The cytotoxic and genotoxic effects of bisphenol A on neuronal cells in vitro

Shannon O'Sullivan


Endocrine disrupting chemicals (EDCs) have the potential to cause adverse effects to human health by disrupting normal homeostasis, reproduction, development and behaviour. They can simultaneously act as cytotoxic and genotoxic agents. Bisphenol A (BPA) is a well-documented EDC, widely used in the manufacturing of plastic and epoxy resins. Humans are regularly exposed to this chemical through ingestion of food and beverages. The adverse effects of BPA on reproduction and development have been thoroughly studied. The potential adverse effect of BPA however, on neuronal development has not been entirely explored. In this study, the potential cytotoxic and genotoxic effects of BPA were investigated on neuroblastoma cells (SH-SY5Y). While the cytotoxicity was determined using the MTT assay, genotoxicity was determined using the comet assay. Time and concentration dependent effects were observed for cellular viability in this cell line following BPA exposure. BPA significantly reduced cell viability at high concentrations (>250 µM) after 24h and (> 100 µM) 48h exposures. Nevertheless, low environmental concentrations were not found to be cytotoxic. No significant increase in DNA damage was observed after a 24h exposure, while 500 nM significantly increased DNA damage after a 48h exposure. Scanning electron microscopy (SEM) results showed no morphological changes after exposure to BPA. This study provides in vitro evidence of the potential adverse effects of BPA on the nervous system and possible effects on neuronal development. However, further investigation would be required to decide if environmental concentrations are likely to be potentially hazardous to human health.

Full Text:



Akingbemi, B.T., Sottas, C.M., Koulova, A.I., Klinefelter, G.R. and Hardy, M.P.

(2013). Inhibition of Testicular Steroidogenesis by the Xenoestrogen Bisphenol A is associated with reduced pituitary Luteinizing hormone secretion and decreased Steroidogenic enzyme gene expression in rat Leydig cells. Endocrinology, 145 (2), pp. 592-603. doi: 10.1210/en.2003-1174.

Arciello, M., Rotilio, G. and Rossi, L. (2005). Copper-dependent toxicity in SH-SY5Y neuroblastoma cells involves mitochondrial damage. Biochemical and Biophysical Research Communications, 327(2), pp. 454–459. Doi: 10.1016/j.bbrc.2004.12.022.

Arnold, A.P. and Gorski, R.A. (1984). Gonadal steroid induction of structural sex differences in the central nervous system. Annual Review of Neuroscience, 7(1), pp. 413–442. Doi: 10.1146/

Audebert, M., Dolo, L., Perdu, E., Cravedi, J.P. and Zalko, D. (2011). Use of the γH2AX assay for assessing the genotoxicity of bisphenol A and bisphenol F in human cell lines. Archives of Toxicology, 85(11), pp. 1463–1473. Doi: 10.1007/s00204-011-0721-2.

Babich, H. and Tipton, D.A. (1999). In Vitro cytotoxicity of bisphenol A to human gingival epithelial S-G cells. In Vitro and molecular toxicology, 12(4), pp. 233–244.

Balakrishnan, B., Henare, K., Thorstensen, E., Ponnampalam, A. and Mitchell, M. (2010). Transfer of bisphenol A across the human placenta. American journal of obstetrics and gynecology, 4(202), pp. 393.e1-393.e7. doi:10.1016/j.ajog.2010.01.025.

Benhusein, G. M., Mutch, E., Aburawi, S. and Williams, F. M. (2010). Genotoxic effect induced by hydrogen peroxide in human hepatoma cells using comet assay. The Libyan Journal of Medicine, 5(10), pp, 1-6.

Bolli, A., Galluzzo, P., Ascenzi, P., Del Pozzo, G., Manco, I., Vietri, M.T., Mita, L., Altucci, L., Mita, D.G. and Marino, M. (2008). Laccase treatment impairs bisphenol a-induced cancer cell proliferation affecting estrogen receptor α-dependent rapid signals. IUBMB Life, 60(12), pp. 843–852. Doi: 10.1002/iub.130.

