{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T21:21:21Z","timestamp":1774473681750,"version":"3.50.1"},"reference-count":150,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T00:00:00Z","timestamp":1648512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ATLANTIDA","award":["NORTE-01-0145-FEDER-000040"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000040"]}]},{"name":"European Regional Development Fund (ERDF)","award":["UID\/Multi\/04423\/2019"],"award-info":[{"award-number":["UID\/Multi\/04423\/2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Synthetic progestins (PGs) are a large family of hormones used in continuously growing amounts in human and animal contraception and medicinal therapies. Because wastewater treatment plants (WWTPs) are unable to eradicate PGs after excretion, they are discharged into aquatic systems, where they can also be regenerated from conjugated PG metabolites. This review summarises the concentrations of 12 PGs in waters from 2015 to 2021. The selected PGs were considered of particular interest due to their wide use, activity, and hormonal derivation (from testosterone, progesterone, and spirolactone). We concluded that PGs had been analysed in WWTPs influents and effluents and, to a lesser extent, in other matrices, including surface waters, where their concentrations range from ng\/L to a few \u00b5g\/L. Because of their high affinity for cell hormone receptors, PGs are endocrine disruptor compounds that may alter the reproductive fitness and development of biota. This review focused on their biological effects in fish, which are the most used aquatic model organisms to qualify the impacts of PGs, highlighting the risks that environmental concentrations pose to their health, fecundity, and fertility. It is concluded that PGs research should be expanded because of the still limited data on their environmental concentrations and effects.<\/jats:p>","DOI":"10.3390\/toxics10040163","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T21:45:51Z","timestamp":1648590351000},"page":"163","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Synthetic Progestins in Waste and Surface Waters: Concentrations, Impacts and Ecological Risk"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8688-8033","authenticated-orcid":false,"given":"Maria","family":"Rocha","sequence":"first","affiliation":[{"name":"Laboratory of Histology and Embryology, Department of Microscopy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto (U.Porto), 4050-313 Porto, Portugal"},{"name":"Histomorphology, Physiopathology, and Applied Toxicology Team, Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), University of Porto (U.Porto), 4450-208 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9813-4389","authenticated-orcid":false,"given":"Eduardo","family":"Rocha","sequence":"additional","affiliation":[{"name":"Laboratory of Histology and Embryology, Department of Microscopy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto (U.Porto), 4050-313 Porto, Portugal"},{"name":"Histomorphology, Physiopathology, and Applied Toxicology Team, Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), University of Porto (U.Porto), 4450-208 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wilson, N.J., Harris, L.M., Nelson, J., and Shah, S.H. (2019). Re-theorizing politics in water governance. Water, 11.","DOI":"10.3390\/w11071470"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4823","DOI":"10.1002\/2014WR016869","article-title":"Water management: Current and future challenges and research directions","volume":"51","author":"Cosgrove","year":"2015","journal-title":"Water Resour. Res."},{"key":"ref_3","unstructured":"EU Water Initiative (EUWI) (2021, December 27). Water Scarcity Management in the Context of WFD. 2006, SCG Agenda Point 8b (WGB\/15160506\/25d). Available online: https:\/\/ec.europa.eu\/environment\/water\/quantity\/pdf\/comm_droughts\/8a_1.pdf."},{"key":"ref_4","unstructured":"EU (2000). Directive 2000\/60\/EC of the European Parliament and of the Council of 23 October 2000 establishing a framework for Community action in the field of water policy. Off. J. Eur. Communities, L327, 0001\u20130073."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"20130569","DOI":"10.1098\/rstb.2013.0569","article-title":"Medicating the environment: Assessing risks of pharmaceuticals to wildlife and ecosystems","volume":"369","author":"Arnold","year":"2014","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1021\/es5051343","article-title":"The Challenge presented by progestins in ecotoxicological research: A critical review","volume":"49","author":"Kumar","year":"2015","journal-title":"Environ. Sci. Technol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.envint.2015.06.012","article-title":"Progestins as endocrine disrupters in aquatic ecosystems: Concentrations, effects and risk assessment","volume":"84","author":"Fent","year":"2015","journal-title":"Environ. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1210\/er.2012-1008","article-title":"Progestogens used in postmenopausal hormone therapy: Differences in their pharmacological properties, intracellular actions, and clinical effects","volume":"34","author":"Stanczyk","year":"2013","journal-title":"Endocr. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/0002-9378(83)91014-1","article-title":"Role of estrogens and progesterone in the etiology and prevention of endometrial cancer: Review","volume":"146","author":"Gambrell","year":"1983","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1016\/0002-9378(92)91401-U","article-title":"The role of progestins in hormone replacement therapy","volume":"166","author":"Lobo","year":"1992","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/S0002-9378(96)80086-X","article-title":"Management of abnormal uterine bleeding","volume":"175","author":"Chuong","year":"1996","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1159\/000218784","article-title":"Placebo-controlled trial of medroxy\u2014Progesterone acetate in gastrointestinal malignancies and cachexia","volume":"19","author":"Kornek","year":"1996","journal-title":"Onc. Res. Treat."},{"key":"ref_13","unstructured":"EU (1999). The European agency for the evaluation of medicinal products. Eval. Med. Insp., 33, 969\u2013978."},{"key":"ref_14","first-page":"1839","article-title":"Using progestins in clinical practice","volume":"62","author":"Apgar","year":"2000","journal-title":"Am. Fam. Physician"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1093\/humupd\/dmi046","article-title":"New progestagens for contraceptive use","volume":"12","year":"2006","journal-title":"Hum. Reprod. Update"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S0010-7824(99)00101-8","article-title":"Nomenclature of the gonane progestins","volume":"60","author":"Edgren","year":"1999","journal-title":"Contraception"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"487","DOI":"10.2147\/TCRM.S6864","article-title":"Use of ethinylestradiol\/drospirenone combination in patients with the polycystic ovary syndrome","volume":"4","author":"Mathur","year":"2008","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1097\/GRF.0b013e318159c2f6","article-title":"The contraceptive implant","volume":"50","author":"Hohmann","year":"2007","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.maturitas.2004.01.001","article-title":"Pharmacological profile of progestins","volume":"47","year":"2004","journal-title":"Maturitas"},{"key":"ref_20","first-page":"45","article-title":"Animal studies on the endocrinological profile of dienogest, a novel synthetic steroid","volume":"23","author":"Katsuki","year":"1997","journal-title":"Drugs Exp. Clin. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/j.1749-6632.1977.tb29427.x","article-title":"Androgenic, synandrogenic, and antiandrogenic actions of progestins","volume":"286","author":"Bullock","year":"1977","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_22","unstructured":"Maddison, J.E., Page, S.W., and Church, D.B. (2008). Chapter 7\u2014Behavior-modifying drugs. Small Animal Clinical Pharmacology, W.B. Saunders. [2nd ed.]."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"105548","DOI":"10.1016\/j.jsbmb.2019.105548","article-title":"Anti-proliferative transcriptional effects of medroxyprogesterone acetate in estrogen receptor positive breast cancer cells are predominantly mediated by the progesterone receptor","volume":"199","author":"Moore","year":"2020","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"F306","DOI":"10.1152\/ajprenal.00062.2005","article-title":"Medroxyprogesterone acetate binds the glucocorticoid receptor to stimulate \u03b1-ENaC and sgk1 expression in renal collecting duct epithelia","volume":"290","author":"Thomas","year":"2006","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S1569-2558(03)34006-8","article-title":"Sex, hormones and the endothelium","volume":"Volume 34","author":"Murphy","year":"2004","journal-title":"Advances in Molecular and Cell Biology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1080\/13697130500330382","article-title":"Pharmacology of different progestogens: The special case of drospirenone","volume":"8","year":"2005","journal-title":"Climacteric"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.maturitas.2008.11.013","article-title":"Reprint of Classification and pharmacology of progestins","volume":"61","author":"Schindler","year":"2008","journal-title":"Maturitas"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.contraception.2010.05.005","article-title":"Non-contraceptive health benefits of intrauterine hormonal systems","volume":"82","author":"Fraser","year":"2010","journal-title":"Contraception"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"34628","DOI":"10.18632\/oncotarget.26015","article-title":"The clinical relevance of progestogens in hormonal contraception: Present status and future developments","volume":"9","author":"Regidor","year":"2018","journal-title":"Oncotarget"},{"key":"ref_30","unstructured":"Melmed, S., Polonsky, K.S., Larsen, P.R., and Kronenberg, H.M. (2016). Chapter 18\u2014Hormonal Contraception. Williams Textbook of Endocrinology, Elsevier. [13th ed.]."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6498","DOI":"10.1021\/acs.est.7b01231","article-title":"Occurrence and ecotoxicological effects of free, conjugated, and halogenated steroids including 17\u03b1-hydroxypregnanolone and pregnanediol in Swiss","volume":"51","author":"Zhang","year":"2017","journal-title":"Environ. Sci. Technol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.scitotenv.2017.10.120","article-title":"Determination of progestogens in surface and waste water using SPE extraction and LC-APCI\/APPI-HRPS","volume":"621","author":"Golovko","year":"2018","journal-title":"Sci. Total Environ."