People Safe: The Link Between Declining Fertility and Environmental Contaminants

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People Safe The Link Between Declining Fertility
and Environmental Contaminants
Amanda Bowes Reproductive Health Technologies
Project Summer Intern Bryn Mawr College
July 31, 2009
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Contents

• Introduction
• What is environmental health?
• The Chemical Connection
• How do we define fertility?
• Related health conditions for infertility
• Endocrine disruptors an introduction
• Current Regulatory Framework - TSCA
• Proposed Regulatory Framework - KSCA
• Key chemical vocabulary
• A filter
• Male reproductive health
• Low sperm count/decreased sperm quality
• Hypospadias
• Cryptorchidism
• Shortened/lengthened ano-genital distance

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Contents

• Female reproductive health
• Recurrent miscarriage/fetal loss
• Endometriosis
• Polycystic ovarian syndrome (PCOS)
• Conclusion
• Discussion
• Recommendations Research
• Recommendations Industry
• Recommendations Policy
• Acknowledgements
• Works Cited

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Introduction
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What is environmental health and justice?

• The environmental health movement dates at
  least to Progressive Era urban reforms including
  clean water supply, more efficient removal of raw
  sewage and reduction in crowded and unsanitary
  living conditions. Todays movement is more
  related to nutrition, preventive medicine, aging
  well, etc..17
• Environmental justice, by contrast, began in
  the 1980s as an effort to minimize the disparate
  impact of air pollution as well as water and food
  chemical contamination on minority and
  poverty-stricken populations.17
• Groups from both the environmental health and
  environmental justice campaigns have emphasized
  chemical contaminants in our environment and
  consumer products as a key concern.

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The Chemical Connection

• While chemical production has increased, human
  and animal health has declined, particularly
  reproductive health. The sudden and steep rates
  for physical and behavioral sexual abnormalities
  suggests an environmental component is at work.4
• Although many of these chemicals have
  demonstrated a negative effect on cancer
  incidence and various developmental processes, I
  would like to focus on infertility as a result of
  toxic chemical exposure.

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How do we define infertility?

• The Centers for Disease Control and Prevention
  defines infertility as the inability to get
  pregnant after trying for one year.
• The CDC reports that in 2002, of the 62 million
  American women of reproductive age, about 1.2
  million, or 2, had an infertility-related
  medical appointment within the previous year, and
  8 had an infertility-related medical visit at
  some point in the past.
• 7 of married couples in which the woman was of
  reproductive age (2.1 million couples) were
  classified as infertile according to the CDC
  definition.3

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Infertility and related conditions

• There are various conditions that either directly
  or indirectly result in infertility or
  reduced-fertility
• Lower sperm count/decreased sperm quality
• Hypospadias
• Cryptorchidisms
• Shortened/lengthened ano-genital distance
• Recurrent miscarriage/Fetal loss
• Endometriosis
• Polycystic ovarian syndrome (PCOS)
• Researchers cite exposure to endocrine disruptors
  as a possible cause of these illnesses.

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Endocrine Disruptors an introduction

• Endocrine disruptor is a term used to describe
  thousands of chemicals that interfere with the
  endocrine system, or an integrated system of
  hormone-producing glands that control various
  body functions.6
• Researchers point to endocrine disrupting
  chemicals, or endocrine disruptors, as the cause
  for conditions such as decreased sperm quality.
  Endocrine disruptors are present in food, the
  environment, and consumer products.
• Many endocrine disruptors affect not only the
  exposed individual, but also his/her offspring
  and future generations.6

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Current Regulatory Framework

• Toxic Substances Control Act (TSCA)
• TSCA was passed in 1976.
• TSCA holds the EPA solely responsible for
  demonstrating the dangers of a particular
  chemical.1 Thus companies are not required to
  prove the safety of the chemicals used in their
  products before they are placed on the market.
• Without manufacturers data for the production
  and use of a chemical, the EPA is often
  ill-equipped to effectively regulate a
  potentially dangerous product.
• There has been a 30 increase in U.S. chemical
  production since 1979, with 80,000 chemicals now
  approved for commercial use, many of which
  exhibit endocrine disrupting qualities.1

