Ref. Ares(2013)206711 - 18/02/2013
Ref. Ares(2015)1359191 - 27/03/2015
BPA-RELATED RISKS
BPA scientific monitoring since May 2009: An
overall assessment
Key Findings from January to March 2012
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A/ BPA scientific monitoring since May 2009: An overall assessment
Number of studies on humans and animals
Showing effects: 256 (94 %)
On animals: 163 (45 of which are in vivo studies that used a BPA dose < ADI (EFSA))
On humans: 93 (Health effects: 43 ; In vitro effects : 50)
Showing no effect: 15
On animals: 8
On humans: 7
B/ BPA scientific monitoring from January to March 2012: A comprehensive overview
EFFECTS ON HUMANS
Adverse pathophysiological effects:
Associations between higher BPA exposure and incident coronary artery disease CAD during >10 years
of follow-up in UK showed trends similar to previously reported cross-sectional findings in the more
highly exposed NHANES respondents.
Based on the examination of 1 380 subjects from the National Health and Nutritional Examination
Survey 2003-2004, urinary BPA levels are associated with hypertension, independent of traditional
risk factors.
Altered DNA methylation at various CpG sites in women undergoing in vitro fertilization was
associated with exposure to mercury, lead or BPA. Further studies are needed to confirm these
associations.
The presence of unconjugated BPA (uBPA) in 152 cord blood samples suggests placental transfer and
fetal exposure but similar uBPA levels in control and cryptorchid groups make the participation of
fetal exposure to uBPA in the physiopathology of undescended testes unlikely.
Low doses of bisphenol-A induce rapid reduction in the K(ATP) channel activity and insulinotropic
effect in pancreatic β-cells and islets of Langerhans in humans and rodents, with stronger actions in
human islets. The results suggest that BPA behaves as a strong estrogen via nuclear ERβ and indicate
that results obtained with BPA in mouse β-cells (insulin release) may be extrapolated to humans
In vitro effects:
BPA can potentiate leptin action (cell proliferation) in human ovarian cancer cells by creating more
binding sites for leptin and extending the time of leptin-induced Stat3, ERK1/2 and Akt
phosphorylation.
Low doses of bisphenol-A induce rapid reduction in the K(ATP) channel activity and insulinotropic
effect in pancreatic β-cells and islets of Langerhans in humans and rodents, with stronger actions in
human islets. The results suggest that BPA behaves as a strong estrogen via nuclear ERβ and indicate
that results obtained with BPA in mouse β-cells (insulin release) may be extrapolated to humans
EFFECTS ON ANIMALS
2/2
Rats:
A nanomolar dose of bisphenol A (10nM) has rapid effects on the spinogenesis of adult rat
hippocampal neurons.
Developmental exposure of male rats to environmental doses of BPA impacts androgen secretion
which, in turn, is alleviated by an increase in Leydig cell numbers. BPA causes biological effects at
environmentally relevant exposure levels and its presence in consumer products potentially has
implication for public health
Perinatal exposure to low doses of BPA or DES resulted in long-lasting effects in femal rats, including
delayed mammary gland differentiation, altered milk yield and modified milk composition.
Perinatal exposure to BPA affects offspring phenotype and epigenetic regulation across multiple
doses, indicating the need to evaluate dose effects in human clinical and population studies.
Fetal exposure to plastic mixture (bisphenol A and phthalates), dioxin (TCDD) or jet fuel induce
transgenerational negative effects on reproduction. The authors have identified exposure-specific
epigenetic biomarkers that may allow for the assessment of ancestral environmental exposures
associated with adult onset disease.
Mice:
Prenatal exposures to BPA, followed by postnatal allergic sensitization and challenges, promote the
development of experimental allergic asthma in mice.
Environmental estrogen contaminants, such as bisphenol A, can have a detrimental effect on the
developmental lumbar bone growth and mineralization in mice.
ENVIRONMENTAL EXPOSURE
Human impregnation studies:
People with lower incomes have higher body burdens of BPA; the reverse was true for PFCs.
Environmental contamination:
Migration tests performed on 277 baby bottles found that bottles made of PP and silicones showed a
greater number of substances in the migration solutions and in greater quantity. Some substances
found were not included in the Community positive list. Phtalates were also detected in silicone
bottles (DiBP, DBP ans DEHP). The presence of components potentially coming from inks was also
detected (potentially coming from instructions leaflets in the bottles) as well as BPA which was
quantified in baby bottles made of PA, but limited to one brand (although labeled BPA free).
BPA: A GENERAL REVIEW
Review that focuses on the developmental effects of estrogenic endocrine disrupting chemicals
(EDCs), and more specifically on effects of exposure to the estrogenic EDC bisphenol A (BPA)
(obesity, reproductive capacity, fetal growth).
The report of a working group from the National Toxicology Program (NTP) concluded that type 2
diabetes and obesity could be linked to exposures to environmental chemicals.
The available data from biomonitoring studies clearly indicate that the general population is at risk
from internal exposure to unconjugated BPA and that the two toxicokinetic studies which suggested
human BPA exposure is negligible have significant deficiencies and are not reliable for risk
assessment.
BPA-RELATED RISKS
PEER-REVIEWED PAPERS (JANUARY-MARCH 2012)
SOURCE: PubMed
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PAPER ANALYSES
A. EFFECTS ON HUMANS
1. ADVERSE PATHOPHYSIOLOGICAL EFFECTS:
Asthma
Spanier AJ, Kahn RS, Kunselman AR,
Hornung R, Xu Y, Calafat AM, Lanphear BP.
Prenatal Exposure to
Bisphenol A and Child Wheeze from Birth to Three Years. Environ Health Perspect. 2012 Feb 14. [Epub
ahead of print]
Penn State Hershey Medical Center.
http://www.ncbi.nlm.nih.gov/pubmed/22334053
This prospective birth cohort study of 398 mother-infant pairs found that there is an association
between wheeze from six months to three years and log-transformed BPA concentration at 16 weeks
gestation only.
Breast cancer
A TD,
Bl S, J W,
Jm H, Dsm B, E AB, G S, E B, J H, C H. Phenol xenoestrogens and mammographic breast
density. Cancer Epidemiol Biomarkers Prev. 2012 Mar;21(3):561-2. Epub 2012 Feb 15.
http://www.ncbi.nlm.nih.gov/pubmed/22337547
This study suggests that higher serum BPA levels in postmenopausal women ages 55-70 years are
associated with a clinically-relevant 5% greater breast density. Further investigation into the potential
influence of BPA on breast cancer risk using human populations is warranted.
Coronary disease
Melzer D, Osborne NJ, Henley WE, Cipelli R, Young A, Money C, McCormack P, Luben R, Khaw KT, Wareham
NJ, Galloway TS. Urinary bisphenol a concentration and risk of future coronary artery disease in
apparently healthy men and women. Circulation. 2012 Mar 27;125(12):1482-90. Epub 2012 Feb 21.
MB,
Epidemiology and Public Health Group, Peninsula College of Medicine and Dentistry, Barrack Road, Exeter
EX2 5DW, United Kingdom.
http://www.ncbi.nlm.nih.gov/pubmed/22354940
Associations between higher BPA exposure and incident coronary artery disease CAD during >10 years
of follow-up in UK showed trends similar to previously reported cross-sectional findings in the more
highly exposed NHANES respondents.
Hypertension
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Shankar A, Teppala S.
Urinary bisphenol A and hypertension in a multiethnic sample of US adults. J Environ
Public Health. 2012;2012:481641. Epub 2012 Jan 27.
Department of Community Medicine, West Virginia
University School of Medicine, Morgantown, WV 26506-9190, USA.
http://www.ncbi.nlm.nih.gov/pubmed/22363351
Based on the examination of 1 380 subjects from the National Health and Nutritional Examination
Survey 2003-2004, urinary BPA levels are associated with hypertension, independent of traditional risk
factors.
Reproduction
Hanna CW, Bloom MS, Robinson WP, Kim D, Parsons PJ, Vom Saal FS, Taylor JA, Steuerwald AJ, Fujimoto VY. DNA methylation changes in whole blood is associated with exposure to the environmental contaminants,
mercury, lead, cadmium and bisphenol A, in women undergoing ovarian stimulation for IVF. Hum Reprod.
