HEALTH EFFECTS OF EXPOSURE TO BPA

Exposure to Bisphenol A (BPA) BPA is found in 93 percent of people sampled.1 Levels were higher in females and children and people with lower household income.2 BPA in babies could be eleven times higher than in adults, due to differences in metabolism and body size.3 BPA crosses the placenta4 and enters the bloodstream of the fetus and is then excreted into amniotic fluid. 5 In one study concentrations found in maternal plasma and placental tissue were within ranges found in animal studies to be toxic to reproductive organs. 6 BPA has also been found in breast milk.7 Health risks of BPA exposure As a hormone disrupting chemical, BPA can alter gene expression8 9 and low dose early life exposure to BPA is associated with numerous health effects. Permanent harm from prenatal exposure at low doses. BPA is linked to significant adverse reproductive and carcinogenic effects.10 Animal studies document low dose effects at exposure levels hundreds of times lower than the level considered safe by the EPA.11 Impacts on the brain and behavior. Prenatal exposure to bisphenol A is linked to altered gender specific behaviors in mice, 12 hyperactivity in mice,13 reduction in maternal behavior in mice,14 and aggression in animals15 and humans.16 One animal study found transgenerational effects on social interaction and neural expression that impacted up to four generations.17 Effects on reproduction. Neonatal exposure of female rodents to BPA was linked to permanent hormonal changes resulting in early puberty,18 adverse effects on egg development,19 and reproductive abnormalities.20 Animal studies also document adverse effects on the male reproductive system21 and links to infertility.22 Links to cancer. BPA stimulates prostate cancer cells,23 increases susceptibility to prostate cancer24 and causes breast tissue changes that resemble early stages of breast cancer.25 26 Chemical obesogen. BPA is an obesogen or fat promoter.27 Perinatal and postnatal exposure to BPA in drinking water was associated with increased mean body weight28 29 and

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total cholesterol in mice.30 Metabolic effects on humans . Higher urinary BPA concentrations were associated with diagnoses of cardiovascular disease and diabetes and with abnormal concentrations of liver enzymes,31 as well as allergic asthma in females.32

Contact: Kathleen Schuler, Institute for Agriculture and Trade Policy, kschuler@iatp.org, 612-870-3468

Calafat AM, Kuklenyik, Reidy J et al. Urinary concentrations of bisphenol A and 4-nonylphenol in a human reference population. Environmental Health Perspectives. 2005;113(4):391-395. 2 Calafat AM, Ye X, Wong L et al. Exposure of the US population to bisphenol A and 4-tertiary-octulphenol: 20032004. Environ Health Perspectives 2008;116(1):39-44. 3 Edginton A, Ritter L. Predicting plasma concentrations of bisphenol A in young children (< two years) following typical feeding schedules using a physiologically-based toxicokenetic model. Environ. Health Perspect. 2009;117(4):645-652. 4 Takahashi ), Oishi S. Disposition of orally administered 2,2-bis(4-hydroxyphenyl)propane (bisphenol A in pregnant rats and the placental transfer to fetuses. Environ Health Perspectives 2000;108:931-935. 5 Ikezuki Y, Tsutsumi O, Takai Y et al. Human biological fluids reveals significant early prenatal exposure. Human Reproduction, 2002;17:2839-41. 6 Schonfelder g, Wittfoht W, Hopp H, et al. Parent bisphenol A accumulation in the human maternal-fetal-placental unit. Environ Health Perspectives 2002;110:A703-A707. 7 Kuruto-Niwa R, Tateoka Y, Usuki Y, Nozawa R. Measurement of bisphenol A concentrations in human colostrum. Chemosphere, 2006;66:116-64. 8 Singh S, Shoei-Lung Li S. Epigenetic effects of environmental chemicals bisphenol A and phthalates. Intern J of Molecular Sciences, 2012;13:10143-53. 9 Muna S, Nahar MS, Liao C, Kannan K, Dolinoy DC. Fetal Liver Bisphenol A Concentrations and Biotransformation Gene Expression Reveal Variable Exposure and Altered Capacity for Metabolism in Humans. Journal of Biochemical and Molecular Toxicology, 2012; Article first published online: 3 DEC 2012 DOI: 10.1002/jbt.21459. 10 R R Newbold, W N Jefferson, E Padilla-Banks. Prenatal Exposure to Bisphenol A at Environmentally-Relevant Doses Adversely Affects the Murine Female Reproductive Tract Later in Life. Environ. Health Perspectives 2009; 117(6):879-85. 11 vom Saal F, Hughes C. An extensive new literature concerning low-dose effects of bisphenol A shows the need for a new risk assessment. Environmental Health Perspectives. 2005;113(8):926-933. 12 Palanza P, Gioisoa L, vom Saal F, Parmiliani S. Effects of developmental exposure to bisphenol, A on brain and behavior in mice. Environ Research,2008;108(20):150-57. 13 Ishido M, Masuo Y, Kunimoto M, Oka S, Morita M. Bisphenol A causes hyperactivity in the rat concomitantly with impairment of tyrosine hydroxylase immunoreactivity. Journal of Neuroscience Research, 2004;76:423-33. 14 Palanza P, Howdesshell KL, Parmigiani S, vom Saal FS. Exposure to a low dose of bisphenol AQ during fetal life or in adulthood alters maternal behavior in mice. Environ Health Perspectives, 2002;110:415-22. 15 Kawai K, Nozaki T, Nishikata H et al. Aggressive behavior and serum testosterone concentration during the maturation process of male mice: the effects of fetal exposure to bisphenol A. Environ Health Perspectives, 2003;111:175-78. 16 Perera F, Vishnevetsky J, Herbstman JB et al. Prenatal bisphenol A exposure and child behavior in an inner-city cohort. Environ Health Perspectives, 2012;120(8):1190-94. 17 Wolstenholme JT, Edwards M, Shetty SR, Gatewood JD et al. Gestational exposure to bisphenol A produces trans generational changes in behaviors and gene expression. Endocrinology 2012; 153(8): 3828-38. 18 M Fernndez, M Bianchi, V Lux-Lantos, C Libertun. Neonatal Exposure to Bisphenol A Alters Reproductive Parameters and Gonadotropin Releasing Hormone Signaling in Female Rats. Environ. Health Perspectives, 2009; 117(5):757-62.