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Proposed Federal Regulatory Frameworks

• Kid-Safe Chemical Act (Kid-Safe)
• In January 2009, the Government Accountability
  Office placed chemical safety to its high risk
  list of areas that should be addressed
  immediately.1
• Kid-Safe was introduced in 2008 as an
  update/reform for TSCA. Advocacy coalitions such
  as Safer Chemicals, Health Families would like it
  to be reintroduced in 2009.
• Kid-Safe would require pre-market testing by
  companies and would expand the list of chemicals
  researched and regulated by the FDA and EPA.1
• Other Chemical Specific Legislation
• Additionally, there has been federal
  chemical-specific regulation proposed, including
  legislation introduced in March 2009 that would
  remove bisphenol A from all food containers.

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Key Chemical Vocabulary

• Kid-Safe encourages the EPA and other agencies to
  regulate chemical production using the following
  terms to describe the risk a chemical poses to
  health
• Persistence- how long the chemical remains in the
  atmosphere or environment before being broken
  down. This is measured by the chemicals
  half-life, or the interval required for the
  quantity to decay to half of its initial value.2
• Ubiquitous- the chemical or toxin is everywhere
  or at least in many different elements of our
  environment.
• Bioaccumulative- a chemical or chemicals
  accumulate in an organism. This occurs when an
  organism absorbs a toxic substance at a rate
  greater than that at which the substance is lost.
  16

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A filter

• For the purposes of my research and this
  presentation, I will examine the relationship
  between individual or specific groups of
  chemicals and these conditions.
• I have highlighted man-made contaminants
  specifically noted in Kids-Safe to demonstrate
  the importance of passing this piece of
  legislation.
• All of the substances described, including
  phthalates, polychlorinated biphenyls, dioxins,
  bisphenol A, diethylstilbestrol are considered
  endocrine disruptors.

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Male Reproductive Health and Infertility
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Low sperm count/decreased sperm quality

• Sperm counts in Western countries appear to have
  declined by half in the past 50 years.4
• In addition to lower sperm concentrations, DNA
  damage in sperm contributes to poorer embryo
  development and lower pregnancy rates among
  partners of men undergoing assisted reproductive
  treatments.5

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Phthalates

• Phthalates are a family of endocrine disrupting
  chemicals that are used in many consumer products
  to soften plastics, from flooring and wall
  coverings, to medical devices and personal-care
  products such as perfumes, lotions and
  cosmetics.6 About a billion pounds of phthalates
  are produced each year.1

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Phthalates and semen quality

• There are only a few epidemiological studies on
  phthalates and semen quality. One large study
  from an infertility clinic in Massachusetts found
  associations between monobutyl phthalate (MBP)
  and decreased sperm motility and sperm
  concentration.4
• In a study by the Harvard School of Public
  Health, at least 90 of the male partners in a
  cohort of infertile couples tested positive for
  MBP.5
• Men exposed to DBP and/or DEHP (two other
  phthalates) during puberty or adulthood
  experienced decreased sperm production.5

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PCBs

• Polychlorinated biphenyls (PCBs) are persistent
  compounds that were widely used in industrial and
  consumer products for decades until they were
  banned in the late 1970s.
• Used in cutting oils, lubricants, and electrical
  insulators.4

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PCBs and semen quality

• In studies done in several different countries,
  including the U.S., the evidence suggests an
  inverse association of PCBs with reduced semen
  quality, specifically reduced sperm motility, or
  the mobility of the sperm towards the egg.4
• Because the associations were found across a
  broad range of PCB levels, there is believed to
  be no threshold of exposure/vulnerability.4
• PCBs can also bioaccumulate up the food chain, so
  that fish, meat, and dairy products we consume
  may increase our risk of exposure.4

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Dioxins

• Dioxins are a class of chemical contaminants that
  are formed during combustion processes such as
  waste incineration, forest fires, and backyard
  trash burning, as well as during some industrial
  processes such as paper pulp bleaching and
  herbicide manufacturing.7

