The origins of safety pharