1. Bisphenol A (BPA) BENJAMIN G. MUÑIZ

2. Origins  First synthesized in 1891 by A. P. Dianin (Hallberg et al., 2008)  Estrogenic properties identified by Edward Charles Dodds in 1930s. (Vogel, 2009)  Used in the 1950s in plastic bottles and in lining of cans as an epoxy resin (Hallberg et al., 2008)  Bayer and GE chemists used it to create polycarbonate in 1957 (Vogel, 2009)  Although its estrogenic properties were known, there was little concern since its dose was considered monotonic and the FDA believed that it provided no risk at low levels (Vogel, 2009)

3. Origins contd.  Numerous studies regarding its possible carcinogenicity in the 1970s were deemed possibly invalid by the GAO due to poor laboratory practices but no review was required (Vogel, 2009)  Reference dose of 50 µg/kg/day was established by taking the lowest dose from the carcinogenesis study as the LOAEL and dividing by 1000 (Vogel, 2009)  BPA’s estrogenicity was revisited in 1993 when researchers at Stanford University determined that BPA was leaching from their plastic tubes and acting as endogenous estrogen in yeast (Vogel, 2009)

4. Frederick vom Saal  Studies by Fred vom Saal (1997, 1998) investigated the low-dose (<50 µg/kg) effects of BPA on mice.  Results showed changes in male reproductive system as well as an increase in prostate gland weight (vom Saal et al. 1997, 1998)

5. Further Studies  NTP reviewed research on low doses of estrogenic compounds and in 2001 concluded that there was credible evidence for effects from BPA exposure at low levels. They also found credible evidence of no effects and determined that further research was needed (Vogel, 2009)  The Harvard Center report in 2004 concluded that there was no evidence of significant effects presented in low-dose studies due to inconsistent effects and a lack of a “single, biologically plausible explanation” (Vogel, 2009)  vom Saal responded that the study was not through and pointed out that of 115 studies conducted between 1997 and 2005, 90% of those that were government funded reported some negative effects while the 11 studies funded by the industry failed to find any effects. (Vogel, 2009)

6. Chapel Hill Consensus Statement  In 2006, a meeting between 38 experts on endocrine disruptors concluded that “BPA at concentrations found in the human body is associated with organizational changes in the prostate, breast, testis, mammary glands, body size, brain structure and chemistry, and behavior of laboratory animals (Vogel, 2009)  A NTP-CERHR report in 2008 declared that “the possibility that bisphenol A may alter human development cannot be dismissed.” (Vogel, 2009)

7. BPA-Free  In 2008, BPA became well known due to articles talking about its widespread use and possible dangers it posed.  Members of congress asked the FDA to look into BPA.  Canada classified BPA as toxic in April, 2008.  European Food Safety Authority as well as the FDA declared that it was safe at normal human exposure levels.  Retailers pulled plastic bottles and baby bottles containing the chemical and manufacturers began producing “BPA-free” products. (Vogel, 2009)

8. Effects of BPA Males  Decreased sperm count  Delay in puberty  Feminization of reproductive organs  Athrophy of reproductive organs  Hormonal alterations (Hallberg et al., 2008) Females  Acceleration in puberty  Decrease in fertility  Altered estrous cyclicity  Ovarian malfunction  Hormonal alterations

9. Epigenetics  Study in viable yellow mice found BPA had an effect on methylation of DNA, histone modification, and expression of non-coding RNA due to in-utero exposure (Singh & Shoei-Lung Li, 2012)  Hypomethylation of mouse Agouti gene can be prevented by maternal supplementation with a source of methyl group, i.e. folic acid.  Result was a shift in coat color to yellow.  Some effects of BPA established as transgenerational (Singh & Shoei-Lung Li, 2012)  Mechanisms still need to be defined in order to predict toxic potential (Singh & Shoei-Lung Li, 2012)

10. References Hallberg, E., Henning, E., Parke, et al. Bisphenol A. (2008, December 15). Retrieved from http://www.enhs.umn.edu/current/2008studentwebsites/pubh6101/bpa/ho me.html vom Saal, F. S., Cooke, P.S., Palanza, P., Thayer, K.A., Nagel, S., Parmigiani, S. and Welshons, W.V. A physiologically based approach to the study of bisphenol A and other estrogenic chemicals on the size of reproductive organs, daily sperm production and behavior. Toxicol. Industrial Health, 14:239-260, 1998. Vogel, S. A. The politics of plastics: the making and unmaking of bisphenol A “safety.” American Journal of Public Health. 99(Suppl 3): S559-566, 2009.

11. References Singh, S., Shoei-Lung Li, S. Epigenetic effects of environmental chemicals bisphenol A and phthalates. International Journal of Molecular Sciences. 13(8):10143-10153. 2012.