Bisphenol A (BPA) pharmacokinetics with daily oral bolus or continuous exposure via silastic capsules in pregnant rhesus monkeys: Relevance for human exposures

Saal, Frederick S. vom; VandeVoort, Catherine A.; Taylor, Julia A.; Welshons, Wade V.; Toutain, P. L.; Hunt, Patricia A.

doi:10.1016/j.reprotox.2014.01.007

Cited by 56 publications

(45 citation statements)

References 50 publications

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“…In this scenario, controversy remains alive in terms of which is the best way of administration of BPA in animal studies for hazard assessment. Interestingly, recent pharmacokinetics studies of BPA have demonstrated that the sc administration of BPA leads to a ratio of serum conjugated‫گ‬to unconjugated BPA within the range reported in human biomonitoring studies, and that this ratio is more similar than the one obtained using oral exposure (55,56). Whether this is applicable to our study needs further clarification.…”

supporting

confidence: 68%

Bisphenol-A Treatment During Pregnancy in Mice: A New Window of Susceptibility for the Development of Diabetes in Mothers Later in Life

et al. 2015

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Evidence now exists supporting the hypothesis that endocrine-disrupting chemicals (EDCs) can harmfully impact glucose metabolism. Thus, EDCs are beginning to be considered important contributors to the increased incidence of diabetes, obesity, or both. The possible effect of exposure to EDCs during pregnancy on glucose homeostasis in mothers later in life is presently unknown. Here we show that several months after delivery, mothers treated with the widespread EDC bisphenol-A (BPA) during gestation, at environmentally relevant doses, exhibit profound glucose intolerance and altered insulin sensitivity as well as increased body weight. These mice presented a decreased insulin secretion both in vivo and in vitro together with reduced pancreatic β-cell mass. The proliferation capacity was decreased in association with a diminished expression of the cell cycle activators: cyclin D2 and cyclin-dependent kinase-4. In addition, the rate of β-cells apoptosis was increased as well as the expression of the cell cycle inhibitors p16 and p53. Conversely, no effects on glucose metabolism or insulin sensitivity were observed when female nonpregnant mice were treated with BPA at the same doses. Taken together, these findings reveal that BPA exposure during gestation has harmful long-term implications in glucose metabolism for the mother. This finding highlights a new window of susceptibility for EDC exposure that may be important for the development of type 2 diabetes.

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supporting

confidence: 68%

Bisphenol-A Treatment During Pregnancy in Mice: A New Window of Susceptibility for the Development of Diabetes in Mothers Later in Life

et al. 2015

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“…Unconjugated BPA was not detectable in serum or urine at any time point in the single previous human oral pharmacokinetic (PK) study where subjects recieved an oral dose of ~54 – 90 μg/kg bw (Volkel and others 2002). However, the limit of detection in that study, 2.28 ng/ml (10 nM), is less sensitive than more recent capabilities of 0.06 to 0.4 ng/ml (0.26 to 1.75 nM) (Mortensen and others 2014; Vandenberg and others 2014; Vom Saal and others 2014). A recent study using a more sensitive method (LOD range of 0.02–0.96 ng/mL) reported a maximum concentration of unconjugated d6-BPA of 0.098 ng/ml (0.43 nM) at 1.6 hours following administration of 30 μg/kg bw of BPA in soup to 10 men (Teeguarden and others 2015).…”

Section: 0 Introductioncontrasting

confidence: 62%

Pharmacokinetics of bisphenol A in humans following a single oral administration

Thayer

Doerge

Hunt

et al. 2015

Environment International

267

197

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Background Human exposures to bisphenol A (BPA) are widespread. The current study addresses uncertainties regarding human pharmacokinetics of BPA. Objective To reduce uncertainties about the metabolism and excretion of BPA in humans following oral administration. Methods We exposed six men and eight women to 100 μg/kg bw of deuterated BPA (d6-BPA) by oral administration and conducted blood and urine analysis over a three day period. The use of d6-BPA allowed administered d6-BPA to be distinguished from background native (unlabelled) BPA. We calculated the rate of oral absorption, serum elimination, half-life, area under the curve (AUC), urinary excretion, and metabolism to glucuronide and sulfate conjugates. Results Mean serum total (unconjugated and conjugated) d6-BPA Cmax of 1711 nM (390 ng/ml) was observed at Tmax of 1.1 ± 0.50 h. Unconjugated d6-BPA appeared in serum within 5–20 min of dosing with a mean Cmax of 6.5 nM (1.5 ng/ml) observed at Tmax of 1.3 ± 0.52 h. Detectable blood levels of unconjugated or total d6-BPA were observed at 48 hours in some subjects at concentrations near the LOD (0.001–0.002 ng/ml). The half-times for terminal elimination of total d6-BPA and unconjugated d6-BPA were 6.4 ± 2.0 h and 6.2 ± 2.6 h, respectively. Recovery of total administered d6-BPA in urine was 84–109%. Most subjects (10 of 14) excreted >90% as metabolites within 24 hours. Conclusions Using more sensitive methods, our study expands the findings of other human oral pharmacokinetic studies. Conjugation reactions are rapid and nearly complete with unconjugated BPA comprising less than 1% of the total d6-BPA in blood at all times. Elimination of conjugates into urine largely occurs within 24 hours.