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5296","DOI":"10.1021\/acs.est.7b06147","article-title":"Occurrence of glucocorticoids, mineralocorticoids, and progestogens in various treated wastewater, rivers, and streams","volume":"52","author":"Weizel","year":"2018","journal-title":"Environ. Sci. Technol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/j.scitotenv.2019.02.327","article-title":"Occurrence and removal of progestagens in municipal wastewater treatment plants from different regions in China","volume":"668","author":"Yu","year":"2019","journal-title":"Sci. Total Environ."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.watres.2018.02.065","article-title":"Two synthetic progestins and natural progesterone are responsible for most of the progestagenic activities in municipal wastewater treatment plant effluents in the Czech and Slovak republics","volume":"137","author":"Golovko","year":"2018","journal-title":"Water Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/j.scitotenv.2017.08.114","article-title":"Determination of two progestin metabolites (17\u03b1-hydroxypregnanolone and pregnanediol) and different classes of steroids (androgens, estrogens, corticosteroids, progestins) in rivers and wastewaters by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS\/MS)","volume":"610\u2013611","author":"Zhang","year":"2018","journal-title":"Sci. Total Environ."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Silva, S., Cardoso, V.V., Duarte, L., Carneiro, R.N., and Almeida, C.M.M. (2021). Characterization of five Portuguese wastewater treatment plants: Removal efficiency of pharmaceutical active compounds through conventional treatment processes and environmental risk. Appl. Sci., 11.","DOI":"10.3390\/app11167388"},{"key":"ref_38","first-page":"816","article-title":"Simultaneous extraction and determination of pharmaceuticals and personal care products (PPCPs) in river water and sewage by solid-phase extraction and liquid chromatography-tandem mass spectrometry","volume":"95","author":"Tan","year":"2015","journal-title":"Int. J. Environ. Anal. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1002\/etc.3304","article-title":"Concentrations of levonorgestrel and ethinylestradiol in wastewater effluents: Is the progestin also cause for concern?","volume":"35","author":"King","year":"2016","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/dta.1829","article-title":"HPLC-MS\/MS analysis of steroid hormones in environmental water samples","volume":"8","author":"Avar","year":"2016","journal-title":"Drug Test. Anal."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.chemosphere.2016.09.077","article-title":"Analysis of emerging contaminants in water and solid samples using high resolution mass spectrometry with a Q Exactive orbital ion trap and estrogenic activity with YES-assay","volume":"166","author":"Chappuis","year":"2017","journal-title":"Chemosphere"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.scitotenv.2018.03.370","article-title":"Seasonal variations of steroid hormones released by wastewater treatment plants to river water and sediments: Distribution between particulate and dissolved phases","volume":"635","author":"Yarahmadi","year":"2018","journal-title":"Sci. Total Environ."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.chroma.2019.01.016","article-title":"Analysis of Environmental Protection Agency priority endocrine disruptor hormones and bisphenol A in tap, surface and wastewater by online concentration liquid chromatography tandem mass spectrometry","volume":"1591","author":"Goeury","year":"2019","journal-title":"J. Chromatogr. A"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"116515","DOI":"10.1016\/j.watres.2020.116515","article-title":"Fate and behavior of progestogens in activated sludge treatment: Kinetics and transformation products","volume":"188","author":"Weizel","year":"2021","journal-title":"Water Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.chroma.2016.01.077","article-title":"Determination of androgens and progestogens in environmental and biological samples using fabric phase sorptive extraction coupled to ultra-high performance liquid chromatography tandem mass spectrometry","volume":"1437","author":"Ciofi","year":"2016","journal-title":"J. Chromatogr. A"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"25442","DOI":"10.1007\/s11356-016-7669-y","article-title":"Occurrence, fate, and risk assessment of selected endocrine disrupting chemicals in wastewater treatment plants and receiving river of Shanghai, China","volume":"23","author":"Xu","year":"2016","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.envpol.2017.05.031","article-title":"Steroid bioaccumulation profiles in typical freshwater aquaculture environments of South China and their human health risks via fish consumption","volume":"228","author":"Liu","year":"2017","journal-title":"Environ. Pollut."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.scitotenv.2018.04.160","article-title":"Pharmaceutical manufacturing facility discharges can substantially increase the pharmaceutical load to US wastewaters","volume":"636","author":"Scott","year":"2018","journal-title":"Sci. Total Environ."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1002\/jssc.201801214","article-title":"Multi-residue analysis of 44 pharmaceutical compounds in environmental water samples by solid-phase extraction coupled to liquid chromatography-tandem mass spectrometry","volume":"42","author":"Miossec","year":"2019","journal-title":"J. Sep. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"329","DOI":"10.2166\/wh.2019.092","article-title":"Presence of emerging contaminants in urban water bodies in southern Brazil","volume":"17","author":"Pivetta","year":"2019","journal-title":"J. Water Health"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3485","DOI":"10.1016\/j.envpol.2009.06.012","article-title":"Progestagens for human use, exposure and hazard assessment for the aquatic environment","volume":"157","author":"Besse","year":"2009","journal-title":"Environ. Pollut."