Implementing ecopharmacovigilance in practice: Challenges and potential opportunities

Drug Safety

Volumn 36, Issue 7, 2013, Pages 533-546

  Holm, Gisela ^a   Snape, Jason R ^b   Murray Smith, Richard ^b   Talbot, John ^c   Taylor, David ^d   Sörme, Pernilla ^a  

^a ASTRAZENECA R AND D   (Sweden)

^b ASTRAZENECA   (United Kingdom)

^c UNIVERSITY OF HERTFORDSHIRE   (United Kingdom)

^d WCA ENVIRONMENT LTD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANASTROZOLE; ATENOLOL; BICALUTAMIDE; DROSPIRENONE; LEVONORGESTREL; OSELTAMIVIR; PROPRANOLOL; TAMOXIFEN;

ARTICLE; CLINICAL PRACTICE; CONCEPTUAL FRAMEWORK; DRUG INDUSTRY; DRUG RESEARCH; DRUG SURVEILLANCE PROGRAM; ECOPHARMACOVIGILANCE; ENVIRONMENTAL FACTOR; ENVIRONMENTAL IMPACT; ENVIRONMENTAL PROTECTION; PRIORITY JOURNAL; RISK ASSESSMENT; RISK MANAGEMENT; SIGNAL DETECTION; STRATEGIC PLANNING;

ANIMALS; ASIA; DICLOFENAC; ENVIRONMENTAL MONITORING; HUMANS; LIFE CYCLE STAGES; PHARMACOVIGILANCE; PUBLIC HEALTH; RISK ASSESSMENT;

EID: 84879971726     PISSN: 01145916     EISSN: 11791942     Source Type: Journal    
DOI: 10.1007/s40264-013-0049-3     Document Type: Article

References (105)