2012 Feb 29. [Epub ahead of print]
Department of Medical Genetics, University of British Columbia,
Vancouver, BC V6T 1Z3, Canada.
http://www.ncbi.nlm.nih.gov/pubmed/22381621
The authors found that altered DNA methylation at various CpG sites in women undergoing in vitro
fertilization was associated with exposure to mercury, lead or BPA. Further studies are needed to
confirm these associations.
Reproduction (cryptorchidism)
Fénichel P, Déchaux H, Harthe C,
Gal J, Ferrari P, Pacini P, Wagner-Mahler K,
Pugeat M, Brucker-Davis F.
Unconjugated bisphenol A cord blood levels in boys with descended or undescended testes. Hum Reprod.
2012 Apr;27(4):983-90. Epub 2012 Jan 20. Department of Reproductive Endocrinology, University Hospital of
Nice,
06602 Nice, France.
http://www.ncbi.nlm.nih.gov/pubmed/22267833
The presence of unconjugated BPA (uBPA) in 152 cord blood samples suggests placental transfer and
fetal exposure but similar uBPA levels in the control and cryptorchid groups make the participation of
fetal exposure to uBPA in the physiopathology of undescended testes unlikely.
Cardiovascular disease
Olsén L, Lind L, Lind PM.
Associations between circulating levels of bisphenol A and phthalate metabolites
and coronary risk in the elderly. Ecotoxicol Environ Saf. 2012 Mar 13. [Epub ahead of print] Department of
Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
http://www.ncbi.nlm.nih.gov/pubmed/22421452
There is a significant association between some phthalate metabolites, but not BPA, and some risk
factors for coronary heart disease in subjects aged 70 years.
2. IN VITRO EFFECTS:
Cancer
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Qin XY, Fukuda T, Yang L, Zaha H, Akanuma H, Zeng Q, Yoshinaga J, Sone H. Effects of bisphenol A exposure
on the proliferation and senescence of normal human mammary epithelial cells. National Institute for
Environmental Studies; Tsukuba, Japan.
Cancer Biol Ther. 2012 Mar 1;13(5). [Epub ahead of print]
http://www.ncbi.nlm.nih.gov/pubmed/22258036
The study suggests that the genetic and epigenetic alterations by BPA might damage human mammary
epithelial cells function and result in complex activities related to cell proliferation and senescence,
playing a role in mammary carcinogenesis.
Lee HR, Hwang KA, Park MA, Yi BR, Jeung EB, Choi KC. Treatment with bisphenol A and methoxychlor
results in the growth of human breast cancer cells and alteration of the expression of cell cycle-related
genes, cyclin D1 and p21, via an estrogen receptor-dependent signaling pathway. Int J Mol Med. 2012
May;29(5):883-90. doi: 10.3892/ijmm.2012.903. Epub 2012 Feb 3.
Laboratory of Veterinary Biochemistry and
Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763,
Republic of Korea.
http://www.ncbi.nlm.nih.gov/pubmed/22307313
This study confirms the carcinogenicity of bisphenol A (BPA) and methoxychlor in vitro.
Ptak A, Gregoraszczuk EL. B
isphenol A induces leptin receptor expression, creating more binding sites for
leptin, and activates the JAK/Stat, MAPK/ERK and PI3K/Akt signalling pathways in human ovarian cancer
cell. Toxicol Lett. 2012 May 5;210(3):332-7. Epub 2012 Feb 10.
Department of Physiology and Toxicology of
Reproduction, Chair of Animal Physiology, Institute of Zoology, Jagiellonian University, Krakow, Poland.
http://www.ncbi.nlm.nih.gov/pubmed/22343039
This study shows that BPA creates more binding sites for leptin (cell proliferation) and extends the
time of leptin-induced Stat3, ERK1/2 and Akt phosphorylation, which may potentiate leptin action in
cancer cells. Confirmation required by in vivo study.
Structural biology
Liu X, Matsushima A, Nakamura M, Costa T, Nose T, Shimohigashi Y. Fine spatial assembly for construction of
the phenol-binding pocket to capture bisphenol A in the human nuclear receptor estrogen-related
receptor γ. J Biochem. 2012 Apr;151(4):403-15. Epub 2012 Jan 31.
Department of Chemistry, Laboratory of
Structure-Function Biochemistry, Faculty and Graduate School of Sciences, Risk Science Research Center,
Kyushu University, Fukuoka 812-8581, Japan, and Laboratorio di Farmacologia, Istituto Superiore di Sanità,
Viale Regina Elena 299, Roma, Italy.
http://www.ncbi.nlm.nih.gov/pubmed/22298789
The authors demonstrated that human estrogen-related receptor γ (ERRγ) residues are essential
structural elements for the strong binding of BPA to ERRγ.
Hormone metabolism
Watanabe M, Ohno S, Nakajin S.
Effects of bisphenol A on the expression of cytochrome P450 aromatase
(CYP19) in human fetal osteoblastic and granulosa cell-like cell lines. Toxicol Lett. 2012 Apr 5;210(1):95-9.
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Epub 2012 Feb 4.
Department of Biochemistry, Hoshi University School of Pharmacy and Pharmaceutical
Sciences, Japan.
http://www.ncbi.nlm.nih.gov/pubmed/22327052
Bisphenol A (BPA) suppresses aromatase (CYP19) activity in a dose-dependent fashion in human
osteoblastic (SV-HFO) and ovarian granulosa-like (KGN) cell lines.
Genotoxicity
Blasiak J, Synowiec E, Tarnawska J, Czarny P, Poplawski T, Reiter RJ.
Dental methacrylates may exert
genotoxic effects via the oxidative induction of DNA double strand breaks and the inhibition of their
repair. Mol Biol Rep. 2012 Feb 12. [Epub ahead of print]
Department of Molecular Genetics, University of
Lodz, Pomorska 141/143, 90-236, Lodz, Poland
http://www.ncbi.nlm.nih.gov/pubmed/22327778
Dental adhesive consisting of 45% 2-hydroxyethyl methacrylate (HEMA) and 55% bisphenol A-diglycidyl
dimethacrylate (Bis-GMA) induces DNA double strand breaks in cultured primary human gingival
fibroblasts through oxidative mechanisms. Vitamin C or melatonin may reduce the detrimental effects
induced by methacrylates applied in dentistry.
Metabolic disorders
Soriano S, Alonso-Magdalena P, García-Arévalo M, Novials A, Muhammed SJ, Salehi A, Gustafsson JA, Quesada
I, Nadal A.
Rapid insulinotropic action of low doses of bisphenol-A on mouse and human islets of
Langerhans: role of estrogen receptor β.PLoS One. 2012;7(2):e31109. Epub 2012 Feb 8.
Instituto
Bioingeniería and CIBER de Diabetes y Enfermedades Metabólicas Asociadas, Universidad Miguel Hernández de
Elche, Elche, Alicante, Spain.
http://www.ncbi.nlm.nih.gov/pubmed/22347437
Low doses of bisphenol-A induce rapid reduction in the K(ATP) channel activity and insulinotropic
effect in pancreatic β-cells and islets of Langerhans in humans and rodents, with stronger actions in
human islets. The results suggest that BPA behaves as a strong estrogen via nuclear ERβ and indicate
that results obtained with BPA in mouse β-cells (insulin release) may be extrapolated to humans.
Effects on genes
Hwang KA, Hyun SH, Jeung EB, Choi KC. B
isphenol a and 17-Beta-oestradiol resulted in the gene alterations
in oestrogen-receptor positive bg-1 ovarian cancer cells. Reprod Fertil Dev. 2011 Dec;24(1):188.
Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National
University, Cheongju, Chungbuk 361-763 Republic of Korea.
http://www.ncbi.nlm.nih.gov/pubmed/22394875
The results indicate that BPA may have an oestrogenic effect by regulating E2-responsive genes in ER-
positive BG-1 ovarian cancer cells and that BG-1 cells would be the best in vitro model to detect these
oestrogenic endocrine disrupting chemicals.
Gene expression
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Sui Y, Ai N, Park SH, Rios-Pilier J, Perkins JT, Welsh WJ, Zhou C.
