Cytotoxicity and mutagenicity of female contraceptives in Allium cepa L.
DOI:
https://doi.org/10.33448/rsd-v11i11.33841Keywords:
Eukaryotic test system; Emergency contraception; Genotoxicity; Lactating; Drospirenone; Injectable contraceptive.Abstract
Currently, a large part of the female population uses contraceptive methods due to the benefits provided by this medication. These drugs can be found in oral or injectable form and are basic compounds for progestogen and estrogen. However, despite the benefits, these contraceptives can cause a number of harmful effects as women, due to continuous and prolonged use, in addition to the problem of these compounds being excreted in the sewers, daily, causing problems to the population and the animals exposed. In this context, the present study aimed to evaluate the cytotoxic and mutagenic potential of different contraceptives, using Allium cepa L. as a eukaryotic test system. Four contraceptives were used: indicated for lactating mothers (A1), the following day pill (A2), a drospirenone (A3) and an injectable (A4). Based on the results, conclude what is the A1 contraceptive, which is indicated for women in the lactation phase, shows cytotoxic effect, with a decrease in the mitotic index. However, none of the contraceptives studied were mutagenic for the eukaryotic cells studied. Thus, the data of the present study indicate that chronic studies must be carried out in order to protect humans and other organisms that may be exposed to these substances in the environment.
References
Adams, E., Neves, B. B., Prola, L. D., de Liz, M. V., Martins, L. R., Ramsdorf, W. A., & de Freitas, A. M. (2021). Ecotoxicity and genotoxicity assessment of losartan after UV/H2O2 and UVC/photolysis treatments. Environmental Science and Pollution Research, 28(19), 23812-23821. https://doi.org/10.1007/s11356-020-11420-9
Ahmad, E., Shadab, G. G. H. A., Azfer, A., & Afzal, M. (2001). Evaluation of genotoxic potential of synthetic progestins-norethindrone and norgestrel in human lymphocytes in vitro. Mutation Research, 494(1-2), 13-20. https://doi.org/10.1016/S1383-5718(01)00164-4.
Álvarez-Ruiz, R., Picó, Y., Alfarhan, A. H., El-Sheikh, M. A., Alshahrani, H. O., & Barceló, D. (2020). Dataset of pesticides, pharmaceuticals and personal care products occurrence in wetlands of Saudi Arabia. Data in brief, 31, 105776. https://doi.org/10.1016/j.dib.2020.105776
Apter, D., Zimmerman, Y., Beekman, L., Mawet, M., Maillard, C., Foidart, J. M., & Coelingh Bennink, H. J. (2017). Estetrol combined with drospirenone: an oral contraceptive with high acceptability, user satisfaction, well-being and favourable body weight control. The European Journal of Contraception & Reproductive Health Care, 22(4), 260-267. https://doi.org/10.1080/13625187.2017.1336532
Barbosa, A. S., & Chaves, C. T. de O. P. . (2021). Consequences of continuous use of contraceptive: an alert to women. Research, Society and Development, 10(15), e349101522949. https://doi.org/10.33448/rsd-v10i15.22949
Bila, D. M., & Dezotti, M. (2007). Desreguladores endócrinos no meio ambiente: efeitos e consequências. Química nova, 30(3), 651-666. https://doi.org/10.1590/S0100-40422007000300027.
Brasil. Ministério da Saúde (MS), Secretaria de Atenção à Saúde. Departamento de Ações Programáticas Estratégicas. (2011). Anticoncepção de emergência: perguntas e respostas para profissionais de saúde 2 ed. (p. 7-8). Brasília: Editora do Ministério da Saúde.
Brasil. Ministério da Saúde (MS). Secretaria de Atenção à Saúde. Departamento de Atenção Básica. (2010). Saúde sexual e saúde reprodutiva (p. 173-174). Brasília: Editora do Ministério da Saúde.
