Air Date: Week of August 1, 1997
Trying to determine the danger of certain chemicals is difficult. Steve talks with Frederick Vom Saal, one of the leading toxicologists, who has found some interesting... and troubling effects... after subjecting pregnant mice to extremely low doses of natural and synthetic estrogens like Diethylstilbestrol or DES.
CURWOOD: Other new research into hormone-mimicking chemicals is finding out that certain substances seem to have paradoxical effects, depending on the amount of exposure. In certain cases, it seems, small doses may be more disruptive to organisms than large ones. Much of the earlier efforts to measure the toxicity of these chemicals was done with the premise that smaller doses would be less toxic. One of the leading researchers in this area is Frederick Vom Saal at the University of Missouri. His research team gave pregnant mice extremely low doses of natural and synthetic estrogens, like diethylstilbestrol, or DES. I asked Professor Vom Saal about his results.
VOM SAAL: What we had found is that, an amount of the natural hormone estradiol, the most potent of our natural estrogens, an increase of less than 1/10 of a trillionth of a gram in a milliliter of blood, was enough in a male fetus, to permanently enlarge the prostate and make the prostate abnormal, essentially for the rest of the animal's life.
CURWOOD: You say you give these mice tiny amounts of estrogen, but something else happened when you gave them larger amounts.
VOM SAAL: Yes.
CURWOOD: What did you get when you gave them high doses?
VOM SAAL: Well, when we gave a very high dose of diethylstilbestrol, we in fact shrank the prostate in the male offspring. So a very low dose enlarged the prostate, a very high dose shrank the prostate.
CURWOOD: One might then extrapolate from what you're saying is that the present epidemic of prostate enlargement and cancer in this society might well be related to these chemicals?
VOM SAAL: Yes. I think it really looks, if you look at a number of hormone dependent diseases, such as breast cancer, and prostate cancer, and testicular cancer, and abnormal reproductive system being observed in newborn children, the incidents of all of these things have been steadily increasing over the last 20 to 30 years.
CURWOOD: Can you explain why there's such a radical difference in response to the doses here?
VOM SAAL: We do not have all of the mechanistic information to provide an answer to that question, however, we have some pieces of the puzzle, that we understand. You can think of a port as having a number of docks in it, that are open to have ships moved into, and what happens is, as you occupy those sites, you can unload things and products can move in. And that's the way that hormones move into cells, into docking sites, and they cause things to happen in the cells. If there are no docking sites, if there are no receptors, then the cells can't respond. If there were no docks, no ships could come in, and nothing would move from the ships. And so, there can be lots of hormone present, but if there are no receptors in the cells for those hormones, then the cells can't respond. It looks like an overloading safety valve effect, where, if you get too much of a stimulation, the system compensates by shutting down. And it means that all studies that are done at very high doses have to now be rethought in terms of the consequences of just looking at very high doses, and think of, "My goodness, hormones operate at very low levels, maybe we need to now retest chemicals that have only been tested at very high doses, to see if in fact, exactly opposite effects of these chemicals will be found at very low doses," which is what the studies that we've conducted suggest may be in fact the case.
CURWOOD: Well, if such infinitesimal amounts could be responsible for this, then it would stand to reason that an awful lot of people are being exposed to these amounts.
VOM SAAL: Yes. Let me give you an example. And this concerns a chemical that's present in polycarbonate plastic, that people store their foods in. It's also a chemical used to make the plastic lining of all food and beverage cans. And it's a chemical used as a dental sealant, that people are having applied to their children's teeth. It's called bisphenol-A. In all of these situations, this chemical is getting into our food, and after application of dental sealants, it's being swallowed because it comes out of the plastic. People had thought that the amounts of the chemical that everybody is consuming would be safe. But we've fed it to pregnant mice, and we looked at the consequences of this, in their offspring. Now, we were hoping that the body's protective system might actually be operating to reduce the potency of some of these chemicals, such as bisphenol-A. Instead, what our studies showed is that, in fact, it's bypassing protective systems, and instead, bisphenol-A turned out to be much more potent an estrogen than anybody had considered. The previous dose that was thought to not produce an effect, when only malformations and gross abnormalities were looked at in response to prenatal exposure to this chemical, is actually 25 million times higher than the amount that, based on our findings, would be calculated to be a safe amount to consume on a daily basis.
CURWOOD: Twenty-five million times higher?
VOM SAAL: That's right. Because in that prior study, that was done on bis-phenol-A, they weren't looking for this chemical to act as a hormone. They were just studying very high doses, and looking for gross abnormalities. Endocrine disrupting chemicals don't produce gross observable abnormalities. You have to do much more detailed functional analysis of tissues, to find adverse outcomes. So you can't find what you don't look for.
CURWOOD: I want to thank you for taking this time with us today.
VOM SAAL: Thank you very much for the interview.
CURWOOD: Frederick Vom Saal is Professor at the University of Missouri. His latest article appears in the "Proceedings of the National Academy of Sciences."
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