Bisphenol a and its analogues activate
human pregnane x receptor. Environ Health Perspect. 2012 Mar;120(3):399-405. Epub 2012 Jan 3.
Graduate
Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky, USA.
http://www.ncbi.nlm.nih.gov/pubmed/22214767
BPA and several of its analogues are potent agonists for human PXR (hPXR) but do not affect mouse
PXR activity. Activation of PXR by BPA may explain some of the adverse effects of BPA in humans.
B. EFFECTS ON ANIMALS
a) RATS:
Cancer: signalisation
Watson CS, Jeng YJ, Hu G, Wozniak A, Bulayeva N, Guptarak J.
Estrogen- and xenoestrogen-induced ERK
signaling in pituitary tumor cells involves estrogen receptor-α interactions with G protein-αi and caveolin
I. Steroids. 2012 Apr;77(5):424-32. Epub 2011 Dec 30.
Dept. of Biochemistry & Molecular Biology, Univ. of
Texas Medical Branch, Galveston, TX 77555-0645, USA.
http://www.ncbi.nlm.nih.gov/pubmed/22230296
This study shows that Xenoestrogens, like physiologic estrogens, can evoke downstream kinase
disruptive actions.
Genotoxicity
Tiwari D, Kamble J, Chilgunde S, Patil P, Maru G, Kawle D, Bhartiya U, Joseph L, Vanage G.
Clastogenic and
mutagenic effects of bisphenol A: An endocrine disruptor. Mutat Res. 2012 Mar 18;743(1-2):83-90. Epub
2012 Jan 9. National Center for Preclinical Reproductive and Genetic Toxicology, National Institute for
Research in Reproductive Health, J.M. Street, Parel, Mumbai 400012, India.
http://www.ncbi.nlm.nih.gov/pubmed/22245107
In this study, adult male and female rats were orally administered with various doses of BPA (2.4μg,
10μg, 5mg and 50mg/kgbw) once a day for six consecutive days. Then, in-vivo and in-vitro assays were
performed to determine genotoxic and mutagenic effects of BPA. The data obtained clearly documents
that BPA is not mutagenic but exhibits genotoxic activity and oxidative stress could be one of the
mechanisms leading to genetic toxicity.
Nervous system
Tanabe N, Yoshino H, Kimoto T, Hojo Y, Ogiue-Ikeda M, Shimohigashi Y, Kawato S.
Nanomolar dose of
bisphenol A rapidly modulates spinogenesis in adult hippocampal neurons. Mol Cell Endocrinol. 2012 Apr
4;351(2):317-25. Epub 2012 Jan 16.
Department of Biophysics and Life Sciences, Graduate School of Arts and
Sciences, The University of Tokyo, Komaba 3-8-1, Meguro, Tokyo 153-8902, Japan.
http://www.ncbi.nlm.nih.gov/pubmed/22281313
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This study demonstrates that a nanomolar dose of bisphenol A (10nM) has rapid effects on the
spinogenesis of adult rat hippocampal neurons.
Hormone disruption mechanism
Quignot N, Arnaud M, Robidel F, Lecomte A, Tournier M, Cren-Olivé C, Barouki R, Lemazurier E.
Characterization of endocrine-disrupting chemicals based on hormonal balance disruption in male and
female adult rats. Reprod Toxicol. 2012 Jan 21. [Epub ahead of print]
Experimental Toxicology Unit, INERIS,
Parc Technologique ALATA, 60550 Verneuil-en-Halatte, France.
http://www.ncbi.nlm.nih.gov/pubmed/22285353
This study shows that atrazine, vinclozolin, methoxychlor, and bisphenol A have different aromatase
regulation profiles between animals with similar estrogen-to-androgen ratios but with different
chemical treatments. The measurement of many endpoints is necessary for good risk assessment.
Reproduction
Nanjappa MK, Simon L, Akingbemi BT. The Industrial Chemical Bisphenol A (BPA) Interferes with
Proliferative Activity and Development of Steroidogenic Capacity in Rat Leydig Cells. Biol Reprod. 2012
Feb 1. [Epub ahead of print]
http://www.ncbi.nlm.nih.gov/pubmed/22302688
Developmental exposure of male rats to environmental doses of BPA impacts androgen secretion
which, in turn, is alleviated by an increase in Leydig cell numbers. BPA causes biological effects at
environmentally relevant exposure levels and its presence in consumer products potentially has
implication for public health.
Effects on mammary gland
Kass L, Altamirano GA, Bosquiazzo VL, Luque EH, Muñoz-de-Toro M.
Perinatal exposure to xenoestrogens
impairs mammary gland differentiation and modifies milk composition in Wistar rats. Reprod Toxicol. 2012
Feb 13. [Epub ahead of print]
Laboratorio de Endocrinología y Tumores Hormonodependientes, Facultad de
Bioquimica y Ciencias Biologicas, Universidad Nacional del Litoral (UNL), Santa Fe, Argentina.
http://www.ncbi.nlm.nih.gov/pubmed/22349186
This study found that perinatal exposure to low doses of BPA or DES resulted in long-lasting effects in
femal rats, including delayed mammary gland differentiation, altered milk yield and modified milk
composition.
Développement
Jones BA, Watson NV. Perinatal BPA exposure demasculinizes males in measures of affect but has no
effect on water maze learning in adulthood. Horm Behav. 2012 Apr;61(4):605-10. Epub 2012 Feb 17.
http://www.ncbi.nlm.nih.gov/pubmed/22370244
Perinatal BPA exposure interferes with the normal development of affective behaviors in a non-linear,
dose-dependent manner, which corresponds to behavioral demasculinization of adult males.
Transgenerational effects
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Anderson OS, Nahar MS, Faulk C, Jones TR, Liao C, Kannan K, Weinhouse C, Rozek LS, Dolinoy DC. Epigenetic
responses following maternal dietary exposure to physiologically relevant levels of bisphenol A. Environ
Mol Mutagen. 2012 Mar 29. doi: 10.1002/em.21692. [Epub ahead of print]
Department of Environmental
Health Sciences, University of Michigan, Ann Arbor, Michigan.
http://www.ncbi.nlm.nih.gov/pubmed/22467340
Perinatal exposure to BPA affects offspring phenotype and epigenetic regulation across multiple doses,
indicating the need to evaluate dose effects in human clinical and population studies.
Tra
nsgenerational effects (reproduction)
Manikkam M, Guerrero-Bosagna C, Tracey R, Haque MM, Skinner MK.
Transgenerational actions of
environmental compounds on reproductive disease and identification of epigenetic biomarkers of
ancestral exposures. PLoS One. 2012;7(2):e31901. Epub 2012 Feb 28.
Center for Reproductive Biology,
School of Biological Sciences, Washington State University, Pullman, Washington, United States of America.
http://www.ncbi.nlm.nih.gov/pubmed/22389676
Fetal exposure to plastic mixture (bisphenol A and phthalates), dioxin (TCDD) or jet fuel induce
transgenerational negative effects on reproduction. The authors have identified exposure-specific
epigenetic biomarkers that may allow for the assessment of ancestral environmental exposures
associated with adult onset disease.
Modelisation /cocktail effect on human
Christiansen S, Kortenkamp A, Axelstad M, Boberg J, Scholze M, Jacobsen PR, Faust M, Lichtensteiger W,
Schlumpf M, Burdorf A, Hass U. Mixtures of endocrine disrupting contaminants modelled on human high
end exposures: an exploratory study in rats.
