Endocrine disrupting effects of widely used substances

Transcription

1 Endocrine disrupting effects of widely used substances Sarah Janssen, M.D., Ph.D., M.P.H. Science Fellow, Natural Resources Defense Council Assistant Professor, University of California, San Francisco

2 Examples of chemical exposures with public health implications Describe how science has informed policy initiatives to limit exposure and improve health Describe how physicians can use this information to address patient concerns

3 Increasing Incidence of Health Conditions Infertility Premature births Birth defects of genitalia Early onset of puberty Cancer - testicular Neurological conditions ADHD, autism Insulin resistance/diabetes Obesity

4 Endocrine Disruptor An exogenous agent that interferes with the synthesis, secretion, transport, binding, action, or elimination of natural hormones in the body that are responsible for the maintenance of homeostasis, reproduction, development, and /or behavior. U.S. EPA, February 1997 Or in simpler terms: A substance which interferes with natural hormones.

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6 Endocrine disruptors and health Abnormal development of reproductive organs or neurological system Reduced fertility male and female Poor birth outcomes LBW/IUGR, SA Development of pre-cancerous/cancerous lesions Lower IQ Behavioral abnormalities

7 Synthetic Estrogens Seven women ages presented at the Massachusetts General Hospital with clear cell adenocarcinoma of the vagina, Herbst, AL. et al N Engl J Med 1971, 284:878. The Wood siblings From:

8 Diethylstilbestrol - DES Estradiol

9 DES Health Effects - Female Vaginal cancer (clear-cell adenocarcinoma) Gross and cellular structural abnormalities of reproductive organs: fallopian tubes, uterus, cervix, and vagina Suppression of cell-mediated immunity Infertility Preterm labor Uterine fibroids Breast cancer Trans-generational effects DES granddaughters

10 DES Health Effects - Male Cryptorchidism Testicular hypoplasia Epididymal cysts Semen abnormalities Reduced fertility Testicular cancer

11 Lessons from DES The placenta is not a barrier Exposure to the mother can have unexpected, delayed effects in the offspring Exposure to a hormonally-active chemical may result in a variety of adverse health effects Unusual diseases are easier to trace to an environmental cause than are common diseases

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13 Children are More Vulnerable to All Toxins Immature brain, blood/brain barrier; Eat, breathe & drink more per kg; GI & skin 2x surface area v. adult; Outside more & closer to ground; Hand/mouth behaviors; Mouth breathers; Lower enzyme levels.

14 Estrogenic agents and obesity Wts of after in utero exposure to 1 part per billion DES Newbold, et al Developmental Exposure to Estrogenic Compounds and Obesity. Birth Defects Research (Part A) 73:

15 Common Endocrine Disruptors Banned in US PCBs Pesticides DDT DBCP Chlordecone (Kepone) Hexachlorobenzene Not intentionally made Dioxins Furans PAHs Still in use Pesticides Atrazine Endosulfan Lindane Flame retardants BFRs/CFRs Plasticizers phthalates bisphenol A Heavy Metals Perchlorate Antimicrobials triclosan/triclocarban

16 Common Exposures of concern Occupational exposures Exposures unique to a community Exposures during vulnerable periods Food or drinking water contamination Breast feeding Toxics in the home

17 Challenges to HCPs Unfamiliarity with the science Science pertains to populations and not individuals Translation of scientific studies done mostly in animals Issues of exposure Mixtures Life stage of exposure Dose

18 Communication about Health Risk Informed Consent vs. Environmental Exposure Risks and benefits Apply to an individual Voluntary procedure or exposure No benefit to exposed Little-no information about the risk Individual risks hard to determine Exposure often unknown

19 Overall approach Take an appropriate Occupational and environmental history Have some knowledge of the contaminant of concern Assess the likelihood of exposure Ability to communicate an effective strategy for reducing exposure Redirecting conversation to exposures which are preventable and controllable

20 Plastics in Consumer Products

21 Bisphenol A Over 6 billion pounds produced each year Developed as estrogenic drug 1930s Building block of polycarbonate plastic Food can lining Dental sealant Cash register receipts 7 PC

22 Animal studies Cancer promoter Prostate hyperplasia/cancer Mammary cancer Developmental toxin - lower sperm counts - altered onset of puberty - decreased anogenital distance - oocyte anueploidy Neurological toxin Obesogen/Insulin Resistance Reproductive Toxicology, Aug 2007

23 Policy BPA has not been banned in any state or country although legislation has been introduced FDA has approved BPA as a food additive April 2008 National Toxicology Program draft report Health Canada - dangerous substance

24 Public perception Market for baby bottles changed Walmart, Toys R Us "Baby Bargains," a best-selling guide to baby products, have advised parents to stop using bottles made of polycarbonate plastic. "If you are shopping for bottles, choose an alternative made from BPA-free plastic or glass," "If you have polycarbonate bottles, throw them out." Market for beverage containers changed Nalgene discontinues production of Lexan bottles

