Are Structural Analogues to Bisphenol A Safe Alternatives?

Rosenmai, Anna Kjerstine; Dybdahl, Marianne; Pedersen, Michael; Vugt-Lussenburg, Barbara M.A. van; Wedebye, Eva Bay; Taxvig, Camilla; Vinggaard, Anne Marie

doi:10.1093/toxsci/kfu030

Cited by 371 publications

(233 citation statements)

References 68 publications

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“…BPA and BPE, in the range of concentrations used in the present study, had inhibitory effects on testosterone similar to those in the human testis. In contrast, BPF inhibited testosterone production only weakly in the NCI-H295R cell line, and inhibition by BPS was slight (Rosenmai et al, 2014;Goldinger et al, 2015), consistent with the result in our system after 24 h of exposure. While BPB suppressed testosterone production here (at 10 -7 M at both 24 and 48 h), its anti-androgenicity was close to that of BPA in the NCI-H295R cell line (Rosenmai et al, 2014).…”

Section: Inhibin Bsupporting

confidence: 91%

“…In contrast, BPF inhibited testosterone production only weakly in the NCI-H295R cell line, and inhibition by BPS was slight (Rosenmai et al, 2014;Goldinger et al, 2015), consistent with the result in our system after 24 h of exposure. While BPB suppressed testosterone production here (at 10 -7 M at both 24 and 48 h), its anti-androgenicity was close to that of BPA in the NCI-H295R cell line (Rosenmai et al, 2014). Further support for our findings comes from a study that used the mouse Leydig cell line, known as the MA-10 cell line (Roelofs et al, 2015).…”

Section: Inhibin Bsupporting

confidence: 91%

“…Like BPA, some BPA-A were also shown to display anti-androgenicity in the steroidogenic NCI-H295R cell line (Rosenmai et al, 2014;Goldinger et al, 2015). BPA and BPE, in the range of concentrations used in the present study, had inhibitory effects on testosterone similar to those in the human testis.…”

Section: Inhibin Bmentioning

confidence: 99%

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Parallel assessment of the effects of bisphenol A and several of its analogs on the adult human testis

et al. 2017

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WHAT IS KNOWN ALREADY:The few epidemiologic studies performed suggest that bisphenols have potential endocrine disruptive properties, but they did not identify clear and direct patterns of endocrine disruption. STUDY DESIGN, SIZE, DURATION:Adult human testis explants in culture were exposed to BPA and the analogs bisphenol F (BPF), bisphenol S (BPS), bisphenol E (BPE), bisphenol B (BPB), and bisphenol A diglycidyl ether (BADGE) at 10 -9 to 10 -5 M for 24 h or 48h.PARTICIPANTS/MATERIALS, SETTING, METHODS: Human adult testes were obtained from prostate cancer patients who had no hormone therapy, or from multiorgan donors. After ex vivo exposure to the investigated bisphenols, the measured outcomes were related to histopathology (gross morphology and germ cell viability determined by anti-caspase 3 immunohistochemistry), and the levels of testosterone, insulin-like fator 3 and inhibin B were measured using immunoassays. The levels of mRNA encoding key enzymes of bisphenol biotransformation were investigated by quantitative PCR: UGT2B15 UDP (glucuronosyltransferase two family, polypeptide B15), GUSB (glucuronidase beta), SULT1A1 and 3 (sulfotransferase family 1 A member 1 and 3) and STS (steroid sulfatase). MAIN RESULTS AND THE ROLE OF CHANCE: A significant dose-dependent inhibition wasfound between testosterone levels measured in the culture medium and concentrations of BPA The active concentrations of BPA and BPA-A used in the study were higher than those found in human biological fluids. WIDER IMPLICATIONS OF THE FINDINGS:Under our experimental conditions, direct exposure to BPA or BPA-A can result in endocrine disturbance in the adult human testis.

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Section: Inhibin Bsupporting

confidence: 91%

Section: Inhibin Bsupporting

confidence: 91%

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Parallel assessment of the effects of bisphenol A and several of its analogs on the adult human testis

et al. 2017

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“…BPS has been detected in paper currency, paper products, foodstuffs, and urine at concentrations similar to those previously reported for BPA (Liao and Kannan, 2013;Liao et al, 2012a, b). The ability of BPS to activate ER in vitro has been documented (Molina-Molina et al, 2013;Rosenmai et al, 2014), but there is a general lack of in vivo studies for comparison. Kang et al (2014) and Hashimoto et al (2001) indicated that BPS was biotransformed to more potent metabolites after incubation with rat liver S9; whereas, Le Fol et al (2015) performed in vitro biotransformation studies and reported that the conjugates of BPS did not exhibit ER activity.…”

