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BPA and related chemicals: why worry? · PDF file chemicals: why worry? Laura N. Vandenberg,...

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  • BPA and related chemicals: why worry?

    Laura N. Vandenberg, PhD UMass Amherst

    School of Public Health & Health Sciences

  • Human Exposures

    Vandenberg et al. EHP 2010

    Vandenberg, CMAJ 2011

  • Sources of Exposure

    0

    0.5

    1

    1.5

    2

    2.5

    no polycarbonate polycarbonate use

    ur in

    ar y

    co nc

    en tra

    tio n

    (n g/

    m l)

    Changes in the composition of can coating

  • BPA is an endocrine disruptor EDCs are exogenous chemicals or chemical mixtures that interfere in some way with hormone action.

  • Understanding EDCs requires an understanding of hormones

  • Hormones act at low doses

  • Hormones act via receptors

    “potency” is endpoint specific

  • Lee et al. 2011

    BM I

    Welshons et al. 2003

    ce ll

    nu m

    be r

    Hormones can have non- monotonic dose responses

    HepG2 cells

    ce ll

    de at

    h

    Gasnier et al. 2009

    proliferation toxicity

    There are hundreds of examples from the hormone and EDC literature where the dose

    does not make the poison.

    Our review concludes that these types of U- and inverted U-shaped curves are common

    and should be expected.

  • Hormone action is dependent on timing of exposure

    “From the day of conception until an individual is born or hatched, the development of each stage of life is fully under the control of hormones. Changes that happen during development are far less reversible [than those occurring in an adult]; you can't go back and rewire the brain”. -Theo Colborn, zoologist, writer

  • Early Prenatal Mid- Late Prenatal Postnatal

    Week 1-16 Week 17-40 Birth – 25 years

    Central nervous system (3wks - 20 years)

    Ear (4-20 wks)

    Kidneys (4-40 wks)

    Heart (3-8)

    Immune system (8-40 wks; competence & memory birth-10yrs)

    Limbs (4- 8wks)

    Lungs (3-40 wks; alveoli birth-10yrs)

    Reproductive system (7-40wks; maturation in puberty)

    Skeleton (1-12 wks)

  • Early Life Exposure to EDCs

    Gestation Childhood Reproductive Life Middle Life Later LifePuberty

    Exposure to EDCs

    The effects of early exposures to EDCs – when organ systems are developing – may be manifested any time in life.

  • Human Disease Trends Over recent decades there has been:

    • significant increase in reproductive problems in some regions of the world, suggesting a strong role for unidentified environmental factors in disease etiology

    • increase in endocrine cancers • significant decrease in human

    fertility rates • increase in use of assisted

    reproductive services • increasing number of chemicals to

    which all humans in industrialized areas are exposed

    Top: Richiardi et al., Cancer Epidem. Biomark. (2004); Bottom: based on data from http://data.euro.who.int/hfadb/

  • Back to BPA… What does it do?

  • Effects of BPA in animals hormone levels

    female reproductive tract

    male reproductive tract

    mammary gland

    reproductive aging cancers (prostate, mammary)

    brain Behaviors (sex specific, maternal, aggression, hyperactivity)

    fertility

    cardiovascular

    pancreas

    immune system metabolic syndrome

    obesity

  • BPA & the mammary gland

    Vandenberg et al. 2007

    Markey et al. 2001

    control

    BPA

    Tharp et al. 2012

    Durando et al. 2007

    A ce

    ve do

    e t a

    l. 20

    13

  • Effects of BPA in humans

    metabolic syndrome

    obesity

    infertility

    abnormal behaviors

    cardiovascular diseases

    hormone levels

    PCOS

  • BPA replacements

  • Changing how we test EDCs?

    • Without appropriate testing, ‘safety’ should not be assumed

    • ‘positive’ effects should trigger chemical abandonment

    BPA and related chemicals: why worry? Human Exposures Sources of Exposure BPA is an endocrine disruptor Slide Number 5 Understanding EDCs requires an understanding of hormones Hormones act at low doses Hormones act via receptors Hormones can have non-monotonic dose responses Hormone action is dependent on timing of exposure Slide Number 11 Slide Number 12 Slide Number 13 Back to BPA… What does it do? Effects of BPA in animals BPA & the mammary gland Effects of BPA in humans BPA replacements Changing how we test EDCs?

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