[link to examples of low-dose studies]

Sheldon Krimsky's book, Hormonal Chaos, describes endocrine disruption as a paradigm shift in toxicology. At the core of this shift are scientific results demonstrating that endocrine disruption has impacts at contamination levels far beneath those of traditional concern to toxicologists. Some of these levels are so low that industry has asserted the results are not reliable.

The old paradigm focused on acute toxicity. How do high levels of contamination affect health? How do they cause cancer? How do they kill directly? How do they overcome the body's defenses, like a massive invading army overwhelming the defenders simply by brute force and large numbers?

The new paradigm recognizes that there are other ways that contamination can work. Think of how terrorists overwhelm larger forces. Instead of using the brute force of large numbers, a small number of molecules can hijack the hormonal control of development and cause intense, life long damage, undermining the immune system, eroding intelligence, diminishing reproductive capacity.

This terrorist attack on fetal development works because some chemicals act as imposters, insinuating themselves in the body's natural hormone system that normally directs fetal development. These natural hormone signals work at very low concentrations. And the imposters do also, sometimes at levels tens of thousands of times lower than the brute force approach considered by traditional toxicology.

The implications of this new paradigm are profound. Every person living today carries measurable levels of several hundred synthetic chemicals, contaminants that did not exist prior to the 20th century. While we are fundamentally ignorant about the health impacts of most of these compounds--and profoundly so about their interactions--toxicologists had come to believe that background levels, the levels experienced by most people, the levels that are virtually unavoidable living in the world today, that those background levels were safe. This assumption of safety was allowed because scientists were considering them under the old paradigm, and with significant exceptions, they were not seeing dead bodies. The new paradigm indicates that an entire generation of science used to examine chemicals for safety was misguided, ignoring vital impacts at low levels of exposure, and likely to have given false assurances of safety.

Part of this new paradigm is also the acknowledgment that old assumptions about the nature of the relationship between dose and response may sometimes be violated. Traditional toxicology assumes that dose-response curves are always monotonic: that is, that higher doses have a greater effect than lower doses. This assumption underpins all regulatory testing: if no effect is found at high levels, then it is assumed that the contaminant is safe. It also usually assumes that there is a threshold level of exposure below which no effect occurs.

It turns out hormone systems aren't always that simple. Sometimes high doses shut off effects that occur at lower levels. This can lead to dose response curves that are non-monotonic: low and intermediate doses produce effects that are larger than high levels. In mathematical terms, the slope of the dose response curve changes sign. The presence of non-monotonic dose response curves in endocrine disruption means that many toxicological tests have led to erroneous conclusions about safety.

Another important assumption of these regulatory approaches is that there is a threshold beneath which no effect occurs. Here, too, endocrine disrupting chemicals violate long-held, but not tested, assumptions.

What this means is that not only have we simply not tested the toxicological impacts of most chemicals, even those that have been tested have not been examined adequately. These tests were all done by beginning at high levels and working back down the dose response curve until the effect seen at high levels disappeared. Once that level of "no-effect" is reached, testing stops, assuming a threshold and ignoring the possibility that non-monotonic effects occur at lower levels.

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