10/24/2013 1 Program on Reproductive Health and the Environment Environmental Contaminants & Reproductive Health: What should we tell our patients? Marya G. Zlatnik, MD, MMS Maternal Fetal Medicine UCSF 'What we have to face is not an occasional dose of poison which has accidentally got into some article of food, but a persistent & continuous poisoning of the whole human environment‘ - Rachel Carson Program on Reproductive Health and the Environment No disclosures • Thanks to Tracey Woodruff, PhD MPH, UCSF Program on Reproductive Health & the Environment 2 Program on Reproductive Health and the Environment Babies ‘R’ Us & BPA • 2007: UCSF Program on Reproductive Health & the Environment formed • 2008: WalMart and Babies ‘R’ Us stop selling baby bottles w/ BPA • 2010: Canada declares BPA to be a "toxic substance" • May 2013: RCOG Scientific Paper • Oct 2013: ACOG/ASRM Opinion 3 Program on Reproductive Health and the Environment Should we panic? No • Effects of these chemicals generally subtle – Chronic exposure often needed to see clinical impact – Not all routes/types of exposures equally concerning – Not everyone susceptible – Often effect only seen clearly on population level • Analogies: – Sometimes forgetting sunscreen & risk of skin cancer – Eating eggs/butter & risk of MI – NOT: one exposure to HPV & cervical Ca 4
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10/24/2013
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Program on Reproductive Health and the Environment
Environmental Contaminants & Reproductive Health: What should we tell our patients?
Marya G. Zlatnik, MD, MMS
Maternal Fetal Medicine
UCSF
'What we have to face is not an
occasional dose of poison which
has accidentally got into some
article of food, but a persistent &
continuous poisoning of the whole
human environment‘
- Rachel Carson
Program on Reproductive Health and the Environment
No disclosures
• Thanks to Tracey Woodruff, PhD MPH,
UCSF Program on Reproductive Health
& the Environment
2
Program on Reproductive Health and the Environment
Babies ‘R’ Us & BPA
• 2007: UCSF Program on Reproductive
Health & the Environment formed
• 2008: WalMart and Babies ‘R’ Us stop
selling baby bottles w/ BPA
• 2010: Canada declares BPA to be a
"toxic substance"
• May 2013: RCOG Scientific Paper
• Oct 2013: ACOG/ASRM Opinion
3Program on Reproductive
Health and the Environment
Should we panic? No
• Effects of these chemicals generally subtle
– Chronic exposure often needed to see clinical impact
– Not all routes/types of exposures equally concerning
– Not everyone susceptible
– Often effect only seen clearly on population level
• Analogies:
– Sometimes forgetting sunscreen & risk of skin cancer
– Eating eggs/butter & risk of MI
– NOT: one exposure to HPV & cervical Ca
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Program on Reproductive Health and the Environment
Objectives
• Concerning trends
• Concepts of endocrine disruption
• Specific chemicals of concern
– BPA, PDBEs
– Lead, TBT, pesticides in syllabus
• Things our pts can do
– Top Ten Changes to make
• Resources in syllabus
– Epigenetic effects
5Program on Reproductive
Health and the Environment
Mutant Fish
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http://www.boisestatepublicradio.org/post/two-headed-trout-leads-scrutiny-mine-pollutionLemly, AD 2004. Aquatic selenium pollution is a global environmental safety issue. Ecotoxicology and Environmental Safety, 59, 44- 56. . http://www.srs.fs.usda.gov/pubs/ja/ja_lemly017.pdf
Program on Reproductive Health and the Environment7
Early Puberty
Program on Reproductive Health and the Environment
ADHD among 5 – 17 year olds
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Program on Reproductive Health and the Environment
Disturbing National Health Trends
Similar trends:PTB, LBW, autism, obesity, GDM, gastroschisis, infertility, hypospadius, childhood cancer
http://www.cdc.gov/media/dpk/2013/dpk-vs-child-obesity.html#graphicshttp://www.cdc.gov/ncbddd/autism/data.htmlhttp://seer.cancer.gov/publications/childhood/ Program on Reproductive
Health and the Environment
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1945 1955 1965 1975 1985 1995 2005
U.S. Chemical Production 1945 - 2007
Federal reserve data on chemical production is only offered as relative production, which is unit-less. A specific reference year is chosen and values are calculated relative to that years production. In this particular data set 2007 is the reference year and is assigned a value of 100.
