The "cocktail effect" finally explained
Why do some harmless chemicals become harmful when mixed together? Researchers in Montpellier have just discovered an explanation for the well-known “cocktail effect.”
Take, on the one hand, a small dose of ethinylestradiol, a compound found in birth control pills. It poses no risk to your health. Now take, on the other hand, a tiny amount of trans-nonachlor, which is found in certain pesticides. In very small amounts, it has no effect. But if you take these same doses at the same time, things go awry: the toxicity of these substances—which belong to the broad family of endocrine disruptors—is amplified. This “cocktail effect” has long remained a mystery.
Researchers from the Center for Structural Biochemistry, the Montpellier Cancer Research Institute, and the Institute of Functional Genomics have elucidated in vitro a molecular mechanism that could contribute to this phenomenon. They demonstrated that certain estrogens, such as ethinyl estradiol, and organochlorine pesticides, such as trans-nonachlor—although very weakly active on their own—have the ability to bind simultaneously to a receptor located in the cell nucleus and activate it synergistically.
A cocktail that gives you a hangover
Molecular-scale analyses indicate that the two compounds bind cooperatively to the receptor; that is, the binding of the first compound promotes the binding of the second. As a result, the mixture induces a toxic effect at concentrations far lower than those of the individual molecules.
These findings pave the way for further studies on this “cocktail effect”: there are, in fact, approximately 150,000 compounds in our environment that are considered safe for human health but whose combined action could have unexpected effects.
Synergistic activation of the human pregnane X receptor by binary cocktails of pharmaceutical and environmental compounds. V. Delfosse, W. Bourguet et al. NatureCommunications http://dx.doi.org/10.1038/ncomms9089