Comparing the Toxicity Effect Induced by Bisphenol A and Bisphenol S In the Zebrafish Model
Abstract
Introduction: With the shift from Bisphenol A (BPA) to Bisphenol S (BPS) in consumer products, there is limited knowledge on BPS's impact on human health. This study compares the toxicity of BPA and BPS on zebrafish embryos. Materials and Methods: Zebrafish embryos (n=10) were exposed to BPA and BPS at concentrations of 10 µM and 20 µM in each well of 24-well plates. Mortality rates were assessed at 120 hours post-fertilization (hpf). Hatching rates were evaluated at 72 and 96 hpf using a modified protocol. Cardiotoxicity was assessed by measuring heart rate and pericardial edema at 96 hpf. Results and Discussion: Neither BPA nor BPS had a significant impact on mortality or hatching rates in zebrafish embryos. In the cardiotoxicity assay, exposure to 10 µM BPA led to an increased heart rate, while 20 µM BPA significantly reduced it. Both BPS concentrations did not significantly alter the embryos’ heart rate compared to the control. Pericardial edema was observed in both 10 µM and 20 µM BPA groups, but not in BPS-treated groups. Conclusion: BPS demonstrates lower toxicity than BPA concerning mortality and cardiotoxicity in zebrafish embryos, though neither compound affected hatching rates.
Keywords:
Mortality, Cardiotoxicity, Hatching rate, microplastic
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References
1. Reif DM, Martin MT, Tan SW, Houck KA, Judson RS, Richard AM, Knudsen TB, Dix DJ, Kavlock RJ. (2010). Endocrine profiling and prioritization of environmental chemicals using ToxCast data. Environ Health Perspect 118(12): 1714-1720.
2. Rochester JR. (2013). Bisphenol A and human health: a review of the literature. Reprod Toxicol 42: 132-155.
3. Thoene M, Dzika E, Gonkowski S, Wojtkiewicz J. (2020). Bisphenol S in food causes hormonal and obesogenic effects comparable to or worse than bisphenol A: a literature review. Nutrients 12(2): 532.
4. Wu LH, Zhang XM, Wang F, Gao CJ, Chen D, Palumbo JR, Guo Y, Zeng EY. (2018). Occurrence of bisphenol S in the environment and implications for human exposure: A short review. Sci Total Environ 615: 87-98.
5. Kuruto-Niwa R, Nozawa R, Miyakoshi T, Shiozawa T, Terao Y. (2005). Estrogenic activity of alkylphenols, bisphenol S, and their chlorinated derivatives using a GFP expression system. Environ Toxicol Pharmacol 19(1): 121-130.
6. Liao C, Liu F, Alomirah H, Loi VD, Mohd MA, Moon HB, Nakata H, Kannan K. (2012). Bisphenol S in urine from the United States and seven Asian countries: occurrence and human exposures. Environ Sci Technol 46(12): 6860-6866.
7. Molina-Molina JM, Amaya E, Grimaldi M, Sáenz JM, Real M, Fernández MF, Balaguer P, Olea N. (2013). In vitro study on the agonistic and antagonistic activities of bisphenol-S and other bisphenol-A congeners and derivatives via nuclear receptors. Toxicol Appl Pharmacol 272(1): 127-136.
8. Héliès-Toussaint C, Peyre L, Costanzo C, Chagnon MC, Rahmani R. (2014). Is bisphenol S a safe substitute for bisphenol A in terms of metabolic function? An in vitro study. Toxicol Appl Pharmacol 280(2): 224-235.
9. Yin N, Liang X, Liang S, Liang S, Yang R, Hu B, Cheng Z, Liu S, Dong H, Liu S, Faiola F. (2019). Embryonic stem cell-and transcriptomics-based in vitro analyses reveal that bisphenols A, F, and S have similar and very complex potential developmental toxicities. Ecotoxicol Environ Saf 176: 330-338.
10. Howe K, Clark MD, Torroja CF, Torrance J, Berthelot C, Muffato M, Collins JE, Humphray S, McLaren K, Matthews L, McLaren S. (2013). The zebrafish reference genome sequence and its relationship to the human genome. Nature 496(7446): 498-503.
