What we know and don't know about the health by err16037

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									What we know and don't know
  about the health risks of
 Bisphenol A and Phthalates



         Jennifer A. Lowry, MD
  Clinical Pharmacology and Medical
               Toxicology
       Children’s Mercy Hospital
     History of Plastics
The first man-made plastic was
created by Alexander Parkes who
publicly demonstrated it at the 1862
Great International Exhibition in
London.
The material called Parkesine was an
organic material derived from cellulose
that once heated could be molded, and
retained its shape when cooled.
       History of Plastics
Celluloid is derived from cellulose and
alcoholized camphor.
John Wesley Hyatt invented celluloid as a
substitute for the ivory in billiard balls in 1868.
He first tried using collodion a natural
substance, after spilling a bottle of it and
discovering that the material dried into a tough
and flexible film.
However, the material was not strong enough to
be used as a billiard ball, until the addition of
camphor, a derivative of the laurel tree.
The new celluloid could be molded with heat
and pressure into a durable shape.
      History of Plastics
Besides billiard balls, celluloid became
famous as the first flexible photographic film
used for still photography and motion
pictures. John Wesley Hyatt created
celluloid in a strip format for movie film. By
1900, movie film was an exploding market
for celluloid.
After cellulose nitrate, formaldehyde was the
next product to advance the technology of
plastic. Around 1897, efforts to manufacture
white chalkboards led to casein plastics
(milk protein mixed with formaldehyde).
     History of Plastics
Timeline - Precursors
  1839 - Natural Rubber - method of
  processing invented by Charles Goodyear
  1843 - Vulcanite - Thomas Hancock
         Gutta-
  1843 - Gutta-Percha - William
  Montgomerie
  1856 - Shellac - Alfred Critchlow, Samuel
  Peck
  1856 - Bois Durci - Francois Charles Lepag
     History of Plastics
Timeline - Beginning of the Plastic
Era with Semi Synthetics
  1839 - Polystyrene or PS discovered -
  Eduard Simon
  1862 - Parkesine - Alexander Parkes
  1863 - Cellulose Nitrate or Celluloid - John
  Wesley Hyatt
  1872 - Polyvinyl Chloride or PVC - first
  created by Eugen Baumann
  1894 - Viscose Rayon - Charles Frederick
  Cross, Edward John Bevan
           History of Plastics
Timeline - Thermosetting Plastics and
Thermoplastics
  1908 - Cellophane ® - Jacques E. Brandenberger
                            Phenol-
  1909 - First true plastic Phenol-Formaldehyde
                Bakelite-
  tradenamed Bakelite- Leo Hendrik Baekeland
  1926 - Vinyl or PVC - Walter Semon invented a
  plasticized PVC.
  1927 - Cellulose Acetate
  1933 - Polyvinylidene chloride or Saran also called PVDC
  - accidentally discovered by Ralph Wiley, a Dow
  Chemical lab worker.
          Low-
  1935 - Low-density polyethylene or LDPE - Reginald
  Gibson and Eric Fawcett
        History of Plastics
Timeline - Thermosetting Plastics and
Thermoplastics
  1936 - Acrylic or Polymethyl Methacrylate
  1937 - Polyurethanes tradenamed Igamid for plastics
  materials and Perlon for fibers. - Otto Bayer and co-
  workers discovered and patented the chemistry of
  polyurethanes
  1938 - Polystyrene made practical
  1938 - Polytetrafluoroethylene or PTFE tradenamed
  Teflon - Roy Plunkett
  1939 - Nylon and Neoprene considered a replacement
  for silk and a synthetic rubber respectively Wallace
  Hume Carothers
  1941 - Polyethylene Terephthalate or Pet - Whinfield
  and Dickson
  1942 - Low Density Polyethylene
         History of Plastics
Timeline - Thermosetting Plastics and
Thermoplastics
  1942 - Unsaturated Polyester also called PET patented
  by John Rex Whinfield and James Tennant Dickson
  1951 - High-density polyethylene or HDPE tradenamed
  Marlex - Paul Hogan and Robert Banks
  1951 - Polypropylene or PP - Paul Hogan and Robert
  Banks
  1953 - Saran Wrap introduced by Dow Chemicals.
  1954 - Styrofoam a type of foamed polystyrene foam
  was invented by Ray McIntire for Dow Chemicals
  1964 - Polyimide
  1970 - Thermoplastic Polyester this includes
  trademarked Dacron, Mylar, Melinex, Teijin, and Tetoron
  1978 - Linear Low Density Polyethylene
  1985 - Liquid Crystal Polymers
      Plastics are Everywhere
  Baby shampoo
   study raises
chemical concerns