Braun, J., Yolton, K., Dietrich, K., Hornung, R., Ye, X., Calafat, A. and Lanphear, B. (2010). Prenatal bisphenol A exposure and early childhood behavior. Environmental health perspectives, 117(12), pp. 1945–52. Doi: 10.1289/ehp.0900979.

Calafat, A. M., Ye, X., Wong, L.Y., Reidy, J. A. and Needham, L.L. (2008). Exposure of the U.S. Population to Bisphenol A and 4-tertiary-Octylphenol: 2003–2004. Environmental Health Perspectives, 116(1), pp. 39–44.

Cao, X., Corriveau, J., Popovic, S., Coughlan, M., Chepelev, N., Willmore, W., Schrader, T. and Jin, X. (2010). Background bisphenol A in experimental materials and its implication to low-dose in vitro study. Chemosphere, 6(81), pp. 817–820. doi:10.1016/j.chemosphere.2010.07.048.

Cavalieri, E.L. and Rogan, E.G. (2010). Is bisphenol A a weak carcinogen like the natural estrogens and diethylstilbestrol. IUBMB Life, 62(10), pp. 746–751. Doi: 10.1002/iub.376.

Chen, X., Xu, B., Han, X., Mao, Z., Talbot, P., Du, G., Liu, J., Wang, X. and Xia, Y. (2013). Effect of bisphenol A on pluripotency of mouse embryonic stem cells and differentiation capacity in mouse embryoid bodies. Toxicology in vitro, 27(8), pp. 2249-2255. doi: 10.1016/j.tiv.2013.09.018.

Collins, A. R., El Yamani, N., Lorenzo, Y., Shaposhnikov, S., Brunborg, G. and Azqueta, A. (2014). Controlling variation in the comet assay. Frontiers in Genetics, 5(359), pp.1-6

Clowry, G., Molnár, Z. and Rakic, P. (2010). Renewed focus on the developing human neocortex. Journal of Anatomy, 217(4), pp. 276–288. doi: 10.1111/j.1469-7580.2010.01281.x.

Della Seta, D., Minder, I., Dessì-Fulgheri, F. and Farabollini, F. (2005). Bisphenol-A exposure during pregnancy and lactation affects maternal behaviour in rats. Brain Research Bulletin, 65(3), pp. 255–260. Doi: 10.1016/j.brainresbull.2004.11.017.

Diamanti-Kandarakis, E., Bourguignon, J.P., Giudice, L.C., Hauser, R., Prins, G.S., Soto, A.M., Zoeller, R.T. and Gore, A.C. (2009). Endocrine-disrupting chemicals: An endocrine society scientific statement. Endocrine Reviews, 30(4), pp. 293–342. doi: 10.1210/er.2009-0002.

Elsworth, J.D., Jentsch, D.J., VandeVoort, C.A., Roth, R.H., Redmond, E.D. and Leranth, C. (2013). Prenatal exposure to bisphenol A impacts midbrain dopamine neurons and hippocampal spine synapses in non-human primates. NeuroToxicology, 35, pp. 113–120. doi: 10.1016/j.neuro.2013.01.001.

Fic, A., Žegura, B., Sollner Dolenc, M., Filipič, M. and Peterlin Mašič, L. (2013). Mutagenicity and DNA damage of Bisphenol A and its structural analogues in Hepg2 cells. Archives of Industrial Hygiene and Toxicology, 64(2), pp. 189–200. doi: 10.2478/10004-1254-64-2013-2319.

Filograna, R., Civiero, L., Ferrari, V., Codolo, G., Greggio, E., Bubacco, L., Beltramini, M. and Bisaglia, M. (2015). Analysis of the Catecholaminergic Phenotype in human SH-SY5Y and BE(2)-M17 neuroblastoma cell lines upon differentiation. PLOS ONE, 10(8): e0136769. doi: 10.1371/journal.pone.0136769.

