Integrated chemical and biological analysis to explain estrogenic potency in bile extracts of red mullet (Mullus barbatus)

Aquatic Toxicology

Volumn 134-135, Issue , 2013, Pages 1-10

  Martínez Gómez, Concepción ^a   Lamoree, M ^b   Hamers, T ^b   van Velzen, M ^b   Kamstra, J H ^b   Fernandez B ^a   Benedicto, J ^a   Leon V M ^a   Vethaak, A D ^b,c  

^a Instituto Español de Oceanografía   (Spain)

^b VU UNIVERSITY AMSTERDAM   (Netherlands)

^c DELTARES   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

1 NAPHTHOL; 1 PYRENOL; 3 HYDROXYBENZO[A]PYRENE; 4 N NONYLPHENOL; 4 TETROCTYLPHENOL; 9 FLUORENOL; 9 PHENANTROL; ALKYLPHENOL; BILE EXTRACT; HYDROXYBENZO[A]PYRENE; POLYCYCLIC AROMATIC HYDROCARBON; UNCLASSIFIED DRUG;

BIOLOGICAL ANALYSIS; CHEMICAL ANALYSIS; CONCENTRATION (COMPOSITION); ESTROGENIC COMPOUND; FISH; HORMONE; METABOLITE; POLLUTION EXPOSURE; WATER POLLUTION;

ARTICLE; CHEMICAL ANALYSIS; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; ENVIRONMENTAL EXPOSURE; FEMALE; FISH; HUMAN; HUMAN CELL; IN VITRO STUDY; LAGOON; MALE; MASS FRAGMENTOGRAPHY; MULLUS BARBATUS; NONHUMAN; PRIORITY JOURNAL; SPAIN;

ANIMALS; BILE; ENVIRONMENTAL MONITORING; ESTROGENS; GAS CHROMATOGRAPHY-MASS SPECTROMETRY; GEOGRAPHY; MALE; MEDITERRANEAN SEA; PHENOLS; POLYCYCLIC HYDROCARBONS, AROMATIC; SMEGMAMORPHA; SPAIN;

MEDITERRANEAN COAST [SPAIN]; SPAIN;

MULLIDAE; MULLUS BARBATUS;

EID: 84875681348     PISSN: 0166445X     EISSN: 18791514     Source Type: Journal    
DOI: 10.1016/j.aquatox.2013.02.015     Document Type: Article

References (88)

1. Aas E., Beyer J., Goksoyr A. Fixed wavelength fluorescence (FF) of bile as a monitoring tool for polyaromatic hydrocarbons exposure in fish: an evaluation of compound specificity, inner filter effect and signal interpretation. Biomarkers 2000, 5:9-23.
2. Arukwe A., Goksøyr A. Eggshell and egg yolk proteins in fish: hepatic proteins for the next generation: oogenetic, population, and evolutionary implications of endocrine disruption. Comparative Hepatology 2003, 2:4. http://www.comparative-hepatology.com/content/2/1/4.
3. Bell A.M. Effects of an endocrine disruptor on courtship and aggressive behaviour of male three-spined stickleback (Gasterosteus aculeatus). Animal Behavior 2001, 62:775-780.
4. Benedicto J., Martínez-Gómez C., Guerrero J., Jornet J., Rodríguez C. Metal contamination in Portmán Bay (Murcia, SE Spain) 15 years after the cessation of mining activities. Ciencias Marinas 2008, 34(3):389-398.
5. Braune B., Outridge P., Fisk A.T., Muir D.G.C., Helm P.A., Hobbs K., Hoekstra P.F., Kuzyk Z.A., Kwan M., Letcher R.J., Lockhart W.L., Norstrom R.J., Stern G.A., Stirling I. Persistent organic pollutants and mercury in marine biota of the Canadian Arctic: an overview of spatial and temporal trends. Science of the Total Environment 2005, 351-352:4-56.
6. Budzinski H., Mazéas O., Tronczynski J., Désaunay Y., Bocquené G., Claireaux G. Link between exposure of fish (Soleasolea) to PAHs and metabolites: application to the Erika oil spill. Aquatic Living Resources 2004, 17:329-334.
7. Carragher J.F., Sumpter J.P. The mobilisation of calcium from calcified tissues of rainbow trout (Oncorhynchus mykiss) induced to synthesize vitellogenin. Comparative Biochemistry and Physiology A: Molecular and Integrative Physiology 1991, 99:169-172.
8. Choe S.Y., Kim S.J., Kim H.G., Lee J.H., Choi Y., Lee H., Kim Y. Evaluation of estrogenicity of major heavy metals. Science of the Total Environment 2003, 312(1-3):15-21.
9. Christiansen T., Korsgaard B., Jespersen Å. Effects of nonylphenol and 17b-oestradiol on vitellogenin synthesis, testicular structure and cytology in male eelpout Zoarces viviparus. Journal of Experimental Biology 1998, 201:179-192.
10. Colborn T., VomSaal F.S., Soto A.M. Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environmental Health Perspectives 1993, 101:378-384.
11. COM, 2001. 262 Final, Communication from the Commission of the Council and the European Parliament, Community Strategy for Endocrine Disrupters. A Range of Substances Suspected of Interfering withed Hormone Systems of Humans and Wildlife, Bruxelles, pp. 1-55.
12. Conesa H.M., Jiménez-Cárceles F.J. The Mar Menor lagoon (SE Spain): a singular natural ecosystem threatened by human activities. Marine Pollution Bulletin 2007, 54:839-849.
13. Damstra T., Barlow S., Bergman A., Kavlock R.J., Van der Kraak G. Global assessment of the state-of-the-science of endocrine disruptors. WHO 2002, 180.
14. Darbre P.D. Metalloestrogens: an emerging class of inorganic xenoestrogens with potential to add to the oestrogenic burden of the human breast. Journal of Applied Toxicology 2006, 26:191-197.
15. De Metrio G., Corriero A., Desantis S., Zubani D., Cirillo F., Deflorio M., Bridges C.R., Eicker J., de la Serna J.M., Megalofonou P., Kime D.E. Evidence of a high percentage of intersex in the mediterranean swordfish (Xiphias gladius L.). Marine Pollution Bulletin 2003, 46:358-361.
16. De Voogt P., Van Hattum B. Critical factors in exposure modeling of endocrine active substances. Pure and Applied Chemistry 2003, 75:1933-1948.
17. Escartín E., Porte C. Assessment of PAH pollution in coastal areas from the NW mediterranean through the analysis of fish bile. Marine Pollution Bulletin 1999, 38(12):1200-1206.
18. Fernandes D., Andreu-Sánchez O., Bebianno M.J., Porte C. Assessment of pollution along the Northern Iberian shelf by the combined use of chemical and biochemical markers in two representative fish species. Environmental Pollution 2008, 155(2):327-335.
19. Fernandes D., Bebianno M.J., Porte C. Assessing pollutant exposure in cultured and wild sea bass (Dicentrarchus labrax) from the Iberian Peninsula. Ecotoxicology 2009, 18(8):1043-1050.
20. Ferreira-Leach A.M.R., Hill E.M. Bioconcentration and distribution of 4-tert-octylphenol residues in tissues of the rainbow trout (Oncorhynchus mykiss). Marine Environment Research 2001, 51(1):75-89.
21. Filby A.L., Thorpe K.L., Maack G., Tyler Ch.R. Gene expression profiles revealing the mechanisms of anti-androgen- and estrogen-induced feminization in fish. Aquatic Toxicology 2007, 81:219-231.
22. Groshart, C.P., Okkerman, P.C., Wassenberg, W.B.A., Pijnenburg, A.M., 2001. Chemical study on alkylphenols. Report: RIKZ/2001.029. Directoraat General Rijkswaterstaat.
23. Gross-Sorokin M.Y., Roast S.D., Brighty G.C. Assessment of feminization of male fish in english rivers by the environment agency of England and Wales. Environmental Health Perspectives 2006, 114:147-151.
24. Herman R.L., Kincaid H.L. Pathological effects of orally administered estradiol to rainbow trout. Aquaculture 1988, 72:165-172.
25. Hernando M.D., Mezcua M., Fernández-Alba A.R., Barceló D. Environmental risk assessment of pharmaceutical residues in wastewater effluents, surface waters and sediments. Talanta 2006, 69:334-342.
26. Houtman C.J., van Oostveen A.M., Brouwer A., Lamoree M.H., Legler J. Identification of estrogenic compounds in fish bile using bioassay directed fractionation. Environmental Science and Technology 2004, 38:6415-6423.
27. Jobling S., Coey S., Whitmore J.G., Kime D.E., van Look K.J.W., McAllister B.G. Wild intersex roach (Rutilus rutilus) have reduced fertility. Biology of Reproduction 2002, 67:515-524.
28. Jobling S., Nolan M., Tyler C.R., Brighty G., Sumpter J.P. Widespread sexual disruption in wild fish. Environmental Science and Technology 1998, 32:2498-2506.
29. Jobling S., Sumpter J.P. Detergent components in sewage effluent are weakly oestrogenic to fish: An in vitro study using rainbow trout (Oncorhynchus mykiss) hepatocytes. Aquatic Toxicology 1993, 27:361-372.
30. Johnson L.L., Arkoosh M.R., Bravo C.F., Collier T.K., Krahn M.M., Meador J.P., Myers M.S., Reichert W.L., Stein J.E. The effects of polycyclic aromatic hydrocarbons in fish from puget sound Washington. The Toxicology of Fishes 2008, 2008:877-923. CRC Press, Taylor and Francis Group, Boca Raton, FL, USA.
31. Jonsson G., Cavcic A., Stokke T.U., Beyer J., Sundt R.C., Brede C. Solid-phase analytical derivatization of alkylphenols in fish bile for gas chromatography-mass spectrometry analysis. Journal of Chromatography A 2008, 1183(1/2):6-14.
32. Kinacigil H.T., Ilkyaz A.T., Akyol O., Matin G., Çira E., Ayaz A. Growth parameters of Red Mullet (Mullus barbatus L., 1758) and seasonal cod-end selectivity of traditional bottom trawl nets in Izmir Bay (Aegean Sea). Acta Adriatic 2001, 42(1):113-123.
33. Kinnberg K., Korsgaard B., Bjerregaard P., Jespersen A. Effects of nonylphenol and 17b-estradiol on vitellogenin synthesis and testis morphology in male platyfish Xiphophorus maculatus. The Journal of Experimental Biology 2000, 203:171-181.
34. Kirby M.F., Allen Y.T., Dyer R.A., Feist S.W., Katsiadaki I., Matthiessen P., Scott A., Smith P.A., Stentiford G.D., Thain J.E., Thomas K.V., Tolhurst L., Waldock M.J. Surveys of plasma vitellogenin and intersex in male flounder (Platichthys flesus) as measures of endocrine disruption by estrogenic contamination in United Kingdom estuaries: temporal trends, 1996-2001. Environmental Toxicology 2004, 23(3):748-758.
35. Kolpin D.W., Furlong E.T., Meyer M.T., Thurman E.M., Zaugg S., Barber L.B., Buxton H.T. Pharmaceuticals, hormones, and other organic wastewater contaminants in US streams, 1999-2000: a national reconnaissance. Environmental Science and Technology 2002, 36(6):1202-1211.
36. Legler J., Jonas A., Lahr J., Vethaak A.D., Brouwer A., Murk A.J. Biological measurement of estrogenic activity in urine and bile conjugates with the in vitro ER-CALUX reporter gene assay. Environmental Toxicology and Chemistry 2002, 21(3):473-479.
37. León V.M., Martínez-Gómez C., García I., Campillo J.A., Benedicto J. Spatial distribution and temporal trends of polycyclic aromatic hydrocarbons in Mytilus galloprovincialis from the Iberian mediterranean coast. Environmental Monitoring 2012, (assessed April 2012). 10.1007/s10661-012-2614-0.
38. Lin E.L.C., Cornier S.M., Racine R.N. Synchronous fluorometric measurement of metabolites of polycyclic aromatic hydrocarbons in the bile of brown bullhead. Environmental Toxicology and Chemistry 1994, 13:707-715.
39. Lye C.M., Frid C.L.J., Gill M.E., Cooper D.W., Jones M. Estrogenic alkylphenols in fish tissues, sediments, and waters from the UK. Tyne and Tees Estuaries. Environmental Science and Technology 1999, 33:1009-1014.
40. Machala M., Ciganek M., Bláha L., Minksová K., Vondrácek J. Aryl hydrocarbon receptor-mediated and estrogenic activities of oxygenated polycyclic aromatic hydrocarbons and azarenes originally identified in extracts of river sediments. Environmental Toxicology and Chemistry 2001, 20:2736-2743.
41. Madsen S.S., Mathiesen A.B., Korsgaard B. Effects of 17-estradiol and 4-nonylphenol on smoltification and vitellogenesis in Atlantic salmon, Salmor salar. Fish Physiology and Biochemistry 1997, 17:303-312.
42. Martínez-Gómez C., Fernández B., Benedicto J.M., Valdés J., Campillo J.A., León V.M., Vethaak A.D. Health status of red mullets from polluted areas of the Spanish Mediterranean coast, with special reference to Portmán (SE Spain). Marine Environment Research 2012, 77:50-59.
43. Martin-Skilton R., Lavado R., Thibaut R., Minier Ch., Porte C. Evidence of endocrine alteration in the red mullet, Mullus barbatus from the NW mediterranean. Environmental Pollution 2006, 141:60-68.
44. Matthiessen P. Endocrine disruption in marine fish, in special topic issue on the implications of endocrine active substances for humans and wildlife. Pure and Applied Chemistry 2003, 75(11/12):2249-2261.
45. Matthiessen P., Gibbs P.E. Critical appraisal of the evidence for tributyltin-mediated endocrine disruption in mollusks. Environmental Toxicology and Chemistry 1998, 17(1):37-43.
46. Miramand P., Lafaurie M., Fowler S.S., Lemaire P., Guary J.C., Bentley D. Reproductive cycle and heavy metals in the organs of red mullet, Mullus barbatus (L.), from the northwestern mediterranean. The Science of the Total Environment 1991, 103:47-56.
47. Moreno-González, R., Campillo, J.A., García, V., León, V.M., in press. Seasonal input of regulated and emerging organic pollutants through surface watercourses to a Mediterranean coastal lagoon. Chemosphere, doi:10.1016/j.chemosphere.2012.12.022.
48. Nakada N., Nyunoya H., Nakamura M., Hara A., Iguchi T., Takada H. Identification of estrogenic compounds in wastewater effluent. Environmental Toxicology and Chemistry 2004, 23:2807-2815.
49. Navas J.M., Segner H. Antiestrogenicity of ß-naphthoflavone and PAHs in cultured rainbow trout hepatocytes: evidence for a role of the arylhydrocarbon receptor. Aquatic Toxicology 2000, 51(1):79-92.
50. Nimrod A.C., Benson W.H. Environmental estrogenic effects of alkylphenolethoxylates. Critical Reviews in Toxicology 1996, 26:335-364.
51. OSPAR, 2009. OSPAR Commission. JAMP Guidelines for Contaminant-Specific Biological Effects (OSPAR Agreement 2008-09). Ref. No. 2008-9. Technical Annex 4: Estrogen-Specific Biological Monitoring, pp. 39-44.
52. Pérez-Ruzafa A., Gilabert J., Gutiérrez J.M., Fernández A.I., Marcos C., Sabah S. Evidence of a planktonic food web response to changes in nutrient input dynamics in the Mar Menor coastal lagoon, Spain. Hydrobiologia 2002, 475/476:359-369.
53. Pérez-Ruzafa A., Navarro S., Barb A., Marcos C., Camara M.A., Salas F., Gutiérrez J.M. Presence of pesticides thorugh trophic compartments of the food web in the Mar Menor lagoon (SE Spain). Marine Pollution Bulletin 2000, 40(2):140-151.
54. Petrovic M., Fernández-Alba A.R., Borrull F., Marce R.M., Mazo E.G., Barceló D. Occurrence and distribution of nonionic surfactants, their degradation products, and linear alkylbenzene sulfonates in coastal waters and sediments in Spain. Environmental Toxicology and Chemistry 2002, 21(1):37-46.
55. Pojana G., Gomiero A., Jonkers N., Marcomini A. Natural and synthetic endocrine disrupting compounds (EDCs) in water, sediment and biota of a coastal lagoon. Environment International 2007, 33(7):929-936.
56. Porte C., Escartín E., García de la Parra L.M., Biosca X., Albaigés J. Assessment of coastal pollution by combined determination of chemical and biochemical markers in Mullus barbatus. Marine Ecology-Progress Series 2002, 235:205-216.
57. Renner R. National fish survey links pesticides with sex hormone imbalance. Environmental Science and Technology 1997, 31:312A-313A.
58. Reynaud S., Deschaux P. The effects of polycyclic aromatic hydrocarbons on the immune system of fish: a review. Aquatic Toxicology 2006, 77(2):229-238.
59. Rice C., Birnbaum L.S., Cogliano J., Mahaffey K., Needham L., Rogan W.J., vomSaal F.S. Exposure assessment for endocrine disruptors: some considerations in the design of studies. Environmental Health Perspectives 2003, 111(13):1683-1690.
60. Richardson D.M., Gubbins M.J., Davies I.M., Moffat C.F., Pollard P.M. Effects of feeding status on biliary PAH metabolite and biliverdin concentrations in plaice (Pleuronectes platessa). Environmental Toxicology and Pharmacology 2004, 17:79-85.
61. Rogers J.M., Denison M.S. Recombinant cell bioassay for endocrine disruptors development of stably transfected human ovarian cell line for the detection of estrogenic and anti-estrogenic chemicals. In Vitro and Molecular Toxicology 2000, 3:67-82.
62. Rosenblatt A.E., Burnstein K.L. Inhibition of androgen receptor transcriptional activity as a novel mechanism of action of arsenic. Molecular Endocrinology 2009, 23(3):412-421.
63. Ruddock P.J., Bird D.J., McCalley D.V. Bile metabolites of polycyclic aromatic hydrocarbons in three species of fish from the Severn estuary. Ecotoxicology and Environmental Safety 2002, 51:97-105.
64. Ruddock P.J., Bird D.J., McEvoy J., Peters L.D. Bile metabolites of polycyclic aromatic hydrocarbons (PAHs) in European eels Anguilla Anguilla from United Kingdom estuaries. Science of the Total Environment 2003, 301:105-117.
65. Scott A.P., Katsiadasi I., Witthames P.R., Hylland K., Davies I.M., McIntosh A.D., Thain J. Vitellogenin in the blood plasma of male cod (Gadus morhua): a sign of oestrogenic endocrine disruption in the open sea?. Marine Environment Research 2006, 61:149-170.
66. Scott A.P., Sanders M., Stentiford G.D., Reese R.A., Katsiadaki I. Evidence for estrogenic endocrine disruption in an offshore flatfish, the dab (Limanda limanda L.). Marine Environmental Research 2007, 64:128-148.
67. Serrano J.F., Sironi J.S. Quantification and evolution of the contaminant load of nutrients and plaguicides in the water of the Mar Menor lagoon and its relationships with the water inputs of the Albujón watercourse and other underground inputs. El Mar Menor 2009, 249-284. Estado actual del conocimiento científico. IEA - Cluster Foundation for the Protection and Conservation of the Mar Menor (Ed.).
68. Servos M., Hewitt M., McMaster M., Parrot J., Munkittrick K. Endocrine-active substances in the Canadian environment. Estrogens and Xeno-Estrogens in the Aquatic Environment: An Integrated Approach for Field Monitoring and Effect Assessment 2006, 425-454. SETAC Press, Pensacola, FL, USA. A.D. Vethaak, S.M. Schrap, P. de Voogt (Eds.).
69. Silva E., Rajapakse N., Kortenkamp A. Something from nothing - eight weak estrogenic chemicals combined at concentrations below NOECs produce significant mixture effects. Environmental Science and Technology 2002, 36(8):1751-1756.
70. Stoica A., Pentecost E., Martin M.B. Effects of arsenite on estrogen receptor-a expression and activity in MCF-7 breast cancer cells. Endocrinology 2000, 141(10):3595-3602.
71. Sumpter J.P., Johnson A.C. Lessons from endocrine disruption and their applications to other issues concerning trace organics in the aquatic environment. Environmental Science and Technology 2005, 39:4321-4332.