                    Phthalates found in urine of
                      infants after they were
                       powdered or lotioned
               Background
Endocrine disruptors –
chemicals that
mimic/antagonize normal
hormones and can have
permanent effects in
organisms as well as progeny

Examples: DES –
diethylstilbesterol, DDT,
Phytoestrogens – soy,
                anti-
  Phthalates - anti-
  androgenic/pro-
  androgenic/pro-estrogenic
                 pro-
  Bisphenol A - pro-estrogenic
  (similar to estradiol)
          Endocrine Disruptors
Obesogens – promote adipogenesis at low
doses
  DES – synthetic estrogen
     Exposure in utero    obese offspring that continued
     to be obese with restricted caloric intake/increased
     exercise   2nd generation also obese
  Bisphenol A
    Alonso-Magdalena, P, S Morimoto, C Ripoll, E Fuentes and A
    Nadal. 2006. The Estrogenic Effect of Bisphenol-A Disrupts the
    Pancreatic ß-Cell Function in vivo and Induces Insulin
    Resistance. Environmental Health Perspectives 114:106-112.
   Masuno, H, T Kidani, K Sekiya, K Sakayama, T Shiosaka, H
    Yamamoto and K Honda. 2002. Bisphenol A in combination
    with insulin can accelerate the conversion of 3T3-L1 fibroblasts
    to adipocytes. Journal of Lipid Research 3:676-684.
The plastics that we use
Some plastics are made with
chemicals called phthalates or BPA
which means bisphenol A
These chemicals can leach from
(come out of) everyday plastic
products like toys, bottles, containers,
and personal care products.
 Scientists and doctors are learning
about these chemicals and the health
effects they may have especially on
children.
      What Parents Ask
How do I know if toys contain phthalates?
Are bottles with bisphenol A harmful?
What are the current regulations?
What health effects should I look for?
What alternatives can my child use?
What are phthalates and BPA?
 Phthalates are man-made chemicals used in
 many different products.
   These chemicals are put in some toys and bottles to
   make plastics flexible.
   They are also used in cosmetics and other personal
   care products like some lotions and shampoos
 Bisphenol A (BPA) is a chemical used to
 make a strong plastic called polycarbonate
 that is used in many things like drinking
 bottles.
   BPA is also used on the inside of many metal food
   cans to keep the cans from rusting.
How can my family be exposed to
     phthalates and BPA?
  Adults and children may be exposed to
  phthalates and BPA in the
  environment and at home.
  Both phthalates and BPA can leach
  out of plastics when they are heated
  and the chemicals get into the food or
  drinks in the plastic containers.
  Scientists are still learning if the
  amount that comes out is dangerous
Where are phthalates and BPA?

  Phthalates             BPA
    Food storage          Metal cans of
    containers            food and infant
    Polyvinyl chloride    formula
    (PVC)                 Hard-plastic baby
    tubing/products       bottles
    (such as water        Sippy cups
    pipes)                Plastic bottles
    Flexible plastics,
    plastic bottles
Where are Phthalates found?
Centers for Disease Control (CDC)
  Report on Human Exposures
Hormonal effects of phthalates
  Why are We Concerned?
Animal Studies – exposure to
pregnant rats
  increased incidence of male genital
  tract abnormalities
  Hypospadias
  undescended testes
  testicular tumors




               Gray et al. 2002
  Why Are We Concerned? Human
              Data
Skakkebaek         2001
• Increased incidence of testicular dysgenesis
  syndrome (hypospadias, undescended testes,
  testicular toxicity) in males in the US and other
  Nordic Countries

Duty et al       2003
• Found a significant association between urine
  phthalate levels and sperm DNA damage in
  adult males
Why are We Concerned? Human
            Data
Main et al        2006
• Found a significant association between
  prenatal phthalate exposures and
  luteinizing hormone (positive) and free
  testosterone levels (negative) in newborn
  boys with cryptorchidism

