Studies of endocrine disruptors: nonylphenol and isomers in biological models
Certain emerging pollutants are among the most widely used chemicals globally, causing widespread concern in relation to their use in products devoted to cleaniness and asepsis. Nonylphenol ethoxylate (NPEOn) is one such contaminant, along with its degradation product, nonylphenol, an active ingredi...
- Autores:
-
De la Parra-Guerra, Ana C.
Acevedo‐Barrios, Rosa
- Tipo de recurso:
- Article of investigation
- Fecha de publicación:
- 2023
- Institución:
- Corporación Universidad de la Costa
- Repositorio:
- REDICUC - Repositorio CUC
- Idioma:
- eng
- OAI Identifier:
- oai:repositorio.cuc.edu.co:11323/10571
- Acceso en línea:
- https://hdl.handle.net/11323/10571
https://repositorio.cuc.edu.co/
- Palabra clave:
- Endocrine disruptor
Environmental pollutant
Nonionic surfactants
Neurotoxic
Toxicology
- Rights
- embargoedAccess
- License
- Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)
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REDICUC - Repositorio CUC |
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|
dc.title.eng.fl_str_mv |
Studies of endocrine disruptors: nonylphenol and isomers in biological models |
title |
Studies of endocrine disruptors: nonylphenol and isomers in biological models |
spellingShingle |
Studies of endocrine disruptors: nonylphenol and isomers in biological models Endocrine disruptor Environmental pollutant Nonionic surfactants Neurotoxic Toxicology |
title_short |
Studies of endocrine disruptors: nonylphenol and isomers in biological models |
title_full |
Studies of endocrine disruptors: nonylphenol and isomers in biological models |
title_fullStr |
Studies of endocrine disruptors: nonylphenol and isomers in biological models |
title_full_unstemmed |
Studies of endocrine disruptors: nonylphenol and isomers in biological models |
title_sort |
Studies of endocrine disruptors: nonylphenol and isomers in biological models |
dc.creator.fl_str_mv |
De la Parra-Guerra, Ana C. Acevedo‐Barrios, Rosa |
dc.contributor.author.none.fl_str_mv |
De la Parra-Guerra, Ana C. Acevedo‐Barrios, Rosa |
dc.subject.proposal.eng.fl_str_mv |
Endocrine disruptor Environmental pollutant Nonionic surfactants Neurotoxic Toxicology |
topic |
Endocrine disruptor Environmental pollutant Nonionic surfactants Neurotoxic Toxicology |
description |
Certain emerging pollutants are among the most widely used chemicals globally, causing widespread concern in relation to their use in products devoted to cleaniness and asepsis. Nonylphenol ethoxylate (NPEOn) is one such contaminant, along with its degradation product, nonylphenol, an active ingredient presents in nonionic surfactants used as herbicides, cosmetics, paints, plastics, disinfectants, and detergents. These chemicals and their metabolites are commonly found in environmental matrices. Nonylphenol and NPEOn, used, are particularly concerning, given their role as endocrine disruptors chemical and possible neurotoxic effects recorded in several biological models, primarily aquatic organisms. Limiting and detecting these compounds remain of paramount importance. The objective of the present review was to evaluate the toxic effects of nonylphenol and NPEOn in different biological models. |
publishDate |
2023 |
dc.date.accessioned.none.fl_str_mv |
2023-11-01T18:55:15Z |
dc.date.available.none.fl_str_mv |
2023-11-01T18:55:15Z 2024-04-14 |
dc.date.issued.none.fl_str_mv |
2023-04-14 |
dc.type.spa.fl_str_mv |
Artículo de revista |
dc.type.coar.spa.fl_str_mv |
http://purl.org/coar/resource_type/c_2df8fbb1 |
dc.type.content.spa.fl_str_mv |
Text |
dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.redcol.spa.fl_str_mv |
http://purl.org/redcol/resource_type/ART |
dc.type.version.spa.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.coarversion.spa.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
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http://purl.org/coar/resource_type/c_2df8fbb1 |
status_str |
publishedVersion |
dc.identifier.issn.spa.fl_str_mv |
0730-7268 |
dc.identifier.uri.none.fl_str_mv |
https://hdl.handle.net/11323/10571 |
dc.identifier.doi.none.fl_str_mv |
10.1002/etc.5633 |
dc.identifier.eissn.spa.fl_str_mv |
1552-8618 |
dc.identifier.instname.spa.fl_str_mv |
Corporación Universidad de la Costa |
dc.identifier.reponame.spa.fl_str_mv |
REDICUC - Repositorio CUC |
dc.identifier.repourl.spa.fl_str_mv |
https://repositorio.cuc.edu.co/ |
identifier_str_mv |
0730-7268 10.1002/etc.5633 1552-8618 Corporación Universidad de la Costa REDICUC - Repositorio CUC |
url |
https://hdl.handle.net/11323/10571 https://repositorio.cuc.edu.co/ |
dc.language.iso.spa.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartofjournal.spa.fl_str_mv |
Environmental Toxicology and Chemistry |
dc.relation.references.spa.fl_str_mv |
Abdel Rahman, A. N., Mahmoud, S. M., Khamis, T., Rasheed, N., Mohamed, D. I., Ghanem, R., Mansour, D. M., Ismail, T. A., & Mahboub, H. H. (2022). Palliative effect of dietary common sage leaves against toxic impacts of nonylphenol in mirror carp (Cyprinus carpio var specularis): Growth, gene expression, immune‐antioxidant status, and histopathological alterations. Aquaculture Reports, 25, 101200. https://doi.org/10. 1016/j.aqrep.2022.101200 Abdulrahman, I., Jamal Mamdoh, T., & Sathianeson, S. (2022). The anti‐ settlement activity of extracts of marine bacteria associated with soft corals against barnacle larvae. Egyptian Journal of Aquatic Biology and Fisheries, 26(3), 885–900. https://doi.org/10.21608/ejabf.2022. 248212 Acir, I. H., & Guenther, K. (2018). Endocrine‐disrupting metabolites of alkylphenol ethoxylates—A critical review of analytical methods, environmental occurrences, toxicity, and regulation. Science of the Total Environment, 635, 1530–1546. https://doi.org/10.1016/j.scitotenv.2018. 04.079 Amaninejad, P., Hosseinzadeh Sahafi, H., Soltani, M., & Hosseini Shekarabi, S. P. (2018). Endocrine disrupting effects of 4‐nonylphenol on plasma vitellogenin, reproductive system and histology in koi carp (Cyprinus carpio). International Aquatic Research; A Journal of Science and Its Applications, 10(3), 263–274. https://doi.org/10.1007/s40071-018- 0203-8 Aronzon, C. M. (2012). Evaluación de la toxicidad de los contaminantes cobre, nonilfenol y diazinón sobre embriones y larvas de Rhinella (Bufo) arenarum [Embryo‐larval toxicity of pollutants, copper, nonylphenol and dizinon on Rhinella (Bufo) arenarum]. Doctoral dissertation, Universidad de Buenos Aires. http://hdl.handle.net/20.500.12110/tesis_n5340_ Aronzon Atienzar, F. A., Billinghurst, Z., & Depledge, M. H. (2002). 4‐n‐Nonylphenol and 17‐β estradiol may induce common DNA effects in developing barnacle larvae. Environmental Pollution, 120(3), 735–738. https://doi. org/10.1016/S0269-7491(02)00184-7 Bednářová, A., Kropf, M., & Krishnan, N. (2020). The surfactant polyethoxylated tallowamine (POEA) reduces lifespan and inhibits fecundity in Drosophila melanogaster–In vivo and in vitro study. Ecotoxicology and Environmental Safety, 188, 109883. https://doi.org/10.1016/j. ecoenv.2019.109883 Bhandari, G., Bagheri, A. R., Bhatt, P., & Bilal, M. (2021). Occurrence, potential ecological risks, and degradation of endocrine disrupter, nonylphenol, from the aqueous environment. Chemosphere, 275, 130013. https://doi.org/10.1016/j.chemosphere.2021.130013 Billinghurst, Z., Clare, A. S., Fileman, T., Mcevoy, J., Readman, J., & Depledge, M. H. (1998). Inhibition of barnacle settlement by the environmental oestrogen 4‐nonylphenol and the natural oestrogen 17β oestradiol. Marine Pollution Bulletin, 36(10), 833–839. https://doi.org/10. 1016/S0025-326X(98)00074-5 Government of Canada. (1999). Canadian Environmental Protection Act, 1999. https://laws-lois.justice.gc.ca/eng/acts/c-15.31/ Careghini, A., Mastorgio, A. F., Saponaro, S., & Sezenna, E. (2015). Bisphenol A, nonylphenols, benzophenones, and benzotriazoles in soils, groundwater, surface water, sediments, and food: A review. Environmental Science and Pollution Research, 22(8), 5711–5741. https://doi. org/10.1007/s11356-014-3974-5 Chen, W., Pan, S., Cheng, H., Sweetman, A. J., Zhang, H., & Jones, K. C. (2018). Diffusive gradients in thin‐films (DGT) for in situ sampling of selected endocrine disrupting chemicals (EDCs) in waters. Water Research, 137, 211–219. https://doi.org/10.1016/j.watres.2018.03.029 Chłopecka, M., Mendel, M., Dziekan, N., & Karlik, W. (2017). The effect of glyphosate‐based herbicide Roundup and its co‐formulant, POEA, on the motoric activity of rat intestine—In vitro study. Environmental Toxicology and Pharmacology, 49, 156–162. https://doi.org/10.1016/j.etap. 2016.12.010 Conselho Nacional Do Meio Ambiente. (2005). Resolução CONAMA no 357, de 17 de março de 2005—4a Câmara—Meio Ambiente e Patrimônio Cultural. https://www.mpf.mp.br/atuacao-tematica/ccr4/dadosda-atuacao/projetos/qualidade-da-agua/legislacao/resolucoes/ resolucao-conama-no-357-de-17-de-marco-de-2005/view Crago, J., Tran, K., Budicin, A., Schreiber, B., Lavado, R., & Schlenk, D. (2015). Exploring the impacts of two separate mixtures of pesticide and surfactants on estrogenic activity in male fathead minnows and rainbow trout. Archives of Environmental Contamination and Toxicology, 68(2), 362–370. https://doi.org/10.1007/s00244-014-0098-3 De la Parra‐Guerra, A., & Olivero‐Verbel, J. (2020). Toxicity of nonylphenol and nonylphenol ethoxylate on Caenorhabditis elegans. Ecotoxicology and Environmental Safety, 187, 109709. https://doi.org/10.1016/j. ecoenv.2019.109709 De la Parra‐Guerra, A., Stürzenbaum, S., & Olivero‐Verbel, J. (2020). Intergenerational toxicity of nonylphenol ethoxylate (NP‐9) in Caenorhabditis elegans. Ecotoxicology and Environmental Safety, 197, 110588. https:// doi.org/10.1016/j.ecoenv.2020.110588 Ding, J., Cheng, Y., Hua, Z., Yuan, C., & Wang, X. (2019). The effect of dissolved organic matter (DOM) on the release and distribution of endocrine‐disrupting chemicals (EDCs) from sediment under hydrodynamic forces, A case study of bisphenol A (BPA) and nonylphenol (NP). International Journal of Environmental Research and Public Health, 16(10), 1724. https://doi.org/10.3390/ijerph16101724 Domene, X., Ramírez, W., Solà, L., Alcañiz, J. M., & Andrés, P. (2009). Soil pollution by nonylphenol and nonylphenol ethoxylates and their effects to plants and invertebrates. Journal of Soils and Sediments, 9(6), 555–567. https://doi.org/10.1007/s11368-009-0117-6 Düring, R.