Re-evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs - Genotoxicity

Genotox-references and abbreviations

Last updated: 01 August 2022


Abdel-Rahman, H.G., Abdelrazek, H., Zeidan, D.W., Mohamed, R.M. and Abdelazim, A.M., 2018. Lycopene: hepatoprotective and antioxidant effects toward bisphenol A-induced toxicity in female Wistar rats. Oxidative medicine and cellular longevity, 2018.

Balabanič, D., Filipič, M., Klemenčič, A.K. and Žegura, B., 2021. Genotoxic activity of endocrine disrupting compounds commonly present in paper mill effluents. Science of The Total Environment, p.148489.

EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF), 2015. Scientific opinion on the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs. EFSA Journal, 13(1), p.3978.

Campen, K.A., Kucharczyk, K.M., Bogin, B., Ehrlich, J.M. and Combelles, C.M., 2018. Spindle abnormalities and chromosome misalignment in bovine oocytes after exposure to low doses of bisphenol A or bisphenol S. Human Reproduction, 33(5), pp.895-904.

Chen, Z.Y., Liu, C., Lu, Y.H., Yang, L.L., Li, M., He, M.D., Chen, C.H., Zhang, L., Yu, Z.P. and Zhou, Z., 2016. Cadmium exposure enhances bisphenol A-induced genotoxicity through 8-oxoguanine-DNA glycosylase-1 OGG1 inhibition in NIH3T3 fibroblast cells. Cellular Physiology and Biochemistry, 39(3), pp.961-974.

De Felice, B., Manfellotto, F., Palumbo, A., Troisi, J., Zullo, F., Di Carlo, C., Sardo, A.D.S., De Stefano, N., Ferbo, U., Guida, M. and Guida, M., 2015. Genome–wide microRNA expression profiling in placentas from pregnant women exposed to BPA. BMC medical genomics, 8(1), pp.1-13.

De Flora, S., Micale, R.T., La Maestra, S., Izzotti, A., D’Agostini, F., Camoirano, A., Davoli, S.A., Troglio, M.G., Rizzi, F., Davalli, P. and Bettuzzi, S., 2011. Upregulation of clusterin in prostate and DNA damage in spermatozoa from bisphenol A–treated rats and formation of DNA adducts in cultured human prostatic cells. Toxicological sciences, 122(1), pp.45-51.

Di Pietro, P., D’Auria, R., Viggiano, A., Ciaglia, E., Meccariello, R., Russo, R.D., Puca, A.A., Vecchione, C., Nori, S.L. and Santoro, A., 2020. Bisphenol A induces DNA damage in cells exerting immune surveillance functions at peripheral and central level. Chemosphere, 254, p.126819.

ECHA (European Chemicals Agency), 2011. Guidance on information requirements and chemical safety assessment Chapter R. 4: Evaluation of available information.

EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF), 2015. Scientific opinion on the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs. EFSA Journal, 13(1), p.3978.
Scientific Opinion on the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs - - 2015 - EFSA Journal - Wiley Online Library

EFSA Scientific Committee, Hardy A, Benford D, Halldorsson T, Jeger MJ, Knutsen KH, More S, Mortensen A, Naegeli H, Noteborn H, Ockleford C, Ricci A, Rychen G, Silano V, Solecki R, Turck D, Aerts M, Bodin L, Davis A, Edler L, Gundert-Remy U, Sand S, Slob W, Bottex B, Cortiñas Abrahantes J, Court Marques D, Kass G and Schlatter J, 2017a. Update: use of the benchmark dose approach in risk assessment. EFSA Journal 2017;15(1):4658, 41 pp. Update: use of the benchmark dose approach in risk assessment - - 2017 - EFSA Journal - Wiley Online Library

EFSA Scientific Committee, Hardy A, Benford D, Halldorsson T, Jeger M, Knutsen HK, More S, Naegeli H, Noteborn H, Ockleford C, Ricci A, Rychen G, Silano V, Solecki R, Turck D, Younes M, Aquilina G, Crebelli R, Gürtler R, Hirsch-Ernst K, Mosesso P, Nielsen E, van Benthem J, Carfì M, Georgiadis N, Maurici D, Parra Morte J and Schlatter J, 2017. Clarification of some aspects related to genotoxicity assessment. EFSA Journal 2017;15(12):5113, 25 pp. Clarification of some aspects related to genotoxicity assessment | EFSA (

Escarda-Castro, E., Herráez, M.P. and Lombó, M., 2021. Effects of bisphenol A exposure during cardiac cell differentiation. Environmental Pollution, p.117567.

