Skip to main content
Log in

Exposure and hazard of bisphenol A, S and F: a multi-biomarker approach in three-spined stickleback

  • Environmental Observation and Monitoring through Space and Time: A Challenge for Ecotoxicology
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

Due to the estrogenic behavior of bisphenol (BP) A, industries have developed many substitutes, such as BPS and BPF. However, due to their structural similarities, adverse effects on reproduction are currently observed in various organisms, including fish. Even if new results have shown impacts of these bisphenols on many other physiological functions, their mode of action remains unclear. In this context, we proposed to better understand the impact of BPA, BPS, and BPF on immune responses (leucocyte sub-populations, cell death, respiratory burst, lysosomal presence, and phagocytic activity) and on biomarkers of metabolic detoxification (ethoxyresorufin-O-deethylase, EROD, and glutathione S-transferase, GST) and oxidative stress (glutathione peroxidase, GPx, and lipid peroxidation with thiobarbituric acid reactive substance method, TBARS) in an adult sentinel fish species, the three-spined stickleback. In order to enhance our understanding of how biomarkers change over time, it is essential to determine the internal concentration responsible for the observed responses. Therefore, it is necessary to explore the toxicokinetics of bisphenols. Thus, sticklebacks were exposed either to 100 μg/L of BPA, BPF or BPS for 21 days, or for seven days to 10 and 100 μg/L of BPA or BPS followed by seven days of depuration. Although BPS has very different TK, due to its lower bioaccumulation compared to BPA and BPF, BPS affect oxidative stress and phagocytic activity in the same way. For those reasons, the replacement of BPA by any substitute should be made carefully in terms of risk assessment on aquatic ecosystems.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Afzal G, Ahmad HI, Hussain R, Jamal A, Kiran S, Hussain T, Saeed S, Nisa MU (2022) Bisphenol A induces histopathological, hematobiochemical alterations, oxidative stress, and genotoxicity in common carp (Cyprinus carpio L.). Oxid Med Cell Longev 2022:5450421

    Article  Google Scholar 

  • Akram R, Iqbal R, Hussain R, Jabeen F, Ali M (2021) Evaluation of oxidative stress, antioxidant enzymes and genotoxic potential of bisphenol A in fresh water bighead carp (Aristichthys nobils) fish at low concentrations. Environ Pollut 268:115896

    Article  CAS  Google Scholar 

  • Andersson C, Katsiadaki I, Lundstedt-Enkel K, Orberg J (2007) Effects of 17 alpha-ethynylestradiol on EROD activity, spiggin and vitellogenin in three-spined stickleback (Gasterosteus aculeatus). Aquat Toxicol 83:33–42

    Article  CAS  Google Scholar 

  • Bado-Nilles A, Betoulle S, Geffard A, Porcher J-M, Gagnaire B, Sanchez W (2013) Flow cytometry detection of lysosomal presence and lysosomal membrane integrity in the three-spined stickleback (Gasterosteus aculeatus L.) immune cells: applications in environmental aquatic immunotoxicology. Environ Sci Pollut Res 20:2692–2704

    Article  CAS  Google Scholar 

  • Bado-Nilles A, Techer R, Porcher JM, Geffard A, Gagnaire B, Betoulle S, Sanchez W (2014) Detection of immunotoxic effects of estrogenic and androgenic endocrine disrupting compounds using splenic immune cells of the female three-spined stickleback, Gasterosteus aculeatus (L.). Environ Toxicol Pharmacol 38:672–683

    Article  CAS  Google Scholar 

  • Billat P-A, Brochot C, Brion F, Beaudouin R (2022) A PBPK model to evaluate zebrafish eleutheroembryos’ actual exposure: bisphenol A and analogs’ (AF, F, and S) case studies. Environ Sci Pollut Res

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  Google Scholar 

  • Catteau A, Le Guernic A, Marchand A, Hani YMI, Palluel O, Turies C, Bado-Nilles A, Dedourge-Geffard O, Geffard A, Porcher JM (2019) Impact of confinement and food access restriction on the three-spined stickleback (Gasterosteus aculeatus, L.) during caging: a multi-biomarker approach. Fish Physiol Biochem 45:1261–1276

