1. Bisphenol A: Exposure in the Environment as it Relates to Health Candace Waynick, RD LD October 24, 2011 NUTN 507: Seminar

2. Objectives  Discuss the synthetic and legal history of Bisphenol A (BPA)  Describe uses of BPA and BPA containing products  Discuss harmful effects of exposure to BPA and controversial methods of testing  Describe the role of dietitians to minimize public health risks associated with BPA

3. Synthetic History  2 phenol compounds and 1 acetone  Recognized for estrogenic properties in 1930’s by Edward Charles Dodd searching for the “mother substance” (synthetic estrogen)  In the 1950’s, BPA is used to synthesize epoxy resins and polycarbonate plastics  Superiority to glass and steel Vogel 2009 Braun et al 2011 Biello 2008 Image: Wikipedia

4. Epoxy Resins  BPA is a monomer in synthesis  Products:  Protective coatings of medical equipment, piping, steel drums, and interior of food/beverage/liquid infant formula cans Vogel 2009 Groff 2010 US FDA Update 2010 Taylor 2011 Image: http://news.consumerreports.org/a/6a00d83451e0d569e20120a69fcb0e970c-800wi

5. Polycarbonate (PC) plastics  Hard plastic formed when BPA is polymerized  Products:  Electronics, safety equipment, automobiles, food containers, plastics with recycling code # 7, intravenous tubing, dental sealant, reusable water and baby bottles Vogel 2009 Groff 2010 US FDA Update 2010 Image: http://www.pacebutler.com/images/recycle/plastic-recycling-symbols-7.jpg

6. Thermal (Carbonless) Paper  Also contains BPA causing transdermal exposure  Products:  Sales receipts, cigarette filters, lottery tickets, fax paper, children’s books, and recycled paper products Groff 2010 US EPA DRAFT 2011 Braun 2011 Taylor 2011 Image: http://www.bikudo.com/preview/292638.jpg

7. Leaching BPA  Monomers of BPA can hydrolyze and leach into foods or liquids  Accelerated by:  High temperatures  Acidic or basic conditions  Damaged surfaces  Le et al study  Exposure to 100 ｡ C (new and used PC water bottles) allowing 24 hrs to cool to room temperature  Results: 15-55 fold increase in those exposed to heat versus room temperature water only Groff 2010 Braun et al 2011 Biello 2008 Le 2008

8. Federal Regulation  1958- FDA approves BPA as indirect food additive  Safety determined by toxicity, not carcinogenicity  1977- National Cancer Institute (NCI) initiated 1st carcinogenesis study of BPA due to increased production  Responsibility of program passed to the National Toxicology Program (NTP) during 2 year study  1988- Environmental Protection Agency (EPA) defines safe exposure levels to BPA as 50 micrograms/kg body weight Vogel 2009 Shaw 2008

9. Health Implications  Endocrine system disruption  Cancer  Obesity  Cognitive and behavior impairment  Cardiovascular Disease (CVD)  Type 2 Diabetes (DM2)  Asthma  Liver enzyme abnormalities Shaw 2008 Ballard 2010 Image: http://bpafreewaterbottlespro.com/wp-content/uploads/2011/08/bpa-health-risks.jpg

10. Endocrine System Disruption  BPA is an endocrine-disrupting compound (EDC)  An exogenous agent that interferes with synthesis, secretion, transport, metabolism, binding, action, or elimination of natural blood- borne hormones that are present in the body and are responsible for homeostasis, reproduction, and developmental processes. Bourguignon et al 2010

11. Studies showing BPA as EDC  Moriyama et al (2002) show BPA inhibiting thyroid hormone receptor (T 3 )-mediated transcription by acting as an antagonist  Ramos et al (2003) exposed rats to BPA in utero indicating prenatal exposure induces transient and permanent age-dependent alterations in the male reproductive axis at different levels Moriyama et al 2002 Ramos 2003 Image: http://electiondebates.com/images/stimulus-pix/rats.png

12. Studies showing BPA as EDC  Song et al (2002) demonstrate BPA inducing NR4A1 gene expression (responsible for activating steroidogenesis) in mouse testicular cells  Akingbemi et al (2004) actually show the opposite with low doses of BPA showing an inhibitory effect on testicular steroidogenesis Song et al 2002 Akingbemi et al 2004

13. Metabolic disturbances  Lang et al use NHANES data to show higher BPA urine levels associated with increased prevalence of CVD, DM2, and liver-enzyme abnormalities Lang et al 2008 US EPA DRAFT 2011 Image: http://www.online-diabetes-information.com/wp-content/uploads/2011/03/diabetes-heart-disease2.jpg

14. Young children, infants, and fetuses at higher risk  Higher BPA concentrations reflective of higher food intake per pound of body mass  Predominant sources:  Fetus- shown to cross the placenta  Infants- breast milk, canned infant formula, and baby bottles  NICU infants exposed to higher levels due to intensive medical interventions  Children- canned food and beverages and school lunches Groff 2010 Lang et al 2008 Bourguignon et al 2010 US EPA DRAFT 2011 Image: http://www.sequoiapediatricgroup.com/images/nicu_baby.gif

15. Exposure outcomes during development  Prenatal exposure associated with aggression and hyperactivity in 2 year old children  Delayed breast development with higher BPA concentrations  More sensitive to adverse outcomes due to exposure during development of neurological and endocrine systems US EPA DRAFT 2011 Bourguignon et al 2010 US FDA Update 2010 Braun et al 2011

