Most of us give little thought to the ingredients inside the brightly colored pills that we rely on to keep our bodies functioning. We refer to them as an aspirin or antihistamine without realizing that for most drugs, the major component by mass is not the drug of interest itself, but compounds classified as “inactive” called excipients. 

While called inactive, excipients such as dyes, stabilizers, and antioxidants that increase shelf life have not been systematically tested to determine whether they interact with molecular targets in the body. Scientists recently analyzed a wide range of these compounds to determine potential unknown side effects. 

The authors first found interaction candidates by predicting how much an excipient looks to the native compounds that act on certain molecular targets, and then tested the hits experimentally. In another approach, the scientists tested widely used excipients against 28 targets that are known to be related to toxicity. Using these two approaches, the authors found 134 side-effect activities. Of these leads, some were further analyzed for their abilities to be toxic to the body and to enter the bloodstream. 

One finding was for an antiseptic commonly found in mouthwash. Predicted to interact with a number of biological targets, this compound was shown to be toxic to the body at low levels, and was able to enter the bloodstream at concentrations high enough to interact with at least one biological target. Overall, 134 side-effect activities for 38 excipients were found. 

This study highlights how compounds in our drugs not normally considered active can alter our bodies. The authors additionally note the widespread use of some excipients in food and cosmetics that are found at even higher doses than drugs, and the issue of populations that juggle more than one medication and therefore have a higher exposure. While a preliminary piece of work, it highlights the importance of paying close attention to what we add to substances that sustain us.