‐A., Krahe, S., & Gäth, S. (2002). Sorption behavior of nonylphenol in terrestrial oils. Environmental Science & Technology, 36(19), 4052–4057. https://doi.org/10.1021/es0103389 Dwivedi, S., D'Souza, L. C., Shetty, N. G., Raghu, S. V., & Sharma, A. (2022). Hsp27, a potential EcR target, protects nonylphenol‐induced cellular and organismal toxicity in Drosophila melanogaster. Environmental Pollution, 293, 118484. https://doi.org/10.1016/J.ENVPOL. 2021.118484 European Commission. (2002). European Union Risk Assessment Report 4‐nonylphenol (branched) and nonylphenol (Vol. 10, Issue EUR 20387 EN). European Commission—Joint Research Centre. Fabbri, R., Montagna, M., Balbi, T., Raffo, E., Palumbo, F., & Canesi, L. (2014). Adaptation of the bivalve embryotoxicity assay for the high throughput screening of emerging contaminants in Mytilus galloprovincialis. Marine Environmental Research, 99, 1–8. https://doi.org/10. 1016/j.marenvres.2014.05.007 Flores‐Nunes, F., Mattos, J. J., Zacchi, F. L., Serrano, M. A. S., Piazza, C. E., Sasaki, S. T., Taniguchi, S., Bicego, M. C., Melo, C. M. R., & Bainy, A. C. D. (2015). Effect of linear alkylbenzene mixtures and sanitary sewage in biochemical and molecular responses in Pacific oyster Crassostrea gigas. Environmental Science and Pollution Research, 22(22), 17386–17396. https://doi.org/10.1007/s11356-015-4486-7 Gao, D., Liu, X., Junaid, M., Liao, H., Chen, G., Wu, Y., & Wang, J. (2022). Toxicological impacts of micro(nano)plastics in the benthic environment. Science of the Total Environment, 836, 155620. https://doi.org/10.1016/ j.scitotenv.2022.155620 Gheorghe, S., Stan, M. S., Mitroi, D. N., Staicu, A. C., Cicirma, M., Lucaciu, I. E., Nita‐Lazar, M., & Dinischiotu, A. (2022). Oxidative stress and histopathological changes in gills and kidneys of Cyprinus carpio following exposure to benzethonium chloride, a cationic surfactant. Toxics, 10(5), 227. https://doi.org/10.3390/toxics10050227 Guéguen, M., Amiard, J.‐C., Arnich, N., Badot, P.‐M., Claisse, D., Guérin, T., & Vernoux, J.‐P. (2011). Shellfish and residual chemical contaminants: Hazards, monitoring, and health risk assessment along French coasts. Reviews of Environmental Contamination and Toxicology, 213, 55–111. https://doi.org/10.1007/978-1-4419-9860-6_3 Guenther, K., Heinke, V., Thiele, B., Kleist, E., Prast, H., & Raecker, T. (2002). Endocrine disrupting nonylphenols are ubiquitous in food. Environmental Science & Technology, 36(8), 1676–1680. https://doi.org/10. 1021/es010199v Hart, C. E., Lauth, M. J., Hunter, C. S., Krasny, B. R., & Hardy, K. M. (2016). Effect of 4‐nonylphenol on the immune response of the Pacific oyster Crassostrea gigas following bacterial infection with Vibrio campbellii. Fish & Shellfish Immunology, 58, 449–461. https://doi.org/10.1016/j.fsi. 2016.09.054 Hong, Y., Feng, C., Yan, Z., Wang, Y., Liu, D., Liao, W., & Bai, Y. (2020). Nonylphenol occurrence, distribution, toxicity and analytical methods in freshwater. Environmental Chemistry Letters, 18(6), 2095–2106. https:// doi.org/10.1007/s10311-020-01060-3 Jacobsen, A. M., Mortensen, G. K., & Hansen, H. C. B. (2004). Degradation and mobility of linear alkylbenzene sulfonate and nonylphenol in sludge‐ amended soil. Journal of Environmental Quality, 33(1), 232–240. https:// doi.org/10.2134/jeq.2004.2320 Kawashima, Y., Onishi, Y., Tatarazako, N., Yamamoto, H., Koshio, M., Oka, T., Horie, Y., Watanabe, H., Nakamoto, T., Yamamoto, J., Ishikawa, H., Sato, T., Yamazaki, K., & Iguchi, T. (2022). Summary of seventeen chemicals evaluated by OECD TG229 using Japanese medaka, Oryzias latipes in EXTEND 2016. Journal of Applied Toxicology, 42(5), 750–777. https://doi.org/10.1002/jat.4255 Kwack, S. J., Kwon, O., Kim, H. S., Kim, S. S., Kim, S. H., Sohn, K. H., Da Lee, R., Park, C. H., Jeung, E. B., & An, B. S. (2002). Comparative evaluation of alkylphenolic compounds on estrogenic activity in vitro and in vivo. Journal Toxicology and Environmental Health Part A, 65, 419–431. https://doi.org/10.1080/15287390252808082 Kwon, Y. S., Jung, J. W., Kim, Y. J., Park, C. B., Shon, J. C., Kim, J. H., & Seo, J. S. (2020). Proteomic analysis of whole‐body responses in medaka (Oryzias latipes) exposed to benzalkonium chloride. Journal of Environmental Science and Health, Part A, 55(12), 1387–1397. https://doi. org/10.1080/10934529.2020.1796117 Lahnsteiner, F., Berger, B., Kletzl, M., & Weismann, T. (2005). Effect of bisphenol A on maturation and quality of semen and eggs in the brown trout, Salmo trutta f. fario. Aquatic Toxicology, 75(3), 213–224. https:// doi.org/10.1016/j.aquatox.2005.08.004 le Gac, F., Thomas, J. L., Mourot, B., & Loir, M. (2001). In vivo and in vitro effects of prochloraz and nonylphenol ethoxylates on trout spermatogenesis. Aquatic Toxicology, 53(3–4), 187–200. https://doi.org/10.1016/ S0166-445X(01)00165-5 Li, C., Jin, F., & Snyder, S. A. (2018). Recent advancements and future trends in analysis of nonylphenol ethoxylates and their degradation product nonylphenol in food and environment. TrAC, Trends in Analytical Chemistry, 107, 78–90. https://doi.org/10.1016/j.trac.2018.07.021 Lu, J., Wu, J., Stoffella, P. J., & Wilson, P. C. (2013). Analysis of bisphenol A, nonylphenol, and natural estrogens in vegetables and fruits using gas chromatography—Tandem mass spectrometry. Journal of Agricultural and Food Chemistry, 61(1), 84–89. https://doi.org/10.1021/ jf304971k Maggioni, S., Balaguer, P., Chiozzotto, C., & Benfenati, E. (2013). Screening of endocrine‐disrupting phenols, herbicides, steroid estrogens, and estrogenicity in drinking water from the waterworks of 35 Italian cities and from PET‐bottled mineral water. Environmental Science and Pollution Research, 20(3), 1649–1660. https://doi.org/10.1007/s11356-012-1075-x Marin, M. G., Rigato, S., Ricciardi, F., & Matozzo, V. (2008). Lethal and estrogenic effects of 4‐nonylphenol in the cockle Cerastoderma glaucum. Marine Pollution Bulletin, 57(6–12), 552–558. https://doi.org/ 10.1016/j.marpolbul.2008.01.041 Martínez‐Zapata, M., Aristizábal, C., & Peñuela, G. (2013). Photodegradation of the endocrine‐disrupting chemicals 4n‐nonylphenol and triclosan by simulated solar UV irradiation in aqueous solutions with Fe (III) and in the absence/presence of humic acids. Journal of Photochemistry and Photobiology A, 251, 41–49. https://doi.org/10.1016/j. jphotochem.2012.10.009 Matozzo, V., Rova, G., Ricciardi, F., & Marin, M. G. (2008). Immunotoxicity of the xenoestrogen 4‐nonylphenol to the cockle Cerastoderma glaucum. Marine Pollution Bulletin, 57(6), 453–459. https://doi.org/10.1016/j. marpolbul.2008.02.019 Mesnage, R., Bernay, B., & Séralini, G. E. (2013). Ethoxylated adjuvants of glyphosate‐based herbicides are active principles of human cell toxicity. Toxicology, 313(2‐3), 122–128. https://doi.org/10.1016/j.tox. 2012.09.006 Mona, M. H., El‐Khodary, G. M., Abdel‐Halim, K. Y., Omran, N. E., Abd El‐Aziz, K. K., & El‐Saidy, S. A. (2022). Histopathological alterations induced by marine environmental pollutants on the bivalve Cerastoderma glaucum (Bruguière 1789) from Temsah Lake, Suez Canal, Egypt. Environmental Science and Pollution Research, 29(7), 9971–9989. https:// doi.org/10.1007/s11356-021-14966-4 Mueller, G. C., & Kim, U.‐H. (1978). Displacement of estradiol from estrogen receptors by simple alkyl phenols*. Endocrinology, 102(5), 1429–1435. https://doi.org/10.1210/endo-102-5-1429 Mukherjee, U., Samanta, A., Biswas, S., Ghosh, S., Das, S., Banerjee, S., & Maitra, S. (2022). Chronic exposure to nonylphenol induces oxidative stress and liver damage in male zebrafish (Danio rerio): Mechanistic insight into cellular energy sensors, lipid accumulation and immune modulation. Chemico‐Biological Interactions, 351, 109762. https://doi. org/10.1016/j.cbi.2021.109762 Müller, A.‐K., Markert, N., Leser, K., Kämpfer, D., Schiwy, S., Riegraf, C., Buchinger, S., Gan, L., Abdallah, A. T., Denecke, B., Segner, H., Brinkmann, M., Crawford, S. E., & Hollert, H. (2021). Bioavailability and impacts of estrogenic compounds from suspended sediment on rainbow trout (Oncorhynchus mykiss). Aquatic Toxicology, 231, 105719. https:// doi.org/10.1016/j.aquatox.2020.105719 Nice, H. E. (2005). Sperm motility in the Pacific oyster (Crassostrea gigas) is affected by nonylphenol. Marine Pollution Bulletin, 50(12), 1668–1674. https://doi.org/10.1016/j.marpolbul.2005.07.006 Nice, H., Morritt, D., Crane, M., & Thorndyke, M. (2003). Long‐term and transgenerational effects of nonylphenol exposure at a key stage in the development of Crassostrea gigas. Possible endocrine disruption? Marine Ecology Progress Series, 256, 293–300. https://doi.org/10.3354/ meps256293 Niu, Y., Zhang, J., Duan, H., Wu, Y., & Shao, B. (2015). Bisphenol A and nonylphenol in foodstuffs: Chinese dietary exposure from the 2007 total diet study and infant health risk from formulas. Food Chemistry, 167, 320–325. https://doi.org/10.1016/j.foodchem.2014.06.115 Noorimotlagh, Z., Mirzaee, S. A., Martinez, S. S., Rachoń, D., Hoseinzadeh, M., & Jaafarzadeh, N. (2020). Environmental exposure to nonylphenol and cancer progression risk—A systematic review. Environmental Research, 184, 109263. https://doi.org/10.1016/j.envres.2020.109263 Pickford, K. A., Thomas‐Jones, R. E., Wheals, B., Tyler, C. R., & Sumpter, J. P. (2003). Route of exposure affects the oestrogenic response of fish to 4‐tert‐nonylphenol. Aquatic Toxicology, 65(3), 267–279. https://doi. org/10.1016/S0166-445X(03)00149-8 Qian, K., Jiang, X., Sun, L., Zhou, G., Ge, H., Fang, X., Xiao, L., & Wu, Q. (2018). Effect of montmorillonite on 4‐Nonylphenol enrichment in zebrafish. International Journal of Environmental Research and Public Health, 15(6), 1217. https://doi.org/10.3390/ijerph15061217 Quesada‐Calderón, S., Bacigalupe, L. D., Toro‐Vélez, A. F., Madera‐Parra, C. A., Peña‐Varón, M. R., & Cárdenas‐Henao, H. (2017). The multigenerational effects of water contamination and endocrine disrupting chemicals on the fitness of Drosophila melanogaster. Ecology and Evolution, 7(16), 6519–6526. https://doi.org/10.1002/ece3.3172 Raecker, T., Thiele, B., Boehme, R. M., & Guenther, K. (2011). Endocrine disrupting nonyl‐ and octylphenol in infant food in Germany: Considerable daily intake of nonylphenol for babies. Chemosphere, 82(11), 1533–1540. https://doi.org/10.1016/j.chemosphere.2010.11.065 Ricciardi, F., Matozzo, V., & Marin, M. G. (2008). Effects of 4‐nonylphenol exposure in mussels (Mytilus galloprovincialis) and crabs (Carcinus aestuarii) with particular emphasis on vitellogenin induction. Marine Pollution Bulletin, 57(6–12), 365–372. https://doi.org/10.1016/j.marpolbul. 