16. National Children’s Study  Started 2009  Examining fetal environment, including BPA exposure  Following pregnant women and offspring until 21 years of age  Goal of 100,000 children participants  Largest, most comprehensive study of its kind in US Groff 2010 Image: http://www.mrothery.co.uk/images/growth.gif

17. Metabolism  Oral ingestion of BPA is metabolized in the intestines and liver to yield metabolite, BPA monoglucuronide, and is excreted in the urine (in humans)  Acute exposure studies show:  rapid metabolism of BPA with urinary elimination to be within 24 hours of exposure based on 4-6 hour half-life Stahlhut 2009 Lang et al 2008 Image: http://image3.examiner.com/images/blog/wysiwyg/image/water_bottle1(1).jpg

18. Metabolism Controversy  BPA monoglucuronide elimination:  humans/primates- from the blood via kidneys into urine  Rodents- bile excretion into feces  Current safety measured on belief that higher doses result in greater effects  If higher doses cause no harm, lower doses are deemed safe? Groff 2010 Lang et al 2008 Taylor et al 2011

19. Studies Addressing Controversy  Stahlhut et al suggest a longer than expected half life attributed to either environmental exposure or accumulation in adipose tissue  Taylor et al compare bioactive BPA (unconjugated) levels in primates and rodents reporting clearance rates are the same Stahlhut et al 2009 Taylor et al 2011 Groff 2010 Image: http://maxcdn.fooyoh.com/files/attach/images/3004/141/953/004/Monkey_facepalm.jpg

20. Exposure  Over 90% of U.S. individuals have measurable concentrations of BPA in their urine  Significantly higher levels of BPA in younger children, women, and incomes < $45,000/year  1997-2005- 115 studies in US, Japan, and Europe show some effects at or below the reference dose Braun et al 2011 Lang et al 2008 Groff 2010 Taylor 2011 Vogel 2009 Image: http://3.bp.blogspot.com/_xo0o9nT5MLI/TOq_bZElPYI/AAAAAAAAAB8/nQspiA_mtwY/s1600/MP900431826.JPG

21. Back to Federal Regulation  2007- Chapel Hill Consensus Statement  BPA, at concentrations found in the human body, is associated with “organizational changes in prostate, breast, testes, mammary glands, body size, brain structure and chemistry, and behavior of laboratory animals.”  2008- The Center for Evaluation of Risks to Human Reproduction (CERHR) within the NTP released two statements regarding BPA at current exposure:  “some concern for effects on the brain, behavior, and prostate gland in fetuses, infants, and children”  “minimal concern for the effects on the mammary gland and an earlier age for puberty for females in fetuses, infants, and children” Vogel 2009 US FDA Update 2010 Image: http://www.knowabouthealth.com/wp-content/uploads/2010/07/BPA.jpg

22. Current Regulation of BPA  January 2010- Food and Drug Administration announces it had some concern about BPA  November 2010- World Health Organization recommend holding off on regulations that limit or ban use of BPA  Several local and state governments in US have limited or banned use of BPA  Oregon Senate Bill: http://gov.oregonlive.com/bill/2011/SB695/ http://gov.oregonlive.com/bill/2011/SB695/  October 2011- American Chemistry Council asks to phase out allowance of BPA in baby products US EPA 2010 Brown 2010 USA Today 2011

23. BPA-free Manufacturers  By March 2009, major baby bottle companies removed BPA from products  Sunoco requires written confirmation of BPA plastic not sold to children ≤ 3 years  2010- General Mills announced next tomato harvest, all Muir Glen tomatoes canned BPA- free  Eden Foods beans have been BPA free since 1999 Vogel 2009 Szabo 2008 USA Today 2011 Image: http://www.kidsbabydesign.com/wp-content/uploads/2009/06/bpa-free-baby-bottles.jpg Image: http://www.greenbiz.com/sites/default/files/imagecache/wide_large/0410Muir.jpg

24. Minimizing Health Risks  Rudel et al conducted a study following participants measuring BPA at baseline and 3 days post intervention (eliminating canned/packaged foods)  50-70% decrease in urinary BPA Rudel et al 2011 Image: http://3.bp.blogspot.com/_4J97xRX7uok/TG4Bj2OHSII/AAAAAAAAAAk/DOb-TqhLJh0/s1600/Fresh+foods+vs+Canned+foods.png

25. Role of the Dietitian  Counsel public to:  Avoid canned foods  Replace recycling #s 3, 6, & 7 with other recycling #s (1, 2, 4, or 5), stainless steel, or glassware  Switch from liquid formula to powdered  Avoid heating BPA plastic  Replace canned foods with fresh or frozen foods  Discard scratched baby bottles/cups  Only use dishwasher safe and microwave safe plastics in appliances Braun 2011 Groff 2010 Bourguignon 2010 US DHHS

26. Summary  BPA found in plastics (code # 7) and canned foods/beverages  Health implications include endocrine system disruption, risk of CVD, neurological impairments, obesity, DM2, and liver enzyme abnormalities  No federal limits or bans on uses  Dietitian can reduce public exposure by suggesting replacements

27. Discussion Image: http://www.sneakerfiles.com/wp-content/uploads/2011/09/Discussion-The-Discussion.jpg