1. Plastics and Human Health O regon P hysicians for S ocial R esponsibility http://www.flickr.com/photos/kfisto/364229989/

2. Chemical background: Current knowledge and regulatory policies Complex Interactions and vulnerability Review of familiar plastics Concerns: Endocrine disruptors Dose response patterns Bisphenol A Phthalates What you and your patients can do Overview Introduction

4. “When an activity raises threats of harm to human health or the environment, precautionary measures should be takeneven if some cause and effect relationships are not fully established scientifically.” Wingspread Conference, 1998 Precautionary Principle Image: http://www.flickr.com/photos/tkneen/319265454/ Introduction

5. Proven Harm Partially Proven Harm Not Yet Recognized Harm Forever Unrecognized Harm Toxic Iceberg http://www.flickr.com/photos/greenpeace_italia/2165953486/ Introduction

6. Our Chemical Environment: Regulatory Control in the U.S. More than 82,000 in U.S. commerce 2,800 produced/imported >1mill. lbs/yr Almost 4.25 billion pounds of toxic chemicals are reported to the EPA as released into the environment each year (TRI) Introduction

7. Hazard Data for Chemicals Produced in Excess of 1 Million lbs/yr 7% Full* Set of Basic Information US E.P.A. (1998) Chemical Hazard Data Availability Study: What Do We Really Know About the Safety of High Production Volume Chemicals? Introduction

8. Historical Perspective ─1920s: many new chemicals in industry ─1940s and 50s: new chemical innovations for the home ─Exposure of developing fetuses ─1960’s: first data associating synthetic chemicals and health impacts ─1976: first over-arching chemical legislation enacted ─Now: no changes have been made to the legislation… http://www.flickr.com/photos/ylvas/1463679843/ Introduction

9. http://www.flickr.com/photos/gonzales2010/9639815/ http://www.flickr.com/photos/celinesphotographer/383275778/ Health Outcomes Complex Interactions Social Environment http://www.flickr.com/photos/thedepartment/86781504/ Genetics http://www.flickr.com/photos/calliope/130384035/ Nutrition Toxic Exposures http://www.flickr.com/photos/lab2112/2036013217/ Introduction

10. Children are More Vulnerable Organs are immature and developing –Brain & blood/brain barrier in infants –Developing immune system –Liver and kidney less efficient –Skin is more permeable, 2x surface area of adults Greater exposure –Ingest more per pound –More surface area/weight in lungs and intestines –More contaminants dwell close to ground –Hand/mouth behaviors http://www.flickr.com/photos/johnmueller/342618825/ Introduction

11. Important Considerations Evaluation of risk is inadequate: –Concurrent exposures to multiple chemicals: Additive and synergistic effects Only single chemical testing –Timing and dose of exposures –Interpretation of animal data With increasing scientific understanding, we often find greater toxicity at lower levels of exposure

12. Types of Plastics

13. Plastics As We Know Them: Safer vs. Not-So-Safe 1 - polyethylene terephthalate (new evidence) 2 - high density polyethylene 3 - polyvinyl chloride 4 - low density polyethylene 5 - polypropylene 6 - polystyrene 7 - other (often polycarbonate) Plastics

14. #1 - Polyethylene Terephthalate Food & beverage containers –Single-use water bottles –Microwave food trays –Food packaging films Clothing –Polyester, polar fleece http://www.flickr.com/photos/brimelow/73092 271/ http://www.flickr.com/photos/caobhin/194534 255/ Plastics Use one time, avoid heating or long-term storage

15. #2 - High Density Polyethylene Opaque bottles –Milk jugs –Detergent bottles Gas tanks Pipes and tubing Plastic Lumber Plastic bags http://www.flickr.com/phot os/tzofia/291301033/ http://www.flickr.com/photos/adamcnelson/2262436 767/ http://www.flickr.com/photos/splorp/9322376/ http://www.flickr.com/photos /fservayge/1472436308/ Plastics

