Bisphenol F (BPF) and Bisphenol S (BPS)

A Systematic Review and Comparison of the Hormonal Activity of Bisphenol A Substitutes

Systematic review is an approach to answering research questions by systematically selecting, evaluating, and integrating scientific evidence.

Evidence that BPA might be harmful to human health due to its actions as an endocrine-disrupting chemical has prompted the industry to seek alternative chemicals.

This analysis summarizes in vivo and in vitro literature and compare the hormonal potency of BPS and BPF to BPA using the in vitro studies.


Increasing concern over bisphenol A (BPA) as an endocrine-disrupting chemical and its possible effects on human health have prompted the removal of BPA from consumer products, often labeled “BPA-free.” Some of the chemical replacements, however, are also bisphenols and may have similar physiological effects in organisms. Bisphenol S (BPS) and bisphenol F (BPF) are two such BPA substitutes.

This review was carried out to evaluate the physiological effects and endocrine activities of the BPA substitutes BPS and BPF. Further, we compared the hormonal potency of BPS and BPF to that of BPA.

We conducted a systematic review based on the Office of Health Assessment and Translation (OHAT) protocol.

We identified the body of literature to date, consisting of 32 studies (25 in vitro only, and 7 in vivo). The majority of these studies examined the hormonal activities of BPS and BPF and found their potency to be in the same order of magnitude and of similar action as BPA (estrogenic, antiestrogenic, androgenic, and antiandrogenic) in vitro and in vivo. BPS also has potencies similar to that of estradiol in membrane-mediated pathways, which are important for cellular actions such as proliferation, differentiation, and death. BPS and BPF also showed other effects in vitro and in vivo, such as altered organ weights, reproductive end points, and enzyme expression.

Based on the current literature, BPS and BPF are as hormonally active as BPA, and they have endocrine-disrupting effects.

BPA alternatives BPAF and BPS also alter mammary gland development

Evaluation of Prenatal Exposure to Bisphenol Analogues on Development and Long-Term Health of the Mammary Gland in Female Mice


Continued efforts to phase out bisphenol A (BPA) from consumer products have been met with the challenges of finding safer alternatives.

This study aimed to determine whether early-life exposure to BPA and its related analogues, bisphenol AF (BPAF) and bisphenol S (BPS), could affect female pubertal mammary gland development and long-term mammary health in mice.

Timed pregnant CD-1 mice were exposed to vehicle, BPA (0.5, 5, 50mg/kg), BPAF (0.05, 0.5, 5mg/kg), or BPS (0.05, 0.5, 5mg/kg) via oral gavage between gestation days 10–17. Mammary glands were collected from resulting female offspring at postnatal day (PND) 20, 28, 35, and 56, and at 3, 8, and 14 months for whole mount, histopathological evaluation, and quantitative real-time polymerase chain reaction (qPCR); serum steroid concentrations were also measured at these time points.

In the bisphenol-exposed mice, accelerated mammary gland development was evident during early puberty and persisted into adulthood. By late adulthood, mammary glands from bisphenol-exposed female offspring exhibited adverse morphology in comparison with controls; most prominent were undifferentiated duct ends, significantly more lobuloalveolar hyperplasia and perivascular inflammation, and various tumors, including adenocarcinomas. Effects were especially prominent in the BPAF 5mg/kg and BPS 0.5mg/kg groups. Serum steroid concentrations and mammary mRNA levels of Esr1, Pgr, Ar, and Gper1 were similar to controls.

These data demonstrate that prenatal exposure of mice to BPAF or BPS induced precocious development of the mammary gland, and that siblings were significantly more susceptible to spontaneous preneoplastic epithelial lesions and inflammation, with an incidence greater than that observed in vehicle- and BPA-exposed animals.

Our findings suggest that exposure to BPAF and BPS by consumers such as women of child-bearing age or infants and children should be restricted. The fetal mammary gland is a sensitive target organ for these chemicals. BPAF and BPS prenatally exposed female mice developed proliferative epithelial lesions by midlife, concomitant with a significant inflammatory response that may predispose them to tumor formation later in life. In fact, animals in the high-dose BPS group developed adenocarcinomas prior to one year of life and those diagnoses triggered a necropsy at 14 months of age in the remaining animals. Most neoplasia incidents in this study (7/8) occurred in the BPS-exposed animals. The extended presence of TEBs into adulthood (confirmed by histopathology), the significant prepubertal spikes in serum estradiol, and the altered immune responses (e.g., increased perivascular inflammation) may have been important modifiers of the persistent adverse effects observed later in life. To our knowledge, this study is the first report of BPAF- and BPS-induced adverse developmental effects in the mammary gland, and these findings warrant further studies to determine relevance of these findings for human breast cancer susceptibility. Featured image credit PNAS.

60 MiNueTs : Toxic Bodies

UCSF Program on Reproductive Health and the Environment, 2017

The University of California San Francisco (UCSF) Program on Reproductive Health and the Environment (PRHE)’s mission is to create a healthier environment for human reproduction and development through advancing scientific inquiry, clinical care and health policies that prevent exposures to harmful chemicals in our environment.

PRHE is housed within the Department of Obstetrics, Gynecology and Reproductive Sciences, in the UCSF School of Medicine, one of the nation’s most prestigious medical schools. The Department is renowned for promoting cutting-edge reproductive science research, extending the frontiers of multidisciplinary women’s health care and professional education, advocating for women’s health at local, state and national levels, and engaging community involvement.

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BPF, BPS and other bisphenol analogues found more estrogenic than BPA

“BPA-free” may mean very little for consumers trying to protect their health from endocrine disrupting chemicals

Six popular BPA alternatives all mimic estrogen in breast cancer cells; three of them more so than BPA itself, according to new research.

2017 Study Abstract

Plasticizers with estrogenic activity, such as bisphenol A (BPA), have been reported to have potential adverse health effects in humans. Due to mounting evidence of these health effects and public pressure, BPA is being phased out by the plastics manufacturing industry and replaced by other bisphenol variants in “BPA-free” products.

We have compared estrogenic activity of BPA to 6 bisphenol analogues (bisphenol S, BPS; bisphenol F, BPF; bisphenol AP, BPAP; bisphenol AF, BPAF; bisphenol Z, BPZ; bisphenol B, BPB) in three human breast cancer cell lines.

Estrogenicity was assessed by cell growth in an estrogen receptor (ER)-mediated cell proliferation assay, and by the induction of estrogen response element (ERE)-mediated transcription in a luciferase assay. Gene expression profiles were determined in MCF-7 human breast cancer cells by microarray analysis and confirmed by Illumina-based RNA sequencing.

All bisphenols showed estrogenic activity in promoting cell growth and inducing ERE-mediated transcription. BPAF was the most potent bisphenol, followed by BPB > BPZ ~ BPA > BPF ~ BPAP > BPS. The addition of ICI 182,780 antagonized the activation of ERs by bisphenols. Data mining of ToxCast high-throughput screening assays confirms our results but also shows divergence in the sensitivities of the assays. The comparison of transcriptome profile alterations resulting from BPA alternatives with an ERα gene expression biomarker further indicates that all BPA alternatives act as ERα agonists in MCF-7 cells. These results were confirmed by RNA sequencing.

In conclusion, BPA alternatives are not necessarily less estrogenic in a human breast cancer cell model. Three bisphenols (BPAF, BPB, and BPZ) were more estrogenic than BPA. The relevance of human exposure to BPA alternatives in hormone-dependent breast cancer risk should be investigated.

Sources and More Information
  • Transcriptome profiling reveals bisphenol A alternatives activate estrogen receptor alpha in human breast cancer cells, bioRxiv, Mar. 2, 2017.
  • BPA-free? Substitutions mimic hormones in breast cancer cells, environmentalhealthnews, March 16, 2017.
  • BPA Free by Mark Morgan.

Fluorene-9-bisphenol may not be safe for the use in materials that come into contact with food

Your BPA-free container may contain other toxic chemicals

BHPF, introduced for the production of so-called ‘BPA-free’ plastics, has been found to be very toxic at extremely low doses.

2017 Study Abstract

Bisphenol A (BPA) is used in the production of plastic but has oestrogenic activity. Therefore, BPA substitutes, such as fluorene-9-bisphenol (BHPF), have been introduced for the production of so-called ‘BPA-free’ plastics.

Here we show that BHPF is released from commercial ‘BPA-free’ plastic bottles into drinking water and has anti-oestrogenic effects in mice. We demonstrate that BHPF has anti-oestrogenic activity in vitro and, in an uterotrophic assay in mice, induces low uterine weight, atrophic endometria and causes adverse pregnancy outcomes, even at doses lower than those of BPA for which no observed adverse effect have been reported. Female mice given water containing BHPF released from plastic bottles, have detectable levels of BHPF in serum, low uterine weights and show decreased expressions of oestrogen-responsive genes. We also detect BHPF in the plasma of 7/100 individuals, who regularly drink water from plastic bottles.