72. Sundt R.C., Baussant T., Beyer J. Uptake and tissue distribution of C4-C7 alkylphenols in Atlantic cod (Gadus morhua) relevance for biomonitoring of produced water discharges from oil production. Marine Pollution Bulletin 2009, 58:72-79.
73. Toft G., Baatrup E. Sexual characteristics are altered by 4-tert-octylphenol and 17ß-estradiol in the adult male guppy (Poecilia reticulata). Ecotoxicology and Environmental Safety 2001, 48(1):76-84.
74. Tuvikene A. Responses of fish to polycyclic aromatic hydrocarbons (PAHs). Annales Zoologici Fennici 1995, 32:295-309.
75. Tyler C.R., Jobling S., Sumpter J.P. Endocrine disruption in wildlife: a critical review of the evidence. Critical Reviews in Toxicology 1998, 28:319-361.
76. UNEP/MAP/MED POL, 2005. Transboundary Diagnostic Analysis (TDA) for the Mediterranean Sea, UNEP/MAP, Athens, pp. 1-228.
77. UNEP/RAMOGE, 1999. Manual on the Biomarkers Recommended for the MED POL Biomonitoring Programme, UNEP, Athens, pp. 1-92.
78. Van der Oost R., Beyer J., Vermeulen N.P.E. Fish bioaccumulation and biomarkers in environmental risk assessment: a review. Environmental Toxicology and Pharmacology 2003, 13:57-149.
79. Van Lipzig M.M.H., Vermeulen N.P.E., Gusinu R., Legler J., Frank H., Seidel A., Meerman H.N., John J.H.N. Formation of estrogenic metabolites of benzo[a]pyrene and chrysene by cytochrome P450 activity and their combined and supra-maximal estrogenic activity. Environmental Toxicology and Pharmacology 2005, 19(1):41-55.
80. Varanasi U., Stein J.E., Nishimoto M. Biotransformation and disposition of PAH in fish. Metabolism of PAH in the Aquatic Environment 1989, 93-149. CRC, Boca Raton, FL, USA. U. Varanasi (Ed.).
81. Vethaak A.D., de Voogt P., Schrap S.M. Integrated monitoring and assessment of estrogenic active substances: final considerations. Estrogens and Xeno-Estrogens in the Aquatic Environment: An Integrated Approach for Field Monitoring and Effect Assessment 2006, 457-467. SETAC Press, Pensacola, FL, USA. A.D. Vethaak, S.M. Schrap, P. de Voogt (Eds.).
82. Vethaak A.D., Lahr J., Schrap S.M., Belfroid A.C., Rijs G.B.J., Gerritsen A., Boer J., de Bulder A.S., Grinwis G.C.M., Kuiper R.V., Legler J., Murk T.A.J., Peijnenburg W., Verhaar H.J.M., de Voogt P. An integrated assessment of estrogenic contamination and biological effects in the aquatic environment of The Netherlands. Chemosphere 2005, 59:511-524.
83. Vethaak A.D., Legler J. Endocrine disruption in wildlife: background, effects and implications. Endocrine Disrupter Risk Assessment: Testing and Prediction Methods 2013, Wiley-Blackwell, http://www.barnesandnoble.com/w/endocrine-disrupters-peter-matthiessen/1111914566. P. Matthiessen (Ed.).
84. Vos J.G., Dybing E., Greim H.A., Ladefoged O., Lambrac C., Tarazona J.V., Brandt I., Vethaak A.D. Health effects of endocrine-disrupting chemicals on wildlife with special reference to the European situation. Critical Reviews in Toxicology 2000, 30:71-133.
85. Vuorinen P.J., Keinänen M., Vuontisjärvi H., Barsiene J., Broeg K., Fölin L., Gercken J., Kopecka J., Köhler A., Parkkonen J., Pempkowiak J., Schiedek D. Use of biliary PAH metabolites as a biomarker of pollution in fish from the Baltic Sea. Marine Pollution Bulletin 2006, 53:479-487.
86. White R., Jobling S., Hoare S.A., Sumpter J.P., Parker M.G. Environmentally persistent alkylphenolic compounds are estrogenic. Endocrinology 1994, 135:175-182.
87. Young, W.F., Whitehouse, P., Johnson, I., Sorokin, N., 2004. Proposed Predicted-No-Effect-Concentrations (PNECS) for Natural and Synthetic Steroid Oestrogens in Surface Waters. R&D Technical Report P2-T04/1, http://www.wrcplc.co.uk/rdbookshop.
88. Zhao J.L., Ying G.G., Liu Y.S., Chen F., Yang J.F., Wang L., Yang X.-B., Stauber J.L., Warne M.T. Occurrence and a screening-level risk assessment of human pharmaceuticals in the Pearl River system, south China. Environmental Toxicology and Chemistry 2010, 29(6):1377-1384.