Int J Androl. 2012 Feb 28. doi: 10.1111/j.1365-
2605.2011.01242.x. [Epub ahead of print]
National Food Institute, Technical University of Denmark, Division
of Toxicology and Risk Assessment, Søborg, Denmark Institute for the Environment, Brunel University,
Kingston Lane, Uxbridge, Middlesex, UK F+B Environmental Consulting, Bremen, Germany GREEN Tox and
University of Zurich, Zurich, Switzerland Department of Public Health, Erasmus MC, Rotterdam, The
Netherlands.
http://www.ncbi.nlm.nih.gov/pubmed/22372636
This study suggests that women of reproductive age may not be protected sufficiently against the
combined effects of chemicals that affect the hormonal milieu required for normal male sexual
differentiation.
b) MICE :
Cytotoxicity and genotoxicity (in vitro)
Li YC, Kuan YH, Huang FM, Chang YC. The role of DNA damage and caspase activation in cytotoxicity and
genotoxicity of macrophages induced by bisphenol-A-glycidyldimethacrylate. Int Endod J. 2012 Jan 14. doi:
10.1111/j.1365-2591.2011.02001.x. [Epub ahead of print]
Department of Pharmacology, Chung Shan Medical
University Department of Dentistry, Chung Shan Medical University Hospital School of Dentistry, Chung Shan
Medical University, Taichung, Taiwan.
http://www.ncbi.nlm.nih.gov/pubmed/22242562
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BisGMA demonstrated a cytotoxic and genotoxic effects on murine macrophage cell line RAW264.7
which are mediated by DNA damage and caspase activation.
Protective Effects of Ginsenosides
Wang L, Hao J, Hu J, Pu J, Lü Z, Zhao L, Wang Q, Yu Q, Wang Y, Li G.
Protective Effects of Ginsenosides
against Bisphenol A-Induced Cytotoxicity in 15P-1 Sertoli Cells via Extracellular Signal-Regulated Kinase
1/2 Signalling and Antioxidant Mechanisms. Basic Clin Pharmacol Toxicol. 2012 Jan 23. doi: 10.1111/j.1742-
7843.2012.00857.x. [Epub ahead of print]
Institute of Life Sciences, Chongqing Medical University, Chongqing,
China.
http://www.ncbi.nlm.nih.gov/pubmed/22269103
Ginsenosides have protective effects against BPA-induced cell damage.
Mutagenic, genotoxic and reproductive effects
Dobrzyńska MM, Radzikowska J.
Genotoxicity and reproductive toxicity of bisphenol A and X-ray/bisphenol
A combination in male mice. Drug Chem Toxicol. 2012 Jan 21. [Epub ahead of print] Department of Radiation
Protection and Radiobiology, National Institute of Public Health-National Institute of Hygiene , Warsaw ,
Poland.
http://www.ncbi.nlm.nih.gov/pubmed/22263531
Both X-rays and BPA administered alone to male mice decreased sperm count and quality. X-rays
induced DNA strand breaks in spleen cells, whereas BPA induced DNA strand breaks in lymphocytes and
in cells from spleen, kidneys, and lung and in germ cells. Results confirmed the mutagenic ability of
BPA which is genotoxic and reprotoxic.
Diabetes
Batista TM, Alonso-Magdalena P, Vieira E, Amaral ME, Cederroth CR, Nef S, Quesada I, Carneiro EM, Nadal A.
Short-term treatment with bisphenol-a leads to metabolic abnormalities in adult male mice. PLoS One.
2012;7(3):e33814. Epub 2012 Mar 28.
Departamento de Anatomia, Biologia Celular, Fisiologia e Biofísica,
Instituto de Biologia, Universidade Estadual de Campinas, UNICAMP, Campinas, Sao Paulo, Brazil.
http://www.ncbi.nlm.nih.gov/pubmed/22470480
Short-term treatment with low doses of BPA slows down whole body energy metabolism and disrupts
insulin signaling in peripheral tissues in mice. These findings support the notion that BPA can be
considered a risk factor for the development of type 2 diabetes.
Cytotoxicity of dental materials (BisGMA)
Kuan YH, Li YC, Huang FM, Chang YC.
The upregulation of tumour necrosis factor-α and surface antigens
expression on macrophages by bisphenol A-glycidyl-methacrylate.
Int Endod J. 2012 Jan 23. doi:
10.1111/j.1365-2591.2012.02017.x. [Epub ahead of print]
Department of Pharmacology, Chung Shan Medical
University, Taichung Department Dentistry, Chung Shan Medical University Hospital, Taichung School of
Dentistry, Chung Shan Medical University, Taichung, Taiwan.
http://www.ncbi.nlm.nih.gov/pubmed/22268514
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BisGMA is cytotoxic to murine macrophage cell line RAW264.7. When exposed to BisGMA, the ability of
macrophages to induce an appropriate immune response has the potential to upregulate tumour
necrosis factor-α production and expression of surface antigens.
Asthma
Nakajima Y, Goldblum RM, Midoro-Horiuti T.
Fetal exposure to bisphenol A as a risk factor for the
development of childhood asthma: an animal model study. Environ Health. 2012 Feb 21;11:8.
Departments
of Pediatrics and Biochemistry and Molecular Biology, The University of Texas Medical Branch, 301 University
Boulevard, Galveston, TX, 77555-0366, USA. http://www.ncbi.nlm.nih.gov/pubmed/22353195
Prenatal exposures to BPA, followed by postnatal allergic sensitization and challenges, promote the
development of experimental allergic asthma in mice.
Reproduction
Nah WH, Park MJ, Gye MC.
Effects of early prepubertal exposure to bisphenol A on the onset of puberty,
ovarian weights, and estrous cycle in female mice. Clin Exp Reprod Med. 2011 Jun;38(2):75-81. Epub 2011
Jun 30.
Department of Life Sciences and Institute for Natural Sciences, Hanyang University, Seoul, Korea.
http://www.ncbi.nlm.nih.gov/pubmed/22384422
Early prepubertal exposure to BPA accelerated the onset of puberty but decreased reproductive
parameters in female mice.
Karavan JR, Pepling ME.
Effects of estrogenic compounds on neonatal oocyte development. Reprod Toxicol.
2012 Mar 3. [Epub ahead of print]
Syracuse University, Syracuse, NY, United States.
http://www.ncbi.nlm.nih.gov/pubmed/22406039
Exposure of neonatal mice to synthetic estrogens, diethylstilbestrol, ethinyl estradiol and bisphenol A
altered cyst breakdown, oocyte survival and follicle development.
Effects on the musculoskeletal system
Al Rowas S, Haddad R, Gawri R, Al Ma'awi A, Chalifour L, Antoniou J, Mwale F. Effect of in utero exposure to
diethystilbesterol on lumbar and femoral bone, articular cartilage and the intervertebral disc in male and
female adult mice progeny with and without swimming exercise. Arthritis Res Ther. 2012 Jan 23;14(1):R17.
[Epub ahead of print]
http://www.ncbi.nlm.nih.gov/pubmed/22269139
This study suggests that environmental estrogen contaminants can have a detrimental effect on the
developmental lumbar bone growth and mineralization in mice. Further studies measuring the impact
of environmental estrogen mimics, such as bisphenol A, are then warranted.
Nervous system
Komada M, Asai Y, Morii M, Matsuki M, Sato M, Nagao T.
Maternal bisphenol A oral dosing relates to the
acceleration of neurogenesis in the developing neocortex of mouse fetuses.
Toxicology. 2012 May
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16;295(1-3):31-8. Epub 2012 Mar 7.
Division of Cell Biology and Neuroscience, Department of Morphological
and Physiological Sciences, Faculty of Medical Sciences, University of Fukui, Eiheiji-cho, Fukui 910-0337,
Japan; Research and Education Program for Life Science, University of Fukui, Fukui, Fukui 910-8507, Japan.
Maternal oral exposure to BPA related to the disruption of the cell cycle in fetal intermediate
progenitor cells (IPCs) and the effects of neurogenesis in the developing neocortex.
Uterine infection
Kendziorski JA, Kendig EL, Gear RB, Belcher SM. Strain specific induction of pyometra and differences in
immune responsiveness in mice exposed to 17α-ethinyl estradiol or the endocrine disrupting chemical
bisphenol A. Reprod Toxicol. 2012 Mar 10. [Epub ahead of print]
Department of Pharmacology and Cell
Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0575, United States.
http://www.ncbi.nlm.nih.gov/pubmed/22429997
Exposure to low doses of 17α-éthinyl oestradiol (EE) or BPA induces pyometra (uterine infection) in
C57BL/6 mice but not in CD1 mice.
Calcic absorption
Otsuka H, Sugimoto M, Ikeda S, Kume S.
Effects of bisphenol A administration to pregnant mice on serum
Ca and intestinal Ca absorption. Anim Sci J. 2012 Mar;83(3):232-7. doi: 10.1111/j.1740-0929.2011.00947.x.