Burns, E. E., Carter, L. J., Kolpin, D. W., Thomas-Oates, J., & Boxall, A. B. (2018). Temporal and spatial variation in pharmaceutical concentrations in an urban river system. Water research, 137, 72-85. https://doi.org/10.1016/j.watres.2018.02.066
Burrows, L. J., Basha, M., & Goldstein, A. T. (2012). The effects of hormonal contraceptives on female sexuality: a review. The journal of sexual medicine, 9(9), 2213-2223. https://doi.org/10.1111/j.1743-6109.2012.02848.x
Düsman, E., Faria, J.S., Toledo, F., Mazeti, C.M., Gonçalves, M.E.K., Vicentini, V.E.P. (2011). Vegetal test-system investigation on cytotoxicity of water from urban streams located in the northeastern region of Maringá, Paraná State, Brazil. Acta Scientiarum. Biological Sciences, 33, 71-77. https://doi.org/10.4025/actascibiolsci.v33i1.4924.
Fatma, F., Verma S., Kamal, A., & Srivastava, A. (2018). Monitoring of morphotoxic, cytotoxic and genotoxic potential of mancozeb using Allium assay. Chemosphere, 195, 864-870. https://doi.org/10.1016/j.chemosphere.2017.12.052.
Fiskesjö, G. (1985). The Allium test as a standard in environmental monitoring. Hereditas, 102(1), 99-112. https://doi.org/10.1111/j.1601-5223.1985.tb00471.x.
Gallo, M. V., Ravenscroft, J., Carpenter, D. O., Frye, C., Cook, B., Schell, L. M., & Akwesasne Task Force on the Environment. (2016). Endocrine disrupting chemicals and ovulation: Is there a relationship?. Environmental Research, 151, 410-418. https://doi.org/10.1016/j.envres.2016.08.007
Garbett, K. A., Tianbing, D., John, A., Carrie, A. G., Brad, A. G., Kevin, G. O., … Sweatt, J. D. (2020). Synthetic female gonadal hormones alter neurodevelopmental programming and behavior in F1 offspring. Hormones and Behavior, 126, 104848. https://doi.org/10.1016/j.yhbeh.2020.104848.
Garcia, L. F., Golveia, J. C. S., & Santiago, M. F. (2014). Avaliação do potencial toxicológico de hormônios sexuais sintéticos utilizando bioensaios. Revista Intertox de Toxicologia, 7(2), 58-75. https://doi.org/10.22280/revintervol7ed2.173.
Gogoi, A., Mazumder, P., Tyagi, V. K., Chaminda, G. T., An, A. K., & Kumar, M. (2018). Occurrence and fate of emerging contaminants in water environment: a review. Groundwater for Sustainable Development, 6, 169-180. https://doi.org/10.1016/j.gsd.2017.12.009
Hall, K. S., & Trussell, J. (2012). Types of combined oral contraceptives used by US women. Contraception, 86(6), 659-665. https://doi.org/10.1016/j.contraception.2012.05.017
Heindel, J. J., Blumberg, B., Cave, M., Machtinger, R., Mantovani, A., Mendez, M. A., ... & Vom Saal, F. (2017). Metabolism disrupting chemicals and metabolic disorders. Reproductive toxicology, 68, 3-33. https://doi.org/10.1016/j.reprotox.2016.10.001
Jia, Y., Hammers-Wirtz, M., Crawford, S. E., Chen, Q., Seiler, T. B., Schäffer, A., & Hollert, H. (2019). Effect-based and chemical analyses of agonistic and antagonistic endocrine disruptors in multiple matrices of eutrophic freshwaters. Science of the Total Environment, 651, 1096-1104. https://doi.org/10.1016/j.scitotenv.2018.09.199
Kurowska, P., Mlyczyńska, E., Dawid, M., Respekta, N., Pich, K., Serra, L., ... & Rak, A. (2022). Endocrine disruptor chemicals, adipokines and reproductive functions. Endocrine, 1-14. https://doi.org/10.1007/s12020-022-03061-4
Laurenson, J. P., Bloom, R. A., Page, S., & Sadrieh, N. (2014). Ethinyl estradiol and other human pharmaceutical estrogens in the aquatic environment: a review of recent risk assessment data. The AAPS journal, 16(2), 299-310. https://doi.org/10.1208/s12248-014-9561-3
Leme, D. M., & Marin-Morales, M. A. (2009). Allium cepa test in environmental monitoring: a review on its application. Mutation Research, 682(1), 71-81. https://doi.org/10.1016/j.mrrev.2009.06.002.