Section: Discussionsupporting

confidence: 76%

A Demonstration of the Uncertainty in Predicting the Estrogenic Activity of Individual Chemicals and Mixtures From anIn VitroEstrogen Receptor Transcriptional Activation Assay (T47D-KBluc) to theIn VivoUterotrophic Assay Using Oral Exposure

et al. 2016

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In vitro estrogen receptor assays are valuable tools for identifying environmental samples and chemicals that display estrogenic activity. However, in vitro potency cannot necessarily be extrapolated to estimates of in vivo potency because in vitro assays are currently unable to fully account for absorption, distribution, metabolism, and excretion. To explore this issue, we calculated relative potency factors (RPF), using 17a-ethinyl estradiol (EE2) as the reference compound, for several chemicals and mixtures in the T47D-KBluc estrogen receptor transactivation assay. In vitro RPFs were used to predict rat oral uterotrophic assay responses for these chemicals and mixtures. EE2, 17b-estradiol (E2), benzyl-butyl phthalate (BBP), bisphenol-A (BPA), bisphenol-AF (BPAF), bisphenol-C (BPC), bisphenol-S (BPS), and methoxychlor (MET) were tested individually, while BPS þ MET, BPAF þ MET, and BPAF þ BPC þ BPS þ EE2 þ MET were tested as equipotent mixtures. In vivo ED 50 values for BPA, BPAF, and BPC were accurately predicted using in vitro data; however, E2 was less potent than predicted, BBP was a false positive, and BPS and MET were 76.6 and 368.3-fold more active in vivo than predicted from the in vitro potency, respectively. Further, mixture ED 50 values were more accurately predicted by the dose addition model using individual chemical in vivo uterotrophic data (0.7-1.5-fold difference from observed) than in vitro data (1.4-86.8-fold). Overall, these data illustrate the potential for both underestimating and overestimating in vivo potency from predictions made with in vitro data for compounds that undergo substantial disposition following oral administration. Accounting for aspects of toxicokinetics, notably metabolism, in in vitro models will be necessary for accurate in vitro-to-in vivo extrapolations.

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“…The limited number of studies available at the present time, dealing with the biological interactions of BPS with the organism, indicate that BPS is also capable of imitating properties of hormones, interacting with ER (Delfosse et al 2012;Rosenmai et al 2014;Le Fol et al 2015), and direct binding to nuclear ERs (Yamasaki et al 2004) and serum albumins (Mathew et al 2014) has been confirmed.…”

Section: Biological Effects Of Bpsmentioning

confidence: 92%

Bisphenol S instead of bisphenol A: a story of reproductive disruption by regretable substitution - a review

Žalmanová¹,

Hošková²,

Nevoral³

et al. 2016

Czech J. Anim. Sci.

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A range of substances that are released into the environment, foodstuffs and drinking water as a result of human activity were originally considered relatively harmless, and it was only later that their adverse effects were discovered. In general the use of such substances is currently restricted, and they are often replaced by other substances. This applies also in the case of a range of endocrine disruptors. These substances have the capacity to disturb the balance of physiological functions of the organism on the level of hormonal regulation, and their pleiotropic spectrum of effects is very difficult to predict. Endocrine disruptors include the currently intensively studied bisphenol A (BPA), a prevalent environmental pollutant and contaminant of both water and foodstuffs. BPA has a significantly negative impact on human health, particularly on the regulation mechanisms of reproduction, and influences fertility. The ever increasingly stringent restriction of the industrial production of BPA is leading to its replacement with analogues, primarily with bisphenol S (BPS), which is not subject to these restrictions and whose impacts on the regulation of reproduction have not yet been exhaustively studied. However, the limited number of studies at disposal indicates that BPS may be at least as harmful as BPA. There is therefore a potential danger that the replacement of BPA with BPS will become one of the cases of regrettable substitution, in which the newly used substances manifest similar or even worse negative effects than the substances which they have replaced. The objective of this review is to draw attention to ill-advised replacements of endocrine disruptors with substances whose effects are not yet tested, and which may represent the same risks for the environment, for the reproduction of males and females, and for human health as have been demonstrated in the case of the originally used substances.

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Are Structural Analogues to Bisphenol A Safe Alternatives?

Abstract: Interference with the endocrine system was the predominant effect of the test compounds. A substitution of BPA with these structural analogues should be carried out with caution.

Cited by 371 publications

References 68 publications

Parallel assessment of the effects of bisphenol A and several of its analogs on the adult human testis

Parallel assessment of the effects of bisphenol A and several of its analogs on the adult human testis

A Demonstration of the Uncertainty in Predicting the Estrogenic Activity of Individual Chemicals and Mixtures From anIn VitroEstrogen Receptor Transcriptional Activation Assay (T47D-KBluc) to theIn VivoUterotrophic Assay Using Oral Exposure

Bisphenol S instead of bisphenol A: a story of reproductive disruption by regretable substitution - a review

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