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

Background
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.

Objectives
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.

Methods
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.

Results
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.

Conclusion
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).

Sources
  • 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.

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.

Abstract

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.

BPA-free products and the next generation of bisphenols

An old culprit but a new story

Abstract

The concept that developmental events shape adult health and disease was sparked by the recognition of a link between maternal undernutrition and coronary disease in adults. From that beginning, a new field—the developmental origins of health and disease—emerged, and attention has focused on the effects of a wide array of developmental perturbations.

Exposure to endocrine-disrupting chemicals has been of particular interest, and a ubiquitous environmental contaminant bisphenol A (BPA) has become the endocrine-disrupting chemical poster child. Bisphenol A has been the subject of intense investigation for nearly two decades, and exposure effects have been described in hundreds of experimental, epidemiological, and clinical studies. From the standpoint of reproductive health, the findings are particularly important, as they suggest that the ovary, testis, and reproductive tract in both sexes are targets of BPA action. The findings and the media and regulatory attention garnered by them have generated increasing public concern and resulted in legislative bans on BPA in some countries.

An old culprit but a new story: bisphenol A and “NextGen” bisphenols, Fertility and Sterility, Volume 106, Issue 4, Pages 820–826, September 15, 2016.

The subsequent introduction of BPA-free products, although a masterful marketing strategy, is in reality only the beginning of a new and complex chapter of the BPA story. In this review we attempt to summarize what we have learned about the reproductive effects of BPA, present the reasons why studying the effects of this chemical in humans is no longer sufficient, and outline the challenges that the growing array of next generation bisphenols represents to clinicians, researchers, federal agencies, and the general public.

BPS accelerates embryonic development, disrupts reproductive system

UCLA research suggests common substitute for BPA is not safer

zebrafish-embryo
On the far right, a zebrafish embryo breaks free from a group of unhatched sibling eggs. Zebrafish Lab.

Abstract

Actions of Bisphenol A and Bisphenol S on the Reproductive Neuroendocrine System During Early Development in Zebrafish, Endocrine Society , doi/10.1210/en.2015-1785, December 10, 2015.

Bisphenol A (BPA) is a well-known environmental endocrine-disrupting chemical and bisphenol S (BPS) has been considered a “safer” alternative for BPA-free products.

The present study aims to evaluate the impact of BPA and BPS on the reproductive neuroendocrine system during zebrafish embryonic and larval development, and to explore potential mechanisms of action associated with estrogen receptor (ER), thyroid hormone receptor (THRs) and enzyme aromatase (AROM) pathways.

Environmentally relevant, low levels of BPA exposure during development led to advanced hatching time, increased numbers of Gonadotropin-Releasing Hormone 3 (GnRH3) neurons in both terminal nerve and hypothalamus, increased expression of reproduction-related genes (kiss1, kiss1r, gnrh3, lhβ, fshβ, and erα) and a marker for synaptic transmission (sv2). Low levels of BPS exposure led to similar effects: increased numbers of hypothalamic GnRH3 neurons and increased expression of kiss1, gnrh3, and erα. Antagonists of ER, THRs and AROM blocked many of the effects of BPA and BPS on reproduction-related gene expression, providing evidence that those three pathways mediate the actions of BPA and BPS on the reproductive neuroendocrine system.

‘BPA-free’ plastic accelerates embryonic development, disrupts reproductive system, University of California, 1-FEB-2016.

This study demonstrates that alternatives to BPA used in the manufacture of BPA-free products are not necessarily safer. Further, this is the first study to describe the impact of low-level BPA and BPS exposure on the Kiss/Kissr system during development. It is also the first report of multiple cellular pathways (ERα, THRs and AROM) mediating the effects of BPA and BPS during embryonic development in any species.

BPA free: estrogenic chemicals often leach from BPA-free plastic products

BPA-free does not mean estrogenic activity free…

Abstract

coffeecup EC image
Many BPA-free PC- replacement products still leached chemicals having significant levels of estrogenic activity, as did BPA-containing PC counterparts they were meant to replace. That is, BPA-free did not mean EA-free…

BACKGROUND:
Xenobiotic chemicals with estrogenic activity (EA), such as bisphenol A (BPA), have been reported to have potential adverse health effects in mammals, including humans, especially in fetal and infant stages. Concerns about safety have caused many manufacturers to use alternatives to polycarbonate (PC) resins to make hard and clear, reusable, plastic products that do not leach BPA. However, no study has focused on whether such BPA-free PC-replacement products, chosen for their perceived higher safety, especially for babies, also release other chemicals that have EA.