Fawzy, E.I., El Makawy, A.I., El-Bamby, M.M. and Elhamalawy, H.O., 2018. Improved effect of pumpkin seed oil against the bisphenol-A adverse effects in male mice. Toxicology reports, 5, pp.857-863.

Fic, A., Sollner Dolenc, M., Filipič, M. and Peterlin Mašić, L., 2013. Mutagenicity and DNA damage of bisphenol A and its structural analogues in HepG2 cells., Archives of Industrial Hygiene & Toxicology 64(2), pp.189-199.

George, V.C. and Rupasinghe, H.V., 2018. DNA damaging and apoptotic potentials of Bisphenol A and Bisphenol S in human bronchial epithelial cells. Environmental toxicology and pharmacology, 60, pp.52-57.

Hercog, K., Maisanaba, S., Filipič, M., Sollner-Dolenc, M., Kač, L. and Žegura, B., 2019. Genotoxic activity of bisphenol A and its analogues bisphenol S, bisphenol F and bisphenol AF and their mixtures in human hepatocellular carcinoma (HepG2) cells. Science of the total environment, 687, pp.267-276.

Hercog, K., Štern, A., Maisanaba, S., Filipič, M. and Žegura, B., 2020. Plastics in cyanobacterial blooms—genotoxic effects of binary mixtures of cylindrospermopsin and bisphenols in HepG2 cells. Toxins, 12(4), p.219.

Huang, Fu-Mei, Yu-Chao Chang, Shiuan-Shinn Lee, Yung-Chyuan Ho, Ming-Ling Yang, Hui-Wen Lin, and Yu-Hsiang Kuan. "Bisphenol A exhibits cytotoxic or genotoxic potential via oxidative stress-associated mitochondrial apoptotic pathway in murine macrophages." Food and Chemical Toxicology 122 (2018): 215-224.

Iso, T., Watanabe, T., Iwamoto, T., Shimamoto, A. and Furuichi, Y., 2006. DNA damage caused by bisphenol A and estradiol through estrogenic activity. Biological and Pharmaceutical Bulletin, 29(2), pp.206-210.

Johnson, G.E. and Parry, E.M., 2008. Mechanistic investigations of low dose exposures to the genotoxic compounds bisphenol-A and rotenone. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 651(1-2), pp.56-63.

Karaman FE, Caglayan M, Sancar-Bas S, Ozal-Coskun C, Arda-Pirincci P and Ozden S, 2019. Global and region-specific post-transcriptional and post-translational modifications of bisphenol A in human prostate cancer cells. Environmental Pollution, 255

Karmakar, P.C., Kang, H.G., Kim, Y.H., Jung, S.E., Rahman, M.S., Lee, H.S., Kim, Y.H., Pang, M.G. and Ryu, B.Y., 2017. Bisphenol A affects on the functional properties and proteome of testicular germ cells and spermatogonial stem cells in vitro culture model. Scientific reports, 7(1), pp.1-14.

Kazmi, S.T.B., Majid, M., Maryam, S., Rahat, A., Ahmed, M., Khan, M.R. and ul Haq, I., 2018. Quercus dilatata Lindl. ex Royle ameliorates BPA induced hepatotoxicity in Sprague Dawley rats. Biomedicine & Pharmacotherapy, 102, pp.728-738.

Klimisch, H.J., Andreae, M. and Tillmann, U., 1997. A Systematic Approach for Evaluating the Quality of Experimental Toxicological and Ecotoxicological Data Regulatory Toxicology and Pharmacology.

Kim, S., Choi, E., Kim, M., Jeong, J.S., Kang, K.W., Jee, S., Lim, K.M. and Lee, Y.S., 2018. Submicromolar bisphenol A induces proliferation and DNA damage in human hepatocyte cell lines in vitro and in juvenile rats in vivo. Food and Chemical Toxicology, 111, pp.125-132.

Kim, S., Gwon, D., Kim, J.A., Choi, H. and Jang, C.Y., 2019. Bisphenol A disrupts mitotic progression via disturbing spindle attachment to kinetochore and centriole duplication in cancer cell lines. Toxicology in Vitro, 59, pp.115-125.