Levin, E.R., & Vitek W.S., & Hammes S.R. (2017). Estrogens, progestins, and the female reproductive tract. Brunton L.L., & Hilal-Dandan R, & Knollmann B.C.(Eds.), Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13e. McGraw Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=2189§ionid=172482097
Li, Q., Wang, P., Chen, L., Gao, H., & Wu, L. (2016). Acute toxicity and histopathological effects of naproxen in zebrafish (Danio rerio) early life stages. Environmental Science and Pollution Research, 23(18), 18832-18841. https://doi.org/10.1007/s11356-016-7092-4
Liang, Y. Q., Huang, G. Y., Ying, G. G., Liu, S. S., Jiang, Y. X., & Liu, S. (2015). Progesterone and norgestrel alter transcriptional expression of genes along the hypothalamic–pituitary–thyroid axis in zebrafish embryos-larvae. Comparative Biochemistry and Physiology - Part C: Toxicology & Pharmacology, 167, 101-107. https://doi.org/10.1016/j.cbpc.2014.09.007.
Liu, Z. H., Kanjo, Y., & Mizutani, S. (2009). Urinary excretion rates of natural estrogens and androgens from humans, and their occurrence and fate in the environment: a review. Science of the Total Environment, 407(18), 4975-4985. https://doi.org/10.1016/j.scitotenv.2009.06.001
Malik, M. Z., Musharavati, F., Khanmohammadi, S., Khanmohammadi, S., & Nguyen, D. D. (2021). Solar still desalination system equipped with paraffin as phase change material: exergoeconomic analysis and multi-objective optimization. Environmental Science and Pollution Research, 28(1), 220-234. https://doi.org/10.1007/s11356-020-10335-9
Matsumoto, S. T., & Marin-Morales, M. A. (2005). Toxic and genotoxic effects of trivalent and hexavalent chromium-a review. Revista Brasileira de Toxicologia, 77-85. http://hdl.handle.net/11449/68282
Mouro, L. B., & Gonçalves, K. A. M. . (2021). The immoderate use of emergency contraception by young women. Research, Society and Development, 10(15), e366101522857. https://doi.org/10.33448/rsd-v10i15.22857
Naz, F., Jyoti, S., Rahul, Akhtar, N., & Siddique, Y. H. (2016). Effect of oral contraceptive pills on the blood serum enzymes and DNA damage in lymphocytes among users. Indian Journal of Clinical Biochemistry, 31(3), 294-301. https://doi.org/10.1007/s12291-015-0533-x.
Orozco-Hernández, L., Gutiérrez-Gómez, A. A., SanJuan-Reyes, N., Islas-Flores, H., García-Medina, S., Galar-Martínez, M., ... & Gómez-Oliván, L. M. (2018). 17β-Estradiol induces cyto-genotoxicity on blood cells of common carp (Cyprinus carpio). Chemosphere, 191, 118-127. https://doi.org/10.1016/j.chemosphere.2017.10.030
Patel, M., Kumar, R., Kishor, K., Mlsna, T., Pittman Jr, C. U., & Mohan, D. (2019). Pharmaceuticals of emerging concern in aquatic systems: chemistry, occurrence, effects, and removal methods. Chemical reviews, 119(6), 3510-3673. https://doi.org/10.1021/acs.chemrev.8b00299
Peña-Guzmán, C., Ulloa-Sánchez, S., Mora, K., Helena-Bustos, R., Lopez-Barrera, E., Alvarez, J., & Rodriguez-Pinzón, M. (2019). Emerging pollutants in the urban water cycle in Latin America: a review of the current literature. Journal of environmental management, 237, 408-423. https://doi.org/10.1016/j.jenvman.2019.02.100
Phillips, S. J., Tepper, N. K., Kapp, N., Nanda, K., Temmerman, M., & Curtis, K. M. (2016). Progestogen-only contraceptive use among breastfeeding women: a systematic review. Contraception, 82(1), 17-37. https://doi.org/10.1016/j.contraception.2010.02.002.