16. #3 - Polyvinyl Chloride (PVC) Teething rings Pacifiers Toys (inflatable) Pipes, Tubing Medical equipment Shower curtains Clothing Synthetic leather Window frames Siding http://www.flickr.com/photos/sisterd imension/540271784/ http://www.flickr.com/photos/artv enturesgallery/184264587/ http://www.flickr.com/ photos/ryosalem/22701 0700/ Plastics Major health concerns – avoid and replace

17. #4 – Low Density Polyethylene Plastic wraps Flexible bottles Plastic baggies Flexible tubing Furniture Dental appliances Lab pipettes and tips http://www.flickr.com/ photos/ingorrr/13533943 90/ http://www.flickr.com/photos/sonnyandsandy/33707 441/ http://www.flickr.com/photos/unprose/154829 034/ Plastics

18. #5 - Polypropylene Trays Food storage containers Some baby bottles http://www.flickr.com/photos/dearbarbz365/22529 98299/ http://www.flickr.com/photos/jdickert /2383258186/ Plastics http://www.flickr.com/photos/seandreilinger/2450683425/

19. #6 - Polystyrene Clear food containers Styrofoam –food trays –Disposable cups, bowls Packaging material Insulation Coolers Lab equipment http://www.flickr.com/photos/mr _enigma/62914044/ http://www.flickr.com/photos/crouching donkey/1162561710/ Plastics http://www.flickr.com/photos/k euynish/163686563/ http://www.flickr.com/photos/tychay/1535108294/

20. #7 “Other” - often Polycarbonate Some baby bottles Reusable drink bottles Lining of food cans Cutlery Food dishes, containers Dental fillings, sealants Eyeglass lenses Compact Discs http://www.flickr.com/photos/miss- frugality/403374907/ http://www.flickr.com/p hotos/darrylh/50534097 7/ http://www.flickr.com/photos/iwantamonkey/12750 1910/ Plastics http://www.flickr.com/photos/ngtj/551390741/ http://www.flickr.co m/photos/reuvenim/ 2523549479/

21. Pros and Cons of Plastics Benefits: Current technology and lifestyle –Medical, sanitary –Construction, transportation –Information transfer Adverse effects: Environment and other organisms Human Health Impacts –Bisphenol-A and Phthalates

22. Health Concerns

23. Endocrine Disruptors May adversely affect: –Development –Reproduction –Nervous function –Immune function Greater risk for fetuses and young children Bisphenol A and Phthalates are examples found in plastics

24. Action of Endocrine Disruptors Mimic estrogen, androgens, progesterone –Block hormones by binding to receptors Interfere with endocrine signaling paths –Interfere with thyroid Researchers expect that more effects will be found. Health

25. Other Endocrine Disruptors DES (diethylstilbestrol) Dioxin and dioxin-like compounds Polychlorinated biphenyls (PCBs) DDT and other pesticides Hormone-containing pharmaceuticals Health

26. Low Dose Historical Reference Doses for toxicity: –Bisphenol A (BPA): 50 μg/kg/day* –Phthalates: DEHP: 20 μg/kg/day DBP: 100 μg/kg/day DEP: 800 μg/kg/day Studies show adverse effects at much lower doses –parts per trillion for some effects of BPA *μg/kg/day = parts per billion (ppb) Health

27. Non-monotonic Dose Response Curve Different from traditional dose-response curve U-shaped and inverted U- shaped Low doses can stimulate response, high can inhibit Many endocrine disruptors have non-monotonic curves http://www.environmentalhealthnews.org/science background/2007/2007-0415nmdrc.html Health

28. Potential Effects of Endocrine Disruption Falling age of puberty in girls Increasing rates of obesity and diabetes Male genital abnormalities Regional decreases in sperm count Increasing rates of endocrine-related cancers –breast, prostate Increasing rates of neurobehavioral problems: autism, hyperactivity Health