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Susiarjo M, Hassold TJ, Freeman E, Hunt PA. Bisphenol A exposure in utero disrupts early oogenesis in the mouse. PLoS Genetics, 2007;3(1):e5.doi:10.1371/journal.pgen.0030005. 20 Newbold RR, Jefferson WR, Banks EP. Long term effects of neonatal exposure to bisphenol A on the murine female reproductive tract. Reproductive Toxicology, 2007;24:253-58. 21 Gupta C. Reproductive malformation of the male offspring following maternal exposure to estrogenic chemicals. Proceedings of the Society of Experimental Biology and Medicine, 2000;224:61-68. 22 Al-Hiyasat AS, Darmani H, Elbetieha Am. Effects of bisphenol A on adult male mouse fertility. European Journal of Oral Sciences, 2002;110:163-67. 23 Wetherill, YB, Petre C, Monk KR et al. The Xenoestrogen Bisphenol A Induces Inappropriate Androgen Receptor Activation and Mitogenesis in Prostatic Adenocarcinoma Cells. Molecular Cancer Therapeutics 2002;1:515524. 24 Prins GS, Tang WY, Belmonte J, Ho Sm. Perinatal exposure to oestradiol and bisphenol A alters the prostate epigenome and increases susceptibility to carcinogenesis. Basic and Clinical Pharmacology and Toxicology, 2008;102(2):134-38. 25 Markey, CM, Luque EH, Munoz de Toro M et al. In Utero Exposure to Bisphenol A Alters the Development and Tissue Organization of the Mouse Mammary Gland. Biology of Reproduction. 2001;65:2151223. 26 Munoz-de-Toro M, Markey C, Wadia PR et al. Perinatal exposure to bisphenol A alters peripubertal mammary gland development in mice. Endocrinology, Endocrinology. 2005;146(9):4138-47. 27 Wang J, Sun B, Hou M, Li X. The environmental obesogen bisphenol A promotes adipogenesis by increasing the amount of 11-Hydroxysteroid dehydrogenase type 1 in the adipose tissue of children. Int J Obes, 2012 Oct 23. Doi:1038/ijo.2012.173. [Epub ahead of print.] 28 Miyawaki J, Sakayama K, Kato H, Yamamoto H, Masuno H. Perinatal and postnatal exposure to bisphenol A increases adipose tissue mass and serum cholesterol level in mice. J Atheroscler Thromb. 2007;14(5):245-52. 29 Rubin BS, Murray MK, Damassa DA, King JC, Soto AM. Perinatal exposure to low doses of bisphenol A affects body weight, patterns of estrous cyclicity, and plasma LH levels. Environ Health Perspect. 2001;109(7):675-80. 30 Miyawki, 2007. 31 IA Lang, TS Galloway, A Scarlett, WE Henley, et al. Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults. JAMA 2008; 300(11): 1303-10. 32 Vaidya SV, Kulkarni H. Association of urinary bisphenol A concentration with allergic asthma: results from the National Health and Nutrition Examination Survey 2005-2006. J Asthma. 2012;49(8):800-6.

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