METHODS:
We used two, well-established, mammalian cell-based, assays (MCF-7 and BG1Luc) to assess the EA of chemicals that leached into over 1000 saline or ethanol extracts of 50 unstressed or stressed (autoclaving, microwaving, and UV radiation) BPA-free PC-replacement products. An EA antagonist, ICI 182,780, was used to confirm that agonist activity in leachates was due to chemicals that activated the mammalian estrogen receptor.

RESULTS:
Many unstressed and stressed, PC-replacement-products made from acrylic, polystyrene, polyethersulfone, and Tritan™ resins leached chemicals with EA, including products made for use by babies. Exposure to various forms of UV radiation often increased the leaching of chemicals with EA. In contrast, some BPA-free PC-replacement products made from glycol-modified polyethylene terephthalate or cyclic olefin polymer or co-polymer resins did not release chemicals with detectable EA under any conditions tested.

CONCLUSIONS:
This hazard assessment survey showed that many BPA-free PC- replacement products still leached chemicals having significant levels of estrogenic activity, as did BPA-containing PC counterparts they were meant to replace. That is, BPA-free did not mean EA-free. However, this study also showed that some PC-replacement products did not leach chemicals having significant levels of EA. That is, EA-free PC-replacement products could be made in commercial quantities at prices that compete with PC-replacement products that were not BPA-free. Since plastic products often have advantages (price, weight, shatter-resistance, etc.) compared to other materials such as steel or glass, it is not necessary to forgo those advantages to avoid release into foodstuffs or the environment of chemicals having EA that may have potential adverse effects on our health or the health of future generations.

Sources and more information
  • Estrogenic chemicals often leach from BPA-free plastic products that are replacements for BPA-containing polycarbonate products, NCBI, PMID: 24886603, 2014 May 28;13(1):41. doi: 10.1186/1476-069X-13-41.
  • Full study NCBI, PMC4063249, Environ Health. 2014; 13: 41.
Mother Jones BPA-free posts

BPS, found in many “BPA-free” Plastic Consumer Products is just as Bad to Human Health

BPS is just as potent as BPA in altering brain development and causing hyperactive behavior. It also disrupts heart rhythms, alters cell proliferation leading to cell death…

Currently, no federal agency tests the toxicity of new materials before they are allowed on the market… ! ? ! ?

Common BPA substitute, BPS, disrupts heart rhythms in females

Abstract:

Soft-Drink-Fast-Food-Plastic-Packaging
A chemical found in many “BPA free” consumer products, known as bisphenol S (BPS), is just as potent as bisphenol A (BPA) in altering brain development and causing hyperactive behavior. It also disrupts heart rhythms, alters cell proliferation leading to cell death…

” … In the current study, the investigators perfused, or flowed, BPS through the arteries of each animal’s pumping heart, after stimulating the heart with the hormone catecholamine to mimic stress. For a control group, 30 rat hearts received only catecholamine and no BPS.

Exposure to BPS rapidly increased the heart rate of female rats and under the stress condition led to arrhythmias—heart rhythm abnormalities—far greater than in the control rats that did not receive BPS, Wang reported. Electocardiograms demonstrated that BPS caused extra heartbeats and a racing heartbeat, also known as ventricular tachycardia. In male rats, BPS reportedly did not have this rapid impact on the heart… ”

Exposure to BPA Substitute Causes Hyperactivity and Brain Changes in Fish

Abstract:

” …At the peak time of neuronal birth, the number of neurons in BPA-exposed fish rose 170 percent compared with unexposed fish, Kurrasch stated. In similar experiments using BPS, the number of neurons in exposed fish increased 240 percent. These results, she explained, suggest that BPA and BPS could lead to altered brain connections and might explain the hyperactivity they observed in another experiment. Specifically, the research team used movement tracking software to evaluate behavioral changes in young fish and found that fish exposed during brain development to either BPA or BPS were hyperactive, but unexposed fish were not… ”

Bisphenol S Disrupts Estradiol-Induced Nongenomic Signaling in a Rat Pituitary Cell Line: Effects on Cell Functions

Abstract:

Background:
Bisphenol-A (BPA) is a well-known endocrine disruptor that imperfectly mimics the effects of physiologic estrogens via membrane-bound estrogen receptors (mERα, mERβ, and GPER/GPR30), thereby initiating nongenomic signaling. Bisphenol S (BPS) is an alternative to BPA in plastic consumer products and thermal paper.

