Testing Chemical Synergy
Air Date: Week of June 14, 1996
A test has been developed to weigh the impact of hormone-like pollutants on animals in ways that may be truer to what happens in daily life where chemicals intermingle. Steve Curwood talks with Lou Gillette, one of the authors of an article about the test that was just published in the journal Science, about how else this test may be used.
CURWOOD: This is Living on Earth. I'm Steve Curwood. The Environmental Protection Agency is considering regulating pesticides and other chemicals based on their potential to disrupt human and animal hormones. But the research has been confusing. There's strong evidence that certain chemicals have an effect in the wild, but they appear weak when tested in the laboratory. But a new study in the journal Science may explain this apparent split between the real world and the test tube. Louis Gillette of the University of Florida in Gainesville helped Steven Arnold and Diane Klotz and their colleagues at Tulane University in New Orleans in laboratory tests of several common pollutants on human estrogen receptors. They found that their impact in combination was much stronger than each one alone. Dr. Gillette says he tried testing these chemicals together after studying wild alligators exposed to a range of pesticides.
GILLETTE: Well, what we found was that if we tested them one by one they were very weak, so that would actually require very high concentrations to give us an effect. And only one chemical that we found in the egg even came close to the concentrations needed to have an effect.
CURWOOD: So then, what did you do?
GILLETTE: Well, we actually began a series of studies to try and understand what happens when you provide mixtures instead of studying these things one by one.
CURWOOD: And what did you find?
GILLETTE: What we found was that much to our surprise, when we added 2 chemicals together, we actually increased the potency of those chemicals by 100 to 1,000-fold over what they are as individuals.
CURWOOD: A hundred- to a thousand-fold?
GILLETTE: Yeah, so it's -- I guess the best example is instead of it being 1 and 1 equals 2 for us, 1 and 1 equaled 100 or 1,000. And so it wasn't arithmetic, it wasn't an additive effect; it was what we call a synergistic effect, a greater than additive effect. So what we're looking at is the ability of these compounds to turn on genes that are controlled by estrogen. If we look under normal conditions, that is, their ability to turn on, let's say, an estrogen-induced gene, we find that they are 1,000 to 10,000 times weaker than the natural estrogen, estradiol. When you mix them 2 together, what you find is that now they're only 10 to maybe 100 times weaker than the natural hormone.
CURWOOD: What chemicals are we talking about here, Dr. Gillette?
GILLETTE: Well, the 4 chemicals that we looked at in detail were toxaphene, endosulphan, chlordane, and dieldrin. Three of those compounds, chlordane, dieldrin, and toxaphene, have all been banned in the United States. However, they still persist in the bodies, stored in the fat, and so therefore they appear in eggs and various other biological fluids.
CURWOOD: And the fourth chemical?
GILLETTE: The fourth chemical is endosulphan, and it's still used, although it's controlled in the United States.
CURWOOD: So what does this tell us about how these chemicals might affect humans and other animals?
GILLETTE: Well, we really can't say how they necessarily affect humans or animals. We don't have the whole animal data yet. But what it tells us is that the hypothesis that chemicals in the environment that we're exposed to every day may in fact pose a health risk or a health effect. And I think what we have to realize is that reality, that is, what we're actually exposed to every day, is not 1 or 2 chemicals or even 3 chemicals given individually. It's a whole mixture, a cocktail if you will, of compounds that we're exposed to. The other thing we should note just so that you're -- is that it doesn't appear that all environmental chemicals when mixed 2 together give us this jump. There are certain classes that seem to work really well. And these pesticides that we're talking about seem to be right now the best examples of this synergism activity that we have.
CURWOOD: How about the PCBs, polychlorinated biphenyls?
GILLETTE: Right. Well, the interesting thing about the PCBs, which we also reported, is that instead of a 100 to 1,000-fold jump, we actually did show that they increased by 6 or 7-fold their potency. But we know that those compounds are already more potent than the pesticides we talked about. So there may be an upper limit in the potential potency of these compounds, but certainly when you add 2 PCBs together, instead of 1 and 1 adding to 2, 1 and 1 give you 6 or 7.
CURWOOD: I'm wondering, Dr. Gillette, now that you've done this research, do you feel that you have more ammunition, as it were, to address the critics of the endocrine disruption hypothesis?
GILLETTE: I don't know if one could actually say that we have ammunition. This data certainly supports the idea that what we thought were relatively weak compounds, that is, weak as far as their hormonal nature, could in fact have a biological effect on the whole organism. However, we still need to collect the data. We do have some whole organism data. We have a study that was previously done on turtles by John McLachlan and David Cruise and his colleagues at the University of Texas, that show that if you add 2 weak PCBs together, you apply them to a turtle egg, you can get sex reversal just like you applied a natural estrogen. And both of those compounds alone do not cause sex reversal. So we do have some whole organismal data, which suggest quite clearly that synergism does work at a whole organismal level, and I believe that our data now provides the molecular basis for this whole argument.
CURWOOD: Thanks so much for joining us.
GILLETTE: You're welcome.
CURWOOD: Dr. Louis Gillette is Professor of Zoology at the University of Florida in Gainesville. He did the research that appeared in Science while on sabbatical at Tulane University with John McLachlan and Steve Arnold. Thank you.
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