2008.02.023 Ringbeck, B., Bury, D., Hayen, H., Weiss, T., Brüning, T., & Koch, H. M. (2021). Determination of specific urinary nonylphenol metabolites by online‐SPE‐LC‐MS/MS as novel human exposure biomarkers. Journal of Chromatography B, 1177, 122794. https://doi.org/10.1016/j.jchromb. 2021.122794 Ríos, F. (2016). Environmental behavior of commercial surfactants: Biodegradability, toxicity and ozonation. Doctoral Thesis, University of Granada. Sadmani, A. A., Andrews, R. C., & Bagley, D. M. (2014). Nanofiltration of pharmaceutically active and endocrine disrupting compounds as a function of compound interactions with DOM fractions and cations in natural water. Separation and Purification Technology, 122, 462–471. https://doi.org/10.1016/j.seppur.2013.12.003 Salgueiro‐González, N., Campillo, J. A., Viñas, L., Beiras, R., López‐Mahía, P., & Muniategui‐Lorenzo, S. (2019). Occurrence of selected endocrine disrupting compounds in Iberian coastal areas and assessment of the environmental risk. Environmental Pollution, 249, 767–775. https://doi. org/10.1016/j.envpol.2019.03.107 Sayed, A. E. D. H., Kataoka, C., Oda, S., Kashiwada, S., & Mitani, H. (2018). Sensitivity of medaka (Oryzias latipes) to 4‐nonylphenol subacute exposure; Erythrocyte alterations and apoptosis. Environmental Toxicology and Pharmacology, 58, 98–104. https://doi.org/10.1016/j.etap. 2017.12.023 Schwaiger, J., Mallow, U., Ferling, H., Knoerr, S., Braunbeck, T., Kalbfus, W., & Negele, R. D. (2002). How estrogenic is nonylphenol. Aquatic Toxicology, 59(3–4), 177–189. https://doi.org/10.1016/S0166-445X(01) 00248-X Schwaiger, J., Spieser, O. H., Bauer, C., Ferling, H., Mallow, U., Kalbfus, W., & Negele, R. D. (2000). Chronic toxicity of nonylphenol and ethinylestradiol: Haematological and histopathological effects in juvenile common carp (Cyprinus carpio). Aquatic Toxicology, 51(1), 69–78. https://doi.org/10.1016/S0166-445X(00)00098-9 Shelley, L. K., Ross, P. S., Miller, K. M., Kaukinen, K. H., & Kennedy, C. J. (2012). Toxicity of atrazine and nonylphenol in juvenile rainbow trout (Oncorhynchus mykiss): Effects on general health, disease susceptibility and gene expression. Aquatic Toxicology, 124–125, 217–226. https:// doi.org/10.1016/j.aquatox.2012.08.007 Soares, A., Guieysse, B., Jefferson, B., Cartmell, E., & Lester, J. N. (2008). Nonylphenol in the environment: A critical review on occurrence, fate, toxicity and treatment in wastewaters. Environment International, 34(7), 1033–1049. https://doi.org/10.1016/j.envint.2008.01.004 Solé, M., & Sanchez‐Hernandez, J. C. (2018). Elucidating the importance of mussel carboxylesterase activity as exposure biomarker of environmental contaminants of current concern: An in vitro study. Ecological Indicators, 85, 432–439. https://doi.org/10.1016/j.ecolind.2017.10.046 Soto, A. M., Sonnenschein, C., Chung, K. L., Fernandez, M. F., Olea, N., & Serrano, F. O. (1995). The E‐SCREEN assay as a tool to identify estrogens: An update on estrogenic environmental pollutants. Environmental Health Perspectives, 103(suppl 7), 113–122. https://doi.org/10.1289/ ehp.95103s7113 Sprague, B. L., Trentham‐Dietz, A., Hedman, C. J., Wang, J., Hemming, J. D., Hampton, J. M., Buist, D. S., Aiello Bowles, E. J., Sisney, G. S., & Burnside, E. S. (2013). Circulating serum xenoestrogens and mammographic breast density. Breast Cancer Research, 15(3), R45. https://doi. org/10.1186/bcr3432 Sturm, A., Cravedi, J. P., Perdu, E., Baradat, M., & Segner, H. (2001). Effects of prochloraz and nonylphenol diethoxylate on hepatic biotransformation enzymes in trout: A comparative in vitro/in vivo‐ assessment using cultured hepatocytes. Aquatic Toxicology, 53(3–4), 229–245. https://doi.org/10.1016/S0166-445X(01)00168-0 Tato, T., Salgueiro‐González, N., León, V. M., González, S., & Beiras, R. (2018). Ecotoxicological evaluation of the risk posed by bisphenol A, triclosan, and 4‐nonylphenol in coastal waters using early life stages of marine organisms (Isochrysis galbana, Mytilus galloprovincialis, Paracentrotus lividus, and Acartia clausi). Environmental Pollution, 232, 173–182. https://doi.org/10.1016/j.envpol.2017.09.031 U.S. Environmental Protection Agency. (2021). Contaminant candidate list 4—CCL 4. https://www.epa.gov/ccl/contaminant-candidate-list-4-ccl-4-0 van den Belt, K., Berckmans, P., Vangenechten, C., Verheyen, R., & Witters, H. (2004). Comparative study on the in vitro/in vivo estrogenic potencies of 17β‐estradiol, estrone, 17α‐ethynylestradiol and nonylphenol. Aquatic Toxicology, 66(2), 183–195. https://doi.org/10.1016/j.aquatox.2003.09.004 Vidal‐Liñán, L., Bellas, J., Salgueiro‐González, N., Muniategui, S., & Beiras, R. (2015). Bioaccumulation of 4‐nonylphenol and effects on biomarkers, acetylcholinesterase, glutathione‐S‐transferase and glutathione peroxidase, in Mytilus galloprovincialis mussel gills. Environmental Pollution, 200, 133–139. https://doi.org/10.1016/j.envpol.2015.02.012 Yang, W., Gao, X., Wu, Y., Wan, L., Tan, L., Yuan, S., Ding, H., & Zhang, W. (2020). The combined toxicity influence of microplastics and nonylphenol on microalgae Chlorella pyrenoidosa. Ecotoxicology and Environmental Safety, 195, 110484. https://doi.org/10.1016/j.ecoenv.2020.110484 Yu, J., Yang, X., Yang, X., Yang, M., Wang, P., Yang, Y., Yang, J., Li, W., & Xu, J. (2018). Nonylphenol aggravates non‐alcoholic fatty liver disease in high sucrose‐high fat diet‐treated rats. Scientific Reports, 8(1), 3232. https://doi.org/10.1038/s41598-018-21725-y Watanabe, H., Horie, Y., Takanobu, H., Koshio, M., Flynn, K., Iguchi, T., & Tatarazako, N. (2017). Medaka Extended One‐Generation Reproduction Test (MEOGRT) evaluating 4‐nonylphenol. Environmental Toxicology and Chemistry, 36(12), 3254–3266. https://doi.org/10.1002/etc.3895 Zaytseva, T. B., Zinoveva, S. V., Kuzikova, I. L., Russu, A. D., Chugunova, M. V., & Medvedeva, N. G. (2020). Impact of nonylphenols on biological activity of loamy soddy‐podzolic soil. Eurasian Soil Science, 53(5), 661–667. https://doi.org/10.1134/S1064229320050178 Zein, M. A., McElmurry, S. P., Kashian, D. R., Savolainen, P. T., & Pitts, D. K. (2015). Toxic effects of combined stressors on Daphnia pulex: Interactions between diazinon, 4‐nonylphenol, and wastewater effluent. 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Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)© 2023 Society of Environmentalhttps://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/embargoedAccesshttp://purl.org/coar/access_right/c_f1cfDe la Parra-Guerra, Ana C.Acevedo‐Barrios, Rosa2023-11-01T18:55:15Z2024-04-142023-11-01T18:55:15Z2023-04-140730-7268https://hdl.handle.net/11323/1057110.1002/etc.56331552-8618Corporación Universidad de la CostaREDICUC - Repositorio CUChttps://repositorio.cuc.edu.co/Certain emerging pollutants are among the most widely used chemicals globally, causing widespread concern in relation to their use in products devoted to cleaniness and asepsis. Nonylphenol ethoxylate (NPEOn) is one such contaminant, along with its degradation product, nonylphenol, an active ingredient presents in nonionic surfactants used as herbicides, cosmetics, paints, plastics, disinfectants, and detergents. These chemicals and their metabolites are commonly found in environmental matrices. Nonylphenol and NPEOn, used, are particularly concerning, given their role as endocrine disruptors chemical and possible neurotoxic effects recorded in several biological models, primarily aquatic organisms. Limiting and detecting these compounds remain of paramount importance. The objective of the present review was to evaluate the toxic effects of nonylphenol and NPEOn in different biological models.12 páginasapplication/pdfengWiley-BlackwellUnited Stateshttps://setac.onlinelibrary.wiley.com/doi/full/10.1002/etc.5633Studies of endocrine disruptors: nonylphenol and isomers in biological modelsArtículo de revistahttp://purl.org/coar/resource_type/c_2df8fbb1Textinfo:eu-repo/semantics/articlehttp://purl.org/redcol/resource_type/ARTinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/version/c_970fb48d4fbd8a85Environmental Toxicology and ChemistryAbdel Rahman, A. N., Mahmoud, S. M., Khamis, T., Rasheed, N., Mohamed, D. I., Ghanem, R., Mansour, D. M., Ismail, T. A., & Mahboub, H. H. (2022). Palliative effect of dietary common sage leaves against toxic impacts of nonylphenol in mirror carp (Cyprinus carpio var specularis): Growth, gene expression, immune‐antioxidant status, and histopathological alterations. Aquaculture Reports, 25, 101200. https://doi.org/10. 1016/j.aqrep.2022.101200Abdulrahman, I., Jamal Mamdoh, T., & Sathianeson, S. (2022). The anti‐ settlement activity of extracts of marine bacteria associated with soft corals against barnacle larvae. Egyptian Journal of Aquatic Biology and Fisheries, 26(3), 885–900. https://doi.org/10.21608/ejabf.2022. 248212Acir, I. H., & Guenther, K. (2018). Endocrine‐disrupting metabolites of alkylphenol ethoxylates—A critical review of analytical methods, environmental occurrences, toxicity, and regulation. Science of the Total Environment, 635, 1530–1546. https://doi.org/10.1016/j.scitotenv.2018. 04.079Amaninejad, P., Hosseinzadeh Sahafi, H., Soltani, M., & Hosseini Shekarabi, S. P. (2018). Endocrine disrupting effects of 4‐nonylphenol on plasma vitellogenin, reproductive system and histology in koi carp (Cyprinus carpio). International Aquatic Research; A Journal of Science and Its Applications, 10(3), 263–274. https://doi.org/10.1007/s40071-018- 0203-8Aronzon, C. M. (2012). Evaluación de la toxicidad de los contaminantes cobre, nonilfenol y diazinón sobre embriones y larvas de Rhinella (Bufo) arenarum [Embryo‐larval toxicity of pollutants, copper, nonylphenol and dizinon on Rhinella (Bufo) arenarum]. Doctoral dissertation, Universidad de Buenos Aires. http://hdl.handle.net/20.500.12110/tesis_n5340_ AronzonAtienzar, F. A., Billinghurst, Z., & Depledge, M. H. (2002). 