1. European Commission. Regulation (EU) No 1235/2010 of the European parliament and of the Council. Volume 1. Pharmaceutical legislation medicinal products for human use. 2010. Available from URL: http://ec.europa.eu/health/ documents/eudralex/vol-1/. Accessed 4 Apr 2013.
2. Alder AC. Consumption and occurrence. In: Ternes TA, Joss A, editors. Human pharmaceuticals, hormones and fragrances: the challenge of micropollutants in urban water management. London: IWA Publishing; 2006.
3. Daughton CG, Ternes TA. Pharmaceuticals and personal care products in the environment: agents of subtle change? Environ Health Perspect. 1999;107(Suppl.6):907-38.
4. Kümmerer K. Drugs in the environment: emission of drugs, diagnostic aids and disinfectants into wastewater by hospitals in relation to other sources: a review. Chemosphere. 2001;45(6-7):957-69.
5. Vanderford BJ, Snyder SA. Analysis of pharmaceuticals in water by isotope dilution liquid chromatography/tandem mass spectrometry. Environ Sci Technol. 2006;40(23):7312-20.
6. Batt AL, Kostich MS, Lazorchak JM. Analysis of ecologically relevant pharmaceuticals in wastewater and surface water using selective solid-phase extraction and UPLC-MS/MS. Anal Chem. 2008;80(13):5021-30.
7. Kasprzyk-Hordern B, Baker DR. Estimation of community-wide drugs use via stereoselective profiling of sewage. Sci Total Environ. 2012;423:142-50.
8. Kümmerer K. The presence of pharmaceuticals in the environment due to human use - present knowledge and future challenges. J Environ Manage. 2009;90(8):2354-66.
9. Cunningham VL, Binks SP, Olson MJ. Human health risk assessment from the presence of human pharmaceuticals in the aquatic environment. Regul Toxicol Pharmacol. 2009;53(1):39-45.
10. Heberer T. Occurrence, fate, and removal of pharmaceutical residues in the aquatic environment: a review of recent research data. Toxicol Lett. 2002;131(1-2):5-17.
11. Fent K, Weston AA, Caminada D. Ecotoxicology of human pharmaceuticals. Aquat Toxicol. 2006;76(2):122-59.
12. Kim SD, Cho J, Kim IS, Vanderford BJ, Snyder SA. Occurrence and removal of pharmaceuticals and endocrine disruptors in South Korean surface, drinking, and waste waters. Water Res. 2007;41(5):1013-21.
13. Daughton CG, Ruhoy IS. Environmental footprint of pharmaceuticals: the significance of factors beyond direct excretion to sewers. Environ Toxicol Chem. 2009;28(12):2495-521.
14. Snyder SA. Pharmaceuticals, personal care products and endcrine disruptors in water: implications for the water industry. Environ Eng Sci. 2003;20:449.
15. Koplin DW. Pharmaceuticals, hormones and other organic wastewater contaminants in US streams, 199-2000: a national reconnaissance. Environ Science Technol. 2002;36:1202-11.
16. Kümmerer K. Pharmaceuticals in the environment: a brief summary. In: Kümmerer K, editor. Pharmaceuticals in the environment. London: Springer; 2008. p. 3-21.
17. Monteiro SC, Boxall AB. Occurrence and fate of human pharmaceuticals in the environment. Rev Environ Contam Toxicol. 2010;202:53-154.
18. Bound JP, Voulvoulis N. Predicted and measured concentrations for selected pharmaceuticals in UK rivers: implications for risk assessment. Water Res. 2006;40(15):2885-92.
19. Barnes KK, Christenson SC, Kolpin DW, Focazio MJ, Furlong ET, Zaugg SD, et al. Pharmaceuticals and other organic waste water contaminants within a leachate plume downgradient of a municipal landfill. Ground Water Monit Remediat. 2004;24(2):119-26.
20. Halling-Sørensen B, Nors Nielsen S, Lanzky PF, Ingerslev F, Holten Lutzhoft HC, Jorgensen SE. Occurrence, fate and effects of pharmaceutical substances in the environment: a review. Chemosphere. 1998;36(2):357-93.
21. Daughton CG, Ruhoy IS. Green pharmacy and pharmEcovigilance: prescribing and the planet. Expert Rev Clin Pharmacol. 2011;4(2):211-32.
22. Thomas KV, Dye C, Schlabach M, Langford KH. Source to sink tracking of selected human pharmaceuticals from two Oslo city hospitals and a wastewater treatment works. J Environ Monit. 2007;9(12):1410-8.
23. Zhang Y, Yang M, Liu M, Dong L, Renli R. Antibiotic pollution from Chinese drug manufacturing: antibiotic resistance. Toxicol Lett. 2012;211(Suppl.:S16).
24. Larsson DGJ, de Pedro C, Paxeus N. Effluent from drug manufactures contains extremely high levels of pharmaceuticals. J Hazard Mater. 2007;148(3):751-5.
25. Li D, Yang M, Hu J, Ren L, Zhang Y, Li K. Determination and fate of oxytetracycline and related compounds in oxytetracycline production wastewater and the receiving river. Environ Toxicol Chem. 2008;27(1):80-6.
26. Murray-Smith RJ, Coombe VT, Grönlund MH, Waern F, Baird JA. Managing emissions of active pharmaceutical ingredients from manufacturing facilities: an environmental quality standard approach. Integr Environ Assess Manage. 2012;8(2):320-30.
27. Snape JR, Lewis C, Murray-Smith R. Pollution: drug firm monitors waste water. Nature. 2011;477:33.
28. US FDA. Guidance for industry: environmental assessment of human drug and biologics application. Silver Spring; US FDA, 1998.
29. Commission European. Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use. Off J Eur Commun. 2004;311:67.
30. Velo GP. Why ecopharmacovigilance. Drug Saf. 2007;30(10):919.
31. Kümmerer K, Velo G. Ecopharmacology: a new topic of importance in pharmacovigilance. Drug Saf. 2006;29(5):371-3.
32. Rahman SZ, Khan RA. Environmental pharmacology: a new discipline. Indian J Pharmacol. 2006;38:229-30.
33. Rahman SZ, Khan RA, Gupta V, Uddin M. Pharmacoenvironmentology: a component of pharmacovigilance. Environ Health. 2007;6:20.
34. Daughton CG, Ruhoy IS. The afterlife of drugs and the role of pharmEcovigilance. Drug Saf. 2008;31(12):1069-82.
35. Taylor D. Ecopharmacostewardship: a pharmaceutical industry perspective. In: Kümmerer K, Hempel M, editors. Green and sustainable pharmacy. Berlin/Heidelberg: Springer; 2010. p. 105-26.
36. World Health Organisation. The importance of pharmacovigilance: safety monitoring of medicinal products. Geneva: World Health Organisation; 2002.
37. Wise L, Parkinson J, Raine J, Breckenridge A. New approaches to drug safety: a pharmacovigilance tool kit. Nat Rev Drug Discov. 2009;8:779-82.
38. Murray-Smith R. Ecopharmacovigilance: a drug company perspective. 10th Annual Meeting of the International Society of Pharmacovigilance, Accra, Ghana. 4 November 2010. Available from URL: http://isop2010.isoponline.org/uploads/ prog/Programme-3rd-7th-November-.pdf. Accessed 4 Apr 2013.
39. Velo G, Moretti U. Ecopharmacovigilance for better health. Drug Saf. 2010;33(11):963-8.
40. Cuklev F, Kristiansson E, Fick J, Asker N, Förlin L, Larsson DGJ. Diclofenac in fish: blood plasma levels similar to human therapeutic levels affect global hepatic gene expression. Environ Toxicol Chem. 2011;30(9):2126-34.
41. Fick J, Lindberg RH, Parkkonen J, Arvidsson B, Tysklind M, Larsson DGJ. Therapeutic levels of levonorgestrel detected in blood plasma of fish: results from screening rainbow trout exposed to treated sewage effluents. Environ Sci Technol. 2010;44(7):2661-6.
42. Ankley GT, Black MC, Garric J, Hutchinson TH, Iguchi T. A framework for assessing the hazard of pharmaceutical materials to aquatic species. In: William RT, editor. Human pharmaceuticals: assessing the impacts on aquatic ecosystems. Florida: SETAC Press; 2005.
43. Gunnarsson L, Jauhiainen A, Kristiansson E, Nerman O, Larsson DGJ. Evolutionary conservation of human drug targets in organisms used for environmental risk assessments. Environ Sci Technol. 2008;42(15):5807-13.
44. Oaks JL, Gilbert M, Virani MZ, Watson RT, Meteyer CU, Rideout BA, et al. Diclofenac residues as the cause of vulture population decline in Pakistan. Nature. 2004;427(6975):630-3.
45. Sumpter J. Pharmaceuticals in the environment: moving from a problem to a solution. In: Kümmerer K, Hempel M, editors. Green and sustainable pharmacy. Berlin: Springer; 2010. p. 11-22.
46. Green RE, Newton I, Shultz S, Cunningham AA, Gilbert M, Pain DJ, et al. Diclofenac poisoning as a cause of vulture population declines across the Indian subcontinent. J Appl Ecol. 2004;41(5):793-800.
47. Green RE, Taggart MA, Senacha KR, Raghavan B, Pain DJ, Jhala Y, et al. Rate of decline of the Oriental White-backed vulture population in India estimated from a survey of diclofenac residues in carcasses of ungulates. PLoS ONE. 2007;2(8):e686.
