The cocktail effect finally explained

Why do some harmless chemical substances become harmful when mixed? Researchers from Montpellier have just found an explanation for the famous "cocktail effect".
Take a small dose of ethinyl estradiol, a compound found in birth control pills. It is safe for you to take. On the other hand, take a tiny amount of trans-nonachlor, which is found in some pesticides. In very small amounts, it's harmless. But if you take these same doses simultaneously, nothing goes wrong: the toxicity of these substances from the large family of endocrine disruptors is multiplied. A "cocktail effect" that has long remained mysterious.
Researchers from the Structural Biochemistry Center, the Montpellier Cancer Research Institute and the Functional Genomics Institute have elucidated in vitro a molecular mechanism that could contribute to this phenomenon. They showed that certain estrogens such as ethinyl estradiol and organochlorine pesticides such as trans-nonachlor, although very weakly active by themselves, have the ability to bind simultaneously to a receptor located in the nucleus of the cells and activate it in a synergistic manner.

A cocktail that gives you a hangover

Molecular level analyses indicate that the two compounds bind cooperatively to the receptor, i.e. the binding of the former promotes the binding of the latter. As a result, the mixture induces a toxic effect at much lower concentrations than the molecules taken separately.
These results pave the way for new studies on this cocktail effect: there are in fact about 150,000 compounds in our environment that are supposed 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. Nature Communication