4‐n‐Nonylphenol and 17‐β estradiol may induce common DNA effects in developing barnacle larvae. Environmental Pollution, 120(3), 735–738. https://doi. org/10.1016/S0269-7491(02)00184-7Bednářová, A., Kropf, M., & Krishnan, N. (2020). The surfactant polyethoxylated tallowamine (POEA) reduces lifespan and inhibits fecundity in Drosophila melanogaster–In vivo and in vitro study. Ecotoxicology and Environmental Safety, 188, 109883. https://doi.org/10.1016/j. ecoenv.2019.109883Bhandari, G., Bagheri, A. R., Bhatt, P., & Bilal, M. (2021). Occurrence, potential ecological risks, and degradation of endocrine disrupter, nonylphenol, from the aqueous environment. Chemosphere, 275, 130013. https://doi.org/10.1016/j.chemosphere.2021.130013Billinghurst, Z., Clare, A. S., Fileman, T., Mcevoy, J., Readman, J., & Depledge, M. H. (1998). Inhibition of barnacle settlement by the environmental oestrogen 4‐nonylphenol and the natural oestrogen 17β oestradiol. Marine Pollution Bulletin, 36(10), 833–839. https://doi.org/10. 1016/S0025-326X(98)00074-5Government of Canada. (1999). Canadian Environmental Protection Act, 1999. https://laws-lois.justice.gc.ca/eng/acts/c-15.31/Careghini, A., Mastorgio, A. F., Saponaro, S., & Sezenna, E. (2015). Bisphenol A, nonylphenols, benzophenones, and benzotriazoles in soils, groundwater, surface water, sediments, and food: A review. Environmental Science and Pollution Research, 22(8), 5711–5741. https://doi. org/10.1007/s11356-014-3974-5Chen, W., Pan, S., Cheng, H., Sweetman, A. J., Zhang, H., & Jones, K. C. (2018). Diffusive gradients in thin‐films (DGT) for in situ sampling of selected endocrine disrupting chemicals (EDCs) in waters. Water Research, 137, 211–219. https://doi.org/10.1016/j.watres.2018.03.029Chłopecka, M., Mendel, M., Dziekan, N., & Karlik, W. (2017). The effect of glyphosate‐based herbicide Roundup and its co‐formulant, POEA, on the motoric activity of rat intestine—In vitro study. Environmental Toxicology and Pharmacology, 49, 156–162. https://doi.org/10.1016/j.etap. 2016.12.010Conselho Nacional Do Meio Ambiente. (2005). Resolução CONAMA no 357, de 17 de março de 2005—4a Câmara—Meio Ambiente e Patrimônio Cultural. https://www.mpf.mp.br/atuacao-tematica/ccr4/dadosda-atuacao/projetos/qualidade-da-agua/legislacao/resolucoes/ resolucao-conama-no-357-de-17-de-marco-de-2005/viewCrago, J., Tran, K., Budicin, A., Schreiber, B., Lavado, R., & Schlenk, D. (2015). Exploring the impacts of two separate mixtures of pesticide and surfactants on estrogenic activity in male fathead minnows and rainbow trout. Archives of Environmental Contamination and Toxicology, 68(2), 362–370. https://doi.org/10.1007/s00244-014-0098-3De la Parra‐Guerra, A., & Olivero‐Verbel, J. (2020). Toxicity of nonylphenol and nonylphenol ethoxylate on Caenorhabditis elegans. Ecotoxicology and Environmental Safety, 187, 109709. https://doi.org/10.1016/j. ecoenv.2019.109709De la Parra‐Guerra, A., Stürzenbaum, S., & Olivero‐Verbel, J. (2020). Intergenerational toxicity of nonylphenol ethoxylate (NP‐9) in Caenorhabditis elegans. Ecotoxicology and Environmental Safety, 197, 110588. https:// doi.org/10.1016/j.ecoenv.2020.110588Ding, J., Cheng, Y., Hua, Z., Yuan, C., & Wang, X. (2019). The effect of dissolved organic matter (DOM) on the release and distribution of endocrine‐disrupting chemicals (EDCs) from sediment under hydrodynamic forces, A case study of bisphenol A (BPA) and nonylphenol (NP). International Journal of Environmental Research and Public Health, 16(10), 1724. https://doi.org/10.3390/ijerph16101724Domene, X., Ramírez, W., Solà, L., Alcañiz, J. M., & Andrés, P. (2009). Soil pollution by nonylphenol and nonylphenol ethoxylates and their effects to plants and invertebrates. Journal of Soils and Sediments, 9(6), 555–567. https://doi.org/10.1007/s11368-009-0117-6Düring, R.‐A., Krahe, S., & Gäth, S. (2002). Sorption behavior of nonylphenol in terrestrial oils. Environmental Science & Technology, 36(19), 4052–4057. https://doi.org/10.1021/es0103389Dwivedi, S., D'Souza, L. C., Shetty, N. G., Raghu, S. V., & Sharma, A. (2022). Hsp27, a potential EcR target, protects nonylphenol‐induced cellular and organismal toxicity in Drosophila melanogaster. Environmental Pollution, 293, 118484. https://doi.org/10.1016/J.ENVPOL. 2021.118484European Commission. (2002). European Union Risk Assessment Report 4‐nonylphenol (branched) and nonylphenol (Vol. 10, Issue EUR 20387 EN). European Commission—Joint Research Centre.Fabbri, R., Montagna, M., Balbi, T., Raffo, E., Palumbo, F., & Canesi, L. (2014). Adaptation of the bivalve embryotoxicity assay for the high throughput screening of emerging contaminants in Mytilus galloprovincialis. Marine Environmental Research, 99, 1–8. https://doi.org/10. 1016/j.marenvres.2014.05.007Flores‐Nunes, F., Mattos, J. J., Zacchi, F. L., Serrano, M. A. S., Piazza, C. E., Sasaki, S. T., Taniguchi, S., Bicego, M. C., Melo, C. M. R., & Bainy, A. C. D. (2015). Effect of linear alkylbenzene mixtures and sanitary sewage in biochemical and molecular responses in Pacific oyster Crassostrea gigas. Environmental Science and Pollution Research, 22(22), 17386–17396. https://doi.org/10.1007/s11356-015-4486-7Gao, D., Liu, X., Junaid, M., Liao, H., Chen, G., Wu, Y., & Wang, J. (2022). Toxicological impacts of micro(nano)plastics in the benthic environment. Science of the Total Environment, 836, 155620. https://doi.org/10.1016/ j.scitotenv.2022.155620Gheorghe, S., Stan, M. S., Mitroi, D. N., Staicu, A. C., Cicirma, M., Lucaciu, I. E., Nita‐Lazar, M., & Dinischiotu, A. (2022). Oxidative stress and histopathological changes in gills and kidneys of Cyprinus carpio following exposure to benzethonium chloride, a cationic surfactant. Toxics, 10(5), 227. https://doi.org/10.3390/toxics10050227Guéguen, M., Amiard, J.‐C., Arnich, N., Badot, P.‐M., Claisse, D., Guérin, T., & Vernoux, J.‐P. (2011). Shellfish and residual chemical contaminants: Hazards, monitoring, and health risk assessment along French coasts. Reviews of Environmental Contamination and Toxicology, 213, 55–111. https://doi.org/10.1007/978-1-4419-9860-6_3Guenther, K., Heinke, V., Thiele, B., Kleist, E., Prast, H., & Raecker, T. (2002). Endocrine disrupting nonylphenols are ubiquitous in food. Environmental Science & Technology, 36(8), 1676–1680. https://doi.org/10. 1021/es010199vHart, C. E., Lauth, M. J., Hunter, C. S., Krasny, B. R., & Hardy, K. M. (2016). Effect of 4‐nonylphenol on the immune response of the Pacific oyster Crassostrea gigas following bacterial infection with Vibrio campbellii. Fish & Shellfish Immunology, 58, 449–461. https://doi.org/10.1016/j.fsi. 2016.09.054Hong, Y., Feng, C., Yan, Z., Wang, Y., Liu, D., Liao, W., & Bai, Y. (2020). Nonylphenol occurrence, distribution, toxicity and analytical methods in freshwater. Environmental Chemistry Letters, 18(6), 2095–2106. https:// doi.org/10.1007/s10311-020-01060-3Jacobsen, A. M., Mortensen, G. K., & Hansen, H. C. B. (2004). Degradation and mobility of linear alkylbenzene sulfonate and nonylphenol in sludge‐ amended soil. Journal of Environmental Quality, 33(1), 232–240. https:// doi.org/10.2134/jeq.2004.2320Kawashima, Y., Onishi, Y., Tatarazako, N., Yamamoto, H., Koshio, M., Oka, T., Horie, Y., Watanabe, H., Nakamoto, T., Yamamoto, J., Ishikawa, H., Sato, T., Yamazaki, K., & Iguchi, T. (2022). Summary of seventeen chemicals evaluated by OECD TG229 using Japanese medaka, Oryzias latipes in EXTEND 2016. Journal of Applied Toxicology, 42(5), 750–777. https://doi.org/10.1002/jat.4255Kwack, S. J., Kwon, O., Kim, H. S., Kim, S. S., Kim, S. H., Sohn, K. H., Da Lee, R., Park, C. H., Jeung, E. B., & An, B. S. (2002). Comparative evaluation of alkylphenolic compounds on estrogenic activity in vitro and in vivo. Journal Toxicology and Environmental Health Part A, 65, 419–431. https://doi.org/10.1080/15287390252808082Kwon, Y. S., Jung, J. W., Kim, Y. J., Park, C. B., Shon, J. C., Kim, J. H., & Seo, J. S. (2020). Proteomic analysis of whole‐body responses in medaka (Oryzias latipes) exposed to benzalkonium chloride. Journal of Environmental Science and Health, Part A, 55(12), 1387–1397. https://doi. org/10.1080/10934529.2020.1796117Lahnsteiner, F., Berger, B., Kletzl, M., & Weismann, T. (2005). Effect of bisphenol A on maturation and quality of semen and eggs in the brown trout, Salmo trutta f. fario. Aquatic Toxicology, 75(3), 213–224. https:// doi.org/10.1016/j.aquatox.2005.08.004le Gac, F., Thomas, J. L., Mourot, B., & Loir, M. (2001). In vivo and in vitro effects of prochloraz and nonylphenol ethoxylates on trout spermatogenesis. Aquatic Toxicology, 53(3–4), 187–200. https://doi.org/10.1016/ S0166-445X(01)00165-5Li, C., Jin, F., & Snyder, S. A. (2018). Recent advancements and future trends in analysis of nonylphenol ethoxylates and their degradation product nonylphenol in food and environment. TrAC, Trends in Analytical Chemistry, 107, 78–90. https://doi.org/10.1016/j.trac.2018.07.021Lu, J., Wu, J., Stoffella, P. J., & Wilson, P. C. (2013). Analysis of bisphenol A, nonylphenol, and natural estrogens in vegetables and fruits using gas chromatography—Tandem mass spectrometry. Journal of Agricultural and Food Chemistry, 61(1), 84–89. https://doi.org/10.1021/ jf304971kMaggioni, S., Balaguer, P., Chiozzotto, C., & Benfenati, E. (2013). Screening of endocrine‐disrupting phenols, herbicides, steroid estrogens, and estrogenicity in drinking water from the waterworks of 35 Italian cities and from PET‐bottled mineral water. Environmental Science and Pollution Research, 20(3), 1649–1660. https://doi.org/10.1007/s11356-012-1075-xMarin, M. G., Rigato, S., Ricciardi, F., & Matozzo, V. (2008). Lethal and estrogenic effects of 4‐nonylphenol in the cockle Cerastoderma glaucum. Marine Pollution Bulletin, 57(6–12), 552–558. https://doi.org/ 10.1016/j.marpolbul.2008.01.041Martínez‐Zapata, M., Aristizábal, C., & Peñuela, G. (2013). Photodegradation of the endocrine‐disrupting chemicals 4n‐nonylphenol and triclosan by simulated solar UV irradiation in aqueous solutions with Fe (III) and in the absence/presence of humic acids. Journal of Photochemistry and Photobiology A, 251, 41–49. https://doi.org/10.1016/j. jphotochem.2012.10.009Matozzo, V., Rova, G., Ricciardi, F., & Marin, M. G. (2008). Immunotoxicity of the xenoestrogen 4‐nonylphenol to the cockle Cerastoderma glaucum. Marine Pollution Bulletin, 57(6), 453–459. https://doi.org/10.1016/j. marpolbul.2008.02.019Mesnage, R., Bernay, B., & Séralini, G. E. (2013). Ethoxylated adjuvants of glyphosate‐based herbicides are active principles of human cell toxicity. Toxicology, 313(2‐3), 122–128. https://doi.org/10.1016/j.tox. 2012.09.006Mona, M. H., El‐Khodary, G. M., Abdel‐Halim, K. Y., Omran, N. E., Abd El‐Aziz, K. K., & El‐Saidy, S. A. (2022). Histopathological alterations induced by marine environmental pollutants on the bivalve Cerastoderma glaucum (Bruguière 1789) from Temsah Lake, Suez Canal, Egypt. Environmental Science and Pollution Research, 29(7), 9971–9989. https:// doi.org/10.1007/s11356-021-14966-4Mueller, G. C., & Kim, U.