The cocktail effect finally explained
Why do certain harmless chemicals become harmful when mixed together? Researchers in Montpellier have just found an explanation for the famous "cocktail effect."
On the one hand, take a small dose of ethinylestradiol, a compound found in birth control pills. It poses no risk to your health. On the other hand, take a tiny amount of trans-nonachlor, which is found in certain pesticides. In very small quantities, it has no effect. But if you take these same doses simultaneously, nothing goes right: the toxicity of these substances, which belong to the large family of endocrine disruptors, is multiplied. This "cocktail effect" remained a mystery for a long time.
Researchers from the Center for Structural Biochemistry, the Montpellier Cancer Research Institute, and the Institute for Functional Genomics have elucidated in vitro a molecular mechanism that could contribute to this phenomenon. They showed that certain estrogens such as ethinylestradiol and organochlorine pesticides such as trans-nonachlor, although very weakly active on their own, have the ability to simultaneously bind 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 promotes the binding of the second. As a result, the mixture induces a toxic effect at concentrations that are significantly lower than those of the molecules taken separately.
These results pave the way for further studies on this cocktail effect: there are around 150,000 compounds in our environment that are considered safe for 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. NatureCommunication http://dx.doi.org/10.1038/ncomms9089