Our Stolen Futurea book by Theo Colborn, Dianne Dumanoski, and John Peterson Myers


Hormonally Active Agents in the Environment
US National Research Council


Hormonally Active Agents (HAAs) is the name the committee gave to the class of chemicals that were covered in the report. The committee focused its attention on synthetic chemicals found to have hormonal activities such as estrogens, antiestrogens and antiandrogens. These are chemicals that have been reported to induce reproductive and developmental defects, neurobehavioral abnormalities, immunologic deficits, carcinogenesis and ecologic effects.


  • In its report, the NRC sought to identify chemicals with hormonal activity. Hormone disruptors include chemicals that act by other pathways, or for which the mechanism is unknown.
  • The panel's review was largely limited to the sex steroid hormones, estrogen and testosterone. The committee chose not to report on chemicals that interfered with other hormonal systems (such as the thyroid or adrenals), primarily because the literature on these effects was quite limited when the committee began its review in 1994. Increasingly, however, it has become clear many other hormone systems are vulnerable to disruption by HAAs.
  • The committee noted that a lack of knowledge about how a chemical affects humans and wildlife does not mean that a reported effect is unconfirmed or unimportant
  The NAS committee was not able to consider most of the literature that was published after June 1997 even though its report was not published until August 1999. This was unfortunate, because many new and revealing studies were published during that period. Among other advances, literature that appeared in recent years suggests that currently used pesticides, as well as chemicals commonly used in consumer products (such as phthalates, phenols and flame retardants) are also HAAs.  


What does the report say about exposure of humans and wildlife to HAAs? Wildlife and people in most of the world carry contaminants at levels known to produce effects in the laboratory.

  • The report states that, "Many of the HAAs are relatively persistent chemicals, and therefore, exposure to one or several of them is virtually guaranteed for most organisms".
  • Moreover, humans are almost universally exposed. In fact, the report continues, "More than 95% of all the U.S. population had detectable concentrations of PCBs, regardless of age, sex, race or geographic location." "Although the concentrations were found to be greatest in older people, even children were not immune from exposure" "5.1% had concentrations greater than 3 ppm."
  What does the report say about effects on wildlife? The report demonstrates clear evidence from wildlife showing endocrine disrupting effects:
  • As the report states, "Many wildlife studies show associations between reproductive and developmental anomalies and exposure to environmental contaminants, some of which are HAAs"
  • These demonstrable, replicated effects include impacts on reproduction, behavior and immune system function. "Reported reproductive disorders in wildlife have included morphologic abnormalities, eggshell thinning, population declines, impaired viability of offspring, altered hormone concentrations, and changes in sociosexual behavior."
  • Overall, the NAS committee concluded, "Laboratory studies illustrate that exogenous exposure to several HAAs (e.g., DDT, methoxychlor, PCBs, dioxin, bisphenol A, octylphenol, BBP, DBP, chlordecone and vinclozolin) during critical periods of development can interfere with normal reproductive development."
  What does the report say about HAAs and human cancer? The cancer risk to humans from HAAs has been studied for only a few chemicals. Moreover, except for DES, extensive human cancer studies have been limited to adult exposures. This leaves the questions of how these chemicals may affect children, or how they affect adults who were exposed in the womb, still unanswered. This is a huge gap in the research literature, because of the DES experience and because of the possibility for several cancers that errors in cell replication laying the groundwork for cancers later in life actually take place during fetal differentiation, i.e., in the womb.
  • "No studies have been conducted to examine associations between risk of any cancer and exposure to any HAAs during development, particularly during fetal life." Until sampling is done throughout development, the associations between HAAs and cancer in humans cannot be ruled out.
  • The report notes, "The data that exist for evaluating the postulated relationships between HAAs and human cancers are mostly limited to studies involving exposure to DDT, DDE, TCDD , and various PCBs. Other compounds with potential hormonal activity have received little attention. Furthermore, exposure to HAAs and their possible effects during susceptible periods such as fetal life or pregnancy and transgenerational effects have not been evaluated in human studies."
  • "The committee agreed that lack of evidence could not be taken as an indication that a proposed process does not operate."
  What does the report say about other health effects? Research on human health effects is still in its infancy, but studies are beginning to reveal effects as well as trends in human health data that are consistent with predictions based upon laboratory experiments with HAAs in animals.
  • For example decreased ano-genital distance in exposed animals predicted an increased risk of the birth defect hypospadias in humans. The rate in humans was found to have doubled over the past twenty years. (Hypospadias is a malformation of the penis in which the opening of the urethra is found on the underside instead of at the tip.)
  • PCBs have been shown to influence neurological development in animals. The report found consistent correlations in people between prenatal exposure to PCBs and cognitive deficits. "Studies of cognitive development .show consistent correlations between prenatal exposure to PCBs and deficits at up to 11 years of age."
  • PCBs in the maternal diet have been linked to developmental effects, in particular, birth weight and growth.
  • The report notes that multinational trend studies support a downward trend in mean sperm concentration. The report goes on to note that this may be confounded by local geographic variation.
  How are these findings likely to affect policy makers and regulators? The report contains several important conclusions that will present significant challenges to risk assessment as it is currently practiced:
  • Effects of HAAs in wildlife and laboratory animals have been shown to occur at levels that are millions of times lower than the traditional range at which toxicological studies are conducted.
  • "Endogenous hormones can be active at concentrations as low as picograms per milliliter in the blood." Only recently has the technology permitted scientists to measure contaminants at these levels.
  • Laboratory data suggest that higher doses do not necessarily result in greater effects. Some chemicals do not behave as traditional toxicology would predict; their dose-response curves are, in fact, nonlinear. In other words, the report says, "Biological responses to some HAAs might be greater at lower doses than at higher doses."
  • For the developing fetus, there is no safe dose. The report notes the unique risks to the developing fetus and addresses effects related to the timing of prenatal exposures.
  • People experience HAAs in complex mixtures, but few mixtures have been studied. The report states; "The committee recognizes that wildlife and humans are exposed to complex mixtures of chemicals and that interactions between chemicals in mixtures cannot always be predicted by examining each chemical individually."




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