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.

Abstract

Background
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.

Objectives
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.

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

Results
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.

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

Pesticide Damage to DNA Found ‘Programmed’ into Future Generations

Atrazine induced epigenetic transgenerational inheritance of disease, lean phenotype and sperm epimutation pathology biomarkers

Dr. Paul Winchester, a pediatrician, and several other researchers including Michael Skinner, professor of biology at Washington State University’s Center for Reproductive Biology, conducted a study to see if there was a link between atrazine in drinking water and birth defects, EcoWatch reports.

“The most alarming (finding) to me is that almost every chemical tested including atrazine reduced fertility in the third generation of offspring.”

2017 Study Abstract

Ancestral environmental exposures to a variety of environmental toxicants and other factors have been shown to promote the epigenetic transgenerational inheritance of adult onset disease. The current study examined the potential transgenerational actions of the herbicide atrazine.

Atrazine is one of the most commonly used herbicides in the agricultural industry, in particular with corn and soy crops. Outbred gestating female rats were transiently exposed to a vehicle control or atrazine. The F1 generation offspring were bred to generate the F2 generation and then the F2 generation bred to generate the F3 generation. The F1, F2 and F3 generation control and atrazine lineage rats were aged and various pathologies investigated. The male sperm were collected to investigate DNA methylation differences between the control and atrazine lineage sperm. The F1 generation offspring (directly exposed as a fetus) did not develop disease, but weighed less compared to controls. The F2 generation (grand-offspring) was found to have increased frequency of testis disease and mammary tumors in males and females, early onset puberty in males, and decreased body weight in females compared to controls. The transgenerational F3 generation rats were found to have increased frequency of testis disease, early onset puberty in females, behavioral alterations (motor hyperactivity) and a lean phenotype in males and females. The frequency of multiple diseases was significantly higher in the transgenerational F3 generation atrazine lineage males and females. The transgenerational transmission of disease requires germline (egg or sperm) epigenetic alterations. The sperm differential DNA methylation regions (DMRs), termed epimutations, induced by atrazine were identified in the F1, F2 and F3 generations. Gene associations with the DMRs were identified. For the transgenerational F3 generation sperm, unique sets of DMRs (epimutations) were found to be associated with the lean phenotype or testis disease. These DMRs provide potential biomarkers for transgenerational disease.

The etiology of disease appears to be in part due to environmentally induced epigenetic transgenerational inheritance, and epigenetic biomarkers may facilitate the diagnosis of the ancestral exposure and disease susceptibility. Observations indicate that although atrazine does not promote disease in the directly exposed F1 generation, it does have the capacity to promote the epigenetic transgenerational inheritance of disease.

The Dangers of Plastic Food Packaging : Food Additives and Child Health Report

Chemicals in Food May Harm Children, Pediatricians’ Group Says

In their Policy Statement and Technical Report, the American Academy of Pediatrics is urging families to limit the use of plastic food containers, cut down on processed meat during pregnancy and consume more whole fruits and vegetables rather than processed food.

Such measures would lower children’s exposures to chemicals in food and food packaging that are tied to health problems such as obesity, Roni Caryn Rabin reports. Featured image credit Fancycrave.com from Pexels.

2018 Technical Report Abstract

Increasing scientific evidence suggests potential adverse effects on children’s health from synthetic chemicals used as food additives, both those deliberately added to food during processing (direct) and those used in materials that may contaminate food as part of packaging or manufacturing (indirect). Concern regarding food additives has increased in the past two decades in part because of studies that increasingly document endocrine disruption and other adverse health effects. In some cases, exposure to these chemicals is disproportionate among minority and low-income populations. This report focuses on those food additives with the strongest scientific evidence for concern. Further research is needed to study effects of exposure over various points in the life course, and toxicity testing must be advanced to be able to better identify health concerns prior to widespread population exposure. The accompanying policy statement describes approaches policy makers and pediatricians can take to prevent the disease and disability that are increasingly being identified in relation to chemicals used as food additives, among other uses.

The Dangers of Plastic Food Packaging : Food Additives and Child Health Statement

Chemicals in Food May Harm Children, Pediatricians’ Group Says

In their Policy Statement and Technical Report, the American Academy of Pediatrics is urging families to limit the use of plastic food containers, cut down on processed meat during pregnancy and consume more whole fruits and vegetables rather than processed food.

Such measures would lower children’s exposures to chemicals in food and food packaging that are tied to health problems such as obesity, Roni Caryn Rabin reports. Featured image credit Fernanda Rodríguez.

