FOSTERING SUSTAINABLE COMMUNITY
Wingspread Journal, Spring 1996

THE WILDLIFE/HUMAN CONNECTION
Consensus Statement from the Work Session on Chemically Induced Alterations in Sexual Development

The following consensus was reached by participants at the 1991 Wingspread Conference.

We are Certain of the Following:

• A large number of man-made chemicals that have been released into the environment, as well as a few natural ones, have the potential to disrupt the endocrine system of animals, including humans. Among these are the persistent, bioaccumulative, organohalogen compounds that include some pesticides (fungicides, herbicides, and insecticides) and industrial chemicals, other synthetic products, and some metals.
• Many wildlife populations are already affected by these compounds. The impacts include thyroid dysfunction in birds and fish; decreased fertility in birds, fish, shellfish, and mammals; decreased hatching success in birds, fish, and turtles; gross birth deformities in birds, fish, and turtles; metabolic abnormalities in birds, fish, and mammals; behavioral abnormalities in birds; demasculinization and feminization of male fish, birds, and mammals; defeminization and masculinization of female fish and birds; and compromised immune systems in birds and mammals.
• The patterns of effects vary among species and among compounds. Four general points can nonetheless be made: (1) the chemicals of concern may have entirely different effects on the embryo, fetus, or perinatal organism than on the adult; (2) the effects are most often manifested in offspring, not in the exposed parent; (3) the timing of exposure in the developing organism is crucial in determining its character and future potential; and (4) although critical exposure occurs during embryonic development, obvious manifestations may not occur until maturity.
• Laboratory studies corroborate the abnormal sexual development observed in the field and provide biological mechanisms to explain the observations in wildlife.
• Humans have been affected by compounds of this nature, too. The effects of DES (diethylstilbestrol), a synthetic therapeutic agent, like many of the compounds mentioned above, are estrogenic. Daughters born to mothers who took DES now suffer increased rates of vaginal clear cell adenocarcinoma, various genital tract abnormalities, abnormal pregnancies, and some changes in immune responses. Both sons and daughters exposed in utero experienced congenital anomalies of their reproductive system and reduced fertility. The effects seen in in utero DES-exposed humans parallel those found in contaminated wildlife and laboratory animals, suggesting that humans may be at risk to the same environmental hazards as wildlife.

We Estimate With Confidence That:

• Some of the developmental impairments reported in humans today are seen in adult offspring of parents exposed to synthetic hormone disruptors (agonists and antagonists) released in the environment. The concentrations of a number of synthetic sex hormone agonists and antagonists measured in the U.S. human population today are well within the range and dosages at which effects are seen in wildlife populations. In fact, experimental results are being seen at the low end of current environmental concentrations.
• Unless the environmental load of synthetic hormone disruptors is abated and controlled, large scale dysfunction at the population level is possible. The scope and potential hazard to wildlife and humans are great because of the probability of repeated and/or constant exposure to numerous synthetic chemicals that are known to be endocrine disruptors.
• As attention is focused on this problem, more parallels in wildlife, laboratory, and human research will be revealed.

Current Models Predict That:

• The mechanisms by which these compounds have their impact vary, but they share the general properties of: (1) mimicking the effects of natural hormones by recognizing their binding sites; (2) antagonizing the effect of these hormones by blocking their interaction with their physiological binding sites; (3) reacting directly and indirectly with the hormone in question; (4) altering the natural pattern of synthesis of hormones; or (5) altering hormone receptor levels.
• Both exogenous (external source) and endogenous (internal source) androgens (male hormones) and estrogens (female hormones) can alter the development of brain function.
• Any perturbation of the endocrine system of a developing organism may alter the development of that organism: typically these effects are irreversible. For example, many sex-related characteristics are determined hormonally during a window of time in the early stages of development and can be influenced by small changes in hormone balance. Evidence suggests that sex-related characteristics, once imprinted, may be irreversible.
• Reproductive effects reported in wildlife should be of concern to humans dependent upon the same resources, e.g., contaminated fish. Food fish is a major pathway of exposure for birds. The avian (bird) model for organochlorine endocrine disruption is the best described to date. It also provides support for the wildlife/human connection because of similarities in the development of the avian and mammalian endocrine systems.

There are Many Uncertainties in our Predictions Because:

• The nature and extent of the effects of exposure on humans are not well established. Information is limited concerning the disposition of these contaminants within humans, especially data on concentrations of contaminants in embryos. This is compounded by the lack of measurable endpoints (biologic markers of exposure and effect) and the lack of multi-generational exposure studies that simulate ambient concentrations.
• While there are adequate quantitative data concerning reduction in reproductive success in wildlife, data are less robust concerning changes in behavior. The evidence, however, is sufficient to call for immediate efforts to fill these knowledge gaps.
• The potencies of many synthetic estrogenic compounds relative to natural estrogens have not been established. This is important because contemporary blood concentrations of some of the compounds of concern exceed those of internally produced estrogens.

Our Judgment is That:

• Testing of products for regulatory purposes should be broadened to include hormonal activity in vivo. There is no substitute for animal studies for this aspect of testing.
• Screening assays for androgenicity and estrogenicity are available for those compounds that have direct hormonal effects. Regulations should require screening all new products and by-products for hormonal activity. If the material tests positive, further testing for functional teratogenicity (loss of function rather than obvious gross birth defects) using multigenerational studies should be required. This should apply to all persistent, bioaccumulative products released in the past as well.
• It is urgent to move reproductive effects and functional teratogenicity to the forefront when evaluating health risks. The cancer paradigm is insufficient because chemicals can cause severe health effects other than cancer.
• A more comprehensive inventory of these compounds is needed as they move through commerce and are eventually released to the environment. This information must be made more accessible. Information such as this affords the opportunity to reduce exposure through containment and manipulation of food chains. Rather than separately regulating contaminants in water, air, and land, regulatory agencies should focus on the ecosystem as a whole.
• Banning the production and use of persistent chemicals has not solved the exposure problem. New approaches are needed to reduce exposure to synthetic chemicals already in the environment and prevent the release of new products with similar characteristics.
• Impacts on wildlife and laboratory animals as a result of exposure to these contaminants are of such a profound and insidious nature that a major research initiative on humans must be undertaken.
• The scientific and public health communities' general lack of awareness concerning the presence of hormonally active environmental chemicals, functional teratogenicity, and the concept of transgenerational exposure must be addressed. Because functional deficits are not visible at birth and may not be fully manifested until adulthood, they are often missed by physicians, parents, and the regulatory community, and the causal agent is never identified.

From: Chemically Induced Alterations in Sexual and Functional Development: The Wildlife/Human Connection. Eds. T. Colborn and C. Clement. Princeton Scientific Publishing, Princeton, NJ, 1992.