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Dioxins and semen quality

• Most exposure to dioxins (roughly 95) occurs
  through eating foods contaminated with these
  toxins. 7,1
• Recent studies suggest that the timing of
  exposure may have an impact upon semen quality.
  Exposure at some ages may result in decreased
  sperm count or sperm motility, whereas at other
  ages there may be a stimulatory or increased
  effect.4

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Hypospadias

• Hypospadias is a condition in which the opening
  to the urethra (the tube through which urine and
  semen travel) forms on the underside of the penis
  or below the penis.
• Hypospadias is the second most common birth
  defect in the U.S.6 The Centers for Disease
  Control and Prevention (CDC) reported a doubling
  of hypospadias cases from 1968 to 1993 in the
  U.S.. Rates are currently highest among whites
  and lowest among Hispanics.8
• Reports of increased rates of hypospadias have
  coincided with increased rates of testicular
  cancer, cryptorchidism, and decreasing semen and
  sperm quality.8

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Chemicals associated with hypospadias

• It is believed that phthalates could interfere
  with the ability of testosterone to masculinize
  the male reproductive tract, resulting in many
  different genital malformations including
  hypospadias.10
• Animals treated with either DBP or DEHP
  (phthalates) developed hypospadias.9
• Diethylstilbestrol (DES), a chemical prescribed
  to pregnant women as a means of preventing
  spontaneous abortions and promoting fetal growth,
  instead caused women to give birth to daughters
  with increased risk for breast, vaginal and
  cervical cancers, and grandsons with a 20-fold
  increase in the development of hypospadias.9

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Cryptorchidism

• Cryptorchidism is a condition in which one or
  both of the testes are missing from the scrotum
  at birth. This usually suggests that the testes
  have failed to descend from the abdominal area
  during fetal development.11
• Again, increased rates of cryptorchidism have
  coincided with increased rates of testicular
  cancer, hypospadias, and decreasing semen and
  sperm quality.8

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Chemical contaminant exposure and cryptorchidism

• Studies show that the prevalence of
  cryptorchidism is variable and geographically
  specific, with increasing trends in some studies
  but not in others.4 The strongest data suggests
  that people that either live in primarily
  agricultural areas or whose parents were exposed
  to various nonorganochlorine pesticides are at
  greater risk for cryptorchidism.
• Cryptorchidism has been observed following
  exposure to DEHP and DBP (phthalates).9

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Shortened/lengthened ano-genital distance

• Ano-genital distance is the measurement of the
  length of the area between the anus and the
  genitals6 and is usually twice as large for
  males versus females.12
• Because testosterone triggers this area to
  lengthen as a part of normal male development, a
  shorter ano-genital distance often suggests an
  interference with either the production or action
  of testosterone.6
• The condition is also associated with
  un-descended testes and/or decreased sperm
  quality.

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Bisphenol A

• BPA is a chemical used in clear and shatter-proof
  plastic food and drink containers, the lining of
  metal food and drink cans, pacifiers and baby
  toys, computers, cell phones, paints, adhesives,
  enamels and varnishes.6 Recent studies show that
  BPA can migrate from the container into the
  contents, especially when heated.10 About 6
  billion pounds of BPA are produced each year.1

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The Trouble with BPA

• In a 2003-2004 bio-monitoring study by the
  Centers for Disease Control, 92.6 of over 2500
  Americans had BPA in their urine.4,1
• BPA has a longer half-life in humans than
  previously thought.4
• Also, BPA appears to have an unusual dose-effect,
  showing an inverted-U dose-response curve.14

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Bisphenol A and ano-genital distance

• Bisphenol A (BPA) has been shown to increase
  ano-genital distance in a study of rats.6
• Although the FDA currently describes BPA as
  safe, Canada and many U.S. states and cities
  have banned the chemical. According to Heather
  Patisaul and Heather Adewale, the fate of BPA
  may ultimately be decided by politics and public
  perception, rather than a regulatory action based
  on a measured evaluation of the scientific
  evidence.10

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Female Reproductive Health and Infertility
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Recurrent miscarriage/fetal loss

