CHE Partner Shanna Swan: Investigating Environmental “Cocktail” of Endocrine Disruptors

In 1981, the California Department of Health Services (CDHS) recruited Dr. Shanna Swan and a number of other environmental scientists for what was then – as she put it – a “new and exciting” program: the Environmental Health Investigations Branch.

“Almost immediately,” she wrote in an email interview, “I was faced with a community in South San Jose that was deeply concerned about a cluster of birth defects and miscarriages, and its possible connection with the contamination of a public water supply by a toxic release from a nearby semiconductor plant.”

The leaked contaminants were organic solvents, primarily trichloroethane and dichloroethylene.

Determining the relationship, if any, between a cluster of health impacts and a suspected contamination source is a daunting scientific challenge.

“Cluster investigations are often unrewarding and frustrating,” says Dr. Ted Schettler, Science Director of the Science and Environmental Health Network and author of Generations at Risk: Reproductive Health and the Environment (MIT Press, 1999). “For one thing, what appears to be a cluster may not be anything more than chance variation in the way health impacts are distributed. Beyond that, even if there is a larger-than-expected cluster of impacts in a community, tracing down the cause can be exceedingly hard. Finally, even if a link appears likely, single clusters of disease often do not involve enough people to have the statistical power to reach statistical significance.
    

“On the other hand, when a finding of significance does emerge, cluster investigations can be very instructive.”       

Dr. Swan tackled the South San Jose situation by initiating a series of studies examining the episode. The research group grew over time into the Reproductive Epidemiology section of CDHS, which she led until 2005. The studies evolved too, to address the broader question of risks conveyed by consumption of tap (vs. bottled) water by pregnant women.    

“Although we demonstrated a dose-response relationship between increasing tap water consumption by pregnant women and risk of spontaneous abortion in some areas of California, we were not, despite more than ten years of research, able to identify an etiologic [causative] agent.”
   
Put more plainly, the researchers found that in some areas of California, the more tap water pregnant women drank, the higher their risk of spontaneous abortion.
   
This doesn’t necessarily mean that the tap water was causing the spontaneous abortions. As the oft-repeated saying goes, correlation doesn’t prove causation. Despite over a decade of research, they were unable to determine exactly what was changing the risk levels.

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Dr. Swan’s work on the San Jose semiconductor plant leak led to her participation in an industry-wide study of the reproductive effects of exposure to organic solvents in semiconductor manufacturing clean rooms. The results showed “significant reproductive toxicity of ethylene glycol ether and other clean-room solvents”, leading to the replacement of those solvents with less-hazardous propylene glycol ethers.
   
Nearly all her subsequent work has related to the effects of environmental contaminants on various aspects of human reproduction - fetal loss, fertility, time to pregnancy, low birth weight, birth defects, growth retardation, semen quality and sex hormones – and related methodological issues.
   
Of great concern to her and an increasing number of other scientists is a group of contaminants known as endocrine-disrupting chemicals, endocrine disruptors or EDCs.
   
According to the EPA, EDCs are synthetic chemicals that interact with the human body’s glands, hormones and hormone receptors, known collectively as the endocrine system.
   
“The function of the system is to regulate a wide range of biological processes, including control of blood sugar, growth and function of reproductive systems, regulation of metabolism, brain and nervous system development, and development of an organism from conception through adulthood and old age. Disruptions in hormone balance at critical life stages may have long-lasting effects.”
   
Dioxin (an industrial byproduct), the U.S.-banned pesticide DDT and an entire class of persistent organic compounds called Polychlorinated Biphenyls (PCBs) are just three known EDCs. Many more are known or suspected.
   
People can be exposed to EDCs in several ways: direct physical contact (for example, handling a pesticide), ingestion of contaminated food or water, and breathing contaminated air.
   
Health effects of EDC exposure can run the gamut, according to the EPA, from cancer to immune, endocrine, neurological and reproductive system impacts.
   
In the mid-1990s, Dr. Swan was appointed to a National Academy of Sciences and National Research Council committee that had formed to investigate the health risks from hormonally active environmental chemicals. She worked with three other respected scientists, Drs. Fred vom Saal, Lou Guillette and Ana Soto (the latter two are also CHE Partners), to summarize the existing body of research on reproductive risks from certain EDCs. Vom Saal has spoken on a past CHE Partnership Call; Guillette and Soto are CHE Partners.
   
The committee was particularly interested in a study that had reported a worldwide decline in semen quality. At the committee’s request, she examined that issue.
   
Uncertainties in the historical data prompted her to approach the question from a new angle.
   
“If sperm counts had declined, I reasoned, and if this was the result of environmental factors, then these factors (unless transient or uniformly distributed) should produce geographic variability in reproductive parameters.”
   
That is, if sperm numbers are down because of something in the environment, and that something isn’t distributed equally, then sperm numbers shouldn’t be down equally.
   
In order to find out if this was the case, she established the Study for Future Families (SFF), a multi-center study of pregnant women, their partners and their children, of which she has been Principal Investigator since 1998. Funding to date from the EPA and the National Institute of Environmental Health Sciences has totaled $6.5 million.
   
SFF’s findings of significant differences in semen quality between men from urban vs. agricultural areas indicate that her reasoning was correct. Those findings led SFF to investigate pesticides as reproductive toxicants, yielding “evidence of significant associations between several herbicides widely used in the Midwest and several semen parameters and related issues.” SFF has also found that prenatal exposure to some phthalates – another chemical class of concern – is associated with incomplete masculinization of the male genital tract.
   
In 2005, three significant things happened for Dr. Swan: she moved to the University of Rochester in New York, where today she is Professor and Associate Chair for Research in the Department of Obstetrics and Gynecology and Director of the Center for Reproductive Epidemiology; she was awarded the Jenifer Altman Award for “outstanding dedication to scientific integrity in environmental health sciences and the pursuit of science in the public interest”.

With that same dedication to the pursuit of environmental health science in the public interest, she had joined a fertility working group of the Collaborative on Health and the Environment (CHE) in 2003.
   
“CHE is revolutionary!” she says via email. “Amazing! It is changing public opinion and spreading the word faster than I thought possible.”

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It's not easy being on the cutting edge of environmental health science. Dr. Swan still remembers a 1999 editorial labeling her and her colleagues on the National Academy of Sciences committee “endocrine disruptor cry-babies”.
   
“Skepticism,” she notes dryly, “from those who resist these new paradigms is an ongoing problem.”
   
She is playing a huge role in advancing those paradigms, in pursuit of what she regards as the most significant potential future development in her field: “Understanding the importance to human health of exposure to a ‘cocktail’ of EDCs.”
   
Leaps forward in this understanding are likely to spring from the 2008 Gordon Research Conference on Environmental Endocrine Disruptors, of which Dr. Swan is Chair.
   
At the University of Rochester, she is working with a wide range of collaborators, including epidemiologists, biostatisticians, toxicologists, geneticists and systems biologists, to develop and apply methods to assist in identifying human health risks from pervasive, low-level environmental exposures – methods which are “sensitive enough to tease out the often subtle health effects of complex mixture”
   
This “professional ‘family’”, as she calls it, “a small and close-knit community”, inspires her groundbreaking work. So do her students, “because of their commitment and curiosity and willingness to explore new avenues of science.”



CHE Administrative Coordinator Shelby Gonzalez has a background in environmental journalism.