Running head: EXPOSURE TO BISPHENOL A Human Exposure to Bisphenol A Jainam Shah Wayne State University Abstract Bisphenol-a (BPA) is an environmental toxin that has recently been at the forefront of health issues. It is believed to mimic the hormone estrogen and cause adverse health affects. Many studies have been conducted in vivo to observe the effects in animals like rodents. These studies reveal that exposure to BPA can lead to early onset of puberty, obesity, decrease in sperm quality, polycystic ovary syndrome, miscarriage and other health effects. Many studies also measure levels of BPA in human tissues and fluids. It is evident that humans are exposed to this chemical, but there are few studies conducted to explain possible health outcomes that may arise from exposure to it. Understanding the effects of BPA is critical because of its effects on human health. In this paper, I will discuss health effects observed in animals, levels of BPA found in human samples and how high levels of BPA during pregnancy is associated with miscarriage/adverse pregnancy outcomes. With this research, I propose that more funding be provided to conduct research on human cells/fluids (in vitro) in order to determine the effects BPA has on human health. Human Exposure to Bisphenol A In today’s society, humans are exposed to a variety of chemicals in the environment. They can be in the air we breathe, in the water we drink, or the foods we eat. Some of these chemicals act as endocrine disruptors which can mimic hormones found in the body and disrupt the endocrine system. This leads to many abnormalities and adverse health effects to those exposed to these chemicals (Lee, Chattopadhyay, Gong, Ahn, Lee, 2003). One such chemical is 2, 2 bis (4-hydroxyphenyl) propane, commonly known as bisphenol-a (BPA). An article written in the Environmental Health Perspectives reports that over 6 billion pounds of BPA is consumed every year (Vom Saal, Claude Hughes, 2005). This chemical is widely produced and is found in baby and water bottles made from polycarbonate plastic, food can liners made from epoxy resins and in dental sealants. Even the water we use to take showers and to drink, along with many other sources, may contain BPA (Vom Saal et al., 2005, Dash, Marcus, Terry, 2006). BPA is a cause for concern since it has been found to leech into the food we eat and drink. The ester bonds that link the molecules in plastics and resins are easily broken by heat, repeated washing of polycarbonates, or in the presence of acid/bases making it easier for the chemical to leech into our system (Vom Saal et al., 2005). With this high exposure, it is important to know what effects BPA has on our health. Many studies have been conducted in vivo with animals to observe the effects of exposure to BPA. There have been few in vitro studies conducted with human tissues and fluids that try to observe and explain the effects of BPA exposure. Bisphenol A exhibits toxic properties and further research must be conducted in order to understand the adverse health effects that can occur in humans. Studies conducted in vivo with animals have shown that BPA is toxic and that it causes many delirious health effects. It has been reported that in utero exposure to BPA results in early onset of puberty and increased body weight (Honma, Suzuki, Buchanan, Katsu, Watanabe, Iguchi, 2002, Nikaido et al., 2004). These studies report that early exposure to BPA results in reproductive abnormalities and other developmental problems in mice. Nikaido and Shizuka observed that female mice exposed to BPA had earlier vaginal openings which caused puberty at a younger age. It was also observed that exposure to BPA resulted in increased fetal body weight which progressed into adulthood. The latter effect is also noted in male rodents. Studies conducted on male rodents’ show that exposure to BPA leads to a decrease in serum testosterone levels which continues on into adulthood (Richter et al., 2007, Chitra, Latchoumycandane, Mathur, 2003). Because BPA mimics the female hormone estrogen, high levels of this chemical in males is found to decrease sperm production and levels of testicular testosterone (Chitra et al., 2007). The above studies also report that exposure to BPA causes an increase in prostate size and other male reproductive abnormalities. It is evident that BPA mimics the hormone estrogen and displays toxic properties which cause adverse affects in animals. What’s vexing is that humans are exposed to this endocrine disruptor from many pathways and little is known about its effects on human health. BPA levels have been measured in humans and are detected in many fluids and tissues. Research by Osamu Tsutsumi (2005) reported at 15 weeks of gestation (critical developmental period in humans) showed that BPA was detected in amniotic fluids at concentrations five times higher than normal. Some studies also found that women with polycystic ovary syndrome (PCOS) and some healthy men have higher levels of serum BPA when compared with normal women (Osamu Tsutsumi. 