Our data suggest that BPA substitutes should be tested for anti-oestrogenic activity and call for further study of the toxicological effects of BHPF on human health.

Download the full PDF study (free access).

  • Fluorene-9-bisphenol is anti-oestrogenic and may cause adverse pregnancy outcomes in mice, Nature Communications, ncomms14585, 01 March 2017.
  • Your BPA-free water bottle may contain another harmful chemical, Quartz, March 01, 2017.
  • Image credit Carsten ten Brink.

Seven famous ecologists discover their contamination from endocrine disruptors

100% of the personalities have traces of Bisphenols, PCBs, pesticides and phthalates

Générations Futures EXPPERT survey number 9 provides the results of tests for the presence of suspected or known endocrine disruptors in hair samples of some leading environmentalists in France. The worrying and conclusive results are the basis for a further call to the European Commission to improve its proposal on criteria for identifying endocrine disrupting chemicals ahead of a possible vote by EU Member States on 28 February 2017.

Paris, Brussels, 24 February 2017 – Seven environmentalists in France have their hair analysed for traces of endocrine disrupting chemicals. Generations Futures, with the support of HEAL and other members of the EDC-Free Europe coalition, published a new report yesterday, the 9th survey of the EXPPERT series on population exposure to chemicals that are suspected or known to disrupt the endocrine system. The results are unchallengeable!

In this new survey, Générations Futures asked personalities from the environmental movement to entrust to us a lock of their hair, which we had analysed by a competent laboratory. The participants were Yann Arthus-Bertrand, Isabelle Autissier, Delphine Batho, José Bové, Nicolas Hulot, Yannick Jadot and Marie-Monique Robin.

Approximately 200 pesticides (products used in agriculture and in the home to get rid of “harmful” or “undesirable” flora and fauna) and pesticide metabolites (resulting from metabolism), three bisphenols (plasticiser used in the composition of the polycarbonate – hard plastic), 13 phthalates and metabolites of phthalates (plasticisers used to soften plastics) and 32 PCB congeners (PCBs have been banned since 1987 but were used massively in electric transformers and as heat transfer fluid.).

100% of the personalities has traces of each of the families of compounds analysed in their bodies!

- – We discover between 36 (D. Batho) and 68 (I. Autissier) endocrine disrupters per personality. The quantities varied from 9 031 μg/mg of endocrine disrupting chemical (D. Batho) to 158 643 μg/mg (I. Autism) – a discrepancy factor of 17.5 times between the least contaminated person (D. Batho) and the most contaminated person (I. Autissier). This clearly shows that individual’s exposure is not uniform but rather varies considerably according to the environment in which they circulate and/or in which they have developed and lived.

- Bisphenols:
All the personalities tested had at least one of the three bisphenols in their hair. Three out of the seven people tested had the renowned Bisphenol A in their hair: M-M. Robin, Y. Arthus-Bertrand and I. Autissier. All 7 had Bisphenol S but none had signs of Bisphenol F.

- Phthalates:
11 of the 13 phthalates or metabolites of phthalates tested for were found at least in one person. Neither MMP or DPP were found in any sample. The number of phthalates and metabolites of phthalates found ranged from eight to 11 depending on the individual. Between six and 10 of these molecules could be quantified in each person.

- PCBs:
All samples that could be analysed contained PCBs: between 14 and 30 PCBs were found in participants’ samples.

- Pesticides:
32 molecules suspected of being endocrine disruptors or endocrine disrupting metabolites were found in at least one person. Between nine and 25 of these pesticides were found in each hair sample tested.

“The hair of the personalities tested all contain an important cocktail of many endocrine disruptors (between 36 and 68 per person) although tests were only carried out on four families of chemicals. And these cocktails pose a problem – what is the health impact of this mixture?”

says Francois Veillerette, Director of Générations Futures.

“This report points out more than ever the need to remove endocrine disrupting substances from our environment. Only a truly protective definition within the European framework will ensure that endocrine disruptors are excluded from the market and protect populations from these hazardous compounds. That is why the vote on the Standing Committee on Plants, Animals, Food and Feed (SCOPAFF) on 28 February is so important! We urge all national governments to reject the European Commission’s proposal on the criteria for endocrine disrupting chemicals in its current form and insist on major changes to ensure that proven, probable or suspected endocrine disruptors to which we are exposed are identified as such. Only in this way will these chemicals be prohibited from use as required in the European legislation voted in 2009, to protect our health.”

he concluded.