48. Swan GE, Cuthbert R, Quevedo M, Green RE, Pain DJ, Bartels P, et al. Toxicity of diclofenac to Gyps vultures. Biol Lett. 2006;2(2):279-82.
49. Rattner BA, Whitehead MA, Gasper G, Meteyer CU, Link WA, Taggart MA, et al. Apparent tolerance of turkey vultures (Cathartes aura) to the non-steroidal anti-inflammatory drug diclofenac. Environ Toxicol Chem. 2008;27(11):2341-5.
50. Cuthbert R, Parry-Jones J, Green RE, Pain DJ. NSAIDs and scavenging birds: potential impacts beyond Asia's critically endangered vultures. Biol Lett. 2007;3(1):90-3.
51. Länge R, Hutchinson TH, Croudace CP, Siegmund F, Schweinfurth H, Hampe P, et al. Effects of the synthetic estrogen 17beta-ethinylestradiol on the life-cycle of the fathead minnow (Pimephales promelas). Environ Toxicol Chem. 2001;20(6):1216-27.
52. Nash JP, Kime DE, Van der Ven LT, Wester PW, Brion F, Maack G, et al. Long-term exposure to environmental concentrations of the pharmaceutical ethynylestradiol causes reproductive failure in fish. Environ Health Perspect. 2004;112(17):1725-33.
53. Caldwell DJ, Mastrocco F, Anderson PD, Länge R, Sumpter JP. Predicted-no-effect concentrations for the steroid estrogens estrone, 17beta-estradiol, estriol, and 17beta-ethinylestradiol. Environ Toxicol Chem. 2012;31(6):1396-406.
54. Jobling S, Nolan M, Tyler CR, Brighty G, Sumpter JP. Widespread sexual disruption in wild fish. Environ Sci Technol. 1998;32(17):2498-506.
55. Jobling S, Tyler CR. Introduction: the ecological relevance of chemically induced endocrine disruption in wildlife. Environ Health Perspect. 2006;114(Suppl. 1):7-8.
56. Soares A, Guieysse B, Jefferson B, Cartmell E, Lester JN. Nonylphenol in the environment: a critical review on occurrence, fate, toxicity and treatment in wastewaters. Environ Int. 2008;34(7):1033-49.
57. Crain AD, Eriksen M, Iguchi T, Jobling S, Laufer H, LeBlanc GA, et al. An ecological assessment of bisphenol-A: evidence from comparative biology. Reprod Toxicol. 2007;24:225-39.
58. Carnevali O, Tosti L, Speciale C, Peng C, Zhu Y, Maradonna F. DEHP impairs zebrafish reproduction by affecting critical factors in oogenesis. PLoS ONE. 2010;5(4):e10201.
59. Kiparissis Y, Balch GC, Metcalfe TL, Metcalfe CD. Effects of the isoflavones genistein and equol on the gonadal development of Japanese medaka (Oryzias latipes). Environ Health Perspect. 2003;111(9):1158-63.
60. Desbrow C, Routledge EJ, Brighty GC, Sumpter JP, Waldock M. Identification of estrogenic chemicals in STW effluent. 1. Chemical fractionation and in vitro biological screening. Environ Sci Technol. 1998;32(11):1549-58.
61. Thorpe KL, Cummings RI, Hutchinson TH, Scholze M, Brighty G, Sumpter JP, et al. Relative potencies and combination effects of steroidal estrogens in fish. Environ Sci Technol. 2003;37(6):1142-9.
62. Kidd KA, Blanchfield PJ, Mills KH, Palace VP, Evans RE, Lazorchak JM, et al. Collapse of a fish population after exposure to a synthetic estrogen. Proc Natl Acad Scis. 2007;104(21):8897-901.
63. Janssen Pharmaceutica. ERAR (European Public Assessment Report) for EVRA (Ref EMEA/H/C/410, attached). 2012. Available from URL: http://www.emea.europa. eu/docs/en-GB/document-library/EPAR-Product-Information/human/000410/ WC500031512.pdf. Accessed Oct 2012.
64. Winter MJ, Owen SF, Murray-Smith R, Panter GH, Hetheridge MJ, Kinter LB. Using data from drug discovery and development to aid the aquatic environmental risk assessment of human pharmaceuticals: concepts, considerations, and challenges. Integr Environ Assess Manag. 2010;6(1):38-51.
65. KNAPPE. Pharmaceutical Products in Environmental Waters (KNAPPE). 2012. Available from URL: http://www.ecologic.eu/2293. Accessed Oct 2012.
66. Duis K, Coors A. Environmental risk assessment of pharmaceuticals (ERAPharm). 2008. Available from URL: http://www.erapharm.org/. Accessed Jan 2008.
67. Sumpter JP, Roig B. Ecological and human health risk assessments of antibiotics and anti-cancer drugs found in the environment. 2012. Available from URL: http://www.pharmas-eu.org/. Accessed May 2012.