2005, Vandenberg, Hauser, Marcus, Olea, Welshons, 2007). Vandenberg et al report that BPA is measured in human urine samples, serum blood and plasma, and breast milk. Of major concern are the high levels of BPA found in maternal serum and amniotic fluids during pregnancy, especially since the fetus can be exposed to the chemical during critical periods of development (2007). Many studies have been conducted in order to measure levels of BPA in humans to show that humans are exposed to this dangerous chemical. In the few studies that are conducted in vitro with human fluids and tissues, experimenters have hypothesized that BPA causes adverse effects in mankind. In one study, experimenters report that increased exposure to BPA can result in recurrent miscarriages in humans. Forty-five patients who had 3 or more first-trimester miscarriages were observed and compared to 32 healthy non-pregnant females who had no history of miscarriage (Sugiura-Ogasawara, Ozaki, Sonta, Makino, Suzumori, 2005). This study found that patients who had miscarried had higher levels of BPA. Because of this relationship, it is believed that exposure to high levels of BPA can lead to recurrent miscarriage in humans. Surprisingly, in a recent study it was found that even low doses of BPA can trigger cell apoptosis which can lead to adverse pregnancy outcomes including miscarriage (Nora Benachour, Aziz Aris, 2009). In this study, 5 placentas were obtained from healthy women who had no medical conditions. The cytotrophoblasts (placental cells) were then isolated and exposed to varying levels of BPA. This study was conducted in vitro on human cells and tries to explain what effects could be observed in vivo with placental cells when they are exposed to BPA. Interestingly, these findings were also observed in animal studies conducted on mice (Hunt et al. 2003). In this study, the mice were exposed to BPA and the experimenters observed abnormal metaphase configurations. It was observed that high exposure to BPA leads to meiotic aneuploidy (abnormal number of chromosomes) which is said to be a leading cause of miscarriage. These in vitro and in vivo studies are useful in understanding what effects can be observed in humans when cells are exposed to BPA. Many studies have been published that discuss the effects varying doses of BPA has on health outcomes in animals. It is unethical to conduct in vivo experiments in humans in order to understand what effects BPA exposure poses. Even so, very few in vitro studies have been conducted with human fluids and tissues to observe effects on certain cells in humans. Additional research is needed in the area concerning the effects BPA has on human health. This area has largely been unexplored even with the extensive knowledge available on effects of endocrine disruptors in animals. Further research needs to be conducted to understand the exact role BPA plays in humans. I propose that more funding be provided so that research can be conducted in vitro with samples in human fluids and tissues. These epidemiological studies will be important in establishing a connection with BPA exposure and adverse health outcomes in humans. Effects seen in animals are widely researched and understood. By understanding the effects this chemical poses on humans, measures can be taken to control the amount of BPA humans are exposed to on a daily basis. This can be done by banning the production of BPA in products that are known to leech the chemical. The first step is to understand what role BPA plays in human health especially since the chemical has been correlated with pregnancy loss in humans. Once we have concluded the effects BPA has on our health, we will be able to create a healthier environment for future generations. References Hyun Ju Lee, Soma Chattopadhyay, Eun-Yeung Gong, Ryun Sup Ahn, Keesook Lee. (2003). Antiandrogenic Effects of Bisphenol A and Nonylphenol on the Function of Androgen Receptor. Toxilogical Sciences, 75. pp 40-46. Frederic S vom Saal, Claude Hughes. (2005). An Extensive New Literature Concerning Low-Dose Effects of Bisphenol A Shows the Need for a New Risk Assessment. Environmental Health Perspectives, 113. pp. 926-933. Chiranjeev Dash, Michele Marcus, Paul D. Terry. (2006). Bisphenol A: Do recent studies of health affects on humans inform the long standing debate? 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