Pillon, D., Cadiou, V., Angulo, L., & Duittoz, A. H. (2012). Maternal exposure to 17-alpha-ethinylestradiol alters embryonic development of GnRH-1 neurons in mouse. Brain research, 1433, 29-37. https://doi.org/10.1016/j.brainres.2011.11.030
Porcu, P., Serra, M., & Concas, A. (2019). The brain as a target of hormonal contraceptives: Evidence from animal studies. Frontiers in Neuroendocrinology, 55, 100799. https://doi.org/10.1016/j.yfrne.2019.100799
Ramírez-Malule, H., Quiñones-Murillo, D. H., & Manotas-Duque, D. (2020). Emerging contaminants as global environmental hazards. A bibliometric analysis. Emerging contaminants, 6, 179-193. https://doi.org/10.1016/j.emcon.2020.05.001
Regidor, P. A. (2018). The clinical relevance of progestogens in hormonal contraception: Present status and future developments. Oncotarget, 9(77), 34628. https://doi.org/10.18632/oncotarget.26015
Rome, E. S., & Issac, V. (2017). Sometimes You Do Get a Second Chance: Emergency Contraception for Adolescents. Pediatric Clinics, 64(2), 371-380. https://doi.org/10.1016/j.pcl.2016.11.006
Scarsi, K. K., Darin, K. M., Chappell, C. A., Nitz, S. M., & Lamorde, M. (2016). Drug–drug interactions, effectiveness, and safety of hormonal contraceptives in women living with HIV. Drug safety, 39(11), 1053-1072. https://doi.org/10.1007/s40264-016-0452-7
Schmid, S., Willi, R. A., Salgueiro-González, N., & Fent, K. (2020). Effects of new generation progestins, including as mixtures and in combination with other classes of steroid hormones, on zebrafish early life stages. Science of The Total Environment, 709, 136262. https://doi.org/10.1016/j.scitotenv.2019.136262
Schmidt, W., & Redshaw, C. H. (2015). Evaluation of biological endpoints in crop plants after exposure to non‐steroidal anti‐inflammatory drugs (NSAIDs): Implications for phytotoxicological assessment of novel contaminants. Ecotoxicology and environmental safety, 112, 212-222. https://doi.org/10.1016/j.ecoenv.2014.11.008
Schutz, D. L., de Marco, I. G., Alves, G. L., Vincoski, J. V. A., Ishikawa, S., de Oliveira Schmitz, A. P., ... & Düsman, E. (2021). Biomonitoring of surface water quality in the Chopim River within the Conservation Unit Campos de Palmas Wildlife Refuge, southern Brazil. Environmental Monitoring and Assessment, 193(11), 1-18. https://doi.org/10.1007/s10661-021-09464-6
Sech, L. A., & Mishell Jr, D. R. (2015). Oral steroid contraception. Women’s Health, 11(6), 743-748. https://doi.org/10.2217/whe.15.82
Sheikh, I. A., Tayubi, I. A., Ahmad, E., Ganaie, M. A., Bajouh, O. S., AlBasri, S. F., ... & Beg, M. A. (2017). Computational insights into the molecular interactions of environmental xenoestrogens 4-tert-octylphenol, 4-nonylphenol, bisphenol A (BPA), and BPA metabolite, 4-methyl-2, 4-bis (4-hydroxyphenyl) pent-1-ene (MBP) with human sex hormone-binding globulin. Ecotoxicology and Environmental Safety, 135, 284-291. https://doi.org/10.1016/j.ecoenv.2016.10.005
Shyama, S. K., Abdul, R. M., & Vijayalaxmi, K. K. (1991). Genotoxic effect of Anovlar 21, an oral contraceptive, on mouse bone marrow. Mutation Research, 260(1), 47-53. https://doi.org/10.1016/0165-1218(91)90079-2.
Siddique, Y. H., Beg, T., & Afzal, M. (2005). Genotoxic potential of ethinylestradiol in cultured mammalian cells. Chemico-Biological Interactions, 151(2), 133-41. https://doi.org/10.1016/j.cbi.2004.10.008.