68. Filipic M. Fate and effects of cytostatic pharmaceuticals in the environment and identification of biomarkers for an improved risk assessment on environmental exposure (CytoThreat). 2012. Available from URL: http://www.cytothreat.eu/. Accessed May 2012.
69. European Commission. Call for tender no. EAHC/2011/Health/12 concerning study on the risks of the environmental effects of medicinal products. 2011. Available from URL: http://ec.europa.eu/eahc/health/tenders-H12-2011.html. Accessed 4 Apr 2013.
70. Gardner M, Comber S, Scrimshaw MD, Cartmell E, Lester J, Ellor B. The significance of hazardous chemicals in wastewater treatment works effluents. Sci Total Environ. 2012;437(0):363-72.
71. Rudén C. Identification and reduction of risks caused by pharmaceuticals (MISTRAPharma). 2012. Available from URL: http://www. mistrapharma.se/. Accessed May 2012.
72. Williams TD, Caunter JE, Lillicrap AD, Hutchinson TH, Gillings EG, Duffell S. Evaluation of the reproductive effects of tamoxifen citrate in partial and full life-cycle studies using fathead minnows (Pimephales Promelas). Environ Toxicol Chem. 2007;26(4):695-707.
73. Giltrow E, Eccles PD, Winter MJ, McCormack PJ, Rand-Weaver M, Hutchinson TH, et al. Chronic effects assessment and plasma concentrations of the ÎÂ-blocker propranolol in fathead minnows (Pimephales promelas). Aquatic Toxicol. 2009;95(3):195-202.
74. Winter MJ, Lillicrap AD, Caunter JE, Schaffner C, Alder AC, Ramil M, et al. Defining the chronic impacts of atenolol on embryo-larval development and reproduction in the fathead minnow (Pimephales promelas). Aquatic Toxicol. 2008;86(3):361-9.
75. Küster A, Alder AC, Escher BI, Duis K, Fenner K, Garric J, et al. Environmental risk assessment of human pharmaceuticals in the European Union: a case study with the B-blocker atenolol. Integr Environ Assess Manag. 2010;6(S1):514-23.
76. Panter GH, Glennon YC, Robinson J, Hargreaves A, Murray-Smith R. Effects of the anti-androgen, bicalutamide, in a reduced life-cycle study with the fathead minnow (Pimephales promelas). Aquatic Toxicol. 2012;114-115:31-8.
77. Zeilinger J, Steger-Hartmann T, Maser E, Goller S, Vonk R, Länge R. Effects of synthetic gestagens on fish reproduction. Environ Toxicol Chem. 2009;28(12):2663-70.
78. ®) under pandemic use conditions to the coastal marine compartment. Environ Int. 2009;35(6):931-6.
79. Straub J. An environmental risk assessment for oseltamivir (Tamiflu) for sewage works and surface waters under seasonal-influenza- and pandemic-use conditions. Ecotoxicol Environ Saf. 2009;72(6):1625-34.
80. World Health Organization. The evolving threat of antimicrobial resistance: options for action. Geneva: World Health Organization; 2012.
81. Szczepanowski R, Linke B, Krahn I, Gartemann K, Gützkow T, Eichler W, et al. Detection of 140 clinically relevant antibiotic-resistance genes in the plasmid metagenome of wastewater treatment plant bacteria showing reduced susceptibility to selected antibiotics. Microbiology. 2009;155(7):2306-19.
82. Jury K, Khan SJ, Vancov T, Stuetz RM, Ashbolt NJ. Are sewage treatment planst promoting antibiotic resistance. Crit Rev Environ Sci Technol. 2011;41:243-70.
83. Börjesson S, Matussek A, Melin S, Löfgren S, Lindgren PE. Methicillin-resistant Staphylococcus aureus (MRSA) in municipal wastewater: an uncharted threat? J Appl Microbiol. 2010;108(4):1244-51.
84. Boxall ABA, Rudd MA, Brooks BW, Caldwell DJ, Choi K, Hickmann S, et al. Pharmaceuticals and personal care products in the environment: what are the big questions? Environ Health Perspect. 2012;120(9):1221-9.
85. Klimisch H, Andreae M, Tillmann U. A systematic approach for evaluating the quality of experimental toxicological and ecotoxicological data. Regul Toxicol Pharmacol. 1997;25(1):1-5.
86. Küster A, Bachmann J, Brandt U, Ebert I, Hickmann S, Klein-Goedicke J, et al. Regulatory demands on data quality for the environmental risk assessment of pharmaceuticals. Regul Toxicol Pharmacol. 2009;55(3):276-80.