Objective:
To characterize the nongenomic activities of BPS, we examined signaling pathways it evoked in GH3/B6/F10 rat pituitary cells alone and together with the physiologic estrogen estradiol (E2). Extracellular signal-regulated kinase (ERK)– and c-Jun-N-terminal kinase (JNK)–specific phosphorylations were examined for their correlation to three functional responses: proliferation, caspase activation, and prolactin (PRL) release.

Methods:
We detected ERK and JNK phosphorylations by fixed-cell immunoassays, identified the predominant mER initiating the signaling with selective inhibitors, estimated cell numbers by crystal violet assays, measured caspase activity by cleavage of fluorescent caspase substrates, and measured PRL release by radioimmunoassay.

Results:
BPS phosphoactivated ERK within 2.5 min in a nonmonotonic dose-dependent manner (10–15 to 10–7 M). When combined with 10–9 M E2, the physiologic estrogen’s ERK response was attenuated. BPS could not activate JNK, but it greatly enhanced E2-induced JNK activity. BPS induced cell proliferation at low concentrations (femtomolar to nanomolar), similar to E2. Combinations of both estrogens reduced cell numbers below those of the vehicle control and also activated caspases. Earlier activation of caspase 8 versus caspase 9 demonstrated that BPS initiates apoptosis via the extrinsic pathway, consistent with activation via a membrane receptor. BPS also inhibited rapid (≤ 1 min) E2-induced PRL release.

Conclusion:
BPS, once considered a safe substitute for BPA, disrupts membrane-initiated E2-induced cell signaling, leading to altered cell proliferation, cell death, and PRL release.

Most Plastic Products Release Estrogenic Chemicals: A Potential Health Problem That Can Be Solved

Abstract

Background:
Chemicals having estrogenic activity (EA) reportedly cause many adverse health effects, especially at low (picomolar to nanomolar) doses in fetal and juvenile mammals.

Objectives:
We sought to determine whether commercially available plastic resins and products, including baby bottles and other products advertised as bisphenol A (BPA) free, release chemicals having EA.

Methods:
We used a roboticized MCF-7 cell proliferation assay, which is very sensitive, accurate, and repeatable, to quantify the EA of chemicals leached into saline or ethanol extracts of many types of commercially available plastic materials, some exposed to common-use stresses (microwaving, ultraviolet radiation, and/or autoclaving).

Results:
Almost all commercially available plastic products we sampled—independent of the type of resin, product, or retail source—leached chemicals having reliably detectable EA, including those advertised as BPA free. In some cases, BPA-free products released chemicals having more EA than did BPA-containing products.

Conclusions:
Many plastic products are mischaracterized as being EA free if extracted with only one solvent and not exposed to common-use stresses. However, we can identify existing compounds, or have developed, monomers, additives, or processing agents that have no detectable EA and have similar costs. Hence, our data suggest that EA-free plastic products exposed to common-use stresses and extracted by saline and ethanol solvents could be cost-effectively made on a commercial scale and thereby eliminate a potential health risk posed by most currently available plastic products that leach chemicals having EA into food products.

Sources and More Information:
  • Common BPA substitute, BPS, disrupts heart rhythms in females, Endocrine Society, Newsroom, 23-Jun-2014.
  • Exposure to BPA Substitute Causes Hyperactivity and Brain Changes in Fish, Endocrine Society, Newsroom, 23-Jun-2014.
  • Bisphenol S Disrupts Estradiol-Induced Nongenomic Signaling in a Rat Pituitary Cell Line: Effects on Cell Functions, Environ Health Perspect., DOI:10.1289/ehp.1205826, March 2013.
  • Most Plastic Products Release Estrogenic Chemicals: A Potential Health Problem That Can Be Solved, Environ Health Perspect., PMC3222987, Jul 1, 2011.