29. Bisphenol A

30. Bisphenol A (BPA) What we know Health Concerns and exposure Consensus Statements Action to regulate What can be done

31. Bisphenol A: What We Know Backbone of Polycarbonate plastic –Resin code: #7 (other) Known since 1930s to be estrogenic Mechanism of action –Binds to both nuclear and cell membrane receptors Rapidly metabolized and cleared –Human exposure is continuous High volume chemical: >6 billion pounds per year BPA Center for the Evaluation of Risks to Human Reproduction

32. http://www.flickr.com/photos/bframe/406051181/ Bisphenol A: Health Concerns Reproductive effects-male and female Insulin resistance, diabetes & obesity Altered brain development Cancer –Prostate –Breast –Decreased antioxidant enzymes Recurrent miscarriages Altered immune function Behavioral effects –Alters attention, activity BPA

33. Human BPA Exposure BPA in 95% of US population (CDC) Widespread use = widespread exposure Concentrations in humans similar to levels causing harm in animals http://www.flickr.com/photos/diarmada/1310673668/ BPA

34. Sources of BPA Exposure Food and drink containers are primary source –Leaching: Into water at room temperature With heating With repeated washing of material With acidic or basic foods/liquids Maternal exposure –Breast milk –Prenatal exposure Indoor & outdoor air Dialysis tubing BPA

35. Literature regarding BPA 115 published in vivo studies of low- dose BPA effects –“Significant” effects in 94 90% of government-funded studies found adverse effects 0% of industry-funded studies found adverse effects BPA

36. National Toxicology Program, April 2008 First government acknowledgement of possible harm Controversy over evaluation of existing data Panel chosen for lack of expertise Chapel Hill Consensus Statement, November 2007 Response to NTP assessment 38 BPA experts Reviewed published BPA literature to date Two Recent Statements on BPA

37. National Toxicology Program, April 2008 First government acknowledgement of possible harm Controversy over evaluation of existing data Panel chosen for lack of expertise Findings: –“some concern…” –“ the possibility that bisphenol A may alter human development cannot be dismissed.” Two Recent Statements on BPA Chapel Hill Consensus Statement, November 2007 Response to NTP assessment 38 BPA experts Reviewed published BPA literature to date Findings: Non-monotonic dose- response curves Concentrations in humans similar to levels causing harm in animals Sensitivity to BPA varies with life stage

38. Recent BPA Decisions December 2006 –San Francisco ban April 2008 –Canada labels BPA as “dangerous substance” –Nalgene will stop using BPA in bottles –Wal-Mart and Toys-R-Us will stop carrying products w/ BPA BPA

39. What You Can Do About BPA Avoid canned foods and drinks Use alternatives to #7 baby bottles: –Breast feed, glass bottles Use alternative sippy cups: –#2,4,5, stainless steel Use alternatives to polycarbonate for storing food and water: –glass, ceramic, safer plastics: #2,4, 5 Never heat/cook/microwave food in any plastic

40. Phthalates

41. What we know Health Concerns and exposure –Reproductive Health Concerns Regulations What you and your patients can do

42. Phthalates: What We Know Large class of chemicals –Large molecules like DEHP make vinyl (PVC) flexible and durable –Smaller molecules (DEP, DBP, DMP) are found in perfumes, lotions, cosmetics, and time- release medications DEHP: http://cerhr.niehs.nih.gov/chemicals/dehp/dehp.html DEHP = di(2-ethylhexyl) phthalate DEP = diethyl phthalate DBP = dibutyl phthalate DMP = dimethyl phthalate Phthalates

43. Sources of Exposure to Phthalates 1 billion pounds produced annually worldwide 2000: CDC found high levels of phthalates in Americans –Women of child-bearing age had highest levels –Found in blood, urine, breast milk, amniotic fluid A ubiquitous contaminant –Found in air, soil, water, sediment Phthalates

44. Phthalates in Consumer Products Vinyl plastic (PVC) –Toys, inflatable mattresses Fragrance –Soap, lotion, detergent, air fresheners, etc. Other common products: –Paint –Adhesives –Car interiors –Wood finishes –Detergents –Solvents –Shower Curtains http://www.flickr.com/photos/desiitaly/2254327579/ Phthalates