87. Ågerstrand M, Küster A, Bachmann J, Breitholtz M, Ebert I, Rechenberg B, et al. Reporting and evaluation criteria as means towards a transparent use of ecotoxicity data for environmental risk assessment of pharmaceuticals. Environ Pollut. 2011;159(10):2487-92.
88. Ankley GT, Bennett RS, Erickson RJ, Hoff DJ, Hornung MW, Johnson RD, et al. Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment. Environ Toxicol Chem. 2010;29(3):730-41.
89. Hutchinson TH, Ankley GT, Segner H, Tyler CR. Screening and testing for endocrine disruption in fish: biomarkers as "signposts", not "traffic Lights", in risk assessment. Environ Health Perspect. 2006;114(Suppl. 1):106-14.
90. Huggett DB, Brooks BW, Peterson B, Foran CM, Schlenk D. Toxicity of select beta adrenergic receptor-blocking pharmaceuticals (B-Blockers) on aquatic organisms. Arch Environ Contam Toxicol. 2002;43(2):229-35.
91. Huggett DB, Khan IA, Foran CM, Schlenk D. Determination of beta-adrenergic receptor blocking pharmaceuticals in United States wastewater effluent. Environ Pollut. 2003;121(2):199-205.
92. Liu Q, Williams HE. Kinetics and degradation products for direct photolysis of B-blockers in water. Environ Sci Technol. 2007;41(3):803-10.
93. Liu Q, Williams TD, Cumming RI, Holm G, Hetheridge MJ, Murray-Smith R. Comparative aquatic toxicity of propranolol and its photodegraded mixtures: algae and rotifer screening. Environ Toxicol Chem. 2009;28(12):2622-31.
94. Owen SF, Huggett DB, Hutchinson TH, Hetheridge MJ, Kinter LB, Ericson JF, et al. Uptake of propranolol, a cardiovascular pharmaceutical, from water into fish plasma and its effects on growth and organ biometry. Aquatic Toxicol. 2009;93(4):217-24.
95. Giltrow E, Eccles PD, Winter MJ, McCormack PJ, Rand-Weaver M, Hutchinson TH, et al. Chronic effects assessment and plasma concentrations of the beta-blocker propranolol in fathead minnows (Pimephales promelas). Aquatic Toxicol. 2009;95(3):195-202.
96. Caldwell DJ, Mastrocco F, Hutchinson TH, Länge R, Heijerick D, Janssen C, et al. Derivation of an aquatic predicted no-effect concentration for the synthetic hormone, 17 alpha-ethinyl estradiol. Environ Sci Technol. 2008;42(19):7046-54.
97. Straub JO, Stewart KM. Deterministic and probabilistic acute-based environmental risk assessment for naproxen for Western Europe. Environ Toxicol Chem. 2007;26(4):795-806.
98. Hannah R, D'Aco VJ, Anderson PD, Buzby ME, Caldwell DJ, Cunningham VL, et al. Exposure assessment of 17B-ethinylestradiol in surface waters of the United States and Europe. Environ Toxicol Chem. 2009;28(12):2725-32.
99. United States Fish and Wildlife Services. Secondary pentobarbital poisoning of wildlife. 2012. Available from URL: http://cpharm.vetmed.vt.edu/ usfws/usfwsfpentobarbfactsheet.pdf. Accessed Oct 2012.
100. LIF. Swedish prescribing guide. 2012. Available from URL: http://www.fass.se/LIF/home/index.jsp. Accessed Jun 2012.
101. AstraZeneca. Environmental risk assessment data. 2012. Available from URL: http://www.astrazeneca.com/Responsibility/The-environment/Pharmaceuticals- in-the-environment/era-data-2012. Accessed June 2012.
102. Heads of Medicines Agency (HMA). HMA/EMA guidance document on the identification of commercially confidential information and personal data within the structure of the Marketing Authorisation (MA) application: release of information after the granting of a marketing authorisation. European Medicines Agency, 2012. Available from URL: http://www.ema.europa.eu/ema/index.jsp?curl= pages/news-and-events/news/2012/03/news-detail-001478.jsp&mid= WC0b01ac058004d5c1. Accessed 4 Apr 2013.
103. Brown AR, Riddle AM, Winfield IJ, Fletcher JM, James JB. Predicting the effects of endocrine disrupting chemicals on healthy and disease impacted populations of perch (Perca fluviatilis). Ecol Model. 2005;189(3):377-95.
104. Harris CA, Hamilton PB, Runnalls TJ, Vinciotti V, Henshaw A, Hodgson D, et al. The consequences of feminization in breeding groups of wild fish. Environ Health Perspect. 2010;119(3):306-11.
105. Roos V, Gunnarsson L, Fick J, Larsson DGJ, Rudén C. Prioritising pharmaceuticals for environmental risk assessment: towards adequate and feasible first-tier selection. Sci Total Environ. 2012;421-422:102-10.