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.2166\/wst.2019.350","article-title":"Levels and distribution of progesterone in receiving waters and wastewaters of a growing urban area","volume":"80","author":"Kasambala","year":"2019","journal-title":"Water Sci. Technol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3612","DOI":"10.1021\/es801952h","article-title":"Fate of conjugated natural and synthetic steroid estrogens in crude sewage and activated sludge batch studies","volume":"43","author":"Gomes","year":"2009","journal-title":"Environ. Sci. Technol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.chemosphere.2015.04.078","article-title":"Evaluating the degradation, sorption, and negative mass balances of pharmaceuticals and personal care products during wastewater treatment","volume":"134","author":"Blair","year":"2015","journal-title":"Chemosphere"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"148306","DOI":"10.1016\/j.scitotenv.2021.148306","article-title":"Steroid hormones in the aquatic environment","volume":"792","author":"Ojoghoro","year":"2021","journal-title":"Sci. Total Environ."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.scitotenv.2004.12.070","article-title":"Review of evidence: Are endocrine-disrupting chemicals in the aquatic environment impacting fish populations?","volume":"343","author":"Mills","year":"2005","journal-title":"Sci. Total Environ."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.cej.2018.06.159","article-title":"Bioaugmentated activated sludge degradation of progesterone: Kinetics and mechanism","volume":"352","author":"Yu","year":"2018","journal-title":"Chem. Eng. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0960-0760(93)90299-C","article-title":"Metabolism of gestodene in human liver cytosol and microsomes in vitro","volume":"46","author":"Ward","year":"1993","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_59","unstructured":"National Library of Medicine (2021, December 27). Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/source\/hsdb\/3594."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0010-7824(02)00321-9","article-title":"Pharmacokinetics of levonorgestrel 0.75 mg tablets","volume":"66","author":"Kook","year":"2002","journal-title":"Contraception"},{"key":"ref_61","unstructured":"(2021, December 27). DrugBank. Available online: https:\/\/www.drugbank.ca\/drugs\/DB00367."},{"key":"ref_62","first-page":"10266","article-title":"Degradation of norgestrel by bacteria from activated sludge: Comparison to progesterone","volume":"47","author":"Liu","year":"2013","journal-title":"Environ. Sci. Technol."},{"key":"ref_63","unstructured":"(2021, December 27). DrugBank. Available online: https:\/\/www.drugbank.ca\/drugs\/DB00294."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/0010-7824(90)90093-B","article-title":"Metabolism of levonorgestrel, norethindrone, and structurally related contraceptive steroids","volume":"42","author":"Stanczyk","year":"1990","journal-title":"Contraception"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"107789","DOI":"10.1016\/j.pharmthera.2020.107789","article-title":"Pharmacokinetics, metabolism and serum concentrations of progestins used in contraception","volume":"222","author":"Bick","year":"2021","journal-title":"Pharmacol. Therapeut."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.steroids.2008.11.008","article-title":"Doping in sport: 3. Metabolic conversion of oral norethisterone to urinary 19-norandrosterone","volume":"74","author":"Walker","year":"2009","journal-title":"Steroids"},{"key":"ref_67","unstructured":"(2021, December 27). DrugBank. Available online: https:\/\/www.drugbank.ca\/drugs\/DB09123."},{"key":"ref_68","unstructured":"(2021, December 27). DrugBank. Available online: https:\/\/www.drugbank.ca\/drugs\/DB13981."},{"key":"ref_69","unstructured":"(2021, December 27). DrugBank. Available online: https:\/\/www.drugbank.ca\/drugs\/DB00603."},{"key":"ref_70","unstructured":"National Library of Medicine (2021, December 27). Compound Summary for CID 6279, Medroxyprogesterone Acetate, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Medroxyprogesterone-acetate."},{"key":"ref_71","unstructured":"National Library of Medicine (2021, December 27). Compound Summary for CID 11683, Megestrol Acetate, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Megestrol-acetate."},{"key":"ref_72","unstructured":"(2021, December 27). DrugBank. Available online: https:\/\/www.drugbank.ca\/drugs\/DB01395."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"11859","DOI":"10.1073\/pnas.1006074107","article-title":"Conservation of progesterone hormone function in invertebrate reproduction","volume":"107","author":"Stout","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Ren, J., Chung-Davidson, Y.-W., Jia, L., and Li, W. (2019). Genomic sequence analyses of classical and non-classical lamprey progesterone receptor genes and the inference of homologous gene evolution in metazoans. BMC Evol. Biol., 19.","DOI":"10.1186\/s12862-019-1463-7"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.chemosphere.2017.04.021","article-title":"Endocrine disruption by environmental gestagens in amphibians\u2014A short review supported by new in vitro data using gonads of Xenopus laevis","volume":"181","author":"Lorenz","year":"2017","journal-title":"Chemosphere"},{"key":"ref_76","unstructured":"Matsuyama, M. (2008). Follicular Steroidogenesis in Fish, CRC Press. [1st ed.]