Metformin chlorination byproducts in drinking water exhibit marked toxicity to nematode worms, human cells, and mice

Metformin (MET), a worldwide used drug for type 2 diabetes, has been found with the largest amount by weight among all drugs in aquatic environment, including the drinking water sources where chlorination inevitably transforms MET into chlorination byproducts. Although MET has health-promoting properties, whether or how its chlorination byproducts affect health remains largely unknown. Here we reveal that MET chlorination byproducts Y (C4H6ClN5) and C (C4H6ClN3) exhibit marked toxicity, even higher than that of the well-known poisonous arsenic, to live worms and human cells. Moreover, both byproducts are harmful to mice and Y at 250 ng/L destroys the mouse small intestine integrity. Strikingly, we detected MET and byproduct C in worldwide drinking water. Both byproducts are increasingly produced with more MET present during chlorination process. Unprecedentedly, we unveil boiling and activated carbon adsorption as effective solutions that are in urgent demand globally for removing these byproducts from water.