• The number of miscarriages and stillbirths have
  increased from 14 per 1,000 pregnancies during
  the 1980s to 16 per 1,000 in the 1990s and
  2000s.1
• About 40-70 of miscarriages are linked to
  chromosomal abnormalities at conception, i.e.
  unusual numbers of individual or entire sets of
  chromosomes.13
• Adult humans exposed to dioxins, PCBs, heavy
  metals such as lead, mercury and cadmium, and
  various phthalates have demonstrated fetal loss.12

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BPA and recurrent miscarriage/fetal loss

• According to recent Japanese study, high in vivo
  (or after a person is born) exposure to BPA may
  be associated with recurrent miscarriage.
• Because measurable amounts of BPA have been found
  in the amniotic fluid and placental tissue of
  pregnant women, it is believed that developing
  fetuses are readily exposed to this chemical.4

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Endometriosis

• Endometriosis is a chronic disease in which women
  develop tissue that usually lines the uterus
  grows abnormally in other locations, such as the
  ovaries and fallopian tubes, and even in distant
  organs like the lungs and heart.12
• About 40 of women diagnosed with endometriosis
  also suffer from infertility.12
• In 2002, the total health care costs in the U.S.
  for diagnosis and treatment of endometriosis was
  approximately 22 billion.4

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Chemicals associated with endometriosis

• Elevated serum levels of dioxin-like compounds
  such as PCBs correlated strongly with
  endometriosis.14
• Rhesus monkeys treated with TCDD developed acute
  endometriosis and women with endometriosis also
  had high plasma concentrations of phthalates in a
  study in India.4
• In an Italian study, a similar association
  between plasma concentrations of phthalates such
  as DEHP and endometriosis was found.14

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Polycystic ovarian syndrome (PCOS)

• Polycystic ovarian syndrome or PCOS can affect a
  woman's menstrual cycle, ability to have
  children, hormones, heart, blood vessels, and
  appearance. Women with PCOS have high level of
  androgens (a typically male hormone), missed or
  irregular periods, and many small cysts in their
  ovaries.15
• The Endocrine Society describes PCOS as a
  leading cause of subfertility.4
• The cost to the health care system for PCOS
  diagnosis and treatment totals 4.4 billion in
  the U.S. in 2004.4

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PCOS and BPA

• Women with PCOS also have higher levels of BPA.4
• A 5-fold higher level of BPA in the amniotic
  fluid of mothers of PCOS patients suggests
  prenatal exposure.4

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Conclusions
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Discussion

• Many of the chemicals included in the Kid-Safe
  legislation have a demonstrated and significant
  impact on humans reproductive health,
  particularly on their fertility.
• Although we must consider the current research,
  more can and should be done to fully understand
  the biological threat these contaminants pose.
• It is critical that government officials,
  advocates, and manufacturers work to bring
  consumers expectations and a products reality
  with regard to long-term use and safety in synch
  by strengthening current chemical regulation.

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Recommendations - Research

• Because individuals or populations are constantly
  exposed to multiple industrial chemicals, it can
  be difficult to establish the effects of one
  compound at a time. Thus more research should be
  conducted to explore the effects of a combination
  of BPA and certain phthalates, for example.
• Research on possible green or safe alternatives
  must be a priority. Current funding for green
  chemistry research represents a very small
  portion of the federal budget.1

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Recommendations Industry

• Manufacturers must be required to provide the EPA
  and the public with basic information with regard
  to a chemicals safety for consumers and workers.
• The chemical industry should be held responsible
  for demonstrating their products safety, similar
  to pharmaceuticals which are subject to stringent
  pre-market testing. Such chemical safety data
  must be published and disseminated to the wider
  public.
• Corporations should be encouraged to research
  green or non-harmful alternative chemicals to
  be used in production.

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Recommendations Policy

• Rep. Ed Markey (D-MA) and Sens. Dianne Feinstein
  (D-CA) and Chuck Schumer (D-NY) introduced
  legislation to ban BPA in all food and beverage
  containers in March 2009.1 Similar
  chemical-specific regulation and overall chemical
  regulation reform is needed.
• The EPA should coordinate more effectively with
  FDA and other agencies to reduce the amounts of
  persistent, bio-accumulative toxicants (PBTs) in
  our environment and consumer products.
• More resources and authority should be given to
  the FDA and CPSC to protect us from harmful
  chemicals in cosmetics and consumer products.