    Article  CAS  Google Scholar 

  • Chelcea I, Örn S, Hamers T, Koekkoek J, Legradi J, Vogs C, Andersson PL (2022) Physiologically based toxicokinetic modeling of bisphenols in zebrafish (Danio rerio) accounting for variations in metabolic rates, brain distribution, and liver accumulation. Environ Sci Technol 56:10216–10228

    Article  CAS  Google Scholar 

  • Chen F, Gong Z, Kelly BC (2017) Bioaccumulation behavior of pharmaceuticals and personal care products in adult zebrafish (Danio rerio): influence of physical-chemical properties and biotransformation. Environ Sci Technol 51:11085–11095

    Article  CAS  Google Scholar 

  • Chilmonczyk S, Monge D (1999) Flow cytometry as a tool for assessment of the fish cellular immune response to pathogens. Fish Shellfish Immunol 9:319–333

    Article  Google Scholar 

  • de Kermoysan G, Péry AR, Porcher JM, Beaudouin R (2013) A non-invasive method based on head morphology to sex mature three-spined stickleback (Gasterosteus aculeatus L.) in rearing conditions. Math Biosci 244:148–153

    Article  Google Scholar 

  • Dodds E, Lawson W (1936) Synthetic strogenic agents without the phenanthrene nucleus. Nature 137:996–996

    Article  CAS  Google Scholar 

  • Dodds EC, Goldberg L, Lawson W, Robinson R (1938) Oestrogenic activity of certain synthetic compounds. Nature 141:247–248

    Article  CAS  Google Scholar 

  • ECHA (2022) Group assessment of bisphenols identifies need for restriction. ECHA/NR/22/08. https://echa.europa.eu/-/group-assessment-of-bisphenols-identifies-need-for-restriction

  • Faheem M, Bhandari RK (2021) Detrimental effects of bisphenol compounds on physiology and reproduction in fish: a literature review. Environ Toxicol Pharmacol 81:103497

    Article  CAS  Google Scholar 

  • Flammarion P, Devaux A, Nehls S, Migeon B, Noury P, Garric J (2002) Multibiomarker responses in fish from the Moselle River (France). Ecotoxicol Environ Saf 51:145–153

    Article  CAS  Google Scholar 

  • Flint S, Markle T, Thompson S, Wallace E (2012) Bisphenol A exposure, effects, and policy: a wildlife perspective. J Environ Manage 104:19–34

    Article  CAS  Google Scholar 

  • Frenzilli G, Martorell-Ribera J, Bernardeschi M, Scarcelli V, Jönsson E, Diano N, Moggio M, Guidi P, Sturve J, Asker N (2021) Bisphenol A and bisphenol S induce endocrine and chromosomal alterations in brown trout. Front Endocrinol 12:645519

  • Gagnaire B, Thomas-Guyon H, Renault T (2004) In vitro effects of cadmium and mercury on Pacific oyster, Crassostrea gigas (Thunberg), haemocytes. Fish Shellfish Immunol 16:501–512

    Article  CAS  Google Scholar 

  • Gushiken Y, Watanuki H, Sakai M (2002) In vitro effect of carp phagocytic cells by bisphenol A and nonylphenol. Fisheries Science 68:178–173

    Article  CAS  Google Scholar 

  • Gyimah E, Zhu X, Zhang Z, Guo M, Xu H, Mensah JK, Dong X, Zhang Z, Gyimah GNW (2022) Oxidative stress and apoptosis in bisphenol AF–induced neurotoxicity in zebrafish embryos. Environ Toxicol Chem 41:2273–2284

    Article  CAS  Google Scholar 

  • Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferases: the first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139

    Article  CAS  Google Scholar 

  • Huang YQ, Wong CKC, Zheng JS, Bouwman H, Barra R, Wahlström B, Neretin L, Wong MH (2012) Bisphenol A (BPA) in China: a review of sources, environmental levels, and potential human health impacts. Environ Int 42:91–99