  1. EXPPERT Survey 1: Which endocrine disrupting insecticides are children exposed to everyday? Press release, Brussels, 25 March 2013.
  2. EXPPERT Survey 2: Endocrine Disrupting Chemicals and banned Pesticides in strawberries. Press release, 25 March 2013.
  3. EXPPERT Survey 3: How are children exposed to Endocrine Disrupting Chemicals? Press release, 9 July 2014.
  4. EXPPERT Survey 4: Nineteen endocrine disrupting pesticides found in samples of women’s hair. Press release, 12 March 2015. Our blog.
  5. EXPPERT Survey 5: Pesticides that are banned or suspected to be EDCs are found in green salads. Press release, 22 September 2015. Our blog.
  6. EXPPERT Survey 6: Homes close to pesticide spraying show all year exposure. Press release, 1 March 2016. Our blog.
  7. EXPPERT Survey 7: Exposure to endocrine-disrupting pesticides. What are the exposures in daily life? Press release, 11 October 2016. Our blog.
  8. EXPPERT Survey 8: Exposure to endocrine-disrupting pesticides in water. Press release, 8 January 2017. Our blog.
  9. EXPPERT Survey 9: Seven French celebrities discover their contamination from endocrine disruptors. Press release, 24 February 2017. Our blog.

Evidence that bisphenol S crosses the human placenta

Common BPA alternative, BPS, crosses into placenta

Bisphenol S (BPS), found in baby bottles, personal care products and thermal receipts, is a replacement chemical for BPA and was introduced when concern was raised about possible health effects of that plastic compound.

As with BPA, there is evidence that BPS is an endocrine disruptor. Canadian and Chinese scientists have found the “first evidence” that BPS can cross the human placenta.

2017 Study Abstract

Human studies show associations between maternal bisphenol A (BPA) exposure and developmental effects in children, yet biomonitoring of BPA metabolites in maternal and fetal serum remains limited, and less is known for BPA alternatives. BPA-glucuronide, BPA-sulfate, and bisphenol S (BPS) were quantified in 61 pairs of maternal and cord sera from Chinese participants.

Bisphenol A Metabolites and Bisphenol S in Paired Maternal and Cord Serum, Environmental Science & Technology, DOI: 10.1021/acs.est.6b05718, January 22, 2017.

Total BPS was only detectable in four maternal (<0.03–0.07 ng/mL) and seven cord sera (<0.03–0.12 ng/mL), indicating low exposure but providing the first evidence that BPS crosses the human placenta. Total BPA metabolites in cord serum were significantly higher than in maternal serum (p < 0.05), suggesting that these may be formed in the fetus or cleared more slowly from the fetoplacental compartment. Unlike the pharmacokinetic results from controlled oral exposure studies in which BPA-glucuronide is the major BPA metabolite, here, BPA-sulfate was the dominant metabolite (GM: 0.06 and 0.08 ng/mL), significantly higher than BPA-glucuronide (GM: 0.02 and 0.04 ng/mL) (p < 0.01) in both maternal and cord sera. Moreover, the proportion of BPA-sulfate increased with total BPA.

These are the first human data for BPA metabolites in paired maternal and cord serum, and results suggest that the human fetus and pregnant mother have unique exposure to BPA metabolites. Direct analysis of BPA metabolites in serum provides complementary information for evaluating early life-stage exposure and risks of BPA.

Perturbateurs endocriniens : tous intoxiqués?

Les nouveaux poisons de notre quotidien

Enquête de santé, Allo Docteurs France 5, 01/02/2017.

Un documentaire / débat diffusé le 31 janvier 2017 sur France 5.



Les perturbateurs endocriniens, substances chimiques, sont présentes dans de nombreux objets de consommation courante : plastiques, résidus de pesticides sur les fruits et légumes, OGM, cosmétiques, lunettes, semelles de chaussures… Ils interagissent avec le système hormonal et seraient responsables de l’augmentation de certains cancers, selon des associations impliquées dans les problèmes de santé liés à l’environnement.