Data from: U.S. Federal Reserve Board, Division of Research and Statistics
Program on Reproductive Health and the Environment
43Chemicals Detected in
Virtually Every Pregnant Woman in the US
Woodruff T.J., Zota A.R., and Schwartz J.M. Environmental
Health Perspectives 2011Program on Reproductive
Health and the Environment
True, True, and Unrelated?Do you think these trends are related?
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Yes,
envi
ronm
e...
No, t
hese p
rob...
No su
re/o
ther
58%
40%
2%
A. Yes, environmental toxins & endocrine
disrupters increase the risk of many
diseases and conditions
B. No, these problems are caused by too
much TV or poor parenting
C. No sure/other
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Program on Reproductive Health and the Environment
Endocrine Disrupting Chemicals:Substances that interfere with normal hormonal activity
Program on Reproductive Health and the Environment
Streams of Evidence for Toxicity Assessment
Regulatory Change: Precautionary Approach
Program on Reproductive Health and the Environment
Patient level: Actions Matter: Pesticides
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Lu C et al. 2006. Organic diets significantly lower children's dietary exposure to organophosphorus pesticides. Environ Health Perspect. 2006;114:260-3.
Organic diet Organic diet
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Program on Reproductive Health and the Environment
Patient level: Actions Matter: BPA
• Harvard cafeteria
• N=75, 5d fresh soup,
5d canned
• Urinary BPA
• 5 bay area families
• 3d catered food: fresh, organic, no BPA or plastics
33Carwile JAMA 2011 Rudel, EHP 2011 Program on Reproductive
Health and the Environment
Health Care: Program on Reproductive
Health & the EnvironmentMission: To create a healthier
environment for human
reproduction & development
by advancing scientific
inquiry, clinical care, &
health policies that
prevent exposures to
harmful chemicals in
our environment
Program on Reproductive Health and the Environment
PRHE: All That Matters Publications
• UCSF Reproductive Environmental Health & Justice elective for Fellows & Residents Program on Reproductive
Health and the Environment
So what can our patients do today?-Top 10
1. Buy organic $$$
– Organic produce has
less pesticide residue
– Wash produce
– Avoid fast food &
processed food
– Limit foods high in
animal fat
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Program on Reproductive Health and the Environment
• Preconception Health Council of California http://www.everywomancalifornia.org
Program on Reproductive Health and the Environment
Program on Reproductive Health and the Environment
Strength of the Evidence
QuickTime™ and a decompressor
are needed to see this picture.
Diamanti-Kandarakis E et al. 2009Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement. Endo Rev 30(4):293-342
Evidence for adverse reproductive outcomes (infertility, cancers, malformations) from exposure to endocrine disrupting chemicals is strong, and there is mounting evidence for effects on … thyroid, neuroendocrine, obesity and metabolism, and insulin and glucose homeostasis.
