Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure

Ikezuki, Yumiko; Tsutsumi, Osamu; Takai, Yasushi; Kamei, Yoshimasa; Taketani, Yuji

doi:10.1093/humrep/17.11.2839

Cited by 800 publications

(535 citation statements)

References 29 publications

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“…BPA is produced at a value of 1.7 billion kg per annum worldwide and used in the manufacture of several very ordinary products (4). BPA discharged into the environment is expected to break down fairly rapidly in air, whereas it is more persistent in water (5-7).…”

Section: Introductionmentioning

confidence: 99%

Expression of Concern: Laccase treatment impairs bisphenol A‐induced cancer cell proliferation affecting estrogen receptor α‐dependent rapid signals

et al. 2008

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SummaryA wide variety of environmental contaminants exert estrogenic actions in wildlife, laboratory animals, and in human beings through binding to nuclear estrogen receptors (ERs). Here, the mechanism(s) of bisphenol A (BPA) to induce cell proliferation and the occurrence of its bioremediation by treatment with laccase are reported. BPA, highly present in natural world and considered as a model of environmental estrogen action complexity, promotes human cancer cell proliferation via ERa-dependent signal transduction pathways. Similar to 17b-estradiol, BPA increases the phosphorylation of both extracellular regulated kinase and AKT. Specific inhibitors of these kinase completely block the BPA effect on cancer cell proliferation. Notably, high BPA concentrations (i.e., 0.1 and 1 mM) are cytotoxic even in ERa-devoid cancer cells, indicating that an ERa-independent mechanism participates to BPA-induced cytotoxicity. On the other hand, BPA oxidation by laccase impairs the binding of this environmental estrogen to ERa loosing at all ERa-dependent effect on cancer cell proliferation. Moreover, the laccase-catalyzed oxidation of BPA reduces the BPA cytotoxic effect. Thus, laccase appears to impair BPA action(s), representing an invaluable bioremediation enzyme.2008 IUBMB IUBMB Life, 60(12): 843-852, 2008

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Section: Introductionmentioning

confidence: 99%

Expression of Concern: Laccase treatment impairs bisphenol A‐induced cancer cell proliferation affecting estrogen receptor α‐dependent rapid signals

et al. 2008

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“…Interestingly, the levels detected in pregnant women were typically higher than those reported for nonpregnant adults; several studies that used analytical chemistry to assess BPA concentrations measured mean concentrations in the blood or serum from pregnant women at > 4 ng/ mL (Lee et al 2008;Padmanabhan et al 2008;Schönfelder et al 2002). However, only two studies collected samples from pregnant and nonpregnant women and directly compared them using identical methods; one reported slightly lower levels in pregnant women (Ikezuki et al 2002), and the other found no differences in these two populations (Kuroda et al 2003). Thus, this is also an important area for future research.…”

Section: Healthymentioning

confidence: 99%

“…Seventeen studies have measured BPA in blood and serum samples from healthy male and nonpregnant female adults (Dirtu et al 2008;Fung et al 2000;He et al 2009;Hiroi et al 2004;Ikezuki et al 2002;Inoue et al 2000Inoue et al , 2001Kaddar et al 2009;Kuroda et al 2003;Liu et al 2007;Sajiki et al 1999;Sugiura-Ogasawara et al 2005;Takeuchi and Tsutsumi 2002;Takeuchi et al 2004;Volkel et al 2005;Yang M et al 2009;Yoshimura et al 2002) (Table 3). Of these studies, five used ELISA, one used a radioimmunoassay (RIA), and the remainder used analytical chemistry to assess BPA concentrations.…”

Section: Internal Dosage Assessment From Blood Measures Of Bpamentioning

confidence: 99%

“…Because of concerns that BPA alters the development of rodents exposed during gestation, several human biomonitoring studies have focused on measuring BPA in serum from pregnant women, and in plasma, serum, and tissue from umbilical cords (Ikezuki et al 2002;Kuroda et al 2003;Lee et al 2008;Padmanabhan et al 2008;Schönfelder et al 2002;Tan and Ali Mohd 2003;Todaka and Mori 2002;Yamada et al 2002) (Tables 4 and 5). Of the eight studies examining these populations, six used analytical chemistry and two used ELISA.…”