Bornehag et al   2005
• Children exposed to phthalates in house
  dust   increased rhinitis, wheezing,
  eczema
 Why are We Concerned? (Human
             Data)

Swan et al          2005
• Found a significant association
  between prenatal phthalate levels and
  decreased anogenital distance in
  infants
             Background
             Decreased Testicular
             Hormone Production,
             Abnormal Germ Cell
             Development



                                      Decreased sperm
Prenatal
                         Shortened    count/quality,
Phthalates
                         Anogenital   Testicular Tumors
                         Distance


             Hypospadias
             Cryptorchidism
             Male Genital Tract
             Abnormalities
How Do Phthalates Get Into Our
          Bodies?
   Intravenous through flexible tubing
   Oral Intake diet / sucking /
   mouthing toys
   Dermal Absorption
   Inhalation
         Phthalates in Childhood
              Populations

Hauser et al         2005
  NICU Setting – found urinary
  levels of DEHP to be 50x higher
  in preterm neonates as compared
  to levels in children from NHANES


**FDA has released a statement saying that
  premature infants may be adversely affected by
  these chemicals
Possible Human Health Impact -
          Phthalates
  Human Studies
    prenatal phthalate exposure associated with a
    decreased anogenital distance (marker of
    androgenization)
    phthalate exposure through breast milk has
    been associated with increased LH, decreased
    free testosterone and increased serum human
    binding globulin in 3 month old male infants
    early childhood exposure to phthalates has been
    associated with increased rhinitis, eczema,
    asthma and wheezing
    several studies relate phthalate exposure with
    abnormal sperm morphology/sperm DNA
    damage in adult males
 Phthalates Legislation
European Union2005
                       toys/child-
 Permanently banned in toys/child-
 care articles
   DEHP, DBP, and BBP
              toys/child-
 Banned from toys/child-care articles
 that can mouthed
   DINP, DIDP, and DNOP
   European Union Guidance
             “that
Document on “that which can be
     placed in the mouth”
Phthalates Legislation in the US

  California 1st state to enact
  Phthalates Ban
    Effective in 2009
    6 phthalates
    All toys and child care products
    Targets children less than 3 years old
    Prohibits manufacture, sale and
    distribution
Bisphenol A (BPA)
  BPA Exposures are
     Widespread
NHANES 2003-2004 Calafat et al.
  US population ages 6-85 years (n=2517)
  BPA present in 93% of population
  Children 6-11 years (n=217)
    geometric mean BPA=4.3 ug/gram
    creatinine
    children >6 years old (p < 0.001) and
    adolescents (p < 0.003) had higher
    levels than adults
              Health Effects
BPA is a weak estrogen and an anti-androgen,
rapidly metabolized (4-6 hours)
- Up-regulates estrogen receptor in human body

Animal studies:
  Male reproductive tract
  Neurocognitive disorders
  Early puberty
  Increased body size
  Low doses       Breast, Uterine and Prostate Tumor
  Cell Proliferation

Human studies limited
                      Health Effects
        • Data used from NHANES study of 1455 adults
          aged 18 through 74 years of age with
          measured BPA and urine creatinine
          concentrations
          Outcome measures: Chronic disease
          diagnoses plus blood markers of liver
          function, glucose homeostasis, inflammation,
          and lipid changes.
          Results:
               Higher Urine BPA concentrations associated with
               cardiovascular diagnoses
               Higher Urine BPA concentrations associated with
               diagnosis of diabetes
               Higher Urine BPA concentrations associated with
               increased GGT/AP
Lang IA, et al. JAMA. 2008; 130: 1303-1310
   The U.S. National Toxicology
Program - Statement on BPA, 2008
                      FDA Findings
   Based on our ongoing review, we believe there is a
   large body of evidence that indicates that FDA-
   regulated products containing BPA currently on the
   market are safe and that exposure levels to BPA
   from food contact materials, including for infants
   and children, are below those that may cause health
   effects.
   At this time, FDA is not recommending that anyone
   discontinue using products that contain BPA while
   we continue our risk assessment process. However,
   concerned consumers should know that several
   alternatives to polycarbonate baby bottles exist,
   including glass baby bottles.

