Take an aspirin tablet. Now imagine cutting it in half. And in half again. Keep doing this, obviously in your imagination, until you have about three million pieces. Now take one of those pieces and dissolve it in a bathtub filled with water. The concentration of aspirin in the water would then be one part per trillion. Toxicologists would agree that at this amazingly low concentration, no effect attributable to aspirin could be detected no matter how much of this water was consumed. But they may well have a different opinion if instead of aspirin this little game were to be played with a hormone such as estrogen. In this case, a physiological response could well be triggered even at the incredibly low part per trillion concentration levels.
Hormones are very powerful substances and can have effects at concentrations where even potent toxins such as cyanide or botulin would be totally harmless. This can be attributed to the specific mechanism by means of which hormones act. These compounds do their work by fitting into receptor sites in cells, much as a key fits a lock, and when the fit is a correct one, a cavalcade of reactions is unleashed. A single molecule of a hormone can be enough to get things going. And there may be another curiosity about hormones. A very small dose may in fact have a more powerful effect than a larger dose, apparently defying the accepted anthem of toxicology, that only the dose makes the poison. How could this be? Perhaps an analogy may clarify this conundrum. Imagine that you have a large crowd of people trying to squeeze through a single door. With all the pushing and shoving, it may well be that nobody gets through. But if you have only a few people around, they can easily get through the door. And so it may be with hormones. At a low dose certain types of cellular activity may be triggered which may not occur at higher doses.
What is the point of all of this? As virtually everyone knows by now, we are exposed to a variety of substances that have been termed environmental estrogens because of their ability to mimic the activity of the body鈥檚 own estrogen. The fact that synthetic chemicals can behave in this fashion was first shown in the 1930s by the ingenious work of E.C. Dodds and Wilfrid Lawson at Middlesex Hospital in London. These researchers removed the ovaries from rats, and then used a microscope to examine cells in vaginal smears taken from the animals. They found that the cells were devoid of the changes normally triggered by estrogen released from the ovaries during estrus, the period when the female is receptive to the advances of a male. But when the rats were injected with certain synthetic compounds, the researchers detected a positive estrus response in the vaginal cells. This was indicative of estrogenic activity.
One of the compounds that Dodds and Lawson tested and found to be estrogenic was bisphenol A. When this substance was later found to be useful in the production of polycarbonate plastics, its potential toxicity had to be addressed. And it was, with standard toxicological tests. The smallest dose that caused no effect in test animals was determined and it was assumed that all doses smaller than this were safe. But the smaller doses were never actually tested because the concept that a smaller dose could be more problematic than a bigger one did not exist. Now, however, we know that hormone- like substances can exhibit bizarre toxicological effects, and that they may not exhibit the usual dose-response relationship. And that鈥檚 why we have to reevaluate the data that has been used to determine the safety of environmental estrogens such as bisphenol A.
