Bulletin de Veille BPA n° 3

Faisant suite aux bulletins précédents en date du Abstract :

This study was conducted to develop a statistical understanding of exposures to bisphenol A (BPA) in aquatic environments in North America and Europe. Concentrations of BPA have been reported by 89 investigations published between 1997 and 2007. On the basis of an analysis of weighted observations (n = 1068 and 848 for North America and Europe, respectively), BPA was reported at concentrations above the detection limit in 20-51% of freshwater samples. Median BPA concentrations for fresh surface waters for North America and Europe were 0.081 and 0.01 microg/L, respectively, while 95th percentiles were 0.47 and 0.35 microg/L, respectively. In contrast to fresh surface waters, only limited data are available for sediments and less for marine ecosystems. For freshwater sediments in North America (n = 71), the median and 90th percentile concentration (the 95th percentile was not calculable) were 0.6 and 3.4 ng/ g-dw, respectively, while the median and 95th percentile concentration in Europe (n = 249) were 16 and 256 ng/g-dw, respectively. To assess the potential ecological significance, we compared exposure concentrations with available regulatory criteria. The results suggest the frequency of locations in which concentrations are likely to cause adverse effects on aquatic ecosystems is low, with the exception of sediments collected from some highly urbanized and industrial locations.cellules humaines à des doses correspondant aux doses d’imprégnation de la population humaine confirment :

- un risque potentiel pour l’issue de la grossesse (via la granulosa, enveloppe protectrice de l’œuf, et le placenta)

- une perte de chance en cas de traitement de tumeurs mammaires par le cisplatine, médicament usuel en chimiothérapie. La question vaut aussi pour les autres utilisations de ce médicament sur d’autres tumeurs.

Effets chez l’animal :

L’étude la plus significatrice est celle menée sur le rat sur plusieurs générations. L’exposition de l’arrière-grand-mère induit une baisse de la fertilité et de la spermatogénèse chez ses fils, petit-fils et arrière-petit-fils. C’est une confirmation de l’effet transgénérationnel.

Cet effet survient à des doses correspondant au 20e et au 40e de la DJA européenne, ce qui montre que celle-ci doit être révisée d’urgence.

Une étude confirme l’induction d’obésité et une autre met en évidence un effet d’asthme peu décrit à ce jour.

Exposition :

Confirmation du passage du BPA dans le biberon, l’effet étant plus marqué selon la température de chauffage.

Confirmation de la pollution de l’eau par le BPA, en présence d’autres perturbateurs endocriniens. Le BPA apparaît moins toxique pour l’écosystème que les alkylphénols.





Effets chez l’homme :

● Effets sanitaires

Joe M. Braun, Kimberly Yolton, Kim N. Dietrich, Richard Hornung, Xiaoyun Ye, Antonia M. Calafat, Bruce P. Lanphear2 Prenatal Bisphenol A Exposure and Early Childhood Behavior doi: 10.1289/ehp.0900979. Online 6 October 2009 ehponline.org

→ Commentaire :

Etude menée auprès de 249 mères et leurs enfants de 2 ans à Cincinnati aux Etats-Unis. Mise en évidence d’un lien entre l’imprégnation maternelle en BPA mesurée à divers stades de la grossesse (16e et 26e semaines ainsi qu’à la naissance) et résultats au test BASC-2, un test psychologique de référence. Le résultat était plus marqué pour la 16e semaine chez les 2 sexes et seulement pour les filles à la 26e semaine.

Ces résultats confirment le lien entre exposition au BPA et troubles du comportement largement documenté à partir de l’expérimentation animale (une trentaine d’études chez le rongeur et le singe à des doses < DJA européenne).

Abstract :

Background: Prenatal exposure Bisphenol A (BPA) increases offspring aggression and diminishes differences in sexually dimorphic behaviors in rodents. Objective: We examined the association between prenatal BPA exposure and behavior in 2-year old children. Methods: We used data from 249 mothers and their children in Cincinnati OH. Maternal urine was collected around 16 and 26 weeks gestation and at birth. BPA concentrations were quantified using high performance liquid chromatography-isotope dilution-tandem mass spectrometry. Child behavior was assessed at 2-years of age using the Behavioral Assessment System for Children-2 (BASC-2). The association between prenatal BPA concentrations and BASC-2 scores was analyzed using linear regression. Results: Median BPA concentrations were 1.8 (16 week), 1.7 (26 week), and 1.3 (birth) ng/ml. Mean externalizing and internalizing scores were 47.6 (standard deviation [SD]:7.8) and 44.8 (SD:7.0), respectively. After adjustment for confounders, log10-transformed mean prenatal BPA concentrations were associated with externalizing scores, but only among females (OR :6.0; 95% confidence interval [CI]:0.1, 12.0). Compared to 26 week and birth concentrations, BPA concentrations collected around 16 weeks were more strongly associated with externalizing scores among all children (OR:2.9; 95% CI: 0.2, 5.7); and this association was stronger in females than males. Among all children, measurements collected < 16 weeks showed a stronger association (OR:5.1; 95% CI:1.5, 8.6) with externalizing scores than measurements taken from 17- 21 weeks (Or:0.6, 95% CI:-2.9, 4.1). Conclusions: These results suggest that prenatal BPA exposure may be associated with externalizing behaviors in two-year old children, especially among female children.