."},{"key":"ref_77","unstructured":"Stacey, N.E., and Sorensen, P.W. (2008). Hormonally Derived Sex Pheromones in Fish, CRC Press. [1st ed.]."},{"key":"ref_78","unstructured":"Pankhurst, N.W. (2008). Gonadal Steroids: Functions and Patterns of Change, CRC Press. [1st ed.]."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.pneurobio.2013.07.006","article-title":"Levels and actions of progesterone and its metabolites in the nervous system during physiological and pathological conditions","volume":"113","author":"Melcangi","year":"2014","journal-title":"Prog. Neurobiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0048-9697(98)00328-3","article-title":"A strategy for assessing the effects of xenobiotics on fish reproduction","volume":"225","author":"Kime","year":"1999","journal-title":"Sci. Total Environ."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"S195","DOI":"10.1111\/j.1440-169X.2008.01019.x","article-title":"Regulation of oocyte maturation in fish","volume":"50","author":"Nagahama","year":"2008","journal-title":"Dev. Growth Differ."},{"key":"ref_82","unstructured":"NIEHS (2021, December 27). Endocrine Disruptors. National Institute of Environmental Health Sciences. U.S. Department of Health and Human Sciences, Available online: www.niehs.nih.gov\/."},{"key":"ref_83","unstructured":"EU (2018). (EU) 2018\/840 of 5 June 2018 establishing a watch list of substances for Union-wide monitoring in the field of water policy pursuant to Directive 2008\/105\/E.C. of the European Parliament and of the Council and repealing Commission Implementing Decision (EU) 2015\/495. Off. J. Eur. Union, 141, 9\u201312."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.ygcen.2012.02.009","article-title":"The synthetic progestogen, levonorgestrel, but not natural progesterone, affects male mate calling behavior of Xenopus laevis","volume":"176","author":"Hoffmann","year":"2012","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1093\/toxsci\/kfr159","article-title":"The synthetic gestagen levonorgestrel impairs metamorphosis in Xenopus laevis by disruption of the thyroid system","volume":"123","author":"Lorenz","year":"2011","journal-title":"Toxicol. Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.envpol.2010.09.028","article-title":"Molecular effects and bioaccumulation of levonorgestrel in the non-target organism Dreissena polymorpha","volume":"159","author":"Lorenz","year":"2011","journal-title":"Environ. Pollut."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.ygcen.2014.03.038","article-title":"Sources, concentrations, and exposure effects of environmental gestagens on fish and other aquatic wildlife, with an emphasis on reproduction","volume":"203","author":"Orlando","year":"2014","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Chaves-Pozo, E., Garcia-Ayala, A., and Cabas, I. (2018). Effects of Sex Steroids on Fish Leukocytes. Biology, 7.","DOI":"10.3390\/biology7010009"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"5991","DOI":"10.1021\/acs.est.6b00799","article-title":"Exposure to the contraceptive progestin, gestodene, alters reproductive behavior, arrests egg deposition, and masculinises development in the fathead minnow (Pimephales promelas)","volume":"50","author":"Frankel","year":"2016","journal-title":"Environ. Sci. Technol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.chemosphere.2017.09.127","article-title":"Reproductive effects of synthetic progestin norgestrel in zebrafish (Danio rerio)","volume":"190","author":"Liang","year":"2018","journal-title":"Chemosphere"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"109912","DOI":"10.1016\/j.ecoenv.2019.109912","article-title":"Chronic simultaneous exposure of common carp (Cyprinus carpio) from embryonic to juvenile stage to drospirenone and gestodene at low ng\/L level caused intersex","volume":"188","author":"Steinbach","year":"2020","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"144570","DOI":"10.1016\/j.scitotenv.2020.144570","article-title":"Reproductive potential of mosquitofish is reduced by the masculinising effect of a synthetic progesterone, gestodene: Evidence from morphology, courtship behaviour, ovary histology, sex hormones and gene expressions","volume":"769","author":"Chen","year":"2021","journal-title":"Sci. Total Environ."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.aquatox.2015.06.013","article-title":"The progestin levonorgestrel affects sex differentiation in zebrafish at environmentally relevant concentrations","volume":"166","author":"Hua","year":"2015","journal-title":"Aquat. Toxicol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.aquatox.2015.01.029","article-title":"Responses to various exposure durations of levonorgestrel during early-life stages of fathead minnows (Pimephales promelas)","volume":"161","author":"Overturf","year":"2015","journal-title":"Aquat. Toxicol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.aquatox.2015.10.009","article-title":"From single chemicals to mixtures\u2014Reproductive effects of levonorgestrel and ethinylestradiol on the fathead minnow","volume":"169","author":"Runnalls","year":"2015","journal-title":"Aquat. Toxicol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.aquatox.2016.06.010","article-title":"Developmental exposure to progestins causes male bias and precocious puberty in zebrafish (Danio rerio)","volume":"177","author":"Svensson","year":"2016","journal-title":"Aquat. Toxicol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.envpol.2017.05.090","article-title":"Warming modulates the effects of the endocrine disruptor progestin levonorgestrel on the zebrafish fitness, ovary maturation kinetics and reproduction success","volume":"229","author":"Cardoso","year":"2017","journal-title":"Environ. Pollut."