‐H. (1978). Displacement of estradiol from estrogen receptors by simple alkyl phenols*. Endocrinology, 102(5), 1429–1435. https://doi.org/10.1210/endo-102-5-1429Mukherjee, U., Samanta, A., Biswas, S., Ghosh, S., Das, S., Banerjee, S., & Maitra, S. (2022). Chronic exposure to nonylphenol induces oxidative stress and liver damage in male zebrafish (Danio rerio): Mechanistic insight into cellular energy sensors, lipid accumulation and immune modulation. Chemico‐Biological Interactions, 351, 109762. https://doi. org/10.1016/j.cbi.2021.109762Müller, A.‐K., Markert, N., Leser, K., Kämpfer, D., Schiwy, S., Riegraf, C., Buchinger, S., Gan, L., Abdallah, A. T., Denecke, B., Segner, H., Brinkmann, M., Crawford, S. E., & Hollert, H. (2021). Bioavailability and impacts of estrogenic compounds from suspended sediment on rainbow trout (Oncorhynchus mykiss). Aquatic Toxicology, 231, 105719. https:// doi.org/10.1016/j.aquatox.2020.105719Nice, H. E. (2005). Sperm motility in the Pacific oyster (Crassostrea gigas) is affected by nonylphenol. Marine Pollution Bulletin, 50(12), 1668–1674. https://doi.org/10.1016/j.marpolbul.2005.07.006Nice, H., Morritt, D., Crane, M., & Thorndyke, M. (2003). Long‐term and transgenerational effects of nonylphenol exposure at a key stage in the development of Crassostrea gigas. Possible endocrine disruption? Marine Ecology Progress Series, 256, 293–300. https://doi.org/10.3354/ meps256293Niu, Y., Zhang, J., Duan, H., Wu, Y., & Shao, B. (2015). Bisphenol A and nonylphenol in foodstuffs: Chinese dietary exposure from the 2007 total diet study and infant health risk from formulas. Food Chemistry, 167, 320–325. https://doi.org/10.1016/j.foodchem.2014.06.115Noorimotlagh, Z., Mirzaee, S. A., Martinez, S. S., Rachoń, D., Hoseinzadeh, M., & Jaafarzadeh, N. (2020). Environmental exposure to nonylphenol and cancer progression risk—A systematic review. Environmental Research, 184, 109263. https://doi.org/10.1016/j.envres.2020.109263Pickford, K. A., Thomas‐Jones, R. E., Wheals, B., Tyler, C. R., & Sumpter, J. P. (2003). Route of exposure affects the oestrogenic response of fish to 4‐tert‐nonylphenol. Aquatic Toxicology, 65(3), 267–279. https://doi. org/10.1016/S0166-445X(03)00149-8Qian, K., Jiang, X., Sun, L., Zhou, G., Ge, H., Fang, X., Xiao, L., & Wu, Q. (2018). Effect of montmorillonite on 4‐Nonylphenol enrichment in zebrafish. International Journal of Environmental Research and Public Health, 15(6), 1217. https://doi.org/10.3390/ijerph15061217Quesada‐Calderón, S., Bacigalupe, L. D., Toro‐Vélez, A. F., Madera‐Parra, C. A., Peña‐Varón, M. R., & Cárdenas‐Henao, H. (2017). The multigenerational effects of water contamination and endocrine disrupting chemicals on the fitness of Drosophila melanogaster. Ecology and Evolution, 7(16), 6519–6526. https://doi.org/10.1002/ece3.3172Raecker, T., Thiele, B., Boehme, R. M., & Guenther, K. (2011). Endocrine disrupting nonyl‐ and octylphenol in infant food in Germany: Considerable daily intake of nonylphenol for babies. Chemosphere, 82(11), 1533–1540. https://doi.org/10.1016/j.chemosphere.2010.11.065Ricciardi, F., Matozzo, V., & Marin, M. G. (2008). Effects of 4‐nonylphenol exposure in mussels (Mytilus galloprovincialis) and crabs (Carcinus aestuarii) with particular emphasis on vitellogenin induction. Marine Pollution Bulletin, 57(6–12), 365–372. https://doi.org/10.1016/j.marpolbul. 2008.02.023Ringbeck, B., Bury, D., Hayen, H., Weiss, T., Brüning, T., & Koch, H. M. (2021). Determination of specific urinary nonylphenol metabolites by online‐SPE‐LC‐MS/MS as novel human exposure biomarkers. Journal of Chromatography B, 1177, 122794. https://doi.org/10.1016/j.jchromb. 2021.122794Ríos, F. (2016). Environmental behavior of commercial surfactants: Biodegradability, toxicity and ozonation. Doctoral Thesis, University of Granada.Sadmani, A. A., Andrews, R. C., & Bagley, D. M. (2014). Nanofiltration of pharmaceutically active and endocrine disrupting compounds as a function of compound interactions with DOM fractions and cations in natural water. Separation and Purification Technology, 122, 462–471. https://doi.org/10.1016/j.seppur.2013.12.003Salgueiro‐González, N., Campillo, J. A., Viñas, L., Beiras, R., López‐Mahía, P., & Muniategui‐Lorenzo, S. (2019). Occurrence of selected endocrine disrupting compounds in Iberian coastal areas and assessment of the environmental risk. Environmental Pollution, 249, 767–775. https://doi. org/10.1016/j.envpol.2019.03.107Sayed, A. E. D. H., Kataoka, C., Oda, S., Kashiwada, S., & Mitani, H. (2018). Sensitivity of medaka (Oryzias latipes) to 4‐nonylphenol subacute exposure; Erythrocyte alterations and apoptosis. Environmental Toxicology and Pharmacology, 58, 98–104. https://doi.org/10.1016/j.etap. 2017.12.023Schwaiger, J., Mallow, U., Ferling, H., Knoerr, S., Braunbeck, T., Kalbfus, W., & Negele, R. D. (2002). How estrogenic is nonylphenol. Aquatic Toxicology, 59(3–4), 177–189. https://doi.org/10.1016/S0166-445X(01) 00248-XSchwaiger, J., Spieser, O. H., Bauer, C., Ferling, H., Mallow, U., Kalbfus, W., & Negele, R. D. (2000). Chronic toxicity of nonylphenol and ethinylestradiol: Haematological and histopathological effects in juvenile common carp (Cyprinus carpio). Aquatic Toxicology, 51(1), 69–78. https://doi.org/10.1016/S0166-445X(00)00098-9Shelley, L. K., Ross, P. S., Miller, K. M., Kaukinen, K. H., & Kennedy, C. J. (2012). Toxicity of atrazine and nonylphenol in juvenile rainbow trout (Oncorhynchus mykiss): Effects on general health, disease susceptibility and gene expression. Aquatic Toxicology, 124–125, 217–226. https:// doi.org/10.1016/j.aquatox.2012.08.007Soares, A., Guieysse, B., Jefferson, B., Cartmell, E., & Lester, J. N. (2008). Nonylphenol in the environment: A critical review on occurrence, fate, toxicity and treatment in wastewaters. Environment International, 34(7), 1033–1049. https://doi.org/10.1016/j.envint.2008.01.004Solé, M., & Sanchez‐Hernandez, J. C. (2018). Elucidating the importance of mussel carboxylesterase activity as exposure biomarker of environmental contaminants of current concern: An in vitro study. Ecological Indicators, 85, 432–439. https://doi.org/10.1016/j.ecolind.2017.10.046Soto, A. M., Sonnenschein, C., Chung, K. L., Fernandez, M. F., Olea, N., & Serrano, F. O. (1995). The E‐SCREEN assay as a tool to identify estrogens: An update on estrogenic environmental pollutants. Environmental Health Perspectives, 103(suppl 7), 113–122. https://doi.org/10.1289/ ehp.95103s7113Sprague, B. L., Trentham‐Dietz, A., Hedman, C. J., Wang, J., Hemming, J. D., Hampton, J. M., Buist, D. S., Aiello Bowles, E. J., Sisney, G. S., & Burnside, E. S. (2013). Circulating serum xenoestrogens and mammographic breast density. Breast Cancer Research, 15(3), R45. https://doi. org/10.1186/bcr3432Sturm, A., Cravedi, J. P., Perdu, E., Baradat, M., & Segner, H. (2001). Effects of prochloraz and nonylphenol diethoxylate on hepatic biotransformation enzymes in trout: A comparative in vitro/in vivo‐ assessment using cultured hepatocytes. Aquatic Toxicology, 53(3–4), 229–245. https://doi.org/10.1016/S0166-445X(01)00168-0Tato, T., Salgueiro‐González, N., León, V. M., González, S., & Beiras, R. (2018). Ecotoxicological evaluation of the risk posed by bisphenol A, triclosan, and 4‐nonylphenol in coastal waters using early life stages of marine organisms (Isochrysis galbana, Mytilus galloprovincialis, Paracentrotus lividus, and Acartia clausi). Environmental Pollution, 232, 173–182. https://doi.org/10.1016/j.envpol.2017.09.031U.S. Environmental Protection Agency. (2021). Contaminant candidate list 4—CCL 4. https://www.epa.gov/ccl/contaminant-candidate-list-4-ccl-4-0van den Belt, K., Berckmans, P., Vangenechten, C., Verheyen, R., & Witters, H. (2004). Comparative study on the in vitro/in vivo estrogenic potencies of 17β‐estradiol, estrone, 17α‐ethynylestradiol and nonylphenol. Aquatic Toxicology, 66(2), 183–195. https://doi.org/10.1016/j.aquatox.2003.09.004Vidal‐Liñán, L., Bellas, J., Salgueiro‐González, N., Muniategui, S., & Beiras, R. (2015). Bioaccumulation of 4‐nonylphenol and effects on biomarkers, acetylcholinesterase, glutathione‐S‐transferase and glutathione peroxidase, in Mytilus galloprovincialis mussel gills. Environmental Pollution, 200, 133–139. https://doi.org/10.1016/j.envpol.2015.02.012Yang, W., Gao, X., Wu, Y., Wan, L., Tan, L., Yuan, S., Ding, H., & Zhang, W. (2020). The combined toxicity influence of microplastics and nonylphenol on microalgae Chlorella pyrenoidosa. Ecotoxicology and Environmental Safety, 195, 110484. https://doi.org/10.1016/j.ecoenv.2020.110484Yu, J., Yang, X., Yang, X., Yang, M., Wang, P., Yang, Y., Yang, J., Li, W., & Xu, J. (2018). Nonylphenol aggravates non‐alcoholic fatty liver disease in high sucrose‐high fat diet‐treated rats. Scientific Reports, 8(1), 3232. https://doi.org/10.1038/s41598-018-21725-yWatanabe, H., Horie, Y., Takanobu, H., Koshio, M., Flynn, K., Iguchi, T., & Tatarazako, N. (2017). Medaka Extended One‐Generation Reproduction Test (MEOGRT) evaluating 4‐nonylphenol. Environmental Toxicology and Chemistry, 36(12), 3254–3266. https://doi.org/10.1002/etc.3895Zaytseva, T. B., Zinoveva, S. V., Kuzikova, I. L., Russu, A. D., Chugunova, M. V., & Medvedeva, N. G. (2020). Impact of nonylphenols on biological activity of loamy soddy‐podzolic soil. Eurasian Soil Science, 53(5), 661–667. https://doi.org/10.1134/S1064229320050178Zein, M. A., McElmurry, S. P., Kashian, D. R., Savolainen, P. T., & Pitts, D. K. (2015). Toxic effects of combined stressors on Daphnia pulex: Interactions between diazinon, 4‐nonylphenol, and wastewater effluent. Environmental Toxicology and Chemistry, 34(5), 1145–1153. https://doi. org/10.1002/etc.290814501439742Endocrine disruptorEnvironmental pollutantNonionic surfactantsNeurotoxicToxicologyPublicationORIGINALStudies of Endocrine Disruptors. Nonylphenol and Isomers in Biological Models.pdfStudies of Endocrine Disruptors. 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ada en las Obras Colectivas.

