46:2427–2435
van den Brandof E, Montforts M (2010) Fish embryo toxicity of carbamazepine, diclofenac and meoprolol. Ecotoxicol Environ Saf 73:1862–1866
van der Ven K, De Wit M, Keil D, Moens L, Van Leeriput K, Naudts B, De Coen W (2005) Development and application of a brain-specific cDNA microarray for effect evaluation of neuro-active pharmaceuticals in zebrafish (Danio rerio). Comp Biochem Physiol B 141:408–417
van Zwieten PA (1994) Amlodipine: an overview of its pharmacodynamic and pharmacokinetic properties. Clin Cardiol 17(Suppl 3):1113–1116
Vandenbergh GF, Adriaens D, Verslycke T, Janssen CR (2003) Effects of 17α-ethinylestradiol on sexual development of the amphipod Hyalella azteca. Ecotoxicol Environ Saf 54:216–222
Vane JR, Botting RM (1998) Mechanism of action of anti-inflammatory drugs. Int J Tissue React 20:3–15
VICH (2000) Environmental impact assessment (EIAs) for veterinary medicinal products (Veterinary medicines) – Phase 1. VICH GL6 (Ecotoxicity Phase 1), June 2000, For Implementation at Phase 7
VICH (2004) Environmental impact assessment for veterinary medicinal products phase II guidance, VICH-GL38. Brussels. Belgium, VICH, p 38, http://vich.eudra.org/
Vos JG, Dybing E, Greim H, Ladefoged O, Lambre C, Tarazona JV, Brandt I, Vethaak AD (2000) Health effects of endocrine-disrupting chemicals on wildlife with special reference to the European situation. Crit Rev Toxicol 30:71–133
Wall MK, Mitchall LA, Maxwell A (2004) Arabidopsis thaliana DNA gyrase is targeted to chloroplasts and mitochondria. Proc Natl Acad Sci USA 101:7821–7826
Walton RJ, Sherif IT, Noy GA, Alberti KG (1979) Improved metabolic profiles in insulin-treated diabetic patients given an alpha-glucoside hydrolase inhibitor. Br Med J 6158:220–221
Wang WH, Lay JP (1989) Fate and effects of salicylic acid compounds in freshwater systems. Ecotoxicol Environ Saf 17(3):308–316
Watts MM, Pascoe D, Carroll K (2002) Population responses of the freshwater amphipod Gammarus pulex (L.) to an environmental oestrogen 17α ethinylestradiol. Environ Toxicol Chem 21:445–450
Watts MM, Pascoe D, Carroll K (2003) Exposure to 17α ethinylestradiol and bisphenol A-effects on larval moulting and mouthpart structure of Chironomus riparius. Ecotoxicol Environ Saf 54:207–215
Webb SF (2001) A data based perspective on the environmental risk assessment of human pharmaceuticals II: aquatic risk characterisation. In: Kümmerer K (ed) Pharmaceuticals in the environment. Sources, fate, effects and risks. Springer, Berlin, pp 319–343
Welborn TL (1969) The toxicity of nine therapeutic and herbicidal compounds to striped bass. The Progressive Fish Culturist 31(1):27–32
Weston A, Caminada D, Galicia H, Fent K (2009) Effects of lipid-lowering pharmaceuticals bezafibrate and clofibric acid on lipid metabolism in fathead minnow (Pimephales promelas). Environ Toxicol Chem 28:2648–2655
Wilford WA (1966) Toxicity of 22 therapeutic compounds to six fishes. US Dept. of the Interior, Fish and Wildlife Service, Bureau of Sports Fisheries and Wildlife, Washington DC (Resource Publication 35)
Williams EMV (1958) The mode of action of quinidine on isolated rabbit atria interpreted from intracellular potential records. Br J Pharmacol Chemother 13:276–287
Winter MJ, Lillicrap AD, Caunter JE, Schaffner C, Alder AC, Ramil M, Ternes TA, Giltrow E, Sumpter JP, Hutchinson TH (2008) Defining the chronic impacts of atenolol on embryo-larval development and reproduction in the fathead minnow (Pimephales promelas). Aquat Toxicol 86:361–369
Wong DT, Perry KW, Bymaster FP (2005) The discovery of fluoxetine hydrochloride (Prozac). Nat Rev Drug Discov 4:764–774
Yamashita N, Yasojima M, Miyajima K, Suzuki Y, Tanaka H (2006) Effects of antibacterial agents, levofloxacin and clarithromycin, on aquatic organisms. Water Sci Technol 53:65–72
Zeilinger J, Steger-Hartmann T, Maser E, Goller S, Vonk R, Lange R (2009) Effects of synthetic gestagens on fish reproduction. Environ Toxicol Chem 28:2663–2670
Zerulla M, Lange R, Steger-Hartmann T, Panter G, Hutchinson T, Dietrich DR (2002) Morphological sex reversal upon short-term exposure to endocrine modulators in juvenile fathead minnow (Pimephales promelas). Toxicol Lett 131:51–63
Zhang X, Oakes KD, Cui SF, Bragg L, Servos MR, Pawliszyn J (2010) Tissue-specific in vivo bioconcentration of pharmaceuticals in rainbow trout (Oncorhynchus mykiss) using space-resolved solid-phase microextraction. Environ Sci Technol 44:3417–3422
Zhou SN, Oakes KD, Servos MR, Pawliszyn J (2008) Application of solid-phase microextraction for in vivo laboratory and field sampling of pharmaceuticals in fish. Environ Sci Technol 42:6073–6079
Zou E, Fingerman M (1997) Synthetic estrogenic agents do not interfere with sex differentiation but do inhibit molting of the cladoceran Daphnia magna. Bull Environ Contam Toxicol 58:596–602
Zuccato E, Castiglioni S, Fanelli R, Bagnati R, Reitano G, Calamari D (2004) Risks related to the discharge of pharmaceuticals in the environment: further research is needed. In: Kümmerer K (ed) Pharmaceuticals in the environment: sources, fate, effects and risks, 2nd edn. Springer, Berlin, Germany, pp 431–437
Zurita JL, Repetto G, Jos A, Salguero M, Lopez-Artiguez M, Camean AM (2007) Toxicological effects of the lipid regulator gemfibrozil in four aquatic systems. Aquat Toxicol 81:106–115
Acknowledgments
We thank Jason P. Berninger for useful discussions and assistance with information used to develop Figure 1.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Brausch, J.M., Connors, K.A., Brooks, B.W., Rand, G.M. (2012). Human Pharmaceuticals in the Aquatic Environment: A Review of Recent Toxicological Studies and Considerations for Toxicity Testing. In: Whitacre, D. (eds) Reviews of Environmental Contamination and Toxicology Volume 218. Reviews of Environmental Contamination and Toxicology, vol 218. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-3137-4_1
Download citation
DOI: https://doi.org/10.1007/978-1-4614-3137-4_1
Published:
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4614-3136-7
Online ISBN: 978-1-4614-3137-4
eBook Packages: Earth and Environmental ScienceEarth and Environmental Science (R0)