Since the early 1990s, proton pump inhibitors (PPIs) have been widely used to treat acid reflux disease. Although clinical tests in the 1980s deemed PPIS to be safe for humans, in 2012 the FDA announced warnings that long-term use of PPIS could increase the risk of bone fractures, kidney disease, and some intestinal infections.

Which statement best explains why the safety of PPIS is now in question when clinical experiments in the 1980s provided evidence that they were safe?