Florent, M., Godard, T., Ballet, J.J., Gauduchon, P. and Sola, B. (1999). Detection by the comet assay of apoptosis induced by lymphoid cell lines after growth factor deprivation. Cell Biology and Toxicology, 15(3), pp. 185–192. doi: 10.1023/a:1007641821779.

Fotakis, G. and Timbrell, J.A. (2006). In vitro cytotoxicity assays: Comparison of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride. Toxicology Letters, 160(2), pp. 171–177. doi: 10.1016/j.toxlet.2005.07.001.

Gupta, R.K., Archambeault, D.R. and Yao, H.H.C. (2010). 11.30 – genetic mouse models for female reproductive toxicology studies. Comprehensive Toxicology (Second Edition), 11, pp. 561–575. doi: 10.1016/B978-0-08-046884-6.01135-0.

Gursoy, E., Cardounel, A. and Kalimi, M. (2001). The environmental estrogenic compound bisphenol A exerts estrogenic effects on mouse hippocampal (HT-22) cells: Neuroprotection against glutamate and amyloid beta protein toxicity. Neurochemistry International, 38(2), pp. 181–186. doi: 10.1016/S0197-0186(00)00072-3.

Hartung, T., Daston, G. (2009). Are in vitro tests suitable for regulatory use? Toxicological Sciences, 111(2), pp. 233–237. Doi: 10.1093/toxsci/kfp149.

Henderson, L., Wolfreys, A., Fedyk, J., Bourner, C. and Windebank, S. (1998). The ability of the comet assay to discriminate between genotoxins and cytotoxins. Mutagenesis, 13(1), pp. 89–94. Doi: 10.1093/mutage/13.1.89.

Hoekstra, E.J. and Simoneau, C. (2013). Release of Bisphenol A from Polycarbonate—A Review. Critical Reviews in Food Science and Nutrition, 53(4), pp. 386–402. doi: 10.1080/10408398.2010.536919.

Hong, S., Hong, Y., Kim, J., Park, E., Shin, M., Kim, B., Yoo, H., Cho, I., Bhang, S. and Cho, S. (2013). Bisphenol A in relation to behavior and learning of school-age children. Journal of child psychology and psychiatry, 54(8), pp. 890–899. doi: 10.1111/jcpp.12050.

Howdeshell, K., Hotchkiss, A., Thayer, K., Vandenbergh, J., vom Saal, F. (1999). Environmental toxins: Exposure to bisphenol A advances puberty. Nature, 401, pp. 763–764. Doi:10.1038/44517.

Hughes, P., Marshall, D., Reid, Y., Parkes, H. and Gelber, C. (2007). The costs of using unauthenticated, over-passaged cell lines: How much more data do we need? BioTechniques, 43(5), pp. 575–586. doi: 10.2144/000112598.

Iarmarcovai, G., Bonassi, S., Botta, A., Baan, R.A. and Orsière, T. (2008). Genetic polymorphisms and micronucleus formation: A review of the literature. Mutation Research, 658(3), pp. 215–233. Doi: 10.1016/j.mrrev.2007.10.001.

Iida, H., Maehara, K., Doiguchi, M., Mōri, T. and Yamada, F. (2003). Bisphenol a-induced apoptosis of cultured rat Sertoli cells. Reproductive toxicology, 17(4), pp. 457–64. Doi:10.1016/S0890-6238(03)00034-0.

Ikezuki, Y., Tsutsumi, O., Takai, Y., Kamei, Y., Taketani, Y. (2002). Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure. Human Reproduction, 17(11), pp. 2839–2841. Doi: 10.1093/humrep/17.11.2839.

Ishido, M. and Masuo, Y. (2014). Temporal effects of Bisphenol A on Dopaminergic Neurons: An experiment on adult rates. Open Environmental Science, 8, pp. 9–17. doi: 10.2174/1876325101408010009.

Ishido, M., Yonemoto, J. and Morita, M. (2007). Mesencephalic neurodegeneration in the orally administered bisphenol a-caused hyperactive rats. Toxicology Letters, 173(1), pp. 66–72. doi: 10.1016/j.toxlet.2007.06.014.