Kose, O., Rachidi, W., Beal, D., Erkekoglu, P., FayyadKazan, H. and Kocer Gumusel, B., 2020. The effects of different bisphenol derivatives on oxidative stress, DNA damage and DNA repair in RWPE1 cells: A comparative study. Journal of Applied Toxicology, 40(5), pp.643-654.

Li, X., Yin, P. and Zhao, L., 2017. Effects of individual and combined toxicity of bisphenol A, dibutyl phthalate and cadmium on oxidative stress and genotoxicity in HepG 2 cells. Food and Chemical Toxicology, 105, pp.73-81.

Mahemuti, L., Chen, Q., Coughlan, M.C., Qiao, C., Chepelev, N.L., Florian, M., Dong, D., Woodworth, R.G., Yan, J., Cao, X.L. and Scoggan, K.A., 2018. Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Archives of toxicology, 92(4), pp.1453-1469.

Majid, M., Ijaz, F., Baig, M.W., Nasir, B., Khan, M.R. and Haq, I.U., 2019. Scientific validation of ethnomedicinal use of Ipomoea batatas L. Lam. as aphrodisiac and gonadoprotective agent against bisphenol A induced testicular toxicity in male Sprague Dawley rats. BioMed research international, 2019.

Masuda, S., Terashima, Y., Sano, A., Kuruto, R., Sugiyama, Y., Shimoi, K., Tanji, K., Yoshioka, H., Terao, Y. and Kinae, N., 2005. Changes in the mutagenic and estrogenic activities of bisphenol A upon treatment with nitrite. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 585(1-2), pp.137-146.

Mohammed, E.T., Hashem, K.S., Ahmed, A.E., Aly, M.T., Aleya, L. and Abdel-Daim, M.M., 2020. Ginger extract ameliorates bisphenol A (BPA)-induced disruption in thyroid hormones synthesis and metabolism: involvement of Nrf-2/HO-1 pathway. Science of the Total Environment, 703, p.134664.

Mokra, K., Kuźmińska-Surowaniec, A., Woźniak, K. and Michałowicz, J., 2017. Evaluation of DNA-damaging potential of bisphenol A and its selected analogs in human peripheral blood mononuclear cells (in vitro study). Food and chemical toxicology, 100, pp.62-69.

Mokra, K., Woźniak, K., Bukowska, B., Sicińska, P. and Michałowicz, J., 2018. Low-concentration exposure to BPA, BPF and BPAF induces oxidative DNA bases lesions in human peripheral blood mononuclear cells. Chemosphere, 201, pp.119-126.

Naik, P. and Vijayalaxmi, K.K., 2009. Cytogenetic evaluation for genotoxicity of bisphenol-A in bone marrow cells of Swiss albino mice. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 676(1-2), pp.106-112.

Nair, V.A., Valo, S., Peltomäki, P., Bajbouj, K. and Abdel-Rahman, W.M., 2020. Oncogenic potential of Bisphenol A and common environmental contaminants in human mammary epithelial cells. International journal of molecular sciences, 21(10), p.3735.

OECD (Organisation for Economic Co-operation and Development), 2005. Manual for the investigation of 14112 HPV chemicals. Chapter 3.1 Guidance for Determining the Quality of Data for the SIDS Dossier 14113 (Reliability, Relevance and Adequacy) (Last updated: December 2005). Available online: Microsoft Word - section_31_Jan06.doc (

Pacchierotti, F., Ranaldi, R., Eichenlaub-Ritter, U., Attia, S. and Adler, I.D., 2008. Evaluation of aneugenic effects of bisphenol A in somatic and germ cells of the mouse. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 651(1-2), pp.64-70.

Panpatil, V.V., Kumari, D., Chatterjee, A., Kumar, S., Bhaskar, V., Polasa, K. and Ghosh, S., 2020. Protective Effect of Turmeric against Bisphenol-A Induced Genotoxicity in Rats. Journal of nutritional science and vitaminology, 66(Supplement), pp.S336-S342.

Pfeifer, D., Chung, Y.M. and Hu, M.C., 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.

Porreca, I., Ulloa Severino, L., D’Angelo, F., Cuomo, D., Ceccarelli, M., Altucci, L., Amendola, E., Nebbioso, A., Mallardo, M., De Felice, M. and Ambrosino, C., 2016. “Stockpile” of slight transcriptomic changes determines the indirect genotoxicity of low-dose BPA in thyroid cells. PloS one, 11(3), p.e0151618.