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Acknowledgements

• Invaluable input and feedback were provided by
  the entire Reproductive Health Technologies
  Project staff, especially Jenn Rogers, acting
  director, and Lydia Stuckey, my supervisor for
  the summer.
• I would also like to thank Bryn Mawr Colleges
  Katharine Houghton Hepburn Center and Susan Wood,
  PhD for the opportunity to work with such an
  amazing organization these past eight weeks.

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Works Cited

• 1 Rushing, Reece. Center for American Progress.
  Reproductive Roulette Declining Reproductive
  Health, Dangerous Chemicals, and a New Way
  Forward. July 2009.
• 2 Half-life. Wikipedia article.
  http//en.wikipedia.org/wiki/Half-life. July 20,
  2009.
• 3 Assisted Reproductive Technology, Home.
  Centers for Disease Control and Prevention,
  Department of Health and Human Services.
  http//www.cdc.gov/ART/. July 20, 2009.
• 4 Diamanti-Kandarakis, Evanthia, et al., the
  Endocrine Society. Endocrine-Disrupting
  Chemicals An Endocrine Society Scientific
  Statement. 2009.
• 5 Hauser, R., et al. DNA damage in human sperm
  is related to urinary levels of phthalate
  monoester and oxidative metabolites. Human
  Reproduction Vol. 22, No. 3, pp. 688-695. 2007.
• 6 Schwartz, Jackie M. et al. Shaping Our Legacy
  Reproductive Health and the Environment.
  University of California San Francisco, Program
  on Reproductive Health and the Environment.
• 7 Dioxins. National Institute of Environmental
  Health Sciences, National Institutes of Health.
  http//www.niehs.nih.gov/health/topics/agents/diox
  ins/index.cfm. July 22, 2009.
• 8 Wang, Ming-Hsien et al. Endocrine Disruptors,
  Genital Development, and Hypospadias. Journal of
  Andrology, Vol. 29, No. 5. September/October
  2008.
• 9 David, Raymond M. Proposed Mode of Action for
  In Utero Effects of Some Phthalate Esters on the
  Developing Male Reproductive Tract. Toxicologic
  Pathology, 34. pp. 209-219. 2006.
• 10 Patisaul, Heather B. and Adewale, Heather B.
  Long-term effects of environmental endocrine
  disruptors on reproductive physiology and
  behavior. Fronteirs in Behavioral Neuroscience,
  Vol. 3, Article 10. pp. 1-18. June 2009.

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Works Cited Continued

• 11 Cryptorchidism. Wikipedia article.
  http//en.wikipedia.org/wiki/Cryptorchidism. July
  23, 2009.
• 12 Luoma, Jon. Challenged Conceptions
  Environmental Chemicals and Fertility. Stanford
  University School of Medicine, Collaborative on
  Health and the Environment. October, 2005.
• 13 Sugiura-Ogasawara, Mayumi et al. Exposure to
  bisphenol A is associated with recurrent
  miscarriage. Human Reproduction, Vol. 20, No. 8.
  pp. 2325-2329. 2005.
• 14 Caserta, D. et al. Impact of endocrine
  disruptor chemicals in gynaecology. Human
  Reproduction Update, Vol. 14, No. 1. pp. 59-72.
  2008.
• 15 Savabieasfahani, Mozhgan et al.
  Developmental Programming Differential Effects
  of Prenatal Exposure to Bisphenol-A or
  Methoxychlor on Reproductive Function.
  Endocrinoogy, Vol. 12, No. 147. pp. 5956-5966.
  2006.
• 16 Bioaccumulation. Wikipedia article.
  http//en.wikipedia.org/wiki/Bioaccumulation.
  July 30, 2009.
• 17 Environmental movement in the United States.
  Wikipedia article. http//en.wikipedia.org/wiki/En
  vironmental_movement_in_the_United_States. July
  30, 2009.

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