Iwakura, T., Iwafuchi, M., Muraoka, D., Yokosuka, M., Shiga, T., Watanabe, C. and Ohtani-Kaneko, R. (2010). In vitro effects of bisphenol A on developing hypothalamic neurons. Toxicology, 272(1-3), pp. 52–58. doi: 10.1016/j.tox.2010.04.005.

Jha, A.N., Hagger, J.A. and Hill, S.J. (2000). Tributyltin induces cytogenetic damage in the early life stages of the marine mussel, Mytilus edulis. Environmental and Molecular Mutagenesis, 35(4), pp. 343–350. Doi: 10.1002/1098-2280(2000)35:4<343::aid-em9>;2-5.

Kafi, M.A., Kim, T.H., An, J.H. and Choi, J.W. (2011). Electrochemical cell-based chip for the detection of toxic effects of bisphenol-A on neuroblastoma cells. Biosensors and Bioelectronics, 26(7), pp. 3371–3375. doi: 10.1016/j.bios.2010.12.030.

Kawaguchi, S., Nakamura, T., Yamamoto, A., Honda, G. and Sasaki, Y. F. (2010). Is the Comet Assay a Sensitive Procedure for Detecting Genotoxicity? Journal of Nucleic Acids, 2010, 541050.

Kim, K., Son, T.G., Kim, S.J., Kim, H.S., Kim, T.S., Han, S.Y. and Lee, J. (2007). Suppressive Effects of Bisphenol A on the Proliferation of Neural Progenitor Cells. Journal of Toxicology and Environmental Health A, 70(15-16), pp. 1288–1295. Doi: 10.1080/15287390701434216.

Krishnan, A., Stathis, P., Permuth, S., Tokes, L. and Feldman, D. (1993). Bisphenol-A: An estrogenic substance is released from polycarbonate flasks during autoclaving. Endocrinology, 132(6), pp. 2279–86. Doi:

Kuo, C.C., Huang, J.K., Chou, C.T., Cheng, J.S., Tsai, J.Y., Fang, Y.C., Hsu, S.S., Liao, W.C., Chang, H.T., Ho, C.M. and Jan, C.R. (2011). Effect of bisphenol A on Ca 2+ fluxes and viability in Madin-Darby canine renal tubular cells. Drug and Chemical Toxicology, 34(4), pp. 454–461. Doi: 10.3109/01480545.2011.556645.

Kumaravel, T.S. and Jha, A.N. (2006). Reliable comet assay measurements for detecting DNA damage induced by ionising radiation and chemicals. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 605(s 1–2), pp. 7–16. Doi: 10.1016/j.mrgentox.2006.03.002.

Kurisawa, T., Hiroi, H., Tsutsumi, O., Ishikawa, T., Osuga, Y., Fujiwara, T., Inoue, S., Muramatsu, M., Momoeda, M. and Taketani, Y. (2002). The activity of Bisphenol A depends on both the estrogen receptor subtype and the cell type. Endocrine Journal, 49(4), pp. 465–471. Doi: 10.1507/endocrj.49.465.

Le, H. H., Carlson, E. M., Chua, J. P. and Belcher, S. M. (2008). Bisphenol A is released from polycarbonate drinking bottles and mimics the neurotoxic actions of estrogen in developing cerebellar neurons. Toxicology Letters, 176(2), pp. 149–156.

Lee, D.Y., Lee, S.S., Joo, W.A., Lee, E.J. and Kim, C.W. (2004). Analysis of Differentially regulated proteins in TM4 cells treated with Bisphenol A. Bioscience, Biotechnology and Biochemistry, 68(6), pp. 1201–1208. Doi: 10.1271/bbb.68.1201.

Lee, M., Kwon, J. and Chung, M.K. (2003). Enhanced prediction of potential rodent carcinogenicity by utilizing comet assay and apoptotic assay in combination. Mutation Research, 541(s 1–2), pp. 9–19. Doi: 10.1016/S1383-5718(03)00175-X.

