The Endocrine Disrupter Hypothesis

Concerns about chemicals possibly affecting human and animal health through mimicry of or interference with normal hormonal processes (so-called “endocrine disruption”) have grown among environmental scientists and toxicologists and have increasingly been reported in the popular press. These are deeply emotional issues relating to our health, our children’s health, our reproduction, and, some would argue, to the health and reproduction of wildlife the world over. Because of their potential significance, the concerns that have led to the endocrine disrupter hypothesis demand attention. Many in the scientific community who now pursue research in this area may not be fully aware of the history of the endocrine disrupter concept and how it came to be so prominent. Hormonal Chaos describes that history. It also describes the difficulties involved in establishing policy when there are scientific uncertainties, as there are regarding endocrine disrupters.

This is an eminently readable book. When it arrived in my office, I opened it half expecting to find another discourse arguing that we are facing an impending disaster because of chemical effects on or through hormonal systems. I seldom find such discourse engaging. However, the book is primarily a narrative, without polemic, and I found it to be a page-turner (perhaps because of my own involvement in the issue). The first two chapters recount the history of the idea of endocrine disruption and how it rose to prominence. The first section, and indeed the entire book, is peppered with details about the efforts of many of the individuals who have figured prominently in the emergence of this concept. As those familiar with this topic know, Theo Colborn, an environmental scientist currently with the World Wildlife Fund, played a critical role in defining this issue, and her involvement and what led her to the issue are discussed extensively.

A balanced view

Concerns about endocrine disruption are based on observations regarding health problems in humans and wildlife that could involve some aspect of endocrine systems. Sheldon Krimsky, a professor in the Department of Urban and Environmental Policy at Tufts University, discusses most of these in terms accessible to most lay readers. Some are mentioned briefly; others are considered at length. Among the latter are three highly publicized concerns regarding humans: the possible environmental chemical effects on sperm count, breast cancer, and behavior or neurophysiology. In considering conflicting views, Krimsky draws not just on the scientific literature but also on the mass media. For example, his discussion of differing views in the literature regarding possible effects on human sperm count refers to an article in the New Yorker, which raised doubts as to whether sperm counts are indeed declining or, if so, whether chemicals can be strongly implicated.

The author uses detailed examples to describe how the issues gained visibility and how governmental and nongovernmental organizations have responded in the United States and around the world. He writes largely as an observer, and there is little with which one might disagree. Congressional hearings, the publication of Coburn’s Our Stolen Future (co-authored with Diane Dumanoski and J.P. Myers), many news reports, and the activities of the Environmental Protection Agency (EPA) and the National Research Council (NRC) are all described from a “behind the scenes” perspective. Two television documentaries that differed somewhat in their views of the threat exemplify the author’s discussion of media involvement. The BBC documentary “Assault on the Male” was considered too biased to be accepted for broadcast in the United States by Nova. The PBS Frontline documentary “Fooling with Nature” presented both sides as a scientific debate. Both were widely viewed, but Krimsky does not reveal which he prefers and concludes that their real impact is not clear.

The perspective in the book is up to the minute. For example, in the section titled “Executive Branch Initiatives” Krimsky relates how an NRC committee resolved internal committee disputes and managed to complete its report Hormonally Active Agents in the Environment, which was released just prior to the publication of Hormonal Chaos. The book and the report are different in nature. The report is largely an evaluation of the primary scientific literature on the subject, whereas the book is a narrative of events with a policy perspective. Yet both stress that more research is needed to assess the nature and extent of possible problems.

Policy implications

The second part of the book deals broadly with social and policy matters in a chapter (“Uncertainty, Values and Scientific Responsibility”) that discusses how we come to know what we know, the responsibilities of science to society, and how scientists may differ in their views on the endocrine disruption issue–indeed, on any such issue. The discussion of differing views of causality and the differing positions one might take regarding the nature of evidence required (in a section titled “Skepticism versus the Precautionary Principle”) will be quite valuable to policymakers and to investigators who may be confronted with a need to consider these topics as they relate to the results of their own research.