Sifakis, S., Androutsopoulos, V. P., Tsatsakis, A. M., & Spandidos, D. A. (2017). Human exposure to endocrine disrupting chemicals: effects on the male and female reproductive systems. Environmental Toxicology and Pharmacology, 51, 56-70. https://doi.org/10.1016/j.etap.2017.02.024
Škrbić, B. D., Kadokami, K., & Antić, I. (2018). Survey on the micro-pollutants presence in surface water system of northern Serbia and environmental and health risk assessment. Environmental research, 166, 130-140. https://doi.org/10.1016/j.envres.2018.05.034
Snow, D. D., Cassada, D. A., Biswas, S., Malakar, A., D’Alessio, M., Carter, L. J., ... & Sallach, J. B. (2019). Detection, occurrence, and fate of emerging contaminants in agricultural environments. Water Environment Research, 91(10), 1103-1113. https://doi.org/10.1002/wer.1204
Su, C., Cui, Y., Liu, D., Zhang, H., & Baninla, Y. (2020). Endocrine disrupting compounds, pharmaceuticals and personal care products in the aquatic environment of China: which chemicals are the prioritized ones?. Science of The Total Environment, 720, 137652. https://doi.org/10.1016/j.scitotenv.2020.137652
Sweeney, M. F., Hasan, N., Soto, A. M., & Sonnenschein, C. (2015). Environmental endocrine disruptors: effects on the human male reproductive system. Reviews in Endocrine and Metabolic Disorders, 16(4), 341-357. https://doi.org/10.1007/s11154-016-9337-4
Tran, N. H., Reinhard, M., & Gin, K. Y. H. (2018). Occurrence and fate of emerging contaminants in municipal wastewater treatment plants from different geographical regions-a review. Water research, 133, 182-207. https://doi.org/10.1016/j.watres.2017.12.029
Trindade, R. E. D., Siqueira, B. B., Paula, T. F. D., & Felisbino-Mendes, M. S. (2021). Uso de contracepção e desigualdades do planejamento reprodutivo das mulheres brasileiras. Ciência & Saúde Coletiva, 26, 3493-3504. https://doi.org/10.1590/1413-81232021269.2.24332019
Valdés, M. E., Huerta, B., Wunderlin, D. A., Bistoni, M. A., Barceló, D., & Rodriguez-Mozaz, S. (2016). Bioaccumulation and bioconcentration of carbamazepine and other pharmaceuticals in fish under field and controlled laboratory experiments. Evidences of carbamazepine metabolization by fish. Science of The Total Environment, 557, 58-67. https://doi.org/10.1016/j.scitotenv.2016.03.045
Viega, B. L., Rocha, A. M., & Düsman, E. (2020). Cosmetics with hormonal composition for bioindicators Artemia salina L. and Allium cepa L. toxic potential. Environmental Science and Pollution Research, 27(6), 6659-6666. https://doi.org/10.1007/s11356-019-07392-0.
Wagner, C. K. (2006). The many faces of progesterone: a role in adult and developing male brain. Frontiers in Neuroendocrinology, 27(3), 340-359. https://doi.org/10.1016/j.yfrne.2006.07.003.
World Health Organization (2015). Medical eligibility criteria for contraceptive use. 5 ed. World Health Organization.
Wu, C. Q., Grandi, S. M., Filion, K. B., Abenhaim, H. A., Joseph, L., & Eisenberg, M. J. (2013). Drospirenone‐containing oral contraceptive pills and the risk of venous and arterial thrombosis: a systematic review. BJOG: An International Journal of Obstetrics & Gynaecology, 120(7), 801-811. https://doi.org/10.1111/1471-0528.12210
Yan, Z., Lu, G., Liu, J., & Jin, S. (2012). An integrated assessment of estrogenic contamination and feminization risk in fish in Taihu Lake, China. Ecotoxicology and environmental safety, 84, 334-340. https://doi.org/10.1016/j.ecoenv.2012.08.010
Zheng, Y., Yuan, J., Meng, S., Chen, J., & Gu, Z. (2019). Testicular transcriptome alterations in zebrafish (Danio rerio) exposure to 17β-estradiol. Chemosphere, 218, 14-25. https://doi.org/10.1016/j.chemosphere.2018.11.092
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2022 Jaqueline Klem Bohrer; Adernanda Paula dos Santos; Aline Perszel; Eduardo Michel Vieira Gomes; Alessandra Paim Berti; Elisângela Düsman
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
