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| Toxic Cocktail? Is a toxic mix more deadly than its parts? March 22, 1997 |
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Questions asked
in this forum:
Where do estrogenic toxins come from? How could combinations of estrogenic toxins be more harmful than its parts? What could be causing the discrepency between the synergy studies? Could a better cellular test be developed to look for synergy? If the Tulane study proves correct, should the EPA lower its acceptable levels for estrogenic toxins by a factor of 1600? If synergy is proven to exist, how should EPA testing of toxins be changed? Additional comments
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Frederick H. Bartlett of Mercerville, NJ, asks: If we assume that the Tulane study is correct, does that mean that we would have to lower the acceptable levels of all estrogen-like chemicals by a factor of 1600?
Prof. Porter of the University of Wisconsin responds:
That would be correct. In this particular instance, whole animal studies do not confirm the synergism. There are studies with other chemical mixes that do indicate at least additive effects, however. It is important to point out that we know almost nothing about mixtures, especially the common ones that occur due to sequential use of different compounds or to adjacent fields where different pesticides are applied.
Dr. Lynn Goldman of the EPA responds:
No. The Tulane study was conducted with a novel genetically engineered yeast-estrogen system. The yeast cell line was engineered to contain genes that code for the human estrogen receptor, and a reporter protein that the cell line produces when an estrogen like compound is bound to the receptor. In addition the Tulane study used human uterine cells which normally contain estrogen receptors, and human estrogen receptors isolated from cells. The 1600-fold synergy was found in isolated human receptors and in yeast cells. Synergy was observed in the uterine cells, but was of much less magnitude. All of the methods used were in vivo methods that allow relatively simple laboratory testing of estrogen receptor binding potential, but do not evaluate whether the observed receptor binding leads to an adverse effect in an intact animal.
Since the appearance of the Tulane study, various researchers have indicated that the synergy results would have to be verified in various animal species to determine if they are relevant to humans and wildlife. The Tulane study referenced several whole animal studies believed to demonstrate synergy. However, there is not universal acceptance that these studies demonstrate synergy. Certain scientists maintain that the effects are only additive. Until scientific verification is complete time, conventional whole animal toxicity test procedures will presumably remain the regulatory standard.
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