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ygcen.2016.01.007","article-title":"Aqueous exposure to the progestin, levonorgestrel, alters anal fin development and reproductive behavior in the eastern mosquitofish (Gambusia holbrooki)","volume":"234","author":"Frankel","year":"2016","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3299","DOI":"10.1002\/etc.3906","article-title":"Exposure effects of levonorgestrel on oogenesis in the fathead minnow (Pimephales promelas)","volume":"36","author":"Frankel","year":"2017","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ecoenv.2017.01.020","article-title":"Complex molecular changes induced by chronic progestogens exposure in roach, Rutilus rutilus","volume":"139","author":"Maasz","year":"2017","journal-title":"Ecotox. Environ. Saf."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1002\/etc.4054","article-title":"Exposure to levonorgestrel increases nest acquisition success and decreases sperm motility in the male fathead minnow (Pimephales promelas)","volume":"37","author":"Frankel","year":"2018","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s00128-018-2436-z","article-title":"Histopathological evaluation of combined impacts of the synthetic progestin levonorgestrel and temperature on the female zebrafish maturation using a semi-quantitative grading analysis\u2014is it enough?","volume":"101","author":"Cardoso","year":"2018","journal-title":"B Environ. Contam. Tox."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.envpol.2017.09.057","article-title":"Regulation of zebrafish (Danio rerio) locomotor behavior and circadian rhythm network by environmental steroid hormones","volume":"232","author":"Zhao","year":"2018","journal-title":"Environ. Pollut."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/j.envpol.2019.06.058","article-title":"Combined effects of increased temperature and levonorgestrel exposure on zebrafish female liver, using stereology and immunohistochemistry against catalase, CYP1A, HSP90 and vitellogenin","volume":"252","author":"Cardoso","year":"2019","journal-title":"Environ. Pollut."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"13849","DOI":"10.1021\/acs.est.0c02892","article-title":"Multigenerational and transgenerational effects of environmentally relevant concentrations of endocrine disruptors in an estuarine fish model","volume":"54","author":"Forbes","year":"2020","journal-title":"Environ. Sci. Technol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1002\/etc.5008","article-title":"Effects of the gestagen levonorgestrel in a life cycle test with zebrafish (Danio rerio)","volume":"41","author":"Teigeler","year":"2021","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"105796","DOI":"10.1016\/j.aquatox.2021.105796","article-title":"Inhibition of swim bladder inflation in Japanese medaka (Oryzias latipes) embryos following exposure to select pharmaceuticals alone and in combination","volume":"234","author":"Pandelides","year":"2021","journal-title":"Aquat. Toxicol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.cbpc.2017.02.005","article-title":"Transcriptional alterations induced by binary mixtures of ethinylestradiol and norgestrel during the early development of zebrafish (Danio rerio)","volume":"195","author":"Liang","year":"2017","journal-title":"Comp. Biochem. Physiol. C Toxicol. Pharmacol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.aquatox.2018.03.014","article-title":"Alterations of secondary sex characteristics, reproductive histology and behaviors by norgestrel in the western mosquitofish (Gambusia affinis)","volume":"198","author":"Hou","year":"2018","journal-title":"Aquat. Toxicol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.ecoenv.2018.12.053","article-title":"Transcriptomic and physiological changes in western mosquitofish (Gambusia affinis) after exposure to norgestrel","volume":"171","author":"Hou","year":"2019","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.scitotenv.2019.01.276","article-title":"Synthetic progestin etonogestrel negatively affects mating behavior and reproduction in Endler\u2019s guppies (Poecilia wingei)","volume":"663","author":"Steinbach","year":"2019","journal-title":"Sci. Total Environ."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/etc.2816","article-title":"Effects of progesterone and norethindrone on female fathead minnow (Pimephales promelas) steroidogenesis","volume":"34","author":"Petersen","year":"2015","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.etap.2019.04.011","article-title":"Alterations to the vision-associated transcriptome of zebrafish (Danio rerio) following developmental norethindrone exposure","volume":"69","author":"Bridges","year":"2019","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"110496","DOI":"10.1016\/j.ecoenv.2020.110496","article-title":"Norethindrone alters mating behaviors, ovary histology, hormone production and transcriptional expression of steroidogenic genes in zebrafish (Danio rerio)","volume":"195","author":"Hou","year":"2020","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"125285","DOI":"10.1016\/j.chemosphere.2019.125285","article-title":"The progestin norethindrone