Section: Healthymentioning

confidence: 99%

“…Of the four studies that measured unconjugated BPA in umbilical cord blood (Table 4), two detected levels higher in fetal blood than in maternal samples (Ikezuki et al 2002;Kuroda et al 2003), and two detected levels higher in maternal samples than in fetal blood (Lee et al 2008;Schön-felder et al 2002). Interestingly, two of these studies detected concentrations in a range (~ 1 ng/ mL) similar to those measured in healthy adults (Kuroda et al 2003;Lee et al 2008).…”

Section: Healthymentioning

confidence: 99%

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Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A

Vandenberg

Chahoud

Heindel³

et al. 2012

Ciênc. saúde coletiva

333

331

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Estudos de biomonitoração do sistema urinário, circulatório e tecidos indicam grande exposição ao Bisfenol A Resumo Bisfenol A (BPA) é um dos produtos quí-micos mais produzido em todo o mundo, e a exposição humana a ele é considerada onipresente. Assim, há preocupações de que a quantidade de BPA para o qual os seres humanos estão expostos podem causar efeitos adversos à saúde. Nós examinamos muitas possibilidades sobre o porquê estudos de biomonitorização e toxicocinética podem chegar a conclusões aparentemente conflitantes. Mais de 80 estudos publicados de biomonitorização humana que mediram a concentração de BPA em tecidos humanos, urina, sangue e outros fluidos, juntamente com dois estudos de toxicocinéti-ca do metabolismo humano BPA foram examinados. BPA não conjugado foi detectado no sangue (nonanogramas por mililitro gama), e BPA conjugado foi detectado na grande maioria das amostras de urina. Em contraste, estudos de toxico-cinética propuseram que os seres humanos não são internamente expostos ao BPA. Dados disponíveis de estudos de biomonitorização indicam que a população em geral está exposta ao BPA e em risco de exposição interna ao BPA não conjugado. Os dois estudos de toxicocinética, que sugeriram a exposição humana ao BPA é insignificante, têm deficiências significativas e estão diretamente refutados por outros estudos e, portanto não são confiáveis para fins de avaliação de risco. Palavras-chave Disruptor endócrino, Exposição humana, Modelo PBPK/PBTK, Gravidez, Avaliação de risco, Toxicocinética Abstract Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide, and human exposure to BPA is thought to be ubiquitous. Thus, there are concerns that the amount of BPA to which humans are exposed may cause adverse health effects. We examined many possibilities for why biomonitoring and toxicokinetic studies could come to seemingly conflicting conclusions. More than 80 published human biomonitoring studies that measured BPA concentrations in human tissues, urine, blood, and other fluids, along with two toxicokinetic studies of human BPA metabolism were examined. Unconjugated BPA was routinely detected in blood (in the nanograms per milliliter range), and conjugated BPA was routinely detected in the vast majority of urine samples (also in the nanograms per milliliter range). In stark contrast, toxicokinetic studies proposed that humans are not internally exposed to BPA. Available data from biomonitoring studies clearly indicate that the general population is exposed to BPA and is at risk from internal exposure to unconjugated BPA. The two toxicokinetic studies that suggested human BPA exposure is negligible have significant deficiencies, are directly contradicted by hypothesis-driven studies, and are therefore not reliable for risk assessment purposes.

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Mechanisms of Reproductive Toxicity

Keating¹,

Hoyer²

2008

Drug Metabolism Handbook

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Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure

Abstract: These results suggest accumulation of BPA in early fetuses and significant exposure during the prenatal period, which must be considered in evaluating the potential for human exposure to endocrine-disrupting chemicals.

Cited by 800 publications

References 29 publications

Expression of Concern: Laccase treatment impairs bisphenol A‐induced cancer cell proliferation affecting estrogen receptor α‐dependent rapid signals

Expression of Concern: Laccase treatment impairs bisphenol A‐induced cancer cell proliferation affecting estrogen receptor α‐dependent rapid signals

Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A

Mechanisms of Reproductive Toxicity

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