Emerging wastewater contaminant metformin causes intersex and reduced fecundity in fish

Chemosphere

Volumn 135, Issue , 2015, Pages 38-45

  Niemuth, Nicholas J ^a   Klaper, Rebecca D ^a  

^a UNIVERSITY OF WISCONSIN MILWAUKEE   (United States)

Author keywords

Contaminants of emerging concern; Diabetes; Endocrine disrupting compounds; Pharmaceuticals and personal care products

Indexed keywords

DRUG PRODUCTS; EFFLUENT TREATMENT; ENDOCRINE DISRUPTERS; ENDOCRINOLOGY; FISH; MEDICAL PROBLEMS; ORGANIC POLLUTANTS; WASTEWATER TREATMENT;

CONTAMINANTS OF EMERGING CONCERNS; ENDOCRINE DISRUPTING COMPOUND; ENDOCRINE DISRUPTION; HORMONE RECEPTOR INTERACTIONS; PHARMACEUTICALS AND PERSONAL CARE PRODUCTS; REPRODUCTIVE TISSUES; WASTEWATER EFFLUENTS; WASTEWATER TREATMENT PLANT EFFLUENT;

EFFLUENTS;

ENDOCRINE DISRUPTOR; METFORMIN; ESTROGEN; WASTE WATER; WATER POLLUTANT;

CHEMICAL POLLUTANT; CONCENTRATION (COMPOSITION); ESTROGENIC COMPOUND; FECUNDITY; FISH; FRESHWATER ECOSYSTEM; INTERSEX; POLLUTION EFFECT; WASTEWATER;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CHROMOSOME PAIRING; CLUTCH SIZE; COMPARATIVE STUDY; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; DISORDER OF SEX DEVELOPMENT; EFFLUENT; FEMALE; FERTILITY; FISH; GONAD; HORMONE RECEPTOR INTERACTION; INTERSEX; LONG TERM EXPOSURE; MALE; NONHUMAN; OOCYTE; PIMEPHALES PROMELAS; REPRODUCTION; SEXUAL DEVELOPMENT; TESTIS; WASTE WATER; ANIMAL; CHEMICALLY INDUCED; CHEMISTRY; CYPRINIDAE; DRUG EFFECTS; ENVIRONMENTAL MONITORING; GROWTH, DEVELOPMENT AND AGING; TOXICITY; WATER POLLUTANT;

PIMEPHALES PROMELAS;

ANIMALS; CYPRINIDAE; DISORDERS OF SEX DEVELOPMENT; ENDOCRINE DISRUPTORS; ENVIRONMENTAL MONITORING; ESTROGENS; FERTILITY; GONADS; MALE; METFORMIN; REPRODUCTION; WASTE WATER; WATER POLLUTANTS, CHEMICAL;

EID: 84930464627     PISSN: 00456535     EISSN: 18791298     Source Type: Journal    
DOI: 10.1016/j.chemosphere.2015.03.060     Document Type: Article

References (47)