alters growth, reproductive histology and gene expression in zebrafish (Danio rerio)","volume":"242","author":"Liang","year":"2020","journal-title":"Chemosphere"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"108819","DOI":"10.1016\/j.cbpc.2020.108819","article-title":"The synthetic progestin norethindrone causes thyroid endocrine disruption in adult zebrafish","volume":"236","author":"Liang","year":"2020","journal-title":"Comp. Biochem. Physiol. C Toxicol. Pharmacol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"141554","DOI":"10.1016\/j.scitotenv.2020.141554","article-title":"The effects of norethindrone on the ontogeny of gene expression along the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes in zebrafish (Danio rerio)","volume":"747","author":"Luo","year":"2020","journal-title":"Sci. Total Environ."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"113345","DOI":"10.1016\/j.ygcen.2019.113345","article-title":"Neurodevelopmental effects of natural and synthetic ligands of estrogen and progesterone receptors in zebrafish eleutheroembryos","volume":"288","author":"Vaillant","year":"2020","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"130049","DOI":"10.1016\/j.chemosphere.2021.130049","article-title":"Norethindrone causes cellular and hepatic injury in zebrafish by compromising the metabolic processes associated with antioxidant defence: Insights from metabolomics","volume":"275","author":"Wang","year":"2021","journal-title":"Chemosphere"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2917","DOI":"10.1038\/s41598-018-21318-9","article-title":"The primodos components norethisterone acetate and ethinyl estradiol induce developmental abnormalities in zebrafish embryos","volume":"8","author":"Brown","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"136262","DOI":"10.1016\/j.scitotenv.2019.136262","article-title":"Effects of new generation progestins, including as mixtures and in combination with other classes of steroid hormones, on zebrafish early life stages","volume":"709","author":"Schmid","year":"2020","journal-title":"Sci. Total Environ."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"12902","DOI":"10.1021\/es502711c","article-title":"Endocrine disrupting compounds affecting corticosteroid signaling pathways in Czech and Swiss waters: Potential impact on fish","volume":"48","author":"Macikova","year":"2014","journal-title":"Environ. Sci. Technol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"4636","DOI":"10.1021\/es505575v","article-title":"Synthetic progestins medroxyprogesterone acetate and dydrogesterone and their binary mixtures adversely affect reproduction and lead to histological and transcriptional alterations in zebrafish (Danio rerio)","volume":"49","author":"Zhao","year":"2015","journal-title":"Environ. Sci. Technol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.aquatox.2019.04.014","article-title":"Medroxyprogesterone acetate affects sex differentiation and spermatogenesis in zebrafish","volume":"212","author":"Shi","year":"2019","journal-title":"Aquat. Toxicol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"110371","DOI":"10.1016\/j.ecoenv.2020.110371","article-title":"Medroxyprogesterone acetate affects eye growth and the transcription of associated genes in zebrafish","volume":"193","author":"Shi","year":"2020","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.aquatox.2014.02.020","article-title":"The synthetic progestin megestrol acetate adversely affects zebrafish reproduction","volume":"150","author":"Han","year":"2014","journal-title":"Aquat. Toxicol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.envpol.2016.03.031","article-title":"The binary mixtures of megestrol acetate and 17\u03b1-ethynylestradiol adversely affect zebrafish reproduction","volume":"213","author":"Hua","year":"2016","journal-title":"Environ. Pollut."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.ecoenv.2018.07.049","article-title":"Endocrine disruption in Chinese rare minnow (Gobiocypris rarus) after long-term exposure to low environmental concentrations of progestin megestrol acetate","volume":"163","author":"Hua","year":"2018","journal-title":"Ecotox. Environ. Saf."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.envpol.2016.03.007","article-title":"Drospirenone intake alters plasmatic steroid levels and cyp17a1 expression in gonads of juvenile sea bass","volume":"213","author":"Blanco","year":"2016","journal-title":"Environ. Pollut."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.aquatox.2016.02.005","article-title":"Activity of binary mixtures of drospirenone with progesterone and 17\u03b1-ethinylestradiol in vitro and in vivo","volume":"174","author":"Rossier","year":"2016","journal-title":"Aquat. Toxicol."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Basak, S.C., Restrepo, G., and Villaveces, J.L. (2015). Chapter 10\u2014Mathematical (Structural) Descriptors in QSAR: Applications in Drug Design and Environmental Toxicology. Advances in Mathematical Chemistry and Applications, Bentham Science Publishers.","DOI":"10.2174\/97816810805291150201"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.aquatox.2014.05.008","article-title":"The progestin levonorgestrel disrupts gonadotropin expression and sex steroid levels in pubertal roach (Rutilus rutilus)","volume":"154","author":"Kroupova","year":"2014","journal-title":"Aquat. Toxicol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1007\/s00244-011-9691-x","article-title":"Tissue-specific uptake and bioconcentration of the oral contraceptive norethindrone in two freshwater fishes","volume":"62","author":"Nallani","year":"2012","journal-title":"Arch. Environ. Con. Tox."