b.	Distribuir copias o fonogramas de las Obras, exhibirlas públicamente, ejecutarlas públicamente y/o ponerlas a disposición pública, incluyéndolas como incorporadas en Obras Colectivas, según corresponda.

c.	Distribuir copias de las Obras Derivadas que se generen, exhibirlas públicamente, ejecutarlas públicamente y/o ponerlas a disposición pública.
Los derechos mencionados anteriormente pueden ser ejercidos en todos los medios y formatos, actualmente conocidos o que se inventen en el futuro. Los derechos antes mencionados incluyen el derecho a realizar dichas modificaciones en la medida que sean técnicamente necesarias para ejercer los derechos en otro medio o formatos, pero de otra manera usted no está autorizado para realizar obras derivadas. Todos los derechos no otorgados expresamente por el Licenciante quedan por este medio reservados, incluyendo pero sin limitarse a aquellos que se mencionan en las secciones 4(d) y 4(e).

4. Restricciones.
La licencia otorgada en la anterior Sección 3 está expresamente sujeta y limitada por las siguientes restricciones:

a.	Usted puede distribuir, exhibir públicamente, ejecutar públicamente, o poner a disposición pública la Obra sólo bajo las condiciones de esta Licencia, y Usted debe incluir una copia de esta licencia o del Identificador Universal de Recursos de la misma con cada copia de la Obra que distribuya, exhiba públicamente, ejecute públicamente o ponga a disposición pública. No es posible ofrecer o imponer ninguna condición sobre la Obra que altere o limite las condiciones de esta Licencia o el ejercicio de los derechos de los destinatarios otorgados en este documento. No es posible sublicenciar la Obra. Usted debe mantener intactos todos los avisos que hagan referencia a esta Licencia y a la cláusula de limitación de garantías. Usted no puede distribuir, exhibir públicamente, ejecutar públicamente, o poner a disposición pública la Obra con alguna medida tecnológica que controle el acceso o la utilización de ella de una forma que sea inconsistente con las condiciones de esta Licencia. Lo anterior se aplica a la Obra incorporada a una Obra Colectiva, pero esto no exige que la Obra Colectiva aparte de la obra misma quede sujeta a las condiciones de esta Licencia. Si Usted crea una Obra Colectiva, previo aviso de cualquier Licenciante debe, en la medida de lo posible, eliminar de la Obra Colectiva cualquier referencia a dicho Licenciante o al Autor Original, según lo solicitado por el Licenciante y conforme lo exige la cláusula 4(c).