Lee, S., Suk, K., Kim, I.K., Jang, I.S., Park, J.W., Johnson, V.J., Kwon, T.K., Choi, B.J. and Kim, S.-H. (2008). Signaling pathways of bisphenol a-induced apoptosis in hippocampal neuronal cells: Role of calcium-induced reactive oxygen species, mitogen-activated protein kinases, and nuclear factor-κB. Journal of Neuroscience Research, 86(13), pp. 2932–2942. Doi: 10.1002/jnr.21739.

Lee, Y.M., Seong, M.J., Lee, J.W., Kim, T.M., Nam, S.Y., Kim, D.J., Yun, Y.W., Han, S.Y. and Hong, J.T. (2007). Estrogen receptor independent neurotoxic mechanism of bisphenol A, an environmental estrogen. Journal of Veterinary Science, 8(1), pp. 27-38. Doi: 10.4142/jvs.2007.8.1.27.

Liao, W., McNutt, M. and Zhu, W. (2009). The comet assay: A sensitive method for detecting DNA damage in individual cells. Methods, 48(1), pp. 46–53 Doi: 10.1016/j.ymeth.2009.02.016..

Masuo, Y. and Ishido, M. (2011). Neurotoxicity of endocrine Disruptors: Possible involvement in brain development and Neurodegeneration. Journal of Toxicology and Environmental Health, Part B Critical Review, 14(5-7), pp. 346–369. Doi: 10.1080/10937404.2011.578557.

McCarthy, M.M. (2008). Estradiol and the Developing Brain. Physiological Reviews, 88(1), pp. 91–134. Doi: 10.1152/physrev.00010.2007.

Milić, N., Četojević-Simin, D., Milanović, M., Sudji, J., Milošević, N., Ćurić, N., Abenavoli, L. and Medić-Stojanoska, M. (2015). Estimation of and exposure to bisphenol A as food contaminant. Food and Chemical Toxicology, 83, pp. 268–274. Doi: 10.1016/j.fct.2015.07.003.

Miyatake, M., Miyagawa, K., Mizuo, K., Narita, M. and Suzuki, T. (2006). Dynamic Changes in Dopaminergic Neurotransmission Induced by a Low Concentration of Bisphenol-A in Neurones and Astrocytes. Journal of Neuroendocrinology, 18(6), pp. 434–444. Doi: 10.1111/j.1365-2826.2006.01434.x.

Mori, C. (2001). Possible effects of endocrine disruptors on male reproductive function: a mini review. Acta Anatomica Nipponica, 76, pp. 361–368.

Muñoz-de-Toro, M., Markey, C. M., Wadia, P. R., Luque, E. H., Rubin, B. S., Sonnenschein, C. and Soto, A. M. (2005). Perinatal Exposure to Bisphenol-A Alters Peripubertal Mammary Gland Development in Mice. Endocrinology, 146(9), pp. 4138–4147.

Olea, N., Pulgar, R., Pérez, P., Olea-Serrano, F., Rivas, A., Novillo-Fertrell, A., Pedraza, V., Soto, A.M. and Sonnenschein, C. (1996). Estrogenicity of resin-based composites and sealants used in dentistry. Environmental Health Perspectives, 104(3), pp. 298–305. Doi: 10.1289/ehp.96104298.

Palanza, P., Gioiosa, L., vom Saal, F.S. and Parmigiani, S. (2008). Effects of developmental exposure to bisphenol A on brain and behaviour in mice. Environmental Research, 108(2), pp. 150–157. Doi: 10.1016/j.envres.2008.07.023.

Palanza, P., Howdeshell, K.L., Parmigiani, S. and vom Saal, F.S (2002). Exposure to a low dose of Bisphenol A during foetal life or in adulthood alters maternal behaviour in mice. Environmental Health Perspectives, 110(s3), pp. 415–422. Doi: 10.1289/ehp.02110s3415.