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“…Dokazano je da BPA koji se nalazi u plastici i u mnogim proizvodima u kojima kupujemo, iz kojih konzumiramo i u kojima držimo hranu, ima štetan uticaj na razvoj mnogih anomalija kao što su karcinom, reproduktivne smetnje, smetnje imunog sistema i kasniji problemi u ponašanju, hiperaktivnosti kod djece (10).…”

Section: Prenatalni I Perinatalni Faktoriunclassified

The Effects of the Environment During the Prenatal and Perinatal Period for Early Growth and Development of the Child

Pištoljević¹

2015

Međunarodni Naučni Simpozij FETALNA MEDICINA: OD LEONARDA DA VINCIJA DO DANAS

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Edus -Edukacija za sve, BiH Sažetak Svake godine nauka pomakne granice i nova saznanja, ponekad promijeni naš način rada i ponašanja iz osnove. Trudnoća, kao jedan od prirodnih i sastavnih dijelova života, nažalost u današnjem svijetu i standardima života, nosi sa sobom nove rizike i saznanja o negativnim efektima okoline na tipičan i zdrav razvoj fetusa i poslije djeteta. Mitovi kako se "prije živjelo i rađalo" uz nauku polako blijede, a mi postajemo društvo svjesnije efekata prenatalnog i natalnog perioda, prvo na rast i razvoj djeteta, pa onda i cjelovječnost i zdravlje čovjeka. Efekti ponašanja i uticaja okoline in utero odjekuju uz naše genetske predispozicije do kraja života. Nauka pomjera granice i danas znamo o efektima prenatalnog, perinatalnog, a i postnatalnog izlaganja alkoholu, kofeinu, dimu cigareta, zagađenju, kancerogenim materijama kao Bisfenol A, lijekovima bez nadgledanja i praćenja od strane ljekara, neprirodnim vidovima poroda (asistirani porodi), na kasnije zdravlje i razvoj djeteta. Ovi rizič-ni faktori tokom trudnoće mogu prouzrokovati cjeloživotne poremećaje kao što su poremećaj autističnog spektra, ADHD, poteškoće u učenju i umanjene kognitivne sposobnosti. Nažalost, poremećaji u razvoju kod djece danas su sve učestaliji i kompleksniji, kako zbog napretka medicine, većeg broja održanih trudnoća i veće stope preživljavanja komplikacija pri porodu, tako zbog sve bolje dijagnostike i detekcije. Neurorazvojni poremećaji se mogu karakterizovati kao zaostatak u tipičnom razvoju djeteta identifikovan u motoričkom razvoju, razvoju komunikacije i govora, kognitivnom i emotivnom razvoju, te mogu biti povezani s nekom od jasnih medicinskih dijagnoza kao što su autizam, epilepsija, razni sindromi i oštećenja, hromozomalne anomalije, ili jednostavno mogu biti uslovljeni psihofizičkom i socijalnom okolinom u kojoj je fetus pa zatim i dijete raslo. U ovom radu osvrnuću se na najnovija svjetska 15 Dr. Nirvana Pištoljević,

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Bisphenol A (BPA) pharmacokinetics with daily oral bolus or continuous exposure via silastic capsules in pregnant rhesus monkeys: Relevance for human exposures

Cited by 56 publications

References 50 publications

Bisphenol-A Treatment During Pregnancy in Mice: A New Window of Susceptibility for the Development of Diabetes in Mothers Later in Life

Bisphenol-A Treatment During Pregnancy in Mice: A New Window of Susceptibility for the Development of Diabetes in Mothers Later in Life

Pharmacokinetics of bisphenol A in humans following a single oral administration

The Effects of the Environment During the Prenatal and Perinatal Period for Early Growth and Development of the Child

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