11. Kimmel CB, Ballard WW, Kimmel SR, Ullmann B, Schilling TF. (1995). Stages of embryonic development of the zebrafish. Dev Dyn 203(3): 253-310.
12. Al-Asmakh M, Majdalawieh AF, Abdullah AM, Younes N, Da’as SI, Radwan AB, Sliem MH, Ech-Cherif H, Pintus G, Nasrallah GK. (2020). AEO-7 surfactant is “super toxic” and induces severe cardiac, liver and locomotion damage in zebrafish embryos. Environ Sci Eur 32: 1-12.
13. Al-Jamal O, Al-Jighefee H, Younes N, Abdin R, Al-Asmakh MA, Radwan AB, Sliem MH, Majdalawieh AF, Pintus G, Yassine HM, Abdullah AM. (2020). Organ-specific toxicity evaluation of stearamidopropyl dimethylamine (SAPDMA) surfactant using zebrafish embryos. Sci Total Environ 741: 140450.
14. Thiagarajan SK, Rama Krishnan K, Ei T, Husna Shafie N, Arapoc DJ, Bahari H. (2019). Evaluation of the effect of aqueous Momordica charantia Linn. extract on zebrafish embryo model through acute toxicity assay assessment. Evidence-Based Complement Altern Med 2019.
15. Fenton SE. (2006). Endocrine-disrupting compounds and mammary gland development: early exposure and later life consequences. Endocrinology 147(6): s18-s24.
16. Karunarathne WAHM, Molagoda IMN, Choi YH, Park SR, Lee S, Kim GY. (2021). Bisphenol A: A potential Toll-like receptor 4/myeloid differentiation factor 2 complex agonist. Environ Pollut 278: 116829.
17. Ji K, Hong S, Kho Y, Choi K. (2013). Effects of bisphenol S exposure on endocrine functions and reproduction of zebrafish. Environ Sci Technol 47(15): 8793-8800.
18. Mu X, Huang Y, Li X, Lei Y, Teng M, Li X, Wang C, Li Y. (2018). Developmental effects and estrogenicity of bisphenol A alternatives in a zebrafish embryo model. Environ Sci Technol 52(5): 3222-3231.
19. Maćczak A, Cyrkler M, Bukowska B, Michałowicz J. (2017). Bisphenol A, bisphenol S, bisphenol F and bisphenol AF induce different oxidative stress and damage in human red blood cells (in vitro study). Toxicol In Vitro 41: 143-149.
20. Rosenmai AK, Dybdahl M, Pedersen M, Alice van Vugt-Lussenburg BM, Wedebye EB, Taxvig C, Vinggaard AM. (2014). Are structural analogues to bisphenol A safe alternatives? Toxicol Sci 139(1): 35-47.
21. Huang Q, Fang C, Chen Y, Wu X, Ye T, Lin Y, Dong S. (2012). Embryonic exposure to low concentration of bisphenol A affects the development of Oryzias melastigma larvae. Environ Sci Pollut Res 19: 2506-2514.
22. Gyimah E, Xu H, Dong X, Qiu X, Zhang Z, Bu Y, Akoto O. (2021). Developmental neurotoxicity of low concentrations of bisphenol A and S exposure in zebrafish. Chemosphere 262: 128045.
23. Yamagami K. (1996). Studies on the hatching enzyme (choriolysin) and its substrate, egg envelope, constructed of the precursors (choriogenins) in Oryzias latipes: a sequel to the information in 1991/1992. Zool Sci 13(3): 331-340.
24. Huang Q, Chen Y, Lin L, Liu Y, Chi Y, Lin Y, Ye G, Zhu H, Dong S. (2017). Different effects of bisphenol A and its halogenated derivatives on the reproduction and development of Oryzias melastigma under environmentally relevant doses. Sci Total Environ 595: 752-758.