● Effets sur cellules

- Cellules mammaires

Lapensee EW, Lapensee CR, Fox S, Schwemberger S, Afton S, Ben-Jonathan N. Cancer Lett. 2009 Sep 29. [Epub ahead of print] Bisphenol A and estradiol are equipotent in antagonizing cisplatin-induced cytotoxicity in breast cancer cells.

Department of Cancer and Cell Biology, University of Cincinnati, Cincinnati, OH 45267, USA.

→ Commentaire :

Confirmation de l’effet déjà publié début 2009 d’une baisse de l’efficacité du traitement de cellules mammaires humaines par le cisplatine, un médicament utilisé en chimiothérapie en cas de coexposition au BPA à des doses de l’ordre du nanomolaire, soit les doses correspondant à l’imprégnation humaine.

Les malades atteintes d’un cancer du sein étant imprégnées comme les autres femmes, c’est donc une perte de chance en cas de chimiothérapie. Plus largement, le cisplatine étant utilisé dans le traitement d’autres cancers comme les cancers du poumon, les lymphomes, les cancers de l’ovaire, de l’utérus et du testcule, les sarcomes…, la question se pose de l’existence d’une telle action du BPA contre le cisplatine sur les autres systèmes cellulaires.

Abstract :

Resistance to chemotherapy is a major problem facing breast cancer patients. Cisplatin, a highly effective DNA-damaging drug, has shown only little success in breast cancer treatment. We are reporting that low nanomolar doses of bisphenol A (BPA) or estradiol antagonize cisplatin cytotoxicity in breast cancer cells, with their effects not mediated via classical estrogen receptors. Although both compounds increase the expression of Bcl-2, a Bcl-2 inhibitor completely blocked the protective effects of BPA while only partially affecting those of estradiol. Blockade of BPA and E2 actions should sensitize ER-negative breast tumors to anti-cancer drugs and allow for the inclusion of cisplatin in treatment regimens

- Cellules placentaires

Benachour N, Aris A. Toxic effects of low doses of Bisphenol-A on human placental cells. Toxicol Appl Pharmacol. 2009 Sep 18. [Epub ahead of print]

Laboratory of Research in Reproductive and Gestational Health, Quebec, Canada.

→ Commentaire :

De faibles doses de BPA, correspondant au niveau d’imprégnation mesurés dans le sérum de femmes enceintes, induisent une apoptose (mort programmée des cellules) et une nécrose (mort par destruction) des cellules.

Ces résultats suggèrent que l’exposition des cellules du placenta au BPA peut conduire à des effets adverses sur l’issue de la grossesse tels que prééclampsie (hypertension de la femme enceinte liée à un défaut de placentation et une mauvaise vascularisation), restriction de la croissance intra-utérine et avortement.

Abstract :

Humans are exposed daily to a great number of xenobiotics and their metabolites present as pollutants. Bisphenol-A (BPA) is extensively used in a broad range of products including baby bottles, food-storage containers, medical equipment, and consumer electronics. Thus, BPA is the most common monomer for polycarbonates intended for food contact. Levels of this industrial product are found in maternal blood, amniotic fluid, follicular fluid, placental tissue, umbilical cord blood, and maternal urine. In this study, we investigated toxic effects of BPA concentrations close to levels found in serum of pregnant women on human cytotrophoblasts (CTB). These cells were isolated from fresh placentas and exposed to BPA for 24 h. Our results showed that very low doses of BPA induce apoptosis (2 to 3 times) as assessed using M30 antibody immunofluorescent detection, and necrosis (1.3 to 1.7 times) as assessed through the cytosolic Adenylate Kinase (AK) activity after cell membrane damage. We also showed that BPA increased significantly the tumor-necrosis factor alpha (TNF-alpha) gene expression and protein excretion as measured by real-time RT-PCR and ELISA luminescent test, respectively. Moreover, we observed that induction of AK activation and TNF-alpha gene expression require lower levels of BPA than apoptosis or TNF-alpha protein excretion. Our findings suggest that exposure of placental cells to low doses of BPA may cause detrimental effects, leading in vivo to adverse pregnancy outcomes such as preeclampsia, intrauterine growth restriction, prematurity and pregnancy loss.

- Cellules de la granulosa

Jakub Kwintkiewicz, Yoshihiro Nishi, Toshihiko Yanase, and Linda C. Giudice. Peroxisome Proliferator-Activated Receptor γ Mediates the Endocrine Disrupter Bisphenol A. Inhibition of FSH-stimulated IGF-I, Aromatase and Estradiol in Human Granulosa Cells doi: 10.1289/ehp.0901161 Online 22 October 2009

→ Commentaire :

La granulosa est une couche de cellules folliculaires entourant l’œuf responsable de la sécrétion de la progestérone au cours du cycle ovarien.

Le BPA perturbe le fonctionnement hormonal des cellules de la granulosa humaine.

Abstract :

Background: Bisphenol A (BPA), a chemical used as a plasticizer, is a potent endocrine disruptor that, even in low concentrations, disturbs normal development and functions of reproductive organs in different species. Objectives: To determine if bisphenol A affects human ovarian granulosa cell function. Methods: The granulosa cell line, KGN, and granulosa from subjects undergoing in vitro fertilization (IVF) were treated with FSH, BPA, or BPA+FSH in a dose- and time dependent manner. Expression of IGF-I, aromatase, and transcription factors known to mediate aromatase induction by FSH, including SF-1, GATA-4, CREB-1, and peroxisome proliferator-activated receptor α(PPAR α were evaluated, awell as estradiol (E2) secretion. KGN cells were transfected with a PPARα−containing vector, followed by assessment of aromatase and IGF-I expression. Results: BPA reduced FSH-induced IGF-I and aromatase expression and E2secretion, in a dose dependent fashion. Similar effects on aromatase were observed in IVF granulosa. SF-1 and GATA-4, but not CREB-1, were reduced after BPA treatment, although PPARα, an inhibitor of aromatase, was significantly up-regulated by BPA in a dose-dependent manner, with simultaneous decrease of aromatase. Over-expression of PPARα in KGN cells reduced FSH-stimulated aromatase and IGF-I mRNAs, with increasing concentrations of the transfected expression vector, mimicking BPA actions. Also, BPA reduced granulose DNA synthesis without changing DNA fragmentation, suggesting that BPA does not induce apoptosis. Conclusions: Overall, the data demonstrate that BPA induces PPAR α, which mediates down-regulation of FSH-stimulated IGF-I, SF-1, GATA4, aromatase, and E2 in human granulosa cells. These observations support a potential role of altered steroidogenesis and proliferation within the ovarian follicular compartment due to this endocrine disruptor.


Effets chez l’animal :

● Reproduction

Salian S, Doshi T, Vanage G. Perinatal exposure of rats to Bisphenol A affects the fertility of male offspring. Life Sci. 2009 Oct 15.

National Center for Preclinical Reproductive and Genetic Toxicology, National Institute for Research in Reproductive Health (ICMR), J M Street, Parel, Mumbai, Maharashtra, 400 012, India.

→ Commentaire :

Observation d’une baisse de la fertilité, de la qualité du sperme (nombre et mobilité) et d’une perturbation des hormones sexuelles dans la descendance mâle de rates exposées pendant la gestation aux doses de 1,2 et 2,4 µg/kg, soit des doses correspondant au 20e et au 40e de la DJA européenne.

C’est une confirmation de l’effet transgénérationnel du BPA. L’exposition des arrière-grand-mères a un impact sur la fertilité et la spermatogénèse de leurs arrière-petit-fils.

Abstract :

AIM: The exposure to endocrine disruptor (ED) induces functional and behavioral abnormalities associated with reproduction. Humans are ubiquitously exposed to Bisphenol A (BPA), an ED, as it leaches from polycarbonate plastics into their contents. The aim of the present study was to determine the effect of perinatal exposure of male rats to BPA on fertility parameters and perturbations in the expression of testicular steroid receptors (SRs) in adult F(1) offspring. These effects were studied in adult males of the F(2) and F(3) generations to determine the vertical transmission of BPA exposure. MAIN METHOD: Pregnant female rats (F(0)) were gavaged with either BPA (1.2 and 2.4 mug/kg bw), a vehicle control or positive control with Diethylstilbestrol (10 mug/kg bw) during the perinatal period. Adult F(1) males were subjected to fertility assessment by mating with unexposed females. The reproductive functions of the subsequent F(2) and F(3) litters were investigated in a similar manner. Immunohistochemical localization of SRs was carried out in the testes of F(1), F(2) and F(3) generation adult rats. KEY FINDINGS: A significant increase in post implantation loss and a decrease in litter size and sperm count and motility were observed in the F(1) male offspring. A reduction in the testicular expression profile of SRs was observed. These effects were very prominent in the subsequent F(2) and F(3) generations. SIGNIFICANCE: Perinatal exposure to environmentally relevant doses of BPA affects the male germ line, leading to impairments in the fertility of F(1) male offspring and their subsequent F(2) and F(3) generations.