Epub 2011 Sep 12.
Graduate School of Agriculture, Kyoto University, Sakyo, Kyoto, Japan.
http://www.ncbi.nlm.nih.gov/pubmed/22435627
This study shows that BPA administration at 20mg/kg body weight/day during pregnancy decreases
serum calcium (Ca) in pre-delivery mice, which may be partly due to decreased paracellular Ca
absorption.
C) MONKEY
Effects on thyroid hormone (In vitro)
Sheng ZG, Tang Y,
Liu YX, Yuan Y, Zhao BQ,
Chao XJ, Zhu BZ.
Low concentrations of bisphenol a suppress
thyroid hormone receptor transcription through a nongenomic mechanism. Toxicol Appl Pharmacol. 2012
Feb 15;259(1):133-42. Epub 2011 Dec 28.
State Key Laboratory of Environmental Chemistry and
Ecotoxicology, Research Center for Eco-Environmental Science, Chinese Academy of Sciences, 18 Shuangqing
Road, Beijing 100085, PR China.
http://www.ncbi.nlm.nih.gov/pubmed/22227104
The results of this study indicate that low concentrations of BPA suppress the thyroid hormone
receptor (TR) transcription by disrupting physiologic concentrations of T3/T4-mediated β3 integrin/c-
Src/MAPK/TR-β1 pathways, followed by recruiting N-CoR/SMRT to TR-β1, providing a novel insight
regarding the TH disruption effects of low concentration BPA.
d) FOWL
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Feminization
Oshima A, Yamashita R, Nakamura K, Wada M, Shibuya K.
In ovo exposure to nonylphenol and bisphenol A
resulted in dose-independent feminization of male gonads in Japanese quail (Coturnix japonica) embryos.
Environ Toxicol Chem. 2012 Mar 2. doi: 10.1002/etc.1787. [Epub ahead of print] Nippon Institute for Biological
Science, Ome, Tokyo, Japan.
http://www.ncbi.nlm.nih.gov/pubmed/22447559
Injection of BPA or nonylphenol into the eggs of Japanese quail just before incubation revealed that
both substances have a dose-independent potential of ovotestis induction (feminization of the male
gonad) in the Japanese quail embryo.
E) FISH AND AMPHIBIANS
Thyroid metabolism
Pelayo S, Oliveira E, Thienpont B, Babin PJ, Raldúa D, André M, Piña B.
Triiodothyronine-induced changes in
the zebrafish transcriptome during the eleutheroembryonic stage: Implications for bisphenol A
developmental toxicity.
Aquat Toxicol. 2012 Apr;110-111:114-22. Epub 2011 Dec 31.
Institute of
Environmental Assessment and Water Research (IDAEA-CSIC), Jordi Girona, 18, 08034 Barcelona, Spain. http://www.ncbi.nlm.nih.gov/pubmed/22281776
The results suggest that BPA disrupts thyroid function by potentiating the effect of endogenous T3 in
early development.
Ecotoxicology
Chow WS, Chan WK, Chan KM. Toxicity assessment and vitellogenin expression in zebrafish (Danio rerio)
embryos and larvae acutely exposed to bisphenol A, endosulfan, heptachlor, methoxychlor and
tetrabromobisphenol A. J Appl Toxicol. 2012 Feb 21. doi: 10.1002/jat.2723. [Epub ahead of print]
Biochemistry Program, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Sha
Tin, N.T., Hong Kong, SAR, China.
http://www.ncbi.nlm.nih.gov/pubmed/22351617
The use of vitellogenin mRNA induction in zebrafish embryos and larvae was found to be a sensitive
biomarker of exposure to organochlorine pesticides tetrabromobisphenol A (flame retardant), and its
precursor compound bisphenol A.
a) INSECTS / WATER SNAILS
Ecotoxiclogy
Martínez-Guitarte JL, Planelló R, Morcillo G.
Overexpression of long non-coding RNAs following exposure to
xenobiotics in the aquatic midge Chironomus riparius. Aquat Toxicol. 2012 Apr;110-111:84-90. Epub 2012
Jan 5.
Grupo de Biología y Toxicología Ambiental, Facultad de Ciencias, Universidad Nacional de Educación a
Distancia, UNED, Senda del Rey 9, 28040 Madrid, Spain.
http://www.ncbi.nlm.nih.gov/pubmed/22277249
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This study shows that Bisphenol A has the ability to activate non-coding sequences mainly located at
telomeres and centromeres. It provides evidence that xenobiotics can induce specific responses in
ncRNAs derived from repetitive sequences that could be relevant in the toxic response.
Ecotoxicology
Sánchez-Argüello P, Aparicio N, Fernández C. Linking embryo toxicity with genotoxic responses in the
freshwater snail Physa acuta: Single exposure to benzo(a)pyrene, fluoxetine, bisphenol A, vinclozolin and
exposure to binary mixtures with benzo(a)pyrene. Ecotoxicol Environ Saf. 2012 Mar 12. [Epub ahead of
print]
Laboratory for Ecotoxicology, Department of the Environment, INIA, Crta, A Coruña km 7, 28040
Madrid, Spain.
http://www.ncbi.nlm.nih.gov/pubmed/22417675
The authors developed assays on the freshwater snail Physa acuta to address correlations between
embryo toxicity and genotoxicity following waterborne pollutant exposure. The results found that
benzo(a)pyrene, fluoxetine and BPA are toxic to embryos. The authors conclude that the embryo
toxicity test is a starting point for the development of a life cycle test with freshwater snails even for
undertaking multigeneration studies.
C. ENVIRONMENTAL EXPOSURE
HUMAN IMPREGNATION STUDIES:
Impregnation during pregnancy
Braun JM, Smith KW, Williams PL
, Calafat AM, Berry K, Ehrlich S, Hauser R.
Variability of Urinary Phthalate
Metabolite and Bisphenol A Concentrations before and during Pregnancy. Environ Health Perspect. 2012
Jan 19. [Epub ahead of print] Harvard University.
http://www.ncbi.nlm.nih.gov/pubmed/22262702
The study found that urinary phthalate metabolites and BPA concentrations were variable before and
during pregnancy, but the magnitude of variability was biomarker specific. A single spot-urine sample
adequately classified MBP and MEP concentrations during pregnancy. The present results should be
replicated in other pregnancy cohorts.
Impregnation and social disparities
Nelson JW, Scammell MK, Hatch EE, Webster TF.
Social disparities in exposures to bisphenol A and
polyfluoroalkyl chemicals: a cross-sectional study within NHANES 2003-2006. Environ Health. 2012 Mar
6;11:10.
Boston University School of Public Health, Department of Environmental Health, 715 Albany Street,
T4W, Boston, Massachusetts 02118, USA. http://www.ncbi.nlm.nih.gov/pubmed/22394520
People with lower incomes had higher body burdens of BPA; the reverse was true for PFCs. For both
BPA and PFCs there was smaller and less consistent associations with education and occupation.
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Maternal and fetal impregnation / ethnicity
Unal ER, Lynn T, Neidich J, Salazar D, Goetzl L, Baatz JE, Hulsey TC, Van Dolah R, Guillette LJ Jr, Newman R. Racial disparity in maternal and fetal-cord bisphenol A concentrations.
J Perinatol. 2012 Mar 8. doi:
10.1038/jp.2012.12. [Epub ahead of print]
Department of Obstetrics and Gynecology, Division of Maternal-
Fetal Medicine, Medical University of South Carolina, Charleston, SC, USA.
http://www.ncbi.nlm.nih.gov/pubmed/22402483
The authors found significant racial/ethnic differences in maternal/fetal BPA concentrations. African-
Americans had the highest maternal serum concentrations; Hispanics had higher fetal concentrations
than non-Hispanics.
Swedish population
Gyllenhammar I, Glynn A, Darnerud PO, Lignell S, van Delft R, Aune M. 4-Nonylphenol and bisphenol A in
Swedish food and exposure in Swedish nursing women. Environ Int. 2012 Mar 29;43C:21-28. [Epub ahead of
print]
National Food Agency, P.O. Box 622, 751 26 Uppsala, Sweden.
http://www.ncbi.nlm.nih.gov/pubmed/22466019
This study found that food is a source of BPA and 4-Nonylphenol (NP) in the general Swedish population
and that there is a continuous source of exposure to those pollutants that is high enough for free NP
and BPA to be detected in some consumers.