Program on Reproductive Health and the Environment
Estrogen: the key
BPA: the paperclip pick-lock
Estrogen Receptor: the key-hole
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Estrogen, DES and BPA: Endocrine Disruption
Science in Products http://scienceinproducts.blogspot.comRuben et al. 2011
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Program on Reproductive Health and the Environment
CDC Lead in Pregnancy 2010http://www.cdc.gov/nceh/lead/publications/LeadandPregnancy2010.pdf
Program on Reproductive Health and the Environment
Lead in unexpected places: ethnic products
• Mexican treatments: Azarcon and greta
(also known as liga, Maria Luisa, alarcon,
coral, rueda)
• Asian treatments: chuifong, tokuwan,
ghasard, bali goli, kandu
• Middle eastern treatments or cosmetics:
alkohl, saoott, cebagin
• Lipstick
Program on Reproductive Health and the Environment
Lesson From the Past: Dibromochloropropane (DBCP)
• DBCP - pesticide widely used in the U.S. (fruit and soybeans)
• 1961 - testicular atrophy documented in three rodent species
• 1977 - Agricultural workers became aware that none had fathered children
• Investigation of sentinel worker cohort found profound and permanent effects on spermatogenesis due to exposure to DBCP
• 1985 DBCP was banned from all food crops in the U.S., its export was not
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Program on Reproductive Health and the Environment
Preventing genes from functioning normally
Multi-generational Impacts of Environmental Exposures
National Research Council. Science and Decisions: Advancing Risk Assessment. Washington, DC: The National Academies Press 2008; National Research Council. Phthalates and Cumulative Risk Assessment: 2008; Welshons, W.V., et al., Large effects from small exposures. I. Mechanisms for endocrine-disrupting chemicals with estrogenic activity. Environ Health Perspect, 2003. 111; Palanza, P., et al., Prenatal exposure to endocrine disrupting chemicals: effects on behavioral development. Neurosci Biobehav Rev, 1999. 23
Interfere w/ hormonal regulation critical to healthy reproduction
Program on Reproductive Health and the Environment
Lesson From the Past: DES
• Rx’d 1940-70s for threatened Ab
– ~ 2-8 million births affected
• Adverse effects in children
– Vaginal CA in female offspring (<0.1%) &
breast CA
– Reproductive tract dysfunction in male
& female offspring (>90%)
• Adverse effects in grandchildren
– Menstrual irregularities, ovarian CA
– Hypospadius
62From Newbold 2007 UCSF/CHE Summit
Program on Reproductive Health and the Environment
Epigenetic Effects
• F0 animals exposed to substance prior to conception and
during pregnancy
• F1 animals were exposed directly during in utero
• F2 animals were potentially exposed as germ cells of the F1.
Effects noted in F1 and F2 generations are termed
“multigenerational” (Skinner 2008).
• F3 animals are the first generation that received no exposure
to TBT at any time, and phenotypes observed in F3 animals
are considered to be transgenerational and permanent
(Anway and Skinner 2006; Jirtle and Skinner 2007).
Program on Reproductive Health and the Environment
“Warnings from a Flabby Mouse”Nicholas Kristof, NY Times 1/19/13
• Tributyltin: fungicide, banned by Intl.
Maritime Org., but persistent in
environment, measurable levels in
humans
• Prenatal TBT exposure increased fat
• TBT reprogrammed MSCs toward fat
cells in all 3 generations
• Prenatal TBT exposure led to fatty
liver & changed liver fat metabolism
in 3 subsequent generations
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Chamorro-García Environmental Health perspectives 2013
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Program on Reproductive Health and the Environment
• Prenatal TBT exposure
led to hepatic lipid
accumulation & up-
regulated hepatic
expression of genes
involved in lipid
storage/transport,
lipogenesis, & lipolysis in
all 3 subsequent
generations
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Chamorro-García Environmental Health perspectives 2013
Program on Reproductive Health and the Environment66
Post pubertal exposure: No increased risk of breast cancer
Prepubertalexposure: 5 fold increased risk of breast cancer
* From Cohn et al. EHP 2007
Lesson From the Past - DDT
Program on Reproductive Health and the Environment
Air Pollution and Autism
67Program on Reproductive
Health and the Environment
~ 87,000 chemicals listed for use or import into U.S.
~ 3,000 chemicals manufactured or imported > 1 million pounds
~ 700 new added chemicals each yearU.S. EPA. What is the TSCA Chemical Substance Inventory. US Environmental Protection Agency 2006; National Research Council. Toxicity Testing for Assessment of Environmental Agents. The National Academies Press. Washington, D.C. 2006; Wilson MP, Chia DA, Ehlers BC. Green Chemistry in California: A Framework for Leadership in Chemicals Policy and Innovation. California Policy Research Center, University of California. 2006. http://www.ucop.edu/cprc/documents/greenchemistryrpt.pdf.
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Program on Reproductive Health and the Environment