    Article  CAS  Google Scholar 

  • Jolly C, Katsiadaki I, Morris S, Le Belle N, Dufour S, Mayer I, Pottinger TG, Scott AP (2009) Detection of the anti-androgenic effect of endocrine disrupting environmental contaminants using in vivo and in vitro assays in the three-spined stickleback. Aquat Toxicol 92:228–239

    Article  CAS  Google Scholar 

  • Krumschnabel G, Manzl C, Berger C, Hofer B (2005) Oxidative stress, mitochondrial permeability transition, and cell death in Cu-exposed trout hepatocytes. Toxicol Appl Pharmacol 209:62–73

    Article  CAS  Google Scholar 

  • Le Fol V, Aït-Aïssa S, Sonavane M, Porcher J-M, Balaguer P, Cravedi J-P, Zalko D, Brion F (2017) In vitro and in vivo estrogenic activity of BPA, BPF and BPS in zebrafish-specific assays. Ecotoxicol Environ Saf 142:150–156

    Article  Google Scholar 

  • Li D, Chen Q, Cao J, Chen H, Li L, Cedergreen N, Xie H, Xie L (2016) The chronic effects of lignin-derived bisphenol and bisphenol A in Japanese medaka Oryzias latipes. Aquat Toxicol 170:199–207

    Article  CAS  Google Scholar 

  • Lindholst C, Pedersen KL, Pedersen SN (2000) Estrogenic response of bisphenol A in rainbow trout (Oncorhynchus mykiss). Aquat Toxicol 48:87–94

    Article  CAS  Google Scholar 

  • Lindholst C, Pedersen SN, Bjerregaard P (2001a) Uptake, metabolism and excretion of bisphenol A in the rainbow trout (Oncorhynchus mykiss). Aquat Toxicol 55:75–84

    Article  CAS  Google Scholar 

  • Lindholst C, Pedersen SN, Bjerregaard P (2001b) Uptake, metabolism and excretion of bisphenol A in the rainbow trout (Oncorhynchus mykiss). Aquat Toxicol 55:75–84

    Article  CAS  Google Scholar 

  • Lindholst C, Wynne PM, Marriott P, Pedersen SN, Bjerregaard P (2003) Metabolism of bisphenol A in zebrafish (Danio rerio) and rainbow trout (Oncorhynchus mykiss) in relation to estrogenic response. Comp Biochem Physiol C Toxicol. Pharmacol 135:169–177

    Article  CAS  Google Scholar 

  • Liu S, Pan C, Tang Y, Chen F, Yang M, Wang KJ (2020) Identification of novel long non-coding RNAs involved in bisphenol A induced immunotoxicity in fish primary macrophages. Fish Shellfish Immunol 100:152–160

    Article  CAS  Google Scholar 

  • Liu Y, Mei C, Liu H, Wang H, Zeng G, Lin J, Xu M (2014) Modulation of cytokine expression in human macrophages by endocrine-disrupting chemical bisphenol-A. Biochem Biophys Res Commun 451:592–598

    Article  CAS  Google Scholar 

  • Lv Y-Z, Yao L, Wang L, Liu W-R, Zhao J-L, He L-Y, Ying G-G (2019) Bioaccumulation, metabolism, and risk assessment of phenolic endocrine disrupting chemicals in specific tissues of wild fish. Chemosphere 226:607–615

    Article  CAS  Google Scholar 

  • Maradonna F, Nozzi V, Dalla Valle L, Traversi I, Gioacchini G, Benato F, Colletti E, Gallo P, Di Marco Pisciottano I, Mita DG, Hardiman G, Mandich A, Carnevali O (2014) A developmental hepatotoxicity study of dietary bisphenol A in Sparus aurata juveniles. Comp Biochem Physiol C Toxicol Pharmacol 166:1–13

    Article  CAS  Google Scholar 

  • Miège C, Peretti A, Labadie P, Budzinski H, Le Bizec B, Vorkamp K, Tronczyński J, Persat H, Coquery M, Babut M (2012) Occurrence of priority and emerging organic compounds in fishes from the Rhone River (France). Anal Bioanal Chem 404:2721–2735

