People Safe: The Link Between Declining Fertility & Environmental Contaminants

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

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

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

Introduction

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. Today’s 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.

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.

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

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
Recurrent miscarriage/Fetal loss
Endometriosis
Researchers cite exposure to endocrine disruptors as a possible cause of these illnesses.

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

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

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.

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 chemical’s “ 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

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 .

Male Reproductive Health and Infertility

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

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

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

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

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

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

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

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

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

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

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

Ano-genital distance is the “measurement of the length of the area between the anus and the genitals” 6 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 .

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

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

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

Female Reproductive Health and Infertility

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

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

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

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

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

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

Conclusions

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 product’s reality with regard to long-term use and safety in synch by strengthening current chemical regulation.

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

Recommendations – Industry
Manufacturers must be required to provide the EPA and the public with basic information with regard to a chemical’s safety for consumers and workers.
The chemical industry should be held responsible for demonstrating their product’s 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.

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.

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 College’s Katharine Houghton Hepburn Center and Susan Wood, PhD for the opportunity to work with such an amazing organization these past eight weeks.

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/dioxins/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.

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/Environmental_movement_in_the_United_States. July 30, 2009.

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