Is a toxic mix more deadly than its parts?
March 22, 1997
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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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Khal Spencer of Honolulu, HI, asks:
The PBS article suggests that synergistic effects of multiple chemical entities may not be adequately tested using what the article calls "a colony of cells". My question is what kinds of cell colonies are being used? Human or other? Also, if animal tests are used, will these mimic synergistic effects that may occur in humans any more reliably than "cell colonies" will? Do we know enough about the synergistic effects of multiple toxins so that we could design cell colonies from various human organs so that individual systems in humans (or animals) could be tested under controlled conditions?
Dr. Lynn Goldman of the EPA responds:
Other studies conducted at EPA's Research Triangle Park Laboratory have been conducted using several different cell lines including human breast cancer cells (MCF-7, and MVLN) and monkey epithelial cells (CV-1). Studies using these cell lines have demonstrated additivity rather than synergy using two of the same chemicals as the Tulane study (endosulfan and dieldrin). Like the Tulane study, these additional studies were conducted in vitro, and did not employ whole animals.
Generally, synergistic effects of toxicants are not well studied. Indeed, the toxic effects of many single chemicals are poorly known, let alone how they act in mixtures. A few specific cases of synergy are well known and documented in rats (carbon tetrachloride and ethanol hepatotoxcity; TCDD and glucocorticoid induction of cleft palate). Synergy is also possible when a mixture of toxicants alters development of the same reproductive organ by different mechanisms. Test systems to examine synergy are being developed in EPA and other laboratories as they have implications for how risk assessments are conducted.
Prof. Porter of the University of Wisconsin responds:
Animals have lots of interacting organ systems, like the immune, endocrine and neurological systems that "talk to" each other continuously. Developmental sequences depend on hormone levels being appropriate at the parts per quadrillion range. Developing organisms are undergoing enormous chemical communications between different cells and tissues. It is unlikely that cell cultures will ever mimic these "system" operations.
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