2018 Policy Statement Abstract

Our purposes with this policy statement and its accompanying technical report are to review and highlight emerging child health concerns related to the use of colorings, flavorings, and chemicals deliberately added to food during processing (direct food additives) as well as substances in food contact materials, including adhesives, dyes, coatings, paper, paperboard, plastic, and other polymers, which may contaminate food as part of packaging or manufacturing equipment (indirect food additives); to make reasonable recommendations that the pediatrician might be able to adopt into the guidance provided during pediatric visits; and to propose urgently needed reforms to the current regulatory process at the US Food and Drug Administration (FDA) for food additives. Concern regarding food additives has increased in the past two decades, in part because of studies in which authors document endocrine disruption and other adverse health effects. In some cases, exposure to these chemicals is disproportionate among minority and low-income populations. Regulation and oversight of many food additives is inadequate because of several key problems in the Federal Food, Drug, and Cosmetic Act. Current requirements for a “generally recognized as safe” (GRAS) designation are insufficient to ensure the safety of food additives and do not contain sufficient protections against conflict of interest. Additionally, the FDA does not have adequate authority to acquire data on chemicals on the market or reassess their safety for human health. These are critical weaknesses in the current regulatory system for food additives. Data about health effects of food additives on infants and children are limited or missing; however, in general, infants and children are more vulnerable to chemical exposures. Substantial improvements to the food additives regulatory system are urgently needed, including greatly strengthening or replacing the “generally recognized as safe” (GRAS) determination process, updating the scientific foundation of the FDA’s safety assessment program, retesting all previously approved chemicals, and labeling direct additives with limited or no toxicity data.

Beware the mixture

Despite growing scientific evidence for enhanced toxicity of chemical mixtures, regulation does not adequately capture such combination effects

Humans and wildlife are continuously exposed to multiple chemicals from different sources and via different routes, both simultaneously and in sequence. Scientific evidence for heightened toxicity from such mixtures is mounting, yet regulation is lagging behind. Ensuring appropriate regulation of chemical mixture risks will require stronger legal stimuli as well as close integration of different parts of the regulatory systems in order to meet the data and testing requirements for mixture risk assessment.

Until about a decade ago, toxicologists, risk assessors, and regulators regarded risks from chemical mixtures as negligible, as long as exposures to all single chemicals in the cocktail were below the levels judged to be safe for each chemical alone. However, an increasing body of scientific evidence has challenged this notion, showing that a neglect of mixture effects can cause chemical risks to be underestimated. International bodies such as the World Health Organization now acknowledge the need for considering mixtures in chemical risk assessment and regulation. This would align toxicological risk assessment with the clinical sciences and their long tradition of investigating drug-drug interactions. Yet, with few exceptions, regulatory systems around the world still focus overwhelmingly on single-chemical assessments, and the translation of scientific evidence about mixture effects into better regulation is extremely slow.

Continue reading Regulate to reduce chemical mixture risk on ScienceMag, 20 Jul 2018.

Towards a more comprehensive EU framework on endocrine disruptors

Health groups warn proposed change to pesticide law would undermine effective identification and ban of endocrine disruptors

Health and Environment Alliance (HEAL) Press Release, 19/07/2018

A discussion on a controversial proposal to amend the European pesticide legislation started between representatives of European governments on 19-20 July. Health groups warn that such a change would undermine the provisions that foresee the ban of pesticides identified as endocrine disruptors and would only benefit the pesticide industry.

As the European Commission consultation on a roadmap for a framework on endocrine disrupting chemicals (EDCs) is coming to a close, a much less publicised process is starting behind closed doors. Representatives of European member states met in Brussels on 19 and 20 July to discuss a proposal by the European Commission to change the conditions that would allow derogations from the ban of endocrine disruptors planned under the pesticide legislation.

This is not the first time the Commission has proposed such changes. This proposal was originally discussed during the negotiations on the identification criteria for EDCs in 2016. Due to strong opposition from civil society and the public health community at the time, it did not garner the needed support by member states to be included in the criteria.

Following the agreement on identification criteria for endocrine disrupting pesticides in December 2017, it is now technically possible for European countries to ban pesticides that meet the criteria. The pesticide regulation foresees a possible derogation to such bans in cases of “negligible exposure” to the substance – namely conditions in which the exposure is well controlled such as in closed systems.

As brought to the public attention by HEAL’s member Pesticide Action Network Europe, the European Commission is suggesting to change the conditions allowing for such a derogation by replacing “negligible exposure” into “negligible risk”. This slight change of wording might first come across as harmless, but carries the potential to change the hazard-based approach that lies at the foundation of the pesticide legislation. If adopted, it would bring a risk element into the discussion.

