Toxicological Synergy
Toxicological synergy is of concern to the public and regulatory agencies because chemicals individually considered safe might pose unacceptable health or ecological risk in combination. Articles in scientific and lay journals include many definitions of chemical or toxicological synergy, often vague or in conflict with each other. Because toxic interactions are defined relative to the expectation under "no interaction", a determination of synergy (or antagonism) depends on what is meant by "no interaction". The United States Environmental Protection Agency has one of the more detailed and precise definitions of toxic interaction, designed to facilitate risk assessment. In their guidance documents, the no-interaction default assumption is dose addition, so synergy means a mixture response that exceeds that predicted from dose addition. The EPA emphasizes that synergy does not always make a mixture dangerous, nor does antagonism always make the mixture safe; each depends on the predicted risk under dose addition.
For example, a consequence of pesticide use is the risk of health effects. During the registration of pesticides in the United States exhaustive tests are performed to discern health effects on humans at various exposure levels. A regulatory upper limit of presence in foods is then placed on this pesticide. As long as residues in the food stay below this regulatory level, health effects are deemed highly unlikely and the food is considered safe to consume.
However, in normal agricultural practice, it is rare to use only a single pesticide. During the production of a crop, several different materials may be used. Each of them has had determined a regulatory level at which they would be considered individually safe. In many cases, a commercial pesticide is itself a combination of several chemical agents, and thus the safe levels actually represent levels of the mixture. In contrast, a combination created by the end user, such as a farmer, has rarely been tested in that combination. The potential for synergy is then unknown or estimated from data on similar combinations. This lack of information also applies to many of the chemical combinations to which humans are exposed, including residues in food, indoor air contaminants, and occupational exposures to chemicals. Some groups think that the rising rates of cancer, asthma, and other health problems may be caused by these combination exposures; others have alternative explanations. This question will likely be answered only after years of exposure by the population in general and research on chemical toxicity, usually performed on animals. Examples of pesticide synergists include Piperonyl butoxide and MGK 264.
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