25 What are the alternatives? Non-polycarbonate plastic or glass baby bottle Born-Free (polyamide) others Polypropylene Unlined stainless steel bottle Eat fresh food when possible, - frozen over canned Buy processed food in cardboard or brick containers

26 Phthalates in consumer products

27 Phthalates: Anti-Androgens Phthalate Syndrome Absent testes, prostate gland, seminal vesicles Testicular atrophy Decreased sperm count Decreased fertility Cryptorchidism Hypospadias decreased AGD Fisher J. Reproduction.127:305-15, 2004

28 Phthalates and PVC Make PVC flexible and soft Not tightly bound, migrates with use Ubiquitous exposure General Uses - Building materials - Toys - Clothing - Childcare Products - Packaging - Cosmetics and - Medical Devices personal care products - Air fresheners

29 Most Sensitive System: Immature Male Reproductive Tract Phthalate syndrome Mechanism of Action testosterone synthesis; interference with Leydig cell differentiation with fetal exposures Target Tissues Sertoli cells, Leydig cells Seminiferous tubules, sperm, epididymis, penis, prostate NTP-CERHR-DEHP-00, Oct 2000 Moore, 2001 EHP 109:229; Gray LE, Toxicol Sci Dec;58(2):

30 Human exposures Routes of exposure: inhalation, dermal, oral, intravenous Phthalates found in blood, urine, amniotic fluid, breast milk and cord blood. NHANES 2000, >97% DEHP, DBP or BBzP Children > adults NHB > Caucasians Increased levels associated with use of application of lotions, PCCPs

31 DEHP in Medical Devices Used to make PVC plastic flexible % by weight; up to 80% in tubing. Not bound to the vinyl; readily leaches. Leaching increased by lipid-like content of fluids, temperature, agitation, storage time.

32 Sources of Medical Exposure to DEHP Intravenous fluids, medications Exchange Transfusions Replacement Transfusions Extra Corporeal Membrane Oxygenation Dialysis Surgery (e.g. large exposures during cardiopulmonary bypass) Hyper-alimentation Gastric Feeding, NG Tubing Artificial Ventilation

33 Testicular Dysgenesis Syndrome Hypospadias Cryptorchidism Leydig cell hyperplasia (micronodules) Sperm density Testicular cancer Skakkebaek NE. Human Reproduction 16:972, 2001 Moller H. APMIS 106:

34 Epidemiology Prenatal exposures Shortened AGD (Swan, 2005) Neonatal exposures Hormonal alterations (Main, 2006) Adult men Poor semen quality (Hauser, 2006 and 2007) Occupational exposures associated with lower ft (Pan, 2006)

35 Air freshener testing 14 air freshener products tested 8 aerosol sprays; 5 continuously-emitting liquids; 1 solid 12 found to contain phthalates None were labeled unscented and all natural products

36 Conclusions of study Preliminary findings More comprehensive, in-depth testing needed Not clear what exposure to individual would be Consumers are not aware of potential danger No labeling Not regulated by CPSC

37 Phthalates in consumer products

38 Recommendations to patients phthalates and plastics Avoid using PVC plastics (#3) Avoid use of soft toys that can be heavily mouthed. Use unscented products Check on-line guides for cosmetics

39 Policy Initiatives around phthalates EU, Argentina, Japan and Mexico banned 6 different types of phthalates from children s toys and products EU also banned phthalates from cosmetics California toxic toy ban September 2007 San Francisco toxic toy ban May 2006

40 Bush expected to sign bill toughening standards on toy safety Jane Kay, Chronicle Environment Writer Thursday, July 31, 2008 (07-31) 19:05 PDT -- The U.S. Senate passed legislation today strengthening enforcement provisions of the nation's consumer products safety agency and banning lead and other harmful chemicals in children's toys. White House spokeswoman Dana Perino said President Bush is expected to sign the bill, which passed the Senate 89-3 and the House of Representatives on Wednesday. The amendment prohibits the manufacture, sale or importation of toys and other products that contain certain phthalates, with different protections for children ranging up to the age of 12. "This is the first legislation of its kind," Feinstein said in an interview. "For the first time, we are essentially able to establish precautionary standards. "It puts the responsibility on the companies to know that what they're pushing is benign and does not impact human health," she said. "Once it's in the product, and in the marketplace, we had to wait for people to get sick from it."

41 What are the alternatives? Toys Cosmetics Air fresheners Medical devices

42 Take home messages Hormonally-active agents exist in drugs, cosmetics, dietary supplements, pesticides, consumer products, and industrial chemicals. Laboratory animal experiments suggest that exposures to these agents could be impacting reproductive health. The developing fetus, infants and children are most vulnerable because their organs are still developing

43 Take home messages, cont d Consequences of early life exposures are sometimes manifest until adulthood and can be permanent and irreversible Chemicals can have multiple sites of action with multiple effects. The impacts of exposures to mixtures of chemicals is not understood

44 Resources Natural Resources Defense Council Simple Steps