This is problematic and should be opposed at all costs for several reasons:

  • The European Commission is suggesting a discussion on this proposal behind closed doors, using the comitology procedure, while the proposed changes touch upon the foundations of the pesticide legislation. Therefore, a fully transparent process involving the European Parliament and the Council (in co-decision) would be the appropriate setting for such a discussion.
    The fact that this is happening just as the public consultation on the roadmap for a framework on EDCs (which HEAL has already criticised for missing concrete measures to reduce exposure to EDCs) comes to a close, also raises questions on the Commission’s willingness to have a fully transparent and democratic debate on such a high profile public health issue.
  • The proposal brings a fundamental change to the hazard-based approach of the pesticide legislation. Based on the precautionary principle, the legislation considers that pesticides identified as EDCs should be banned by default, unless in case of “negligible exposure”. If adopted, the Commission’s proposal would introduce a risk assessment following the EDC identification, based on the flawed idea that safe conditions and levels of exposure exist for EDCs and the risk related to this exposure can be controlled. This would make the evaluation process of pesticides even more lengthy. It would also open a pandora’s box to industry arguments that attempt to justify that a risk is negligible under hypothetical conditions of use and wrongly promote a supposedly safe use of certain chemicals that the pesticide legislation explicitly singled out as dangerous to human health.
    This is even more worrying as the data used to assess supposedly negligible risks will be prepared by companies. While the current derogation in case of negligible exposure foresees that the exposure has to be well controlled (for instance in a closed environment), an approach based on risk would open the door to allowing for a much wider use of endocrine disrupting pesticides – for instance through spraying in the environment – when they should by default be banned under the law.

The Health and Environment Alliance (HEAL) together with members such as PAN Europe and partners of the EDC-Free Europe coalition will continue to oppose this proposed change. We urge member states to defend the existing approach foreseen in the pesticide legislation and strive for its full implementation in the future.

Endocrine Disrupting Chemicals and Behavior

Special issue of Hormones and Behavior, Volume 101, Pages 1-148, May 2018

The peer-reviewed journal Hormones and Behavior, Volume 101, Pages 1-148 (May 2018), raises concern about how many of the 90,000+ chemicals in use today may disrupt our most basic endocrine systems with significant consequences for neurodevelopment, neurophysiology, healthy brain aging, and behavior.

Several articles address bisphenol A :

About PDBEs, triclosan, and other replacement chemicals :

Other studies included in this special issue address behavioral effects of voluntary taken pharmaceuticals, including birth control pills, and pain medications.

About DES and the BRAIN :

Prenatal exposure to several replacement chemicals linked to hyperactivity, problem behaviors in children

Exposure to perfluoroalkyl substances during pregnancy and child behaviour at 5 to 9 years of age

2018 Study Highlights

  • Serum levels of perfluoroalkyl substances were measured in 1023 pregnant women.
  • Child behaviour was assessed by use of the Strength and Difficulties Questionnaire
  • Prenatal perfluorohexane sulfonic acid (PFHxS) was associated with problem behaviour
  • Prenatal perfluorononanoic acid (PFNA) was associated with hyperactive behaviour
  • Prenatal perfluorodecanic acid (PFDA) was associated with hyperactive behaviour.

Abstract

We examined associations between prenatal exposure to perfluorohexane sulfonic acid (PFHxS), perfluoroheptanoic acid (PFHpA), perfluorononanoic acid (PFNA), and perfluorodecanic acid (PFDA) – and child behaviour (SDQ-total) and hyperactivity (sub-scale) at 5–9 years of age in birth cohorts from Greenland and Ukraine.

Pregnancy serum samples (N = 1023) were analysed for perfluoroalkyl substances (PFASs) and categorised into tertiles and also used as continuous exposure variables. Problem behaviour and hyperactivity were assessed, using the Strength and Difficulties Questionnaire (SDQ) and categorised as normal/borderline and abnormal. Associations were analysed using multiple logistic and linear regression.

High compared to low prenatal PFHxS exposure was associated with 1.16 (95% confidence interval (CI): 0.08; 2.25) point higher SDQ-total (more problem behaviour) in Greenland and 0.80 (CI: 0.06; 1.54) point higher SDQ-total in the combined analyses, whereas no association was present in Ukraine alone. One natural log-unit increase in prenatal PFNA exposure was associated with 0.90 (CI: 0.10; 1.71) points higher SDQ-total in Greenland and 0.72 (CI: 0.13; 1.31) points higher in the combined analysis and no association in Ukraine. Prenatal PFAS exposure was unrelated to problem behaviour (abnormal SDQ-total). In the combined analysis, odds ratio (OR) (CI) for hyperactivity was 1.8 (1.0; 3.2) for one natural log-unit increase in prenatal PFNA and 1.7 (1.0; 3.1) for one natural log-unit increase in prenatal PFDA exposure.