FDA report written by industry - American Chemistry Council’s Steve Hentges
         Current Policy
Canada says BPA is harmful to infants and
children and proposes to reduce exposure
though bans of polycarbonate bottles/canned
infant formula. . .
Wal-Mart announced they will not sell BPA
containing bottles
Nalgene announces that they will stop selling
BPA-containing water bottles
US, April 30, 2008 – Bill to ban BPA Sen.
Charles E. Schumer (D-N.Y.), Sens. Hillary
Rodham Clinton (N.Y.), Richard J. Durbin
(Ill.), Dianne Feinstein (Calif.), John F. Kerry
(Mass.) and Robert Menendez (N.J.).
        Current US Bills
HR 2749 – Passed July 2009
  Requires the Secretary to notify Congress whether
  the available scientific data supports a determination
  that there is a reasonable certainty of no harm for
  approved uses of polycarbonate plastic and epoxy
  resin made with bisphenol A in food and beverage
  containers under the conditions of use prescribed in
  current FDA regulations. Requires the Secretary to
  notify Congress of the actions the Secretary intends
  to take if such a determination cannot be made.
Has gone to Senate for vote. Not yet
introduced.
       What can I do to prevent
             exposures?
Don’t microwave polycarbonate plastic food
containers. Polycarbonate is strong and durable, but
over time it may break down from repeated use at high
temperatures.
Avoid plastic containers with the #7 on the bottom
http://www.recyclenow.org/r_plastics.html
Don’t wash polycarbonate plastic containers in the
dishwasher with harsh detergents.
Reduce your use of canned foods. Eat fresh or frozen
foods.
When possible, opt for glass, porcelain or stainless
steel containers, particularly for hot food or liquids.
Use infant formula bottles that are BPA free and look
for toys that are labeled BPA-free.
            Precautionary Approach:
              Alternative Products
                                                   Select Glass Food Containers
       Choose alternatives to canned
         foods: Fresh fruits and
         vegetables




Consider alternatives to canned infant formulas:
                Breast is Best!
    PEHSU: Pediatric Environmental
        Health Specialty Unit

Serve health care providers,
public health professionals,
communities, and families

Unique interface of pediatric
medicine-toxicology-
medicine-toxicology-
teratology-epidemiology-
teratology-epidemiology-
exposure sciences

Evidence-
Evidence-based Consultation
and Education

UW PEHSU: OR, ID, AK, WA
    Mid-
    Mid-America Pediatric
Environmental Health Specialty
       Unit (MAPEHSU)
      Mid-
 The Mid-America Pediatric Environmental
 Health Specialty Unit (MAPEHSU) is one of
 13 PEHSUs located in the continental
                                  Mexico.
 United States and in Canada and Mexico.
 MAPEHSU provides service to EPA Region
 7 which includes
           ▪ Iowa
           ▪ Kansas
           ▪ Missouri
           ▪ Nebraska
        PEHSU Staff


*Project director
*Project coordinator
*Pediatrician
*OEM physician
*Other specialists (toxicologist)
Jennifer Lowry, MD              Gary Wasserman, DO
Director of MAPEHSU             Toxicologist for MAPEHSU
    Clinical Pharmacology and      Clinical Professor
    Medical Toxicology             Department of Pediatrics
    Pediatrician                   Children’s Mercy Hospital
    Department of Pediatrics
    Children’s Mercy Hospital   D. Adam Algren, MD
                                Toxicologist for MAPEHSU
H. William Barkman, MD, MSPH        Clinical Assistant Professor
OEM Physician                       Department of Pediatrics,
                                    CMH
   Director, Center for             Department of Emergency
   Environmental and                Medicine,
   Occupational Health
   KUMC Campus                      Truman Medical Center

                                Lisa Oller, RPh
                                Project Coordinator and
                                   Manager for MAPEHSU
                                   University of Kansas
                                   Hospital Poison Control
                                   Center
                          Our Partners
Center for Environmental & Occupational Health
   The University of Kansas Medical Center
                     913-588-
          Number: 1-913-588-7146

University of Kansas Hospital Poison Control Center
          Toll-               800-222-
          Toll-free number: 1-800-222-1222

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          Toll-free number: 1-800-222-1222
          Toll-               800-222-

Missouri Regional Poison Center
          Toll-               800-222-
          Toll-free number: 1-800-222-1222

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         Toll-               800-222-
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    WHO WE SERVE

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