Salian S, Doshi T, Vanage G. Neonatal exposure of male rats to Bisphenol A impairs fertility and expression of sertoli cell junctional proteins in the testis. Toxicology. 2009 Sep 25. [Epub ahead of print].

National Center for Preclinical Reproductive and Genetic Toxicology, National Institute for Research in Reproductive Health (ICMR), JM Street, Parel, Mumbai 400 012, Maharashtra, India.

→ Commentaire :

Article complémentaire du précédent et publié par la même équipe. L’objectif était de comprendre le mécanisme d’action de la baisse de fertilité sous l’effet du BPA.

Mise en évidence d’un effet via les protéines de jonctions des cellules de Sertoli (les cellules de soutien des spermatozoïdes). La dose utilisée est supérieure à celle utilisée précédemment (2 à 32 fois plus élevée que la DJA européenne).

Abstract :

BACKGROUND: Sertoli cell junctional proteins (SCJP) (viz. adhesion, gap and tight junctions) are important for spermatogenesis and perturbations in expression of these proteins are associated with impairments in process of sperm production. Bisphenol A (BPA) is an endocrine disrupter that has been associated with impaired spermatogenesis. However the mechanistic basis of impaired spermatogenesis is unknown, whether BPA is a Sertoli cell toxicant has not yet been fully investigated. OBJECTIVES: The present study was undertaken to decipher the effects of neonatal exposure of male rats to BPA on fertility and its effect on the testicular expression of SCJP during development. METHODS: Neonatal male rats were s.c. injected with BPA at doses ranging from 0.6 to 10mug/rat (100-1600mug/kg bw of BPA) on post-natal days (PNDs) 1-5, and controls received vehicle. Diethylstilbestrol (DES) was used as a positive control. Male fertility was assessed during adulthood and the lowest dose of BPA that was most effective at impairing fertility was determined. Immunohistochemical localization for Connexin 43 (Cx-43, gap junctional), Zona Occludin-1 (ZO-1, tight junctions) and N-cadherin (adherens junction) was carried out on testicular tissue sections obtained from PNDs 15, 30, 45 and 90 of rats exposed to lowest dose of BPA that impaired fertility. RESULTS: Females mated with male rats that were exposed neonatally to various concentrations of BPA showed a significant increase in post-implantation loss and a decrease in litter size. There were significant changes in sperm count along with hormonal imbalances in the rats exposed neonatally to BPA. The 2.4mug dose (400mug/kg bw) of BPA was determined as the lowest dose that was capable of impairing male fertility. A significant reduction in the expression of Cx-43 (PND 45 and 90) and increases in the expression of N-cadherin (PND 45 and 90) and ZO-1 (PND 90) were observed in the testes of rats exposed neonatally to effective dose of BPA. Interestingly, there was an altered expression pattern of Cx43 amongst the sloughed cells in the testes of the experimental rats as compared to controls. CONCLUSION: Neonatal exposure of BPA to rats impairs their fertility and has the potential to induce perturbations in SCJP. These perturbations may be one of the contributing factors that lead to impairments in spermatogenesis in the exposed animals and can be used as potential biomarkers to study BPA-induced effects on testes.

● Obésité

Emmanuel Somm, Valérie M. Schwitzgebel, Audrey Toulotte, Christopher R. Cederroth, Christophe Combescure, Serge Nef, Michel L. Aubert, and Petra S. Hüppi Perinatal Exposure to Bisphenol A alters Early Adipogenesis in the Rat Environmental Health Perspectives Volume 117, Number 10, October 2009 117:1549-1555 (2009)Faculty of Medicine, University of Geneva, Geneva, Switzerland; Department of Pediatrics, Geneva University Hospitals, Geneva, Switzerland; Department of Genetic Medicine and Development and National Center for Competence in Research—Frontiers in Genetics, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Department of Clinical Epidemiology, Geneva University Hospitals, Geneva, Switzerland