Perera, F., Vishnevetsky, J., Herbstman, J. B., Calafat, A. M., Xiong, W., Rauh, V. and Wang, S. (2012). Prenatal Bisphenol A Exposure and Child Behavior in an Inner-City Cohort. Environmental Health Perspectives, 120(8), pp.1190–1194.

Pfau, W., Martin, F.L., Cole, K.J., Venitt, S., Phillips, D.H., Grover, P.L. and Marquardt, H. (1999). Heterocyclic aromatic amines induce DNA strand breaks and cell transformation. Carcinogenesis, 20(4), pp. 545–551. Doi: 10.1093/carcin/20.4.545.

Pfeifer, D., Chung, Y.M. and Hu, M.C.T. (2015). Effects of low-dose Bisphenol A on DNA damage and proliferation of breast cells: The role of c-myc. Environmental Health Perspectives, 123(12), pp. 1271–1279. Doi: 10.1289/ehp.1409199.

Ptak, A., Wróbel, A. and Gregoraszczuk, E. (2011). Effect of bisphenol-a on the expression of selected genes involved in cell cycle and apoptosis in the OVCAR-3 cell line. Toxicology letters, 202(1), pp. 30–5. Doi: 10.1016/j.toxlet.2011.01.015.

Richter, C.A., Birnbaum, L.S., Farabollini, F., Newbold, R.R., Rubin, B.S., Talsness, C.E., Vandenbergh, J.G., Walser-Kuntz, D.R. and vom Saal, F.S. (2007). In vivo effects of bisphenol A in laboratory rodent studies. Reproductive Toxicology (Elmsford, N.Y.), 24(2), pp. 199–224. Doi: 10.1016/j.reprotox.2007.06.004.

Rochester, J.R. (2013). Bisphenol A and human health: A review of the literature. Reproductive Toxicology, 42, pp. 132–155. Doi: 10.1016/j.reprotox.2013.08.008.

Roy, D. and Liehr, J.G. (1999). Estrogen, DNA damage and mutations. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 424(s 1–2), pp. 107–115. Doi: 10.1016/S0027-5107(99)00012-3.

Sastry, P.S. and Rao, K.S. (2001). Apoptosis and the nervous system. Journal of Neurochemistry, 74(1), pp. 1–20. Doi: 10.1046/j.1471-4159.2000.0740001.x.

Schönfelder, G., Wittfoht, W., Hopp, H., Talsness, C.E., Paul, M. and Chahoud, I. (2002). Parent bisphenol A accumulation in the human maternal-fetal-placental unit. Environ Health Perspectives, 110(11), pp. A703–A707.

Sekizawa, J. (2008). Low-dose effects of bisphenol A: A serious threat to human health? The Journal of toxicological sciences, 33(4), pp. 389–403.

Sheng, Z.G. and Zhu, B. Z. (2011). Low Concentrations of Bisphenol A Induce Mouse Spermatogonial Cell Proliferation by G Protein–Coupled Receptor 30 and Estrogen Receptor-α. Environmental Health Perspectives, 119(12), pp. 1775–1780.

Tayama, S., Nakagawa, Y. and Tayama, K. (2008). Genotoxic effects of environmental estrogen-like compounds in CHO-K1 cells. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 649(s 1–2), pp. 114–125.doi:10.1016/j.mrgentox.2007.08.006.

Terasaka, H., Kadoma, Y., Sakagami, H. and Fujisawa, S. (2005). Cytotoxicity and Apoptosis-inducing Activity of Bisphenol A and Hydroquinone in HL-60 Cells. Anticancer Research, 25(3B), pp. 2241–2247.

Tsai, W.T. (2006). Human health risk on environmental exposure to Bisphenol-A: A review. Journal of Environmental Science and Health, Part C, 24(2), pp. 225–255. doi: 10.1080/10590500600936482.

Tsutsui, T. and Barrett, J.C. (1997). Neoplastic transformation of cultured mammalian cells by estrogens and estrogen like chemicals. Environmental Health Perspectives, 105(Suppl 3), pp. 619–624. doi: 10.1289/ehp.97105s3619.