Many BPA-free Brands advertised as Safe while messing with Your Hormones

Estrogenic chemicals often leach from #BPA-free plastic products that are replacements for BPA-containing polycarbonate products

Abstract

BioMed Central twitter logo
Estrogenic chemicals often leach from BPA-free plastic products that are replacements for BPA-containing polycarbonate products.

BACKGROUND:
Xenobiotic chemicals with estrogenic activity (EA), such as Bisphenol-A (BPA), have been reported to have potential adverse health effects in mammals, including humans, especially in fetal and infant stages. Concerns about safety have caused many manufacturers to use alternatives to polycarbonate (PC) resins to make hard and clear, reusable, plastic products that do not leach BPA. However, no study has focused on whether such BPA-free PC-replacement products, chosen for their perceived higher safety, especially for babies, also release other chemicals that have EA.

METHODS:
We used two, well-established, mammalian cell-based, assays (MCF-7 and BG1Luc) to assess the EA of chemicals that leached into over 1000 saline or ethanol extracts of 50 unstressed or stressed (autoclaving, microwaving, and UV radiation) BPA-free PC-replacement products. An EA antagonist, ICI 182,780, was used to confirm that agonist activity in leachates was due to chemicals that activated the mammalian estrogen receptor.

RESULTS:
Many unstressed and stressed, PC-replacement-products made from acrylic, polystyrene, polyethersulfone, and TritanTM resins leached chemicals with EA, including products made for use by babies. Exposure to various forms of UV radiation often increased the leaching of chemicals with EA. In contrast, some BPA-free PC-replacement products made from glycol-modified polyethylene terephthalate or cyclic olefin polymer or co-polymer resins did not release chemicals with detectable EA under any conditions tested.

CONCLUSIONS:
This hazard assessment survey showed that many BPA-free PC- replacement products still leached chemicals having significant levels of estrogenic activity, as did BPA-containing polycarbonate counterparts they were meant to replace. That is, BPA-free did not mean EA-free. However, this study also showed that some PC-replacement products did not leach chemicals having significant levels of EA. That is, EA-free PC-replacement products could be made in commercial quantities at prices that compete with PC-replacement products that were not BPA-free. Since plastic products often have advantages (price, weight, shatter-resistance, etc.) compared to other materials such as steel or glass, it is not necessary to forgo those advantages to avoid release into foodstuffs or the environment of chemicals having EA that may have potential adverse effects on our health or the health of future generations.

Sources and Press Articles
  • Estrogenic chemicals often leach from BPA-free plastic products that are replacements for BPA-containing polycarbonate products, NCBI, PMID: 24886603, 2014 May 28.
  • Full text, Environmental Health, doi:10.1186/1476-069X-13-41, 2014 May 28.
  • Parents shocked to learn ‘BPA-free’ baby bottles are loaded with other estrogen mimickers: Born Free, Weil Baby, CamelBak and more, NaturalNews, 045585_BPA-free_baby_bottles_estrogen_mimickers, June 16, 2014.
  • These Popular Plastic Bottles May Be Messing With Your Hormones, MotherJones, bpa-free-plastics-tritan-nalgene-dangerous, Jun. 16, 2014.

Are BPA-free Plastic Containers really Safe?

What is the BPS compound?

Registered dietitian Nancy Dell reviews bisphenol-A (BPA), BPA-free, BPS and plastic packaging.

More information

BPA-free Plastics going on Trial in Texas

Are BPA-free plastics really safe?

BPA-Free Plastics Going On Trial In Texas
PlastiPure helps manufacturers create water bottles and other plastic products that have no estrogenic activity

Scientists and lawyers are scheduled to debate the safety of certain “BPA-free” plastics this week in a U.S. District Court in Austin, Texas.

At issue is whether a line of plastic resins marketed by Eastman Chemical contains chemicals that can act like the hormone estrogen, and perhaps cause health problems.

Read BPA-Free Plastics Going On Trial In Texas, NPR Shots
by Jon Hamilton, 15 July 2013.

Related post:
Are BPA-free Plastics really safe?