→ Commentaire :

Des rates gestantes ont reçu dans leur eau une dose d’1 mg/L de BPA soit au maximum 70 µg BPA par kg et par jour, soit une dose de l’ordre de la DJA européenne (50 µg/m3). Aucune modification physiologique n’est notée chez les mères ni changement de sex-ratio ou nombre de petits dans les portées. Le poids des petits à la naissance, tant femelles que mâles, exposés au BPA au travers du placenta, est en revanche significativement supérieur au contrôle. Au sevrage, après exposition supplémentaire au BPA via le lait maternel donc, le sexe devient un paramètre décisif : le poids des petites femelles reste supérieur à celui de femelles non exposées par leurs mères, au contraire de celui des mâles, équivalent. D’autres études ont montré que pour des doses significativement supérieures, les femelles ne stockaient pas davantage de graisse alors que les mâles si. La prise de graisse à la croissance des petites femelles exposées de manière périnatale est indépendante de la richesse du régime alimentaire, tandis que les mâles ne stockent de graisse qu’avec un régime alimentaire riche en graisses. Il a également été observé une sur-expression des enzymes et facteur de transcription lipogénique dans le foie. Les résultats sont en accord avec ceux des études in vitro existantes.

Chercher à expliquer ces constats semble particulièrement pertinent à l’heure où l’obésité chez les enfants progresse mondialement et quand les biberons sont susceptibles de contenir du BPA. En outre, le mécanisme de prise de poids suite à exposition périnatale au BPA gagnerait à être analysé en lien avec la fonction thyroïdienne, la régulation thermique et l’homéostasie énergétique. Enfin, on ne peut négliger la poursuite de l’exposition tout au long de la vie.

Abstract :

Background: The causes of the current obesity pandemic have not been fully elucidated. Implication of environmental endocrine disruptors such as bisphenol A (BPA) on adipose tissue development has been poorly investigated. Objectives: The aim of the present study was to evaluate the effects of perinatal exposure to BPA on early adipose storage at weaning. Methods: Pregnant Sprague-Dawley rats had access to drinking water containing 1 mg/L BPA from day 6 of gestation through the end of lactation. Pups were weaned on postnatal day (PND) 21. At that time, we investigated perigonadal adipose tissue of pups (weight, histology, gene expression). For the remaining animals, we recorded body weight and food intake for animals on either standard chow or a high-fat diet. Results: Gestational exposure to BPA did not alter the sex ratio or litter size at birth. On PND1, the weight of male and female BPA-exposed pups was increased. On PND21, body weight was increased only in females, in which parametrial white adipose tissue (pWAT) weight was increased about 3-fold. This excess of pWAT was associated with adipocyte hypertrophy and overexpression of lipogenic genes such as C/EBP-α (CAAT enhancer binding protein alpha), PPAR-γ (peroxisome proliferator-activated receptor gamma) , SREBP-1C (sterol regulatory element binding protein-1C) , LPL (lipoprotein lipase), FAS (fatty acid synthase), and SCD-1 (stearoyl-CoA desaturase 1) . In addition, gene expression of SREBP-1C, FAS, and ACC (acetyl-CoA carboxylase) was also increased in liver from BPA-exposed females at PND21, without a change in circulating lipids and glucose. After weaning, perinatal BPA exposure predisposed to overweight in a sex- and diet-dependent manner. We observed no change in food intake due to perinatal BPA exposure in rats on either standard chow or a high-fat diet. Conclusions: Perinatal exposure to a low dose of BPA increased adipogenesis in females at weaning. Adult body weight may be programmed during early life, leading to changes dependent on the sex and the nutritional status. Although further studies are required to understand the mechanisms of BPA action in early life, these results are particularly important with regard to the increasing prevalence of childhood obesity and the context-dependent action of endocrine disruptors.

● Asthme

Midoro-Horiuti T, Tiwari R, Watson CS, Goldblum RM. 2009. Maternal Bisphenol A Exposure Promotes the Development of Experimental Asthma in Mouse Pups Environ Health Perspect: doi:10.1289/ehp.0901259. [Online 5 October 2009]

Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, Pingtung, Taiwan.

→ Commentaire :

Développement d’asthme chez les jeunes souris nées de mères exposées à 10 µg/kg/j dans l’eau de boisson, soit 1/5 de la DJA européenne. Cet effet a été peu décrit à ce jour.

