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 a tiny amount of trans-nonachlor, found in certain pesticides. In very small quantities, it has no effect. But if you take these same doses simultaneously, things go awry: the toxicity of these substances—which belong to the large family of endocrine disruptors—is amplified. A “cocktail effect” that 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 ethinylestradiol, 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-level analyses indicate that the two compounds bind cooperatively to the receptor, meaning that the binding of the first compound enhances 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 new studies on this cocktail effect: there are, in fact, approximately 150,000 compounds in our environment that are presumed to be harmless to human health but whose combined action could have unexpected effects.
Synergistic activation of 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