Findings are compatible with weak effects on child behaviour of prenatal exposure to some PFASs although spurious results are not entirely unlikely. The associations were strongest in Greenland.

Behavioral effects of prenatal and postnatal PBDE exposures

Exposure to polybrominated diphenyl ethers (PBDEs) and child behavior: Current findings and future directions

2018 Study Highlights

  • Prenatal PBDEs are associated with executive function impairments and inattention.
  • Prenatal and postnatal PBDE exposures increase externalizing problems in children.
  • PBDEs’ association with internalizing, adaptive, and social behaviors is not clear.
  • PBDE exposure adversely affects behavioral development in children.

Abstract

Polybrominated diphenyl ethers (PBDEs) are recognized neurotoxicants, but the extent to which PBDEs influence various domains of behavior in children is not fully understood.

As such, we reviewed epidemiologic studies published to date to provide an overview of the current state of knowledge on PBDEs’ potential role in behavioral development.

We identified 19 epidemiologic studies reporting on associations of prenatal and childhood concentrations of PBDEs with behaviors assessed in children from 1 to 12 years, including executive function, attention, externalizing and internalizing behaviors, adaptive skills, and social behaviors/Autism Spectrum Disorder (ASD).

While the mechanisms of PBDE neurotoxicity in humans are still not clearly elucidated, findings from this review indicate that PBDE exposure during fetal development is associated with impairments in executive function and poorer attentional control in children. Results from large prospective cohorts demonstrate that prenatal and postnatal PBDE exposure adversely impacts externalizing behavior (e.g., hyperactivity and conduct problems). Additional studies are needed to determine whether PBDEs are associated with internalizing problems, adaptive skills, and social behaviors/ASD in children.

Future studies will help better understand the potential neurotoxic effects of PBDE exposures during adolescence, possible sex-dependent effects, and the impact of exposure to BDE-209 and alternative flame retardants. Future studies should also examine chemical mixtures to capture real-world exposures when examining PBDEs and their impact on various behavioral domains in the context of multiple chemical exposures.

All species are exposed to EDCs and at risk for adverse neurodevelopmental outcomes

Behavioral and molecular analyses of olfaction-mediated avoidance responses of Rana (Lithobates) catesbeiana tadpoles: Sensitivity to thyroid hormones, estrogen, and treated municipal wastewater effluent

2018 Study Highlights

  • Olfaction is critical in tadpoles for predator avoidance and food location.
  • Thyroid hormones (THs) change olfactory tissues dramatically during metamorphosis.
  • T3 & municipal wastewater effluent, but not T4 or E2, disrupt avoidance behavior.
  • Thra and thibz mRNAs are significantly higher in T3 versus T4 olfactory epithelium.
  • Further bioindicator candidates are needed to link to adverse behavior outcomes.

Abstract

Olfaction is critical for survival, facilitating predator avoidance and food location. The nature of the olfactory system changes during amphibian metamorphosis as the aquatic herbivorous tadpole transitions to a terrestrial, carnivorous frog. Metamorphosis is principally dependent on the action of thyroid hormones (THs), l-thyroxine (T4) and 3,5,3′-triiodothyronine (T3), yet little is known about their influence on olfaction during this phase of postembryonic development.

We exposed Taylor Kollros stage I-XIII Rana (Lithobates) catesbeiana tadpoles to physiological concentrations of T4, T3, or 17-beta-estradiol (E2) for 48 h and evaluated a predator cue avoidance response.

The avoidance response in T3-exposed tadpoles was abolished while T4- or E2-exposed tadpoles were unaffected compared to control tadpoles. qPCR analyses on classic TH-response gene transcripts (thra, thrb, and thibz) in the olfactory epithelium demonstrated that, while both THs produced molecular responses, T3 elicited greater responses than T4. Municipal wastewater feed stock was spiked with a defined pharmaceutical and personal care product (PPCP) cocktail and treated with an anaerobic membrane bioreactor (AnMBR). Despite substantially reduced PPCP levels, exposure to this effluent abolished avoidance behavior relative to AnMBR effluent whose feed stock was spiked with vehicle. Thibz transcript levels increased upon exposure to either effluent indicating TH mimic activity.

The present work is the first to demonstrate differential TH responsiveness of the frog tadpole olfactory system with both behavioral and molecular alterations. A systems-based analysis is warranted to further elucidate the mechanism of action on the olfactory epithelium and identify further molecular bioindicators linked to behavioral response disruption.