Abstract :

Background: We recently reported that various environmental estrogens induce mast cell degranulation and enhance IgE-mediated release of allergic mediators in vitro. Objectives: We hypothesized that environmental estrogens would enhance allergic sensitization as well as bronchial inflammation and responsiveness. To test this hypothesis we exposed fetal and neonatal mice to the common environmental estrogen bisphenol A via maternal loading, and assessed the pups’ response to allergic sensitization and bronchial challenge. Methods: Female BALB/c mice received 10 µg/ml bisphenol A in their drinking water from one week prior to impregnation to the end of the study. Infant mice were given a single 5 µg intraperitoneal dose of ovalbumin with aluminum hydroxide on day 4 and 3% ovalbumin by nebulization for 10 min for on day 13, 14 and 15. Forty-eight hours after the last nebulization, serum IgE antibodies to ovalbumin were assessed by enzyme-linked immunosorbent assay and airway inflammation and hyperresponsiveness by enumerating eosinophils in bronchoalveolar lavage fluid and whole body barometric plethysmography and a forced oscillation technique. Results: Infants from bisphenol A-exposed mothers responded to this “suboptimal” sensitization with higher serum IgE anti-ovalbumin concentrations, compared to infants from unexposed mothers (p<0.05). Similarly, eosinophilic inflammation in their airways was significantly greater. Finally, airway responsiveness of the ovalbumin -sensitized infants from bisphenol A –treated mothers was enhanced relative to the infants from mothers that were not exposed (p<0.05). Conclusions: Perinatal exposure to bisphenol A enhances allergic sensitization and bronchial inflammation and responsiveness in a susceptible animal model of asthma.


Exposition :

Becker K, Güen T, Seiwert M, Conrad A, Pick-Fuß H, Müller J, Wittassek M, Schulz C, Kolossa-Gehring M. GerES IV: Phthalate metabolites and bisphenol A in urine of German children. Int J Hyg Environ Health. 2009 Sep 1. [Epub ahead of print]

Federal Environment Agency (UBA), Dessau-Rosslau/Berlin, Germany.

→ Commentaire :

Confirmation de l’imprégnation de la totalité de la population. Le niveau moyen correspond à celui observé aux Etats-Unis. La conclusion de l’article (cette exposition correspond au centième de la dose qui correspond à la norme européenne) n’est pas recevable, puisque la norme européenne repose sur un mode de calcul erroné (non prise en compte des effets sur le nouveau-né). Avec un mode de calcul correspondant aux bonnes pratiques en évaluation des risques, la norme devrait être au minimum 5 000 fois plus basse. Il serait plus pertinent de conclure que le niveau d’imprégnation mesuré chez cette population d’enfants allemands correspond à celui induisant des effets chez l’animal.

Abstract :

Urine samples from GerES IV were analysed for concentrations of the metabolites of DEHP (MEHP, 5OH-MEHP, 5oxo-MEHP, 5cx-MEPP, and 2cx-MMHP), DnBP and DiBP (MnBP and MiBP), BBzP (MBzP), DiNP (7OH-MMeOP, 7oxo-MMeOP and 7cx-MMeHP), and bisphenol A (BPA) to assess the exposure of German children on a representative basis. 600 morning urine samples had been randomly chosen from stored 1800 GerES IV samples originating from 3 to 14 year old children living in Germany. All metabolites could be detected in nearly all urine samples (N=599). Descriptive data analysis leads to mean concentrations of 5-OH-MEHP and 5-oxo-MEHP of 48mug/l and 37mug/l, respectively. The mean concentration of 7OH-MMeOP was 11mug/l. MnBP, MiNP, MBzP showed mean levels of 96mug/l, 94mug/l, and 18mug/l, respectively. The concentrations of the phthalate metabolites decreased with increasing age. Compared to German adults all children showed three to five fold higher urine concentrations than adults analysed in the same decade. For some children the levels of the sum of 5OH-MEHP and 5oxo-MEHP in urine were higher than the German human biomonitoring value (HBM I) of 500mug/l, which indicates that adverse health effects cannot be excluded for these subjects with sufficient certainty. The mean concentration of BPA in urine was 2.7mug/l. A rough calculation of the daily intakes on the basis of the measured concentrations in urine resulted in daily intakes two orders of magnitude lower than the current EFSA reference dose of 50mug/kgbw/d.


De Coensel N, David F, Sandra P. Study on the migration of bisphenol-A from baby bottles by stir bar sorptive extraction-thermal desorption-capillary GC-MS. J Sep Sci. 2009 Oct 7. [Epub ahead of print]

University of Ghent, Gent, Belgium.

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Confirmation de la migration du BPA dans le liquide contenu dans un biberon. Celle-ci est d’autant plus forte que la température de chauffe est élevée.