Dental composite fillings
Chung SY, Kwon H, Choi YH, Karmaus W, Merchant AT, Song KB, Sakong J, Ha M, Hong YC, Kang D. Dental
composite fillings and bisphenol A among children: a survey in South Korea. Int Dent J. 2012 Apr;62(2):65-
69. doi: 10.1111/j.1875-595X.2011.00089.x.
Department of Preventive Dentistry, School of Dentistry,
Kyungpook National University, Daegu, South Korea Department of Preventive Medicine, College of Medicine,
Dankook University, Choongnam, South Korea Department of Epidemiology and Biostatistics, Arnold School of
Public Health, University of South Carolina, Columbia, SC, USA
http://www.ncbi.nlm.nih.gov/pubmed/22420473
This study, conducted on a total of 495 children aged 8-9 years, found that having many dental
composite filling surfaces on teeth may increase the urinary BPA concentration in children.
Bioaccumulation
Geens T, Neels H, Covaci A.
Distribution of bisphenol-A, triclosan and n-nonylphenol in human adipose
tissue, liver and brain. Chemosphere. 2012 May;87(7):796-802. Epub 2012 Jan 24.
Toxicological Centre,
Department of Pharmaceutical Sciences, University of Antwerp, Belgium.
http://www.ncbi.nlm.nih.gov/pubmed/22277880
BPA could be detected in almost all adipose tissue, liver and brain samples from 11 individuals. Its
potential for bioaccumulation is low though. The reported concentrations of free BPA in the various
tissues are in slight disagreement with pharmacokinetic models in humans and rats.
ENVIRONMENTAL CONTAMINATION
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Baby bottles
Simoneau C, Van den Eede L, Valzacchi S.
Identification and quantification of the migration of chemicals
from plastic baby bottles used as substitutes for polycarbonate. Food Addit Contam Part A Chem Anal
Control Expo Risk Assess. 2012;29(3):469-80. doi: 10.1080/19440049.2011.644588. Epub 2012 Jan 18.
European Commission, Joint Research Centre, Institute for Health and Consumer Protection, Unit Chemical
Assessment and Testing, Italy.
http://www.ncbi.nlm.nih.gov/pubmed/22257226
Migration tests performed on 277 baby bottles found that bottles made of PP and silicones showed a
greater number of substances in the migration solutions and in greater quantity (alkanes and benzene
derivatives). Some substances found were not included in the Community positive list. Phtalates were
also detected in silicone bottles (DiBP, DBP ans DEHP). The presence of components potentially coming
from inks was also detected (potentially coming from instructions leaflets in the bottles) as well as
BPA which was quantified in baby bottles made of PA, but limited to one brand (although labeled BPA
free) .
Food
Gyllenhammar I, Glynn A, Darnerud PO, Lignell S, van Delft R, Aune M. 4-Nonylphenol and bisphenol A in
Swedish food and exposure in Swedish nursing women. Environ Int. 2012 Mar 29;43C:21-28. [Epub ahead of
print]
National Food Agency, P.O. Box 622, 751 26 Uppsala, Sweden.
http://www.ncbi.nlm.nih.gov/pubmed/22466019
This study found that food is a source of BPA and 4-Nonylphenol (NP) in the general Swedish population
and that there is a continuous source of exposure to those pollutants that is high enough for free NP
and BPA to be detected in some consumers.
Dentistery
Michelsen VB, Kopperud HB, Lygre GB, Björkman L, Jensen E, Kleven IS, Svahn J, Lygre H.
Detection and
quantification of monomers in unstimulated whole saliva after treatment with resin-based composite
fillings in vivo. Eur J Oral Sci. 2012 Feb;120(1):89-95. doi: 10.1111/j.1600-0722.2011.00897.x. Epub 2012 Jan
25.
Department of Clinical Dentistry, University of Tromsø, Tromsø, Norway.
http://www.ncbi.nlm.nih.gov/pubmed/22288926
Monomers from resin-based composite materials used in dentistry such as bisphenol-A diglycidyl
methacrylate (Bis-GMA) are detected in the saliva of patients shortly after restorative therapy. One
week after treatment, no monomers could be detected in patients' saliva samples.
Hsu WY, Wang VS,
Lai CC, Tsai FJ. Simultaneous determination of components released from dental
composite resins in human saliva by liquid chromatography/multiple-stage ion trap mass spectrometry.
Electrophoresis. 2012 Feb;33(4):719-25. doi: 10.1002/elps.201100571.
Department of Medical Research, China
Medical University Hospital, Taichung, Taiwan.
http://www.ncbi.nlm.nih.gov/pubmed/22451066
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This study was able to successfully quantify monomers (TEGDMA, UDMA, et Bis-GMA) and their
principal biodegradation products from dental composite resins in human saliva.
Consumer Products
Dodson RE, Nishioka M, Standley LJ, Perovich LJ, Brody JG, Rudel RA
. Endocrine Disruptors and Asthma-
Associated Chemicals in Consumer Products. Environ Health Perspect. 2012 Mar 8. [Epub ahead of print]
Silent Spring Institute.
http://www.ncbi.nlm.nih.gov/pubmed/22398195
The authors found 55 endocrine disruptors and asthma-related chemicals in a range of cosmetics,
personal care products, cleaners, sunscreens, and vinyl products, many of which were not listed on
labels.
Seawater
Salgueiro-González N, Concha-Graña E, Turnes-Carou I, Muniategui-Lorenzo S, López-Mahía P, Prada-Rodríguez
D.
Determination of alkylphenols and bisphenol A in seawater samples by dispersive liquid-liquid
microextraction and liquid chromatography tandem mass spectrometry for compliance with
environmental quality standards (Directive 2008/105/EC). J Chromatogr A. 2012 Feb 3;1223:1-8. Epub 2011
Dec 9.
Department of Analytical Chemistry, University of A Coruña, Campus da Zapateira, Rúa da Fraga 10,
E-15008 A Coruña, Spain.
http://www.ncbi.nlm.nih.gov/pubmed/22227360
A new sensitive and green analytical chemistry method was used to detect the presence of BPA (0.035
μg L⁻
¹) and nonylphenol (0.14 μg L⁻
¹) in seawater samples from different sites of A Coruña (Northwest
of Spain).
Seawater and outfall
discharges (Spain)
de los Ríos A, Juanes JA, Ortiz-Zarragoitia M, López de Alda M, Barceló D, Cajaraville MP. Assessment of the
effects of a marine urban outfall discharge on caged mussels using chemical and biomarker analysis. Mar
Pollut Bull. 2012 Mar;64(3):563-73. Epub 2012 Jan 31.
Laboratory of Cell Biology and Histology, Science and
Technology Faculty, University of the Basque Country, Sarriena z/g, Leioa, Basque Country, Spain.
http://www.ncbi.nlm.nih.gov/pubmed/22296624
There were no significant differences in contamination levels by EDs between the environmental
mixing zone of the outfall of the Santander sanitation system and control sites except for 4-tert-
octylphenol which was higher in the outfall site.
Source waters (Spain)
Bono-Blay F, Guart A, de la Fuente B, Pedemonte M, Pastor MC, Borrell A, Lacorte S.
Survey of phthalates,
alkylphenols, bisphenol A and herbicides in Spanish source waters intended for bottling. Environ Sci Pollut
Res Int. 2012 Mar 16. [Epub ahead of print]
Department of Environmental Chemistry, IDAEA-CSIC, Jordi
Girona 18-26, 08034, Barcelona, Catalonia, Spain.
http://www.ncbi.nlm.nih.gov/pubmed/22421799
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Bisphenol a, triazine herbicides, alkylphenols, and phthalates were detected in a very low
concentration in a few water sources intended for bottling in Spain. Spring water intended for
consumption remains of good quality.