b.	Usted no puede ejercer ninguno de los derechos que le han sido otorgados en la Sección 3 precedente de modo que estén principalmente destinados o directamente dirigidos a conseguir un provecho comercial o una compensación monetaria privada. El intercambio de la Obra por otras obras protegidas por derechos de autor, ya sea a través de un sistema para compartir archivos digitales (digital file-sharing) o de cualquier otra manera no será considerado como estar destinado principalmente o dirigido directamente a conseguir un provecho comercial o una compensación monetaria privada, siempre que no se realice un pago mediante una compensación monetaria en relación con el intercambio de obras protegidas por el derecho de autor.

c.	Si usted distribuye, exhibe públicamente, ejecuta públicamente o ejecuta públicamente en forma digital la Obra o cualquier Obra Derivada u Obra Colectiva, Usted debe mantener intacta toda la información de derecho de autor de la Obra y proporcionar, de forma razonable según el medio o manera que Usted esté utilizando: (i) el nombre del Autor Original si está provisto (o seudónimo, si fuere aplicable), y/o (ii) el nombre de la parte o las partes que el Autor Original y/o el Licenciante hubieren designado para la atribución (v.g., un instituto patrocinador, editorial, publicación) en la información de los derechos de autor del Licenciante, términos de servicios o de otras formas razonables; el título de la Obra si está provisto; en la medida de lo razonablemente factible y, si está provisto, el Identificador Uniforme de Recursos (Uniform Resource Identifier) que el Licenciante especifica para ser asociado con la Obra, salvo que tal URI no se refiera a la nota sobre los derechos de autor o a la información sobre el licenciamiento de la Obra; y en el caso de una Obra Derivada, atribuir el crédito identificando el uso de la Obra en la Obra Derivada (v.g., "Traducción Francesa de la Obra del Autor Original," o "Guión Cinematográfico basado en la Obra original del Autor Original"). Tal crédito puede ser implementado de cualquier forma razonable; en el caso, sin embargo, de Obras Derivadas u Obras Colectivas, tal crédito aparecerá, como mínimo, donde aparece el crédito de cualquier otro autor comparable y de una manera, al menos, tan destacada como el crédito de otro autor comparable.