1. Ankley G.T., Jensen K.M., Kahl M.D., Korte J.J., Makynen E.A. Description and evaluation of a short-term reproduction test with the fathead minnow (Pimephales promelas). Environ. Toxicol. Chem. 2001, 20:1276-1290.
2. Ben Sahra I., Le Marchand-Brustel Y., Tanti J.-F., Bost F. Metformin in cancer therapy: a new perspective for an old antidiabetic drug?. Mol. Cancer Ther. 2010, 9:1092-1099.
3. Bjerregaard L.B., Korsgaard B., Bjerregaard P. Intersex in wild roach (Rutilus rutilus) from Danish sewage effluent-receiving streams. Ecotoxicol. Environ. Saf. 2006, 64:321-328.
4. Blair R.M., Fang H., Branham W.S., Hass B.S., Dial S.L., Moland C.L., Tong W., Shi L., Perkins R., Sheehan D.M. The estrogen receptor relative binding affinities of 188 natural and xenochemicals: structural diversity of ligands. Toxicol. Sci. 2000, 54:138-153.
5. Blair B.D., Crago J.P., Hedman C.J., Klaper R.D. Pharmaceuticals and personal care products found in the Great Lakes above concentrations of environmental concern. Chemosphere 2013, 93:2116-2123.
6. Blair B.D., Crago J.P., Hedman C.J., Treguer R.J.F., Magruder C., Royer L.S., Klaper R.D. Evaluation of a model for the removal of pharmaceuticals, personal care products, and hormones from wastewater. Sci. Total Environ. 2013, 444:515-521.
7. Blazer V.S., Iwanowicz L.R., Henderson H., Mazik P.M., Jenkins J.A., Alvarez D.A., Young J.A. Reproductive endocrine disruption in smallmouth bass (Micropterus dolomieu) in the Potomac River basin: spatial and temporal comparisons of biological effects. Environ. Monit. Assess. 2012, 184:4309-4334.
8. Brausch J.M., Connors K.A., Brooks B.W., Rand G.M. Human pharmaceuticals in the aquatic environment: a review of recent toxicological studies and considerations for toxicity testing. Rev. Environ. Contam. Toxicol. 2012, 218:1-99.
9. Charles B., Norris R., Xiao X., Hague W. Population pharmacokinetics of metformin in late pregnancy. Ther. Drug Monit. 2006, 28:67-72.
10. Chen M., Ohman K., Metcalfe C. Pharmaceuticals and endocrine disruptors in wastewater treatment effluents and in the water supply system of Calgary, Alberta, Canada. Water Qual. Res. J. Can. 2006, 41:351-364.
11. Chou C.H. Uptake and dispersion of metformin in the isolated perfused rat liver. J. Pharm. Pharmacol. 2000, 52:1011-1016.
12. Dammann A.A., Shappell N.W., Bartell S.E., Schoenfuss H.L. Comparing biological effects and potencies of estrone and 17β-estradiol in mature fathead minnows, Pimephales promelas. Aquat. Toxicol. 2011, 105:559-568.
13. Diamanti-Kandarakis E., Bourguignon J.-P., Giudice L.C., Hauser R., Prins G.S., Soto A.M., Zoeller R.T., Gore A.C. Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr. Rev. 2009, 30:293-342.
14. Fatta-Kassinos D., Meric S., Nikolaou A. Pharmaceutical residues in environmental waters and wastewater: current state of knowledge and future research. Anal. Bioanal. Chem. 2011, 399:251-275.
15. Feig D.S., Moses R.G. Metformin therapy during pregnancy: good for the goose and good for the gosling too?. Diabetes Care 2011, 34:2329-2330.
16. Ghoshdastidar A.J., Fox S., Tong A.Z. The presence of the top prescribed pharmaceuticals in treated sewage effluents and receiving waters in Southwest Nova Scotia, Canada. Environ. Sci. Pollut. Res. Int. 2014, 22:689-700.
17. Heberer T. Occurrence, fate, and removal of pharmaceutical residues in the aquatic environment: a review of recent research data. Toxicol. Lett. 2002, 131:5-17.
18. Jobling S., Nolan M., Tyler C.R., Brighty G., Sumpter J.P. Widespread sexual disruption in wild fish. Environ. Sci. Technol. 1998, 32:2498-2506.
19. Jobling S., Burn R.W., Thorpe K., Williams R., Tyler C. Statistical modeling suggests that antiandrogens in effluents from wastewater treatment works contribute to widespread sexual disruption in fish living in English rivers. Environ. Health Perspect 2009, 117:797-802.
20. Johns S.M., Denslow N.D., Kane M.D., Watanabe K.H., Orlando E.F., Sepúlveda M.S. Effects of estrogens and antiestrogens on gene expression of fathead minnow (Pimephales promelas) early life stages. Environ. Toxicol. 2011, 26:195-206.
21. Koops M.A., Hutchings J.A., McIntyre T.M. Testing hypotheses about fecundity, body size and maternal condition in fishes. Fish Fish. 2004, 5:120-130.
22. Länge R., Hutchinson T.H., Croudace C.P., Siegmund F., Schweinfurth H., Hampe P., Panter G.H., Sumpter J.P. Effects of the synthetic estrogen 17α-ethinylestradiol on the life-cycle of the fathead minnow (Pimephales promelas). Environ. Toxicol. Chem. 2001, 20:1216-1227.
23. Lange A., Paull G.C., Hamilton P.B., Iguchi T., Tyler C.R. Implications of persistent exposure to treated wastewater effluent for breeding in wild roach (Rutilus rutilus) populations. Environ. Sci. Technol. 2011, 45:1673-1679.
24. Lattier D.L., Reddy T.V., Gordon D.A., Lazorchak J.M., Smith M.E., Williams D.E., Wiechman B., Flick R.W., Miracle A.L., Toth G.P. 17alpha-ethynylestradiol-induced vitellogenin gene transcription quantified in livers of adult males, larvae, and gills of fathead minnows (Pimephales promelas). Environ. Toxicol. Chem. 2002, 21:2385-2393.