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1016\/j.chemosphere.2010.09.043","article-title":"The influence of gill and liver metabolism on the predicted bioconcentration of three pharmaceuticals in fish","volume":"81","author":"Gomez","year":"2010","journal-title":"Chemosphere"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1016\/j.etap.2013.09.013","article-title":"Tissue-specific bioconcentration of the synthetic steroid hormone medroxyprogesterone acetate in the common carp (Cyprinus carpio)","volume":"36","author":"Steele","year":"2013","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1021\/es903440m","article-title":"Therapeutic levels of levonorgestrel detected in blood plasma of fish: Results from screening rainbow trout exposed to treated sewage effluents","volume":"44","author":"Fick","year":"2010","journal-title":"Environ. Sci. Technol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1080\/714044797","article-title":"A theoretical model for utilising mammalian pharmacology and safety data to prioritise potential impacts of human pharmaceuticals to fish","volume":"9","author":"Huggett","year":"2003","journal-title":"Hum. Ecol. Risk Assess."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0166-445X(01)00174-6","article-title":"Branchial elimination of superhydrophobic organic compounds by rainbow trout (Oncorhynchus mykiss)","volume":"55","author":"Fitzsimmons","year":"2001","journal-title":"Aquat. Toxicol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"3267","DOI":"10.1002\/etc.3894","article-title":"Transcriptional and histological alterations in gonad of adult zebrafish after exposure to the synthetic progestin norgestrel","volume":"36","author":"Shi","year":"2017","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.watres.2010.08.046","article-title":"Occurrence of androgens and progestogens in wastewater treatment plants and receiving river waters: Comparison to estrogens","volume":"42","author":"Chang","year":"2011","journal-title":"Water Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S0378-4274(03)00257-1","article-title":"Probabilistic hazard assessment of environmentally occurring pharmaceuticals toxicity to fish, daphnids and algae by ECOSAR screening","volume":"144","author":"Sanderson","year":"2003","journal-title":"Toxicol. Lett."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1016\/j.scitotenv.2011.01.054","article-title":"A new risk assessment approach for the prioritisation of 500 classical and emerging organic microcontaminants as potential river basin specific pollutants under the European Water Framework Directive","volume":"409","author":"Dulio","year":"2011","journal-title":"Sci. Total Environ."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.envint.2011.03.004","article-title":"Distribution, fate and risk assessment of antibiotics in sewage treatment plants in Hong Kong, South China","volume":"42","author":"Leung","year":"2012","journal-title":"Environ. Int."},{"key":"ref_144","unstructured":"ECHA (2008). Guidance on Information Requirements and Chemical Safety Assessment: Characterisation of Dose [Concentration]-Response for Environment, European Chemicals Agency. Chapter R.10."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/ieam.1764","article-title":"A risk-based, product-level approach for assuring aquatic environmental safety of cleaning products in the context of sustainability: The Environmental Safety Check (ESC) scheme of the AISE Charter for Sustainable Cleaning","volume":"13","author":"Pickup","year":"2017","journal-title":"Integr. Environ. Assess."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.taap.2016.05.019","article-title":"Several synthetic progestins disrupt the glial cell specific-brain aromatase expression in developing zebrafish","volume":"305","author":"Garoche","year":"2016","journal-title":"Toxicol. Appl. Pharm."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.aquatox.2015.01.006","article-title":"Long-term exposure to environmentally relevant concentrations of progesterone and norgestrel affects sex differentiation in zebrafish (Danio rerio)","volume":"160","author":"Liang","year":"2015","journal-title":"Aquat. Toxicol."},{"key":"ref_148","unstructured":"Bayer (2009). Short-Term Reproduction Test with Dienogest (ZK 37659) on the Fathead Minnow (Pimephales promelas), Bayer."},{"key":"ref_149","unstructured":"FASS (2021, December 27). Estradiol & Nomegestrolacetat. Available online: https:\/\/www.fass.se\/LIF\/product?-1.-documentTabPanel-tabs-panel-article~tools~bottom-articletools-printbiglink&userType=2&nplId=20100226000021&docType=78."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"5183","DOI":"10.1021\/es300231y","article-title":"Progestins and antiprogestins affect gene expression in early development in zebrafish (Danio rerio) at environmental concentrations","volume":"46","author":"Zucchi","year":"2012","journal-title":"Environ. Sci. Technol."}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/10\/4\/163\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:45:56Z","timestamp":1760136356000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/10\/4\/163"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,29]]},"references-count":150,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["toxics10040163"],"URL":"https:\/\/doi.org\/10.3390\/toxics10040163","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,29]]}}}