d.	Para evitar toda confusión, el Licenciante aclara que, cuando la obra es una composición musical:

i.	Regalías por interpretación y ejecución bajo licencias generales. El Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública o la ejecución pública digital de la obra y de recolectar, sea individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, SAYCO), las regalías por la ejecución pública o por la ejecución pública digital de la obra (por ejemplo Webcast) licenciada bajo licencias generales, si la interpretación o ejecución de la obra está primordialmente orientada por o dirigida a la obtención de una ventaja comercial o una compensación monetaria privada.

ii.	Regalías por Fonogramas. El Licenciante se reserva el derecho exclusivo de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, los consagrados por la SAYCO), una agencia de derechos musicales o algún agente designado, las regalías por cualquier fonograma que Usted cree a partir de la obra (“versión cover”) y distribuya, en los términos del régimen de derechos de autor, si la creación o distribución de esa versión cover está primordialmente destinada o dirigida a obtener una ventaja comercial o una compensación monetaria privada.

e.	Gestión de Derechos de Autor sobre Interpretaciones y Ejecuciones Digitales (WebCasting). Para evitar toda confusión, el Licenciante aclara que, cuando la obra sea un fonograma, el Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública digital de la obra (por ejemplo, webcast) y de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, ACINPRO), las regalías por la ejecución pública digital de la obra (por ejemplo, webcast), sujeta a las disposiciones aplicables del régimen de Derecho de Autor, si esta ejecución pública digital está primordialmente dirigida a obtener una ventaja comercial o una compensación monetaria privada.

5. Representaciones, Garantías y Limitaciones de Responsabilidad.
A MENOS QUE LAS PARTES LO ACORDARAN DE OTRA FORMA POR ESCRITO, EL LICENCIANTE OFRECE LA OBRA (EN EL ESTADO EN EL QUE SE ENCUENTRA) “TAL CUAL”, SIN BRINDAR GARANTÍAS DE CLASE ALGUNA RESPECTO DE LA OBRA, YA SEA EXPRESA, IMPLÍCITA, LEGAL O CUALQUIERA OTRA, INCLUYENDO, SIN LIMITARSE A ELLAS, GARANTÍAS DE TITULARIDAD, COMERCIABILIDAD, ADAPTABILIDAD O ADECUACIÓN A PROPÓSITO DETERMINADO, AUSENCIA DE INFRACCIÓN, DE AUSENCIA DE DEFECTOS LATENTES O DE OTRO TIPO, O LA PRESENCIA O AUSENCIA DE ERRORES, SEAN O NO DESCUBRIBLES (PUEDAN O NO SER ESTOS DESCUBIERTOS). ALGUNAS JURISDICCIONES NO PERMITEN LA EXCLUSIÓN DE GARANTÍAS IMPLÍCITAS, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.

6. Limitación de responsabilidad.
A MENOS QUE LO EXIJA EXPRESAMENTE LA LEY APLICABLE, EL LICENCIANTE NO SERÁ RESPONSABLE ANTE USTED POR DAÑO ALGUNO, SEA POR RESPONSABILIDAD EXTRACONTRACTUAL, PRECONTRACTUAL O CONTRACTUAL, OBJETIVA O SUBJETIVA, SE TRATE DE DAÑOS MORALES O PATRIMONIALES, DIRECTOS O INDIRECTOS, PREVISTOS O IMPREVISTOS PRODUCIDOS POR EL USO DE ESTA LICENCIA O DE LA OBRA, AUN CUANDO EL LICENCIANTE HAYA SIDO ADVERTIDO DE LA POSIBILIDAD DE DICHOS DAÑOS. ALGUNAS LEYES NO PERMITEN LA EXCLUSIÓN DE CIERTA RESPONSABILIDAD, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.

7. Término.

a.	Esta Licencia y los derechos otorgados en virtud de ella terminarán automáticamente si Usted infringe alguna condición establecida en ella. Sin embargo, los individuos o entidades que han recibido Obras Derivadas o Colectivas de Usted de conformidad con esta Licencia, no verán terminadas sus licencias, siempre que estos individuos o entidades sigan cumpliendo íntegramente las condiciones de estas licencias. Las Secciones 1, 2, 5, 6, 7, y 8 subsistirán a cualquier terminación de esta Licencia.

b.	Sujeta a las condiciones y términos anteriores, la licencia otorgada aquí es perpetua (durante el período de vigencia de los derechos de autor de la obra). No obstante lo anterior, el Licenciante se reserva el derecho a publicar y/o estrenar la Obra bajo condiciones de licencia diferentes o a dejar de distribuirla en los términos de esta Licencia en cualquier momento; en el entendido, sin embargo, que esa elección no servirá para revocar esta licencia o que deba ser otorgada , bajo los términos de esta licencia), y esta licencia continuará en pleno vigor y efecto a menos que sea terminada como se expresa atrás. La Licencia revocada continuará siendo plenamente vigente y efectiva si no se le da término en las condiciones indicadas anteriormente.

8. Varios.

a.	Cada vez que Usted distribuya o ponga a disposición pública la Obra o una Obra Colectiva, el Licenciante ofrecerá al destinatario una licencia en los mismos términos y condiciones que la licencia otorgada a Usted bajo esta Licencia.

b.	Si alguna disposición de esta Licencia resulta invalidada o no exigible, según la legislación vigente, esto no afectará ni la validez ni la aplicabilidad del resto de condiciones de esta Licencia y, sin acción adicional por parte de los sujetos de este acuerdo, aquélla se entenderá reformada lo mínimo necesario para hacer que dicha disposición sea válida y exigible.

c.	Ningún término o disposición de esta Licencia se estimará renunciada y ninguna violación de ella será consentida a menos que esa renuncia o consentimiento sea otorgado por escrito y firmado por la parte que renuncie o consienta.

d.	Esta Licencia refleja el acuerdo pleno entre las partes respecto a la Obra aquí licenciada. No hay arreglos, acuerdos o declaraciones respecto a la Obra que no estén especificados en este documento. El Licenciante no se verá limitado por ninguna disposición adicional que pueda surgir en alguna comunicación emanada de Usted. Esta Licencia no puede ser modificada sin el consentimiento mutuo por escrito del Licenciante y Usted.
 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