One factor that Krimsky suggests may influence a scientist’s views on this issue is association with industry. He describes in a less-than-favorable light the views of some researchers who have at times received research money from industry sources. The implication seems to be that objectivity is no longer possible when research dollars come from industry. If this is true, then is it not also true that investigators who depend on federal research funds benefit when funding for particular research topics grows, which would be likely to occur when those topics are viewed as being of greater concern? Might such scientists then engage in hyperbole in describing the potential problems? The implication, by Krimsky or anyone else, that either group might be so disingenuous is disconcerting. People should judge the science first on its own merits.

In “The Policy Conundrum,” Krimsky rightly concludes that nagging scientific uncertainty most often occurs in instances when policy decisions must be made regarding environmental chemicals. He implies that acting on “weight of evidence” in advance of conclusive data (that is, before the detailed mechanisms are known) can be worthwhile, citing examples of the benefits of acting to control exposures to radon, lead, and other hazards. However, the examples cited refer to single agents with well-defined effects, whereas endocrine disruption involves a broad mix of chemicals with numerous and sometimes poorly connected effects.

The NRC report recommended the development of screening and testing protocols, and the EPA had already established the Endocrine Disrupter Screening and Testing Advisory Committee to consider ways to accomplish such testing. Krimsky describes the proposed system, however, as “ponderous, complex, and replete with ambiguities.” Clearly, the complexity of the possible effects, chemicals, species, and combinations thereof makes this an unusually difficult problem, and uncertainty is likely to plague policymakers for some time to come.

There are some errors in the book. For example, in the prepublication copy reviewed, the author offers some explanations as to why developing individuals might be more sensitive to xenobiotic exposures than newborns or young children. First among these is that detoxification mechanisms do not develop until after birth. This is factually incorrect.

Through most of the book, Krimsky succeeds in striking a balance among differing views of specific issues that are part of the hypothesis. There is a subtle bias, however, that is most evident in the concluding chapter. Here Krimsky views the endocrine disrupter hypothesis as contributing to an entirely new way of thinking about chemical effects. He also refers to the “hypothesis,” the term used throughout most of the book, as a theory, thus raising its factual status; and he criticizes those who regard it as a hypothesis only.

On the last page of the text, Krimsky asserts that “The fact that a particular chemical or a particular species fails to corroborate one mechanism does not invalidate the utility of the general framework but suggests . . . mechanistic variations of signaling transductions by xenobiotics.” Certainly this is true, but if different mechanisms might be involved, does it make sense to lump effects together under a term that implies related mechanisms? An example appears in an earlier section regarding cognitive function, where Krimsky says that “Although no mechanism has been proposed to account for the cognitive and developmental effects associated with exposure to PCBs, . . . factors suggest increased vulnerability of fetuses to low level xenobiotic exposure, which is consistent with other findings associated with the environmental endocrine hypothesis.” To me, this implies that any developmental effect might be associated with the endocrine disrupter hypothesis, even in the absence of mechanistic information that might link the effect in question to disruption of an endocrine system. The effects might just as well occur through other toxicological processes that do not primarily involve the endocrine system. Obviously, proving the mechanism(s) and the causal agent(s) is important to health, with or without the endocrine disrupter hypothesis.

If a supposed endocrine effect results from some non-endocrine mechanism, it does not necessarily mean that the endocrine disrupter “hypothesis” is diminished, as Krimsky correctly asserts. But does it mean that the hypothesis needs to be stated more carefully? Probably. Given the untidy nature of the terminology, it is surprising that Krimsky seems almost disdainful of the NRC committee’s use of the term “hormonally active agents” as an alternative to endocrine disrupters. He fails to mention that the committee’s careful search for another term was undertaken largely because endocrine disrupter is not a neutral term but instead presumes an adverse effect.

Few issues in science have galvanized so many so quickly, and Krimsky has accomplished the difficult task of chronicling the history of this contentious idea without being drawn too far into the fray. Minor problems in no way diminish my enthusiasm for this book. It is full of insights that apply not only to how we consider endocrine disrupters but also are equally important in environmental toxicology in general. Indeed, as a detailed case study, the book could well form the basis for a course dealing with environmental toxicology issues.