25. Qiu W, Zhan H, Hu J, Zhang T, Xu H, Wong M, Xu B, Zheng C. (2019). The occurrence, potential toxicity, and toxicity mechanism of bisphenol S, a substitute of bisphenol A: A critical review of recent progress. Ecotoxicol Environ Saf 173: 192-202.
26. Huang W, Wang X, Zheng S, Wu R, Liu C, Wu K. (2021). Effect of bisphenol A on craniofacial cartilage development in zebrafish (Danio rerio) embryos: a morphological study. Ecotoxicol Environ Saf 212: 111991.
27. Sampurna BP, Audira G, Juniardi S, Lai YH, Hsiao CD. (2018). A simple ImageJ-based method to measure cardiac rhythm in zebrafish embryos. Inventions 3(2): 21.
28. Belcher SM, Gear RB, Kendig EL. (2015). Bisphenol A alters autonomic tone and extracellular matrix structure and induces sex-specific effects on cardiovascular function in male and female CD-1 mice. Endocrinology 156(3): 882-895.
29. Lombó M, Fernández-Díez C, González-Rojo S, Navarro C, Robles V, Herráez MP. (2015). Transgenerational inheritance of heart disorders caused by paternal bisphenol A exposure. Environ Pollut 206: 667-678.
30. Chen J. (2013). Impaired cardiovascular function caused by different stressors elicits a common pathological and transcriptional response in zebrafish embryos. Zebrafish 10(3): 389-400.
31. Cano-Nicolau J, Vaillant C, Pellegrini E, Charlier TD, Kah O, Coumailleau P. (2016). Estrogenic effects of several BPA analogs in the developing zebrafish brain. Front Neurosci 10: 112.
32. Gorelick DA, Iwanowicz LR, Hung AL, Blazer VS, Halpern ME. (2014). Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to environmental water samples. Environ Health Perspect 122(4): 356-362.
33. Pinto C, Hao R, Grimaldi M, Thrikawala S, Boulahtouf A, Ait-Aissa S, Brion F, Gustafsson JÅ, Balaguer P, Bondesson M. (2019). Differential activity of BPA, BPAF, and BPC on zebrafish estrogen receptors in vitro and in vivo. Toxicol Appl Pharmacol 380: 114709.
34. Pinto C, Grimaldi M, Boulahtouf A, Pakdel F, Brion F, Aït-Aïssa S, Cavaillès V, Bourguet W, Gustafsson JA, Bondesson M, Balaguer P. (2014). Selectivity of natural, synthetic, and environmental estrogens for zebrafish estrogen receptors. Toxicol Sci 137(1): 181-190.
1. Reif DM, Martin MT, Tan SW, Houck KA, Judson RS, Richard AM, Knudsen TB, Dix DJ, Kavlock RJ. (2010). Endocrine profiling and prioritization of environmental chemicals using ToxCast data. Environ Health Perspect 118(12): 1714-1720.
2. Rochester JR. (2013). Bisphenol A and human health: a review of the literature. Reprod Toxicol 42: 132-155.
3. Thoene M, Dzika E, Gonkowski S, Wojtkiewicz J. (2020). Bisphenol S in food causes hormonal and obesogenic effects comparable to or worse than bisphenol A: a literature review. Nutrients 12(2): 532.
4. Wu LH, Zhang XM, Wang F, Gao CJ, Chen D, Palumbo JR, Guo Y, Zeng EY. (2018). Occurrence of bisphenol S in the environment and implications for human exposure: A short review. Sci Total Environ 615: 87-98.
5. Kuruto-Niwa R, Nozawa R, Miyakoshi T, Shiozawa T, Terao Y. (2005). Estrogenic activity of alkylphenols, bisphenol S, and their chlorinated derivatives using a GFP expression system. Environ Toxicol Pharmacol 19(1): 121-130.
6. Liao C, Liu F, Alomirah H, Loi VD, Mohd MA, Moon HB, Nakata H, Kannan K. (2012). Bisphenol S in urine from the United States and seven Asian countries: occurrence and human exposures. Environ Sci Technol 46(12): 6860-6866.