45. Phthalates in Medicine Tubing IV bags Gloves Bags containing plasma Time-released drugs http://www.flickr.com/photos/59334544@N00/2322167178/ Phthalates

46. Exposure Issues with Phthalates People exposed to many simultaneously –84% exposed to 6+ at the same time Multiple exposures not considered when EPA determines safe dose Different phthalates have the same mechanism of action –Effect is additive Phthalates

47. Phthalates Toxicity Degree of toxicity related to: –Metabolites (different from parent compounds) –Route of exposure: Inhalation, ingestion, injection, dermal –Age at exposure Phthalates

48. Phthalates: Health Concerns Endocrine system –Thyroid –Insulin resistance Obesity Diabetes –Male reproductive problems Allergies, asthma Phthalates

49. Phthalates: Potential Reproductive Effects High dose and low dose risk Early puberty in females Male reproductive effects: –Lowered semen quality –Testes (Leydig) cells vulnerable –Reproductive effects in infants Swan, et al. (2005) study on male infants: –Urine levels of mothers’ phthalate metabolites postive correlation with shorter ano-genital distance (AGD) http://www.flickr.com/photos/nirak/206930221/ Phthalates

50. Phthalates: Reproductive Effects Swan, et al., 2005 - Human male infants: –85 mother-son pairs –Measured 9 phthalate metabolites in prenatal urine samples –Examined Ano-Genital Distance (AGD) in newborn males (5-16 mo) –Urine levels of 4 metabolites inversely correlated w/ AGD –Shorter AGD increased risk of undescended testes, smaller penis size, and small scrotum Phthalates

51. Regulation of Phthalates European Union 2005 –Banned 3 phthalates in all toys and childcare products; 3 others banned in mouthing toys San Francisco 2006 –Banned manufacture, distribution, or sale of toys intended for ages < 3 years with certain levels of six phthalates California 2009 –Similar restrictions to take effect 1/1/09 Phthalates

52. What You Can Do (and Advise Patients to Do) About Phthalates Avoid using PVC (#3) –Use phthalate-free medical equipment –Toys, bottles, sippy cups Use fragrance-free products –Laundry –Personal care products –Cleaning –Air fresheners

54. What You Can Do About Plastics Avoid using plastic containers in microwave, all cooking. –Cling wraps: beware especially in microwave or oven Use alternative packaging; especially with food & drink. Avoid plastic bottled water unless water supply questionable Bring your own take-home containers to restaurants Avoid over-use of detergents or overly abrasive cleaners for plastic items Use alternatives to non-stick cookware, stain resistant products

55. Guiding Principles Toxic exposures are preventable. Traditional toxicological paradigms may not be appropriate for every toxicant. Since “proof” of harm materializes slowly, generations are at risk and may be harmed before adequate regulatory response occurs. A regulatory system capable of preventing (as well as responding to) exposures is needed to truly protect health.

56. Resources Environmental Health Perspectives http://www.ehponline.org/ http://www.ehponline.org/ The Collaborative on Health and the Environment http://www.healthandenvironment.org/ http://www.healthandenvironment.org/ Environmental Working Group www.ewg.orgwww.ewg.org Agency for Toxic Substances and Disease Control Registry www.atsdr.cdc.gov/www.atsdr.cdc.gov/ Oregon Department of Environmental Quality (DEQ) http://www.oregon.gov/DEQ/ http://www.oregon.gov/DEQ/ National Toxicology Program-Center for the Evaluation of Risks to Human Reproduction (CERHR); http://cerhr.niehs.nih.gov/reports/index.html http://cerhr.niehs.nih.gov/reports/index.html Our Stolen Future http://www.ourstolenfuture.orghttp://www.ourstolenfuture.org Health Care Without Harm http://www.noharm.orghttp://www.noharm.org