25. Liney K.E., Jobling S., Shears J.A., Simpson P., Tyler C.R. Assessing the sensitivity of different life stages for sexual disruption in roach (Rutilus rutilus) exposed to effluents from wastewater treatment works. Environ. Health Perspect 2005, 113:1299-1307.
26. Liney K.E., Hagger J.A., Tyler C.R., Depledge M.H., Galloway T.S., Jobling S. Health effects in fish of long-term exposure to effluents from wastewater treatment works. Environ. Health Perspect 2006, (Suppl 114):81-89.
27. Luckenbach T., Kilian M., Triebskorn R., Oberemm A. Fish early life stage tests as a tool to assess embryotoxic potentials in small streams. J. Aquat. Ecosyst. Stress Recover 2001, 8:355-370.
28. Niemuth N.J., Jordan R., Crago J., Blanksma C., Johnson R., Klaper R.D. Metformin exposure at environmentally relevant concentrations causes potential endocrine disruption in adult male fish. Environ. Toxicol. Chem. 2015, 34:291-296.
29. Novak P.J., Arnold W.A., Blazer V.S., Halden R.U., Klaper R.D., Kolpin D.W., Kriebel D., Love N.G., Martinović-Weigelt D., Patisaul H.B., Snyder S.A., Vom Saal F.S., Weisbrod A.V., Swackhamer D.L. On the need for a National (U.S.) research program to elucidate the potential risks to human health and the environment posed by contaminants of emerging concern. Environ. Sci. Technol. 2011, 45:3829-3830.
30. American Diabetes Association, 2013. Standards of medical care in diabetes - 2013. Diabetes Care. vol. 36, S11-S66.
31. Oosterhuis M., Sacher F., Ter Laak T.L. Prediction of concentration levels of metformin and other high consumption pharmaceuticals in wastewater and regional surface water based on sales data. Sci. Total Environ. 2013, 442:380-388.
32. Parrott J.L., Blunt B.R. Life-cycle exposure of fathead minnows (Pimephales promelas) to an ethinylestradiol concentration below 1 ng/L reduces egg fertilization success and demasculinizes males. Environ. Toxicol. 2005, 20:131-141.
33. Pawlowski S., van Aerle R., Tyler C.R., Braunbeck T. Effects of 17alpha-ethinylestradiol in a fathead minnow (Pimephales promelas) gonadal recrudescence assay. Ecotoxicol. Environ. Saf. 2004, 57:330-345.
34. Pollock M.S., Fisher S.E., Squires A.J., Pollock R.J., Chivers D.P., Dubé M.G. Relative body size influences breeding propensity in fathead minnows: implications for ecotoxicology testing procedure. Water Qual. Res. J. Can. 2008, 43:257-264.
35. Rotroff D.M., Dix D.J., Houck K.A., Knudsen T.B., Martin M.T., McLaurin K.W., Reif D.M., Crofton K.M., Singh A.V., Xia M., Huang R., Judson R.S. Using in vitro high throughput screening assays to identify potential endocrine-disrupting chemicals. Environ. Health Perspect 2013, 121:7-14.
36. Scheurer M., Michel A., Brauch H.-J., Ruck W., Sacher F. Occurrence and fate of the antidiabetic drug metformin and its metabolite guanylurea in the environment and during drinking water treatment. Water Res. 2012, 46:4790-4802.
37. Sharma V.K., Nautiyal V., Goel K.K., Sharma A. Assessment of thermal stability of metformin hydrochloride. Asian J. Chem. 2010, 22:3561-3566.
38. Sowers A.D., Gaworecki K.M., Mills M.A., Roberts A.P., Klaine S.J. Developmental effects of a municipal wastewater effluent on two generations of the fathead minnow, Pimephales promelas. Aquat. Toxicol. 2009, 95:173-181.
39. Tang T., Lord J.M., Norman R.J., Yasmin E., Balen A.H. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst. Rev. 2012, 5:CD003053.
40. Tartarin P., Moison D., Guibert E., Dupont J., Habert R., Rouiller-Fabre V., Frydman N., Pozzi S., Frydman R., Lecureuil C., Froment P. Metformin exposure affects human and mouse fetal testicular cells. Hum. Reprod. 2012, 27:3304-3314.
41. Tetreault G.R., Bennett C.J., Shires K., Knight B., Servos M.R., McMaster M.E. Intersex and reproductive impairment of wild fish exposed to multiple municipal wastewater discharges. Aquat. Toxicol. 2011, 104:278-290.
42. U.S. Environmental Protection Agency, 2011. Endocrine Disruptor Screening Program for the 21st Century (EDSP21 Work Plan). The Incorporation of In Silico Models and In Vitro High Throughput Assays in the Endocrine Disruptor Screening Program (EDSP) for Prioritization and Screening. [WWW Document]. http://www.epa.gov/endo/pubs/edsp21_work_plan_summary%20_overview_final.pdf.
43. U.S. Environmental Protection Agency, 2012. Tier 1 Screening Battery [WWW Document]. http://www.epa.gov/endo/pubs/assayvalidation/tier1battery.htm.
44. Van Aerle R., Pounds N., Hutchinson T.H., Maddix S., Tyler C.R. Window of sensitivity for the estrogenic effects of ethinylestradiol in early life-stages of fathead minnow, Pimephales promelas. Ecotoxicology 2002, 11:423-434.
45. Van Aerle R., Runnalls T.J., Tyler C.R. Ontogeny of gonadal sex development relative to growth in fathead minnow. J. Fish Biol. 2004, 64:355-369.
46. Viollet B., Guigas B., Sanz Garcia N., Leclerc J., Foretz M., Andreelli F. Cellular and molecular mechanisms of metformin: an overview. Clin. Sci. 2012, 122:253-270.
47. Zang Q., Rotroff D.M., Judson R.S. Binary classification of a large collection of environmental chemicals from estrogen receptor assays by quantitative structure-activity relationship and machine learning methods. J. Chem. Inf. Model. 2013, 53:3244-3261.