7. Molina-Molina JM, Amaya E, Grimaldi M, Sáenz JM, Real M, Fernández MF, Balaguer P, Olea N. (2013). In vitro study on the agonistic and antagonistic activities of bisphenol-S and other bisphenol-A congeners and derivatives via nuclear receptors. Toxicol Appl Pharmacol 272(1): 127-136.
8. Héliès-Toussaint C, Peyre L, Costanzo C, Chagnon MC, Rahmani R. (2014). Is bisphenol S a safe substitute for bisphenol A in terms of metabolic function? An in vitro study. Toxicol Appl Pharmacol 280(2): 224-235.
9. Yin N, Liang X, Liang S, Liang S, Yang R, Hu B, Cheng Z, Liu S, Dong H, Liu S, Faiola F. (2019). Embryonic stem cell-and transcriptomics-based in vitro analyses reveal that bisphenols A, F, and S have similar and very complex potential developmental toxicities. Ecotoxicol Environ Saf 176: 330-338.
10. Howe K, Clark MD, Torroja CF, Torrance J, Berthelot C, Muffato M, Collins JE, Humphray S, McLaren K, Matthews L, McLaren S. (2013). The zebrafish reference genome sequence and its relationship to the human genome. Nature 496(7446): 498-503.
11. Kimmel CB, Ballard WW, Kimmel SR, Ullmann B, Schilling TF. (1995). Stages of embryonic development of the zebrafish. Dev Dyn 203(3): 253-310.
12. Al-Asmakh M, Majdalawieh AF, Abdullah AM, Younes N, Da’as SI, Radwan AB, Sliem MH, Ech-Cherif H, Pintus G, Nasrallah GK. (2020). AEO-7 surfactant is “super toxic” and induces severe cardiac, liver and locomotion damage in zebrafish embryos. Environ Sci Eur 32: 1-12.
13. Al-Jamal O, Al-Jighefee H, Younes N, Abdin R, Al-Asmakh MA, Radwan AB, Sliem MH, Majdalawieh AF, Pintus G, Yassine HM, Abdullah AM. (2020). Organ-specific toxicity evaluation of stearamidopropyl dimethylamine (SAPDMA) surfactant using zebrafish embryos. Sci Total Environ 741: 140450.
14. Thiagarajan SK, Rama Krishnan K, Ei T, Husna Shafie N, Arapoc DJ, Bahari H. (2019). Evaluation of the effect of aqueous Momordica charantia Linn. extract on zebrafish embryo model through acute toxicity assay assessment. Evidence-Based Complement Altern Med 2019.
15. Fenton SE. (2006). Endocrine-disrupting compounds and mammary gland development: early exposure and later life consequences. Endocrinology 147(6): s18-s24.
16. Karunarathne WAHM, Molagoda IMN, Choi YH, Park SR, Lee S, Kim GY. (2021). Bisphenol A: A potential Toll-like receptor 4/myeloid differentiation factor 2 complex agonist. Environ Pollut 278: 116829.
17. Ji K, Hong S, Kho Y, Choi K. (2013). Effects of bisphenol S exposure on endocrine functions and reproduction of zebrafish. Environ Sci Technol 47(15): 8793-8800.
18. Mu X, Huang Y, Li X, Lei Y, Teng M, Li X, Wang C, Li Y. (2018). Developmental effects and estrogenicity of bisphenol A alternatives in a zebrafish embryo model. Environ Sci Technol 52(5): 3222-3231.
19. Maćczak A, Cyrkler M, Bukowska B, Michałowicz J. (2017). Bisphenol A, bisphenol S, bisphenol F and bisphenol AF induce different oxidative stress and damage in human red blood cells (in vitro study). Toxicol In Vitro 41: 143-149.
20. Rosenmai AK, Dybdahl M, Pedersen M, Alice van Vugt-Lussenburg BM, Wedebye EB, Taxvig C, Vinggaard AM. (2014). Are structural analogues to bisphenol A safe alternatives? Toxicol Sci 139(1): 35-47.