Santovito, A., Cannarsa, E., Schleicherova, D. and Cervella, P., 2018. Clastogenic effects of bisphenol A on human cultured lymphocytes. Human & experimental toxicology, 37(1), pp.69-77.

Sharma, A.K., Boberg, J. and Dybdahl, M., 2018. DNA damage in mouse organs and in human sperm cells by bisphenol A. Toxicological & Environmental Chemistry, 100(4), pp.465-478.

Šutiaková, I., Kovalkovičová, N. and Šutiak, V., 2014. Micronucleus assay in bovine lymphocytes after exposure to bisphenol A in vitro. In Vitro Cellular & Developmental Biology-Animal, 50(6), pp.502-506.

Tiwari, D., Kamble, J., Chilgunde, S., Patil, P., Maru, G., Kawle, D., Bhartiya, U., Joseph, L. and Vanage, G., 2012. Clastogenic and mutagenic effects of bisphenol A: an endocrine disruptor. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 743(1-2), pp.83-90.

Tiwari, D. and Vanage, G., 2013. Mutagenic effect of Bisphenol A on adult rat male germ cells and their fertility. Reproductive Toxicology, 40, pp.60-68.

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.

Xin, F., Jiang, L., Liu, X., Geng, C., Wang, W., Zhong, L., Yang, G. and Chen, M., 2014. Bisphenol A induces oxidative stress-associated DNA damage in INS-1 cells. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 769, pp.29-33.

Yang L, Baumann C, De La Fuente R and Viveiros MM, 2020. Mechanisms underlying disruption of oocyte 14988 spindle stability by bisphenol compounds. Reproduction, 159(4), 383—396.

Yin, L., Siracusa, J.S., Measel, E., Guan, X., Edenfield, C., Liang, S. and Yu, X., 2020. High-content image-based single-cell phenotypic analysis for the testicular toxicity prediction induced by bisphenol A and its analogs bisphenol S, Bisphenol AF, and tetrabromobisphenol a in a three-dimensional testicular cell co-culture model. Toxicological Sciences, 173(2), pp.313-335.

Yu, H., Chen, Z., Hu, K., Yang, Z., Song, M., Li, Z. and Liu, Y., 2020. Potent Clastogenicity of Bisphenol Compounds in Mammalian Cells—Human CYP1A1 Being a Major Activating Enzyme. Environmental Science & Technology, 54(23), pp.15267-15276.

Yuan, J., Kong, Y., Ommati, M.M., Tang, Z., Li, H., Li, L., Zhao, C., Shi, Z. and Wang, J., 2019. Bisphenol A-induced apoptosis, oxidative stress and DNA damage in cultured rhesus monkey embryo renal epithelial Marc-145 cells. Chemosphere, 234, pp.682-689.

Yuan, J., Che, S., Zhang, L., Li, X., Yang, J., Sun, X. and Ruan, Z., 2021. Assessing the combinatorial cytotoxicity of the exogenous contamination with BDE-209, bisphenol A, and acrylamide via high-content analysis. Chemosphere, 284, p.131346.

Zhou, Y., Wang, Z., Xia, M., Zhuang, S., Gong, X., Pan, J., Li, C., Fan, R., Pang, Q. and Lu, S., 2017. Neurotoxicity of low bisphenol A (BPA) exposure for young male mice: Implications for children exposed to environmental levels of BPA. Environmental pollution, 229, pp.40-48.

Zemheri F and Uguz C, 2016. Determining mutagenic effect of nonylphenol and bisphenol A by using Ames/Salmonella/microsome test. Journal of Applied Biological Sciences, 10(3), pp.09-12.







Bisphenol A


Bisphenol AF


birth weight


chromosomal aberrations




cytokinesis blocked micronucleus assay

CHO cells

chinese hamster ovary cells


Dichlorofluorescein Diacetate Assay


dibutyl phthalate




European Chemicals Agency




health outcome category






microtubule organizing centres


mode of action




nuclear division index


olive tail moment






spindle assembly checkpoint


Sprague Dawley


peripheral blood mononuclear cells


pumpkin seed oil


reactive oxygen species


working group


weight of evidence