The Environmental Endocrine Hypothesis and the Formulation of Environmental Health Policy

The Environmental Endocrine Hypothesis and the Formulation of

Environmental Health Policy

Are we swimming in a sea of estrogens? Has pollution created an environment in which fish, birds and animals are doomed to be feminized? The environmental endocrine hypothesis is a hotly contested concept that is currently being scrutinized by scientists in pure research and applied environments. The development of public policy involves government regulatory agencies, industry trade associations, environmental groups, scientists working in each of these areas, the media, and public sentiment. The environmental endocrine hypothesis (EEH), which "asserts that a diverse group of agricultural and industrial chemicals in contact with humans and wildlife have the capacity to mimic or obstruct hormone function" (Krimsky 1999, p. 2) has moved from relative obscurity to the top of the Environmental Protection Agency's agenda in less than ten years and is now a well-funded area of research. It is significant because of the challenges it poses to fundamental assumptions and practices used in evaluation of public health risks of exposure to industrial and agricultural chemicals. The course of the debate so far suggests that all stakeholders will use new technology for communication, in particular the Internet, to gain support for their views in the public's perception. The direction of public policy on the EEH is critical because of the large numbers of people who may be at risk, and the human and financial resources required to evaluate the risk. This paper will briefly describe the evolution of the environmental endocrine hypothesis (EEH), reaction to it, and consider ways in which competing agendas and priorities are shaping the debate about policy.

What are environmental endocrine disrupters?

Endocrine disrupters are also known as environmental estrogens, estrogenic xenobiotics, and xenoestrogens (Gist 1998), although the some of the chemicals identified as endocrine disrupters demonstrate anti-estrogenic effects, and others may interfere with androgens, such as is vinclozolin, a chemical once used as a fungicide for grapes. Male pups born to exposed mothers had many female reproductive characteristics, leading the researchers to suggest that the chemical was binding to androgen receptors, and blocking the transcription of DNA (Lutz 1993, p. 13). Another class of ED's interferes with the thyroid system, resulting in mental retardation and neurological problems in offspring exposed early in the gestation period (Colburn et al 1993). However, it is estrogenic effect that has been most commonly observed in vitro and in vivo and it is the environmental estrogens that have been most controversial.

Today at least 500 measurable chemicals are present in human tissue that were not there before the 1920's (Colburn 1998). Examples of chemicals reported to have reproductive and endocrine disrupting effects include: pesticides (2,4 D, atrazine); fungicides (hexachlorobenzene, vinclozolin); insecticides (aldrin, chlordane, DDT and metabolites, dieldrin, methoxychlor, parathion, toxaphene); and industrial chemicals (4-OH alkyl phenol, bisphenol A, dioxin, PCBs, and phthalates (Colburn et al 1993). A major source of ED's is sewage, in which approximately 3,000 out of a possible 60,000 man-made organic pollutants have been identified (Gist 1998).

In a chapter written for a recent medical text, Colburn identified six different categories of mechanisms of action for endocrine disrupters:

1. binding to receptors and enhancing effects as agonists;

2. blocking receptors and inhibiting effects as antagonists;

3. directly interfering with endogenous hormones;

4. indirectly interfering with endogenous hormones or other

naturally produced chemical messengers;

5. altering steroidogenesis, metabolism, and excretion;

6. altering hormone receptor levels (1998, p. 807).

The development of the environmental endocrine hypothesis

A detailed narrative of the development of the EEH is provided in a recent book, Hormonal Chaos (Krimsky 1999). The author, an environmental scientist himself, traces the roots of the EEH to three independent research programs: work on intergenerational effects of the potent xenoestrogen DES (diethylstilbestrol), a large body of studies linking reproductive problems in wildlife with chemicals in municipal and industrial waste and pesticides, and investigation of a postulated global decline in sperm counts. Krimsky credits Theo Colburn, a zoologist working for the non-profit Conservation Foundation, with synthesizing the data into a general hypothesis, and compares her to Rachel Carson, whose book Silent Spring (1962) was crucial in creating public awareness of environmental dangers. Like Carson, Colburn published her ideas in a popular book, Our Stolen Future (Colburn et al 1996), but she is recognized as a legitimate researcher based on her technical publications and a series of working groups she organized to discuss the EEH beginning in 1991.

DES, the first synthetic estrogen, figures into the modern controversy for two reasons. First, it is a clear and well-documented example of a xenoestrogen causing developmental problems with the reproductive system, both in humans and laboratory animals. Beginning in the 1940's diethylstilbestrol was used as a growth promoter in commercial poultry and livestock operations and prescribed for menopausal and pregnant women. In 1971 it was discovered that daughters born to mothers who had taken DES were at risk for a rare form of vaginal cancer (Herbst et al). During the 1970's research on the carcinogenic effects of pesticides such as DDT was also expanding, and John McLachlan, a toxicologist working at the NIEHS (National Institute of Environmental Health Sciences) emerged as the central investigator working to apply the results of DES cancer research to other synthetic substances (Krimsky 1999, p.11). The structural similarity of DDT and DES led him to consider the possibilities of using the DES model to study carcinogenic and teratogenic effects of DDT, and in 1979 he organized the first research symposia on estrogens in the environment (McLachlan 1980). Later he would be a participant in the interdisciplinary meetings organized by Colburn and link his findings with her studies of developmental problems in wildlife and exposure to hormonally active chemicals. The results of this liaison are evident in article written in 1993 suggesting a new approach he called "functional toxicology," which would emphasize analysis of in vitro effects of chemicals on receptors and the genes they activate so that chemicals could be "defined more by their function than their chemistry (McLachlan 1993, p. 387).

In 1987 Colburn began working for the Conservation Foundation doing background research on wildlife in the Great Lakes region, known for its pollution. Her extensive literature search included more than 2500 articles and government publications and resulted in the book Great Lakes, Great Legacy? (Colburn et al 1990). Contrary to the prevailing paradigm with its emphasis on carcinogenicity, Colburn concluded that in species that were declining, developmental and reproductive problems were more evident than cancer or toxic poisoning.

Evidence from other parts of the U.S. seemed to parallel Colburn's findings. One of the most dramatic examples was the Lake Apopka case, where a massive spill of a pesticide similar to DDT in one of Florida's largest fresh-water lakes in 1980 resulted in severely reduced egg hatching rates of alligators for years after the incident. Researchers also found serious reproductive anomalies in those that did hatch, including low levels of circulating testosterone and small penises in males (Lutz 1993, Colburn 1996).

Colburn expanded her research to include evidence of human responses to ED's and continued to reach out to researchers in other disciplines to see how the EEH might relate to their studies and succeeded in building what Krimsky calls a "scientific constituency." At the same time the hypothesis was being introduced to the conservation, public health and philanthropic communities by colleagues focused on the creating a greater public awareness of the concept (Krimsky 1999).

Particularly interest-grabbing was the fact that in addition to the previously recognized carcinogenic effects of some EDs, the EEH seemed to provide a possible explanation for other conditions and diseases of the reproductive systems connected with infertility such as cystic ovaries and endometriosis in women and in males, hypospadias, cryptorchidism, prostate and testicular cancers and semen quality (Harrison 2001). Another flashpoint issue in the 1990's, breast cancer, also attracted media attention when it was linked with ED's in the scientific literature. Noting that it is generally accepted that known breast cancer risks are linked to lifetime exposure to bioavailable estrogen and that established risk factors only accounted for about 30% of cases of breast cancer, Davis et (1993) argued that exposure to xenoestrogens could be one reason for increasing rates of breast cancer in industrial countries. Noting citing evidence of estrogenicity in a number of organochlorines and clinical