Sediments (Germany)
Schmitt S, Reifferscheid G, Claus E,
Schlüsener M, Buchinger S. Effect directed analysis and mixture effects
of estrogenic compounds in a sediment of the river Elbe. Environ Sci Pollut Res Int. 2012 Mar 16. [Epub
ahead of print]
Federal Institute of Hydrology, Am Mainzer Tor 1, 56068, Koblenz, Germany.
http://www.ncbi.nlm.nih.gov/pubmed/22421800
A sediment sample from the river Elbe/Germany was found to be contaminated with xenoestrogens:
17β-estradiol, estrone, 4-iso-nonylphenols, bisphenol A, stigmasterol and chlorophene.
Sediments (China)
Li Y, Hu XF, Oh K, Motegi M, Ohtsuka N, Hosono S, Du Y, Jiang Q, Li S, Feng JW. [
Spatial distribution of
three endocrine disrupting chemicals in sediments of the Suzhou Creek and their environmental risks].
Huan Jing Ke Xue. 2012 Jan;33(1):239-46. [Article in Chinese] Department of Environmental Science and
Engineering, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China.
Detection of endocrine disrupting chemicals (nonylphenol (NP), octylphenol (4-t-OP) and bisphenol A
(BPA)), in sediments of the Suzhou Creek (China) and its branches. The accumulation of pollutants
closely related to the intensity of anthropogenic activities.
Surface water and sediment (China)
Wang B, Huang B, Jin W, Wang Y, Zhao S, Li F, Hu P, Pan X.
Seasonal distribution, source investigation and
vertical profile of phenolic endocrine disrupting compounds in Dianchi Lake, China. J Environ Monit. 2012
Apr 1;14(4):1274-81. Epub 2012 Mar 15. Faculty of Environment Science and Engineering, Kunming University
of
Science and Technology, Kunming 650500, China.
http://www.ncbi.nlm.nih.gov/pubmed/22421980
Pollution of Dianchi Lake, China, with phenolic endocrine disrupting compounds including nonylphenol-
di-, nonylphenol-mono-ethoxylate, 4-nonylphenol, bisphenol A, 4-cumylphenol and 4-tert-octylphenol.
This pollution comes mainly from industry, agriculture and daily life.
Wang G, Ma P, Zhang Q, Lewis J, Lacey M, Furukawa Y, O'Reilly SE,
Meaux S, McLachlan J, Zhang S. Endocrine
disrupting chemicals in New Orleans surface waters and Mississippi Sound sediments. J Environ Monit. 2012
Mar 22. [Epub ahead of print]
Department of Chemistry, Xavier University of Louisiana, New
Orleans, LA
70125, U.S.A. xxxxx@xxxx.xxx.
http://www.ncbi.nlm.nih.gov/pubmed/22438038
Sediment from the Gulf of Mexico, New Orleans surface water, and the influent and effluent of a New
Orleans municipal sewage treatment plant are contaminated with EDCs, including organochlorine
pesticides, polychlorinated biphenyls, bisphenol A and steroid hormones.
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Mortazavi S, Riyahi Bakhtiari A, Sari AE, Bahramifar N,
Rahbarizade F. Phenolic endocrine disrupting
chemicals (EDCs) in Anzali Wetland, Iran: Elevated concentrations of 4-nonylphenol, octhylphenol and
bisphenol A. Mar Pollut Bull. 2012 Mar 27. [Epub ahead of print] Environmental Forensic Laboratory,
Department of Env
ironmental Sciences, Faculty of Natural Resource and Marine Science, Tarbiat Modares
University, P.O. Box 46414 356, Noor, Mazandaran, Iran.
http://www.ncbi.nlm.nih.gov/pubmed/22459496
This study found that sediments from Anzali Wetland, Iran, are contaminated with 4-nonylphenol (4-
NP), octylphenol (OP) and bisphenol A (BPA). High levels of alkylphenols and BPA were also found near
urban areas.
Sewage sludge (California)
Yu Y, Wu L.
Analysis of endocrine disrupting compounds, pharmaceuticals and personal care products in
sewage sludge by gas chromatography-mass spectrometry. Talanta. 2012 Jan 30;89:258-63. Epub 2011 Dec
17. Department of Environmental Sciences, University of California, Riverside, CA 92521, USA.
http://www.ncbi.nlm.nih.gov/pubmed/22284489
High concentrations of EDCs (bisphenol A, estrone, nonylphenol and octylphenol) and personal care
products (acetylsalicylic acid, carbamazepine, clofibric acid, diclofenac, gemfibrozil, ibuprofen,
ketoprofen, naproxen, paracetamol and triclosan) were found in sewage sludge, from sewage
treatment plants in southern California.
D. METABOLISM AND BIOMONITORING
Excretion via sweat
Genuis SJ, Beesoon S, Birkholz D, Lobo RA.
Human excretion of bisphenol A: blood, urine, and sweat (BUS)
study. J Environ Public Health. 2012;2012:185731. Epub 2011 Dec 27. Faculty of Medicine, University of
Alberta, Edmonton, Canada.
http://www.ncbi.nlm.nih.gov/pubmed/22253637
The study shows that BPA can be found in human sweat, even in individuals with no BPA detected in
their serum or urine samples. The authors conclude that Biomonitoring of BPA through blood and/or
urine testing may underestimate the total body burden of this potential toxicant and that sweat
analysis should be considered as an additional method for monitoring bioaccumulation of BPA in
humans.
Pharmacokinetics
Doerge DR, Twaddle NC, Vanlandingham M, Fisher JW.
Pharmacokinetics of bisphenol A in serum and
adipose tissue following intravenous administration to adult female CD-1 mice. Toxicol Lett. 2012 Mar 20.
[Epub ahead of print] Division of Biochemical Toxicology, National Center for Toxicological Research, U.S.
Food and Drug Administration, Jefferson, AR 72079, United States.
http://www.ncbi.nlm.nih.gov/pubmed/22465602
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The study of BPA pharmacokinetics in mice shows that less than 0.01% of the administered dose
remains in adipose tissue after 24h. The authors underscore the non-persistent nature of BPA.
US and Canadian population exposure
Lakind JS, Levesque J, Dumas P, Bryan S, Clarke J, Naiman DQ.
Comparing United States and Canadian
population exposures from National Biomonitoring Surveys: Bisphenol A intake as a case study. J Expo Sci
Environ Epidemiol. 2012 Feb 15. doi: 10.1038/jes.2012.1. [Epub ahead of print] 1]
LaKind Associates, LLC,
Catonsville, Maryland, USA [2] Department of Epidemiology and Public Health, University of Maryland School
of Medicine, Baltimore, Maryland, USA [3] Department of Pediatrics, Pennsylvania State University College of
Medicine, Hershey, Pennsylvania, USA.
http://www.ncbi.nlm.nih.gov/pubmed/22333730
This study compares human exposure to BPA in the US and Canada using biomonitoring data from the
American NHANES and Canadian CHMS. After they have examined CHMS and NHANES methodologies,
the authors conclude that BPA intakes for both countries are below health-based guidance values set
by the US, Canada and the European Food Safety Authority.
E. BPA: A GENERAL REVIEW
Autism
de Cock M, Maas YG, van de Bor M.
Does perinatal exposure to endocrine disruptors induce autism
spectrum and attention deficit hyperactivity disorders? Review. Acta Paediatr. 2012 Mar 28. doi:
10.1111/j.1651-2227.2012.02693.x. [Epub ahead of print]
Department of Health and Life Sciences, VU
University, Amsterdam, Netherlands.
http://www.ncbi.nlm.nih.gov/pubmed/22458970
Perinatal exposure to EDCs such as BPA, pesticides, phthalates, PCBs etc. appears to be associated with
the occurrence of autism spectrum (ASD) as well as attention deficit hyperactivity (ADHD) disorders.
Alternative mechanisms
Alonso-Magdalena P, Ropero AB, Soriano S, García-Arévalo M, Ripoll C, Fuentes E, Quesada I, Nadal A.
Bisphenol-A acts as a potent estrogen via non-classical estrogen triggered pathways. Mol Cell Endocrinol.
2011 Dec 31. [Epub ahead of print]
Instituto de Bioingeniería and CIBERDEM, Universidad Miguel Hernández
de Elche, 03202 Elche, Spain.
http://www.ncbi.nlm.nih.gov/pubmed/22227557
This review analyzes with substantiated scientific evidence the strong estrogenic activity of BPA at
very low concentrations when it acts through alternative mechanisms of action at least in certain cell
types.