Abstract :

Migration of bisphenol-A (BPA), the principal monomer of polycarbonate (PC) baby bottles, was investigated using an aqueous migration simulant. BPA was determined in 200 mL water samples using stir bar sorptive extraction (SBSE) after in situ derivatization with acetic acid anhydride followed by thermal desorption (TD)-capillary GC-MS. The concentration of BPA was calculated using the deuterated internal standard d6-BPA. Calibration for BPA was shown to be linear in a concentration range from 1 ng/L to 10 mug/L with a correlation coefficient >0.99. The LOD for BPA (as acetate) was 0.12 ng/L and LOQ 0.40 ng/L (ppt). PC bottles were heated in a water bath and in a microwave oven at four different temperatures (37, 53, 65, and 85 degrees C). The higher the temperature, the more the BPA was released, and after a few heating cycles, the released concentrations became constant. At normal use, i.e. at 37 degrees C, concentrations are ca. 10 ng/L. No significant difference was noted between water bath and microwave heating illustrating that migration of BPA is mainly temperature dependent.


Chen TC, Shue MF, Yeh YL, Hsieh CY, Kuo YT, Kuo CT. Variation, correlation, and toxicity of phenolic endocrine-disrupting compounds in surface water. Environ Sci Health A Tox Hazard Subst Environ Eng. 2009 Oct;44(12):1244-50.

→ Commentaire :

Mise en évidence de différents perturbateurs endocriniens (PE) dans l’eau de surface, dont le BPA. L’impact observé est plus fort dans les échantillons prélevés le jour que dans ceux prélevés la nuit, ce qui suggère une source anthopogénique. Le risque pour les organismes aquatiques (HQ ou quotient de danger) est supérieur à la valeur de référence 1, la valeur pour le BPA étant la moins forte parmi ce groupe de PE.

Abstract :

This study investigated the variation in toxicity of phenolic endocrine-disrupting compounds (EDCs) and determined the correlation between their concentrations. All twenty-four samples acquired from a polluted river contained five phenolic EDCs. The EDC nonylphenol (NP) concentration was found to be the highest (4.26 +/- 2.74 mug/L) in the river water. In addition the concentrations of nonylphenol diethoxylate, (NP(2)EO), octylphenol (OP), nonylphenol monoethoxylate (NP(1)EO), and bisphenol A (BPA) were 1.58 +/- 1.37 mug/L; 2.90 +/- 2.77 mug/L; 2.89 +/- 2.15 mug/L; and 2.25 +/- 0.96 mug/L, respectively. Concentrations of NP, NP(1)EO, and OP were significantly greater in the daytime than in the nighttime samples. Furthermore, concentrations of NP, NP(1)EO, and NP(2)EO showed a strong correlation due to similar parent compounds while BPA and OP did not. NP(1)EO had the highest risk to aquatic organisms (hazard quotient, HQ = 26.3) and BPA the lowest (HQ = 2.24).The accumulative HQ sum (hazard index, HI) was 81.3 within all the samples. The HI was 110.3 in the daytime samples. This was 97% higher than in the nighttime HI (56.3), which suggested daytime anthropogenic discharges were an important source of toxicity to aquatic organisms.


Kuch B, Kern F, Metzger JW, von der Trenck KT. Effect-related monitoring: estrogen-like substances in groundwater.Environ Sci Pollut Res Int. 2009 Sep 4. [Epub ahead of print] Institut für Siedlungswasserbau, Wassergüte- und Abfallwirtschaft, Bandtäle 2, 70569,Stuttgart, Germany.

→ Commentaire :

Cette étude a détecté une activité oestrogénique dans des échantillons d’eau prélevés dans la nappe phréatique, comportant notamment du BPA mais aussi des PCB ou des HAP, principalement à proximité de décharges. Cela montre qu’il faut considérer les perturbateurs endocriniens de façon globale et non pas substance par substance. Elle confirme que l’eau peut être un vecteur important d’exposition de la population.