U.S. Food and Drug Administration. (2012) Public health focus - Bisphenol A (BPA): Use in food contact application. Available at: (Accessed: 14 February 2016).

Valdiglesias, V., Fernández-Tajes, J., Pásaro, E., Méndez, J. and Laffon, B. (2012). Identification of differentially expressed genes in SHSY5Y cells exposed to okadaic acid by suppression subtractive hybridization. BMC Genomics, 13(1), p. 46. Doi: 10.1186/1471-2164-13-46.

Visser, M.J.T., van Lennep, A.C.D., van Bockel, J.H., van Hinsbergh, V.W.M., van der Keur, M. and Hermans, J. (1996). Evaluation of various methods to quantify endothelial cells attached to vascular Prostheses: Comparison with a new “Gold Standard” FACS method. Journal of Surgical Research, 61(1), pp. 237–243. Doi: 10.1006/jsre.1996.0110.

van Meerloo, J., Kaspers, G.J. and Cloos, J. (2011). Cell sensitivity assays: The MTT assay. Methods in Molecular Biology, 731, pp. 237–245. Doi: 10.1007/978-1-61779-080-5_20.

Vom Saal, F.S. and Hughes, C. (2005). An Extensive New Literature Concerning Low-Dose Effects of Bisphenol A Shows the Need for a New Risk Assessment. Environmental Health Perspectives, 113(8), pp. 926–933.

Wang, X., Dong, Q., Chen, Y., Jiang, H., Xiao, Q., Wang, Y., Li, W., Bai, C., Huang, C. and Yang, D. (2013). Bisphenol A affects axonal growth, musculature and motor behavior in developing zebrafish. Aquatic Toxicology, 142–143, pp. 104–113. Doi: 10.1016/j.aquatox.2013.07.011.

Wetherill, Y.B., Akingbemi, B.T., Kanno, J., McLachlan, J.A., Nadal, A., Sonnenschein, C., Watson, C.S., Zoeller, R.T. and Belcher, S.M. (2007). In vitro molecular mechanisms of bisphenol A action. Reproductive toxicology (Elmsford, N.Y.), 24(2), pp. 178–98. doi:10.1016/j.reprotox.2007.05.010.

Wolstenholme, J.T., Rissman, E.F. and Connelly, J.J. (2011). The role of Bisphenol A in shaping the brain, epigenome and behavior. Hormones and Behavior, 59(3), pp. 296–305. doi: 10.1016/j.yhbeh.2010.10.001.

Xin, L., Lin, Y., Wang, A., Zhu, W., Liang, Y., Su, X., Hong, C., Wan, J., Wang, Y. and Tian, H. (2015). Cytogenetic evaluation for the genotoxicity of bisphenol-a in Chinese hamster ovary cells. Environmental Toxicology and Pharmacology, 40(2), pp. 524–529. Doi: 10.1016/j.etap.2015.08.002.

Xu, J., Osuga, Y., Yano, T., Morita, Y., Tang, X., Fujiwara, T., Takai, Y., Matsumi, H., Koga, K., Taketani, Y. and Tsutsumi, O. (2002). Bisphenol A induces Apoptosis and G2-to-M arrest of ovarian Granulosa cells. Biochemical and Biophysical Research Communications, 292(2), pp. 456–462. Doi: 10.1006/bbrc.2002.6644.

Zoeller, R.T., Bansal, R. and Parris, C. (2005). Bisphenol-A, an environmental Contaminant that acts as a thyroid hormone receptor antagonist in vitro, increases serum thyroxine, and alters RC3/Neurogran in expression in the developing rat brain. Endocrinology, 146(2), pp. 607–612. Doi: 10.1210/en.2004-1018.


  • There are currently no refbacks.

Creative Commons License 
This work is licensed under a Creative Commons Attribution 3.0 License

ISSN 1754-2383 [Online] ©University of Plymouth