Brain Development
Itoh K, Yaoi T, Fushiki S. Bisphenol A, an endocrine-disrupting chemical, and brain development.
Neuropathology. 2012 Jan 12. doi: 10.1111/j.1440-1789.2011.01287.x. [Epub ahead of print]
Department of
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19
Pathology & Applied Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of
Medicine, Kyoto, Japan.
http://www.ncbi.nlm.nih.gov/pubmed/22239237
This review focuses on the effects of prenatal and lactational exposure to low doses of BPA on brain
development in mice. Functionally, BPA exposure disturbs murine behavior accompanied with a
disrupted neurotransmitter system, in the postnatal development period and in adult mice. Epigenetic
alterations in promoter-associated CpG islands might underlie some of the effects on brain
development.
Inventory of the situation in Israel
Berman T, Amitai Y, Almog S, Richter ED.
Human biomonitoring in Israel: past, present, future. Int J Hyg
Environ Health. 2012 Feb;215(2):138-41. Epub 2012 Jan 2. P
ublic Health Services, Israel Ministry of Health,
King David Street 20, Jerusalem, Israel. http://www.ncbi.nlm.nih.gov/pubmed/22218107
This article reports on human biomonitoring studies carried out in Israel.
Obesity - diabetes
Vom Saal FS, Nagel SC, Coe BL, Angle BM, Taylor JA.
The estrogenic endocrine disrupting chemical
bisphenol A (BPA) and obesity. Mol Cell Endocrinol. 2012 May 6;354(1-2):74-84. Epub 2012 Jan 10. Division
of Biological
Sciences, University of Missouri - Columbia, Columbia, MO 65211, USA.
http://www.ncbi.nlm.nih.gov/pubmed/22249005
This review focuses on the developmental effects of estrogenic endocrine disrupting chemicals (EDCs),
and more specifically on effects of exposure to the estrogenic EDC bisphenol A (BPA) (obesity,
reproductive capacity, fetal growth).
Thayer KA, Heindel JJ, Bucher JR,
Gallo MA. Role of Environmental Chemicals in Diabetes and Obesity: A
National Toxicology Program Workshop Report. Environ Health Perspect. 2012 Feb 1. [Epub ahead of print]
NIEHS.
http://www.ncbi.nlm.nih.gov/pubmed/22296744
The report of a working group from the National Toxicology Program (NTP) concluded that type 2
diabetes and obesity could be linked to exposures to environmental chemicals.
García-Mayor RV, Larrañaga Vidal A,
Docet Caamaño MF, Lafuente Giménez A. Endocrine disruptors and
obesity: obesogens. Endocrinol Nutr. 2012 Jan 31. [Epub ahead of print]
Unidad de Investigación Compartida
«Obesógenos» Sergas, Servicio de Endocrinología, Diabetes, Nutrición y Metabolismo, Universidad de Vigo,
Vigo, España.
http://www.ncbi.nlm.nih.gov/pubmed/22300604
There is evidence of the obesogenic effect of polluting chemical substances (DES, genistein, bisphenol
A, organotins, and phthalates) in tissues and experimental animals, but few data are available in
humans.
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Human exposure
Vandenberg LN, Chahoud I, Heindel JJ, Padmanabhan V, Paumgartten FJ, Schoenfelder G.
Urinary,
circulating, and tissue biomonitoring studies indicate widespread exposure to bisphenol A. Cien Saude
Colet. 2012 Feb;17(2):407-34. Tufts Center for Regenerative and Developmental Biology, Department of
Biology, Tufts University, Medford, MA 02155, USA.
http://www.ncbi.nlm.nih.gov/pubmed/22267036
This review concludes that available data from biomonitoring studies clearly indicate that the general
population is at risk from internal exposure to unconjugated BPA and that the two toxicokinetic
studies which suggested human BPA exposure is negligible have significant deficiencies and are not
reliable for risk assessment.
Dermal exposure
Weschler CJ, Nazaroff WW.
SVOC exposure indoors: fresh look at dermal pathways. Indoor Air. 2012 Feb 7.
doi: 10.1111/j.1600-0668.2012.00772.x. [Epub ahead of print] Environmental and Occupational Health
Sciences Institute, UMDNJ-Robert Wood Johnson Medical School and Rutgers University, Piscataway, NJ, USA
International Centre for Indoor Environment and Energy, Technical University of Denmark, Lyngby, Denmark
http://www.ncbi.nlm.nih.gov/pubmed/22313149
This paper argues that human exposure to indoor pollutants through the dermal pathway is
underestimated. Health consequences vary with exposure pathway. For example, an SVOC that enters
the blood through the skin does not encounter the same detoxifying enzymes that an ingested SVOC.
Reproduction
Mruk DD, Cheng CY.
Environmental contaminants: Is male reproductive health at risk? Spermatogenesis.
2011 Oct;1(4):283-290. Epub 2011 Oct 1.
The Mary M. Wohlford Laboratory for Male Contraceptive Research;
Center for Biomedical Research; The Population Council; New York, NY USA.
http://www.ncbi.nlm.nih.gov/pubmed/22332111
The authors of this review discuss how environmental toxicants (cadmium, bisphenol A and lead) may
affect reproductive function and how toxicant-induced damage may be effectively managed so that
fertility can be maintained.
Cardiovascular disease
Lind L, Lind PM.
Can persistent organic pollutants and plastic-associated chemicals cause cardiovascular
disease? J Intern Med. 2012 Feb 28. doi: 10.1111/j.1365-2796.2012.02536.x. [Epub ahead of print] From the
Department of Medical Sciences Occupational and Environmental Medicine; Uppsala University, Uppsala,
Sweden.
http://www.ncbi.nlm.nih.gov/pubmed/22372998
This review of the scientific literature reports that there exist associations between plastic-associated
chemicals (BPA, phthalates), persistent organic pollutants, and overt cardiovascular disease.
Cell Signaling
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Marino M, Pellegrini M, La Rosa P, Acconcia F. Susceptibility of estrogen receptor rapid responses to
xenoestrogens: Physiological outcomes. Steroids. 2012 Mar 5. [Epub ahead of print]
Department of Biology,
University Roma TRE, viale G. Marconi, 446, I-00146 Rome, Italy.
http://www.ncbi.nlm.nih.gov/pubmed/22410438
Extra-nuclear ER signals are highly susceptible to different ligands such as BPA that, by unbalancing
E2-induced cell functions, drive cells to different functional endpoints.
F. METHODOLOGY
Reproduction: antigestagenic effects
Fischer L, Deppert WR, Pfeifer D, Stanzel S, Weimer M, Hanjalic-Beck A, Stein A, Straßer M, Zahradnik HP,
Schaefer WR. Potential hazards to embryo implantation: A human endometrial in vitro model to identify
unwanted antigestagenic actions of chemicals. Toxicol Appl Pharmacol. 2012 Mar 6. [Epub ahead of print]
Department of Obstetrics & Gynecology, University Hospital Freiburg, Germany.
http://www.ncbi.nlm.nih.gov/pubmed/22414680
The authors developped a flexible in vitro model based on human endometrial Ishikawa cells to study
quantitatively effects of antiprogestin-like chemicals on endometrial target genes. Assays found, inter
alia, that 4-nonylphenol, bisphenol A and apigenin have antagonistic effects on progesterone.
Potentiel de perturbation endocrinienne
Lee HK, Kim TS, Kim CY, Kang IH, Kim MG, Kyung Jung K, Kim HS, Han SY, Yoon HJ, Rhee GS. Evaluation of in
vitro screening system for estrogenicity: comparison of stably transfected human estrogen receptor-α
transcriptional activation (OECD TG455) assay and estrogen receptor (ER) binding assay. J Toxicol Sci.
2012;37(2):431-7.
Health Effects Analysis Team, National Institute of Food and Drug Safety Evaluation,
Korea.
http://www.ncbi.nlm.nih.gov/pubmed/22467034
According to OECD test guideline 455(TG455), the estrogenic activity of BBP, BPA and NP are weaker
than 17β-estradiol whereas DEHP, DBP and DEP did not show any estrogenicity activity in a STTA assay.
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