Abstract :

BACKGROUND, AIM, AND SCOPE: Concentration monitoring as a basis for risk assessment is a valid approach only if there is an unambiguous relation between concentration and effect. In many cases, no such unambiguous relation exists, since various substances can exert the same effect with differing potencies. If some or all of these substances contributing to a biological effect are unknown, effect-related monitoring becomes indispensable. Endocrine-disrupting substances in water bodies, including the groundwater, are a prominent example of such a case. The aim of the investigations described here was to detect hormonally active substances in the groundwater downstream of obsolete landfills by using the E-screen assay and to possibly assign the biological effect to individual chemical compounds by means of instrumental analyses carried out in parallel. MATERIALS AND METHODS: Grab samples of the groundwater were collected downstream from abandoned landfills and prepared by liquid/liquid extraction. The total estrogenic activity in these samples was determined in vitro by applying the E-screen assay. The human breast cancer cells (MCF-7) used in the E-screen proliferate in response to the presence of estrogenically active compounds. Expressed in concentration units of the reference substance 17beta-estradiol (E2), the test system allows the quantification of estrogenicity with a limit of detection (LOD) in the range of 0.1 ng/L. Aliquots of the samples were screened using gas chromatography/mass spectrometry (GC/MS) in order to quantify known estrogenically active substances and to identify unknown compounds. Estrogen-positive samples were extracted at different pH values, split into acidic, neutral, and basic fractions and analyzed by GC/MS, searching for individual components that display estrogenic activity. RESULTS AND DISCUSSION: Estrogenic activity exceeding the LOD and the provisional benchmark of 0.5 ng E2/L was found at three out of seven abandoned waste disposal sites tested. The low concentrations of known xenoestrogens such as bisphenol-A, nonylphenols, or phthalic acid esters determined by GC/MS, however, were not sufficient to explain the detected activity. Neither natural nor synthetic hormones have caused the activity because these chemical structures are readily degradable and cannot persist in abandoned landfills for decades. The highest activity in the E-screen assay was found in the acidic fractions. Hydroxy-polychlorinated biphenyls (PCBs), hydroxylated polycyclic aromatic hydrocarbons (PAHs) and hetero-PAHs, as well as alkylphenols could be identified as further compounds with possible hormonal activity. CONCLUSIONS: Estrogenically active substances may occur in the groundwater below obsolete landfills, especially those that contain PCBs or waste from gasworks. These substances are not part of analytical programs routinely applied to contaminated sites and may therefore escape detection and assessment. Analyses using the E-screen assay and GC/MS in parallel have shown that the total estrogenic activity found in groundwater samples is to be ascribed to a multitude of individual compounds, some of which cannot be quantified due to lack of standard substances or assessed due to lack of a standardized procedure for determination of their estrogenic potency. By comparison with provisional guide values for estradiol (0.5 ng/L) and ethynylestradiol (0.3 ng/L), the damaging potential of the total estrogenic activity in groundwater samples can in fact be assessed, but specific remediation measures are impossible unless the hormonal activity can be attributed to individual chemical substances. RECOMMENDATIONS AND OUTLOOK: On the one hand, further analyses of samples taken from possible pollution sources should be conducted in order to characterize the extent of groundwater pollution with xenoestrogens. On the other hand, the most potent individual compounds should be identified according to their estrogenic potency. To this end, bioassay-directed fractionation and structure elucidation should be carried out with concentrated samples.


Klecka GM, Staples CA, Clark KE, Van der Hoeven N, Thomas DE, Hentges SG. Exposure analysis of bisphenol A in surface water systems in North America and Europe. Environ Sci Technol. 2009 Aug 15;43(16):6145-50.

The Dow Chemical Company, Midland, Michigan 48674, USA. gmklecka@dow.com

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Mise en évidence de BPA dans l’eau de surface (20 à 51% des échantillons), mais aussi dans les sédiments. Les auteurs considèrent que les risques pour l’écosystème sont faibles, au regard des critères de la réglementation, sauf dans les zones industrielles et fortement urbanisées.

Abstract :

This study was conducted to develop a statistical understanding of exposures to bisphenol A (BPA) in aquatic environments in North America and Europe. Concentrations of BPA have been reported by 89 investigations published between 1997 and 2007. On the basis of an analysis of weighted observations (n = 1068 and 848 for North America and Europe, respectively), BPA was reported at concentrations above the detection limit in 20-51% of freshwater samples. Median BPA concentrations for fresh surface waters for North America and Europe were 0.081 and 0.01 microg/L, respectively, while 95th percentiles were 0.47 and 0.35 microg/L, respectively. In contrast to fresh surface waters, only limited data are available for sediments and less for marine ecosystems. For freshwater sediments in North America (n = 71), the median and 90th percentile concentration (the 95th percentile was not calculable) were 0.6 and 3.4 ng/ g-dw, respectively, while the median and 95th percentile concentration in Europe (n = 249) were 16 and 256 ng/g-dw, respectively. To assess the potential ecological significance, we compared exposure concentrations with available regulatory criteria. The results suggest the frequency of locations in which concentrations are likely to cause adverse effects on aquatic ecosystems is low, with the exception of sediments collected from some highly urbanized and industrial locations.