Sur le même sujet

Le Distilbène, Perturbateur Endocrinien

Occurrence and migration of a wide range EDCs from intact surfaces of baby teethers

Migration of Parabens, Bisphenols, Benzophenone-Type UV Filters, Triclosan, and Triclocarban from Teethers and Its Implications for Infant Exposure

Certain teething products often used for young children and babies may contain bisphenols, parabens, triclosan and harmful chemicals – including those marked BPA-free – all materials that are used in personal care products and plastics that have been banned or restricted by the EU and US governments.


Parabens (p-hydroxybenzoic acid esters), bisphenols, benzophenone-type UV filters, triclosan, and triclocarban are used in a variety of consumer products, including baby teethers. Nevertheless, the exposure of infants to these chemicals through the use of teethers is still unknown.

In this study, 59 teethers, encompassing three types, namely solid plastic, gel-filled, and water-filled (most labeled “bisphenol A-free”), were collected from the U.S. market and analyzed for 26 potential endocrine-disrupting chemicals (EDCs) from intact surfaces through migration/leaching tests performed with Milli-Q water and methanol.

Migration of Parabens, Bisphenols, Benzophenone-Type UV Filters, Triclosan, and Triclocarban from Teethers and Its Implications for Infant Exposure Environmental Science and Technology, DOI: 10.1021/acs.est.6b04128, December 7, 2016.

baby booty by pinprick.

The total amount of the sum of six parent parabens (Σ6 Parabens) leached from teethers ranged from 2.0 to 1990 ng, whereas that of their four transformation products (Σ4 Parabens) ranged from 0.47 to 839 ng. The total amount of the sum of nine bisphenols (Σ9 bisphenols) and 5 benzophenones (Σ5 benzophenones) leached from teethers ranged from 1.93 to 213 ng and 0.59 to 297 ng, respectively. Triclosan and triclocarban were found in the extracts of teethers at approximately 10-fold less amounts than were bisphenols and benzophenones.

Based on the amount leached into Milli-Q water, daily intake of these chemicals was estimated from the use of teethers by infants at 12 months of age. This is the first study to document the occurrence and migration of a wide range EDCs from intact surfaces of baby teethers.

Launch of the European Human Biomonitoring Initiative

The HBM4EU consortium included lead partners from each of the participating countries, as well as the EEA

A conference to launch the “European Human Biomonitoring Initiative” (HBM4EU) took place on 8 December 2016 in Brussels. It was followed by a half-day stakeholders meeting on 9 December.

HBM4EU is a joint effort of 26 countries and the European Commission, co-funded by Horizon 2020, to coordinate and advance human biomonitoring (HBM) activities in Europe. The stated aim is “to provide better evidence in support of policy making”.

The launch event introduced the initiative and presented some of the key activities to be undertaken. Long-standing HBM activities from programmes outside the European Union, including US, Canada and Japan, were be presented to give participants a perspective on how the EU project fits into the international landscape.

Launch of EU human biomonitoring initiative, env-health, 8 December 2016.

Although 26 countries are involved, biomonitoring will take place in 25 countries, including 22 EU members and three non-members. They are Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Finland, Germany, Greece, Iceland, Ireland, Israel, Italy, Latvia, Lithuania, Netherlands, Norway, Poland, Portugal, Slovakia, Slovenia, Spain, Sweden, Switzerland, United Kingdom. Information on the national organisations participating in the consortium can be found here.

The nine substance groupings that will be the focus of the European Human Biomonitoring Initiative in the first two years (2017-2018) are:

  • phthalates and Hexamoll® DINCH,
  • bisphenols,
  • per-/polyfluorinated compounds,
  • flame retardants,
  • cadmium and chromium,
  • PAHs,
  • aniline family,
  • chemical mixtures,
  • and emerging substances.

A half-day technical consultation took place the following day. It will be the first in a series of more in-depth discussions with stakeholders that accompanies annual work plans. Génon Jensen, HEAL Executive Director spoke at the introductory session on the project and its stakeholder process on: “Human biomonitoring to inform and empower citizens”. This main session was followed by break-out groups on research and stakeholder expectations.

HEAL has become the informal coordinator on human biomonitoring for NGOs working on chemicals because of our long involvement in promoting human biomonitoring for better health and environmental policy. In 2006, HEAL undertook a small-scale biomonitoring programme on mercury, which resulted in health moving to the centre of international discussions on mercury.

More Information

  • The role of human biomonitoring in assessing and managing chemical risks,
  • The initial prioritisation exercise and selected substances,