21. Huang Q, Fang C, Chen Y, Wu X, Ye T, Lin Y, Dong S. (2012). Embryonic exposure to low concentration of bisphenol A affects the development of Oryzias melastigma larvae. Environ Sci Pollut Res 19: 2506-2514.
22. Gyimah E, Xu H, Dong X, Qiu X, Zhang Z, Bu Y, Akoto O. (2021). Developmental neurotoxicity of low concentrations of bisphenol A and S exposure in zebrafish. Chemosphere 262: 128045.
23. Yamagami K. (1996). Studies on the hatching enzyme (choriolysin) and its substrate, egg envelope, constructed of the precursors (choriogenins) in Oryzias latipes: a sequel to the information in 1991/1992. Zool Sci 13(3): 331-340.
24. Huang Q, Chen Y, Lin L, Liu Y, Chi Y, Lin Y, Ye G, Zhu H, Dong S. (2017). Different effects of bisphenol A and its halogenated derivatives on the reproduction and development of Oryzias melastigma under environmentally relevant doses. Sci Total Environ 595: 752-758.
25. Qiu W, Zhan H, Hu J, Zhang T, Xu H, Wong M, Xu B, Zheng C. (2019). The occurrence, potential toxicity, and toxicity mechanism of bisphenol S, a substitute of bisphenol A: A critical review of recent progress. Ecotoxicol Environ Saf 173: 192-202.
26. Huang W, Wang X, Zheng S, Wu R, Liu C, Wu K. (2021). Effect of bisphenol A on craniofacial cartilage development in zebrafish (Danio rerio) embryos: a morphological study. Ecotoxicol Environ Saf 212: 111991.
27. Sampurna BP, Audira G, Juniardi S, Lai YH, Hsiao CD. (2018). A simple ImageJ-based method to measure cardiac rhythm in zebrafish embryos. Inventions 3(2): 21.
28. Belcher SM, Gear RB, Kendig EL. (2015). Bisphenol A alters autonomic tone and extracellular matrix structure and induces sex-specific effects on cardiovascular function in male and female CD-1 mice. Endocrinology 156(3): 882-895.
29. Lombó M, Fernández-Díez C, González-Rojo S, Navarro C, Robles V, Herráez MP. (2015). Transgenerational inheritance of heart disorders caused by paternal bisphenol A exposure. Environ Pollut 206: 667-678.
30. Chen J. (2013). Impaired cardiovascular function caused by different stressors elicits a common pathological and transcriptional response in zebrafish embryos. Zebrafish 10(3): 389-400.
31. Cano-Nicolau J, Vaillant C, Pellegrini E, Charlier TD, Kah O, Coumailleau P. (2016). Estrogenic effects of several BPA analogs in the developing zebrafish brain. Front Neurosci 10: 112.
32. Gorelick DA, Iwanowicz LR, Hung AL, Blazer VS, Halpern ME. (2014). Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to environmental water samples. Environ Health Perspect 122(4): 356-362.
33. Pinto C, Hao R, Grimaldi M, Thrikawala S, Boulahtouf A, Ait-Aissa S, Brion F, Gustafsson JÅ, Balaguer P, Bondesson M. (2019). Differential activity of BPA, BPAF, and BPC on zebrafish estrogen receptors in vitro and in vivo. Toxicol Appl Pharmacol 380: 114709.
34. Pinto C, Grimaldi M, Boulahtouf A, Pakdel F, Brion F, Aït-Aïssa S, Cavaillès V, Bourguet W, Gustafsson JA, Bondesson M, Balaguer P. (2014). Selectivity of natural, synthetic, and environmental estrogens for zebrafish estrogen receptors. Toxicol Sci 137(1): 181-190.
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Saad, M., Abdullah, M., Lim, V., & Yong, Y. (2025). Comparing the Toxicity Effect Induced by Bisphenol A and Bisphenol S In the Zebrafish Model. International Journal of Advancement in Life Sciences Research, 8(3), 112-120. https://doi.org/https://doi.org/10.31632/ijalsr.2025.v08i03.010
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