    Article  Google Scholar 

  • Mihaich E, Rhodes J, Wolf J, van der Hoeven N, Dietrich D, Hall AT, Caspers N, Ortego L, Staples C, Dimond S, Hentges S (2012) Adult fathead minnow, Pimephales promelas, partial life-cycle reproductive and gonadal histopathology study with bisphenol A. Environ Toxicol Chem 31:2525–2535

    Article  CAS  Google Scholar 

  • Moreman J, Lee O, Trznadel M, David A, Kudoh T, Tyler CR (2017) Acute toxicity, teratogenic, and estrogenic effects of bisphenol A and its alternative replacements bisphenol S, bisphenol F, and bisphenol AF in zebrafish embryo-larvae. Environ Sci Technol 51:12796–12805

    Article  CAS  Google Scholar 

  • 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 52:3222–3231

    Article  CAS  Google Scholar 

  • Navas JM, Segner H (2001) Estrogen-mediated suppression of cytochrome P4501A (CYP1A) expression in rainbow trout hepatocytes: role of estrogen receptor. Chem Biol Interact 138:285–298

    Article  CAS  Google Scholar 

  • Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  CAS  Google Scholar 

  • Porseryd T, Larsson J, Kellner M, Bollner T, Dinnétz P, Porsch Hällström I (2019) Altered non-reproductive behavior and feminization caused by developmental exposure to 17α-ethinylestradiol persist to adulthood in three-spined stickleback (Gasterosteus aculeatus). Aquat Toxicol 207:142–152

    Article  CAS  Google Scholar 

  • Prokkola JM, Katsiadaki I, Sebire M, Elphinstone-Davis J, Pausio S, Nikinmaa M, Leder EH (2016) Microarray analysis of di-n-butyl phthalate and 17α ethinyl-oestradiol responses in three-spined stickleback testes reveals novel candidate genes for endocrine disruption. Ecotoxicol Environ Saf 124:96–104

    Article  CAS  Google Scholar 

  • Qiu W, Shao H, Lei P, Zheng C, Qiu C, Yang M, Zheng Y (2018a) Immunotoxicity of bisphenol S and F are similar to that of bisphenol A during zebrafish early development. Chemosphere 194:1–8

    Article  CAS  Google Scholar 

  • Qiu W, Yang M, Liu J, Xu H, Luo S, Wong M, Zheng C (2019) Bisphenol S-induced chronic inflammatory stress in liver via peroxisome proliferator-activated receptor gamma using fish in vivo and in vitro models. Environ Pollut 246:963–971

    Article  CAS  Google Scholar 

  • Qiu W, Yang M, Liu S, Lei P, Hu L, Chen B, Wu M, Wang K-J (2018b) Toxic effects of bisphenol S showing immunomodulation in fish macrophages. Environ Sci Technol 52:831–838

    Article  CAS  Google Scholar 

  • Qiu W, Zhan H, Tian Y, Zhang T, He X, Luo S, Xu H, Zheng C (2018c) The in vivo action of chronic bisphenol F showing potential immune disturbance in juvenile common carp (Cyprinus carpio). Chemosphere 205:506–513

    Article  CAS  Google Scholar 

  • Rehberger K, Escher BI, Scheidegger A, Werner I, Segner H (2021) Evaluation of an in vitro assay to screen for the immunotoxic potential of chemicals to fish. Sci Rep 11:3167

    Article  CAS  Google Scholar 

  • Risso-de Faverney C, Devaux A, Lafaurie M, Girard JP, Bailly B, Rahmani R (2001) Cadmium induces apoptosis and genotoxicity in rainbow trout hepatocytes through generation of reactive oxygene species. Aquat Toxicol 53:65–76

    Article  CAS  Google Scholar 

  • Sanchez W, Aït-Aïssa S, Palluel O, Ditche J-M, Porcher J-M (2007) Preliminary investigation of multi-biomarker responses in three-spined stickleback (Gasterosteus aculeatu L.) sampled in contaminated streams. Ecotoxicol 16:279–287

    Article  CAS  Google Scholar 

  • Schultz IR, Orner G, Merdink JL, Skillman A (2001) Dose-response relationships and pharmacokinetics of vitellogenin in rainbow trout after intravascular administration of 17 alpha-ethynylestradiol. Aquat Toxicol 51:305–318

    Article  CAS  Google Scholar 

  • Shehna Mahim S, Anjali VR, Remya VS, Reshmi S, Aruna Devi C (2021) Oxidative stress responses of a freshwater fish, Labeo rohita, to a xenobiotic, bisphenol S. J Biochem Mol Toxicol 35:e22820

    Article  CAS  Google Scholar 

  • Sun L, Lin X, Jin R, Peng T, Peng Z, Fu Z (2014) Toxic effects of bisphenol A on early life stages of Japanese medaka (Oryzias latipes). Bull Environ Contam Toxicol 93:222–227

    Article  CAS  Google Scholar 

  • Wang H, Qi S, Mu X, Yuan L, Li Y, Qiu J (2022) Bisphenol F induces liver-gut alteration in zebrafish. Sci Total Environ 851:157974

    Article  CAS  Google Scholar 

  • Wang Q, Chen M, Qiang L, Wu W, Yang J, Zhu L (2020) Toxicokinetics and bioaccumulation characteristics of bisphenol analogues in common carp (Cyprinus carpio). Ecotoxicol Environ Saf 191:110183

    Article  CAS  Google Scholar 

  • Wootton R (1984) Functional biology of sticklebacks. Department of Zoology, University of Sheffield, London

    Book  Google Scholar 

  • Wu L-H, Zhang X-M, Wang F, Gao C-J, 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

    Article  CAS  Google Scholar 

  • Yang M, Qiu W, Chen B, Chen J, Liu S, Wu M, Wang K-J (2015) The in vitro immune modulatory effect of bisphenol A on fish macrophages via estrogen receptor α and nuclear factor-κB signaling. Environ Sci Technol 49:1888–1895

    Article  CAS  Google Scholar 

  • Yin D-Q, Hu S-Q, Gu Y, Wei L, Liu S-S, Zhang A-Q (2007) Immunotoxicity of bisphenol A to Carassius auratus lymphocytes and macrophages following in vitro exposure. J Environ Sci 19:232–237

    Article  CAS  Google Scholar 

  • Zhao N, Hu H, Zhao M, Liu W, Jin H (2021) Occurrence of free-form and conjugated bisphenol analogues in marine organisms. Environ Sci Technol 55:4914–4922

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the French National program EC2CO (Ecosphère Continentale et Côtière) as part of the DERBI project and by the French Ministry of ecological transition (P190). This work was carried out in the framework of the European Partnership for the Assessment of Risks from Chemicals (PARC) and has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the Health and Digital Executive Agency. Neither the European Union nor the granting authority can be held responsible for them.

Author information

Authors and Affiliations

Authors

Contributions

Corentin MIT: methodology, formal analysis, investigation, visualization, project administration, and writing—original draft. Rémy Beaudouin: conceptualization, methodology, formal analysis, investigation, writing—original draft, visualization, supervision, and project administration. Olivier Palluel: investigation. Cyril Turiès: investigation and project administration. Gaëlle Daniele: formal analysis and investigation. Barbara Giroud: formal analysis and investigation. Anne Bado-Nilles: conceptualization, methodology, formal analysis, investigation, writing—original draft, visualization, supervision, and project administration. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Anne Bado-Nilles.

Ethics declarations

Ethics approval

Experimental protocols were conducted following the European directive 2010/63/UE for the protection of animals used for scientific purposes at INERIS, registration number E60–769–02. The experimental protocols were submitted and reviewed by a French nationally recognized ethical committee, CREMEAPS, registration number 96.

Conflict of interest

The authors declare no competing interests.

Additional information

Responsible Editor: Philippe Garrigues

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

ESM 1

(DOCX 664 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mit, C., Beaudouin, R., Palluel, O. et al. Exposure and hazard of bisphenol A, S and F: a multi-biomarker approach in three-spined stickleback. Environ Sci Pollut Res (2023). https://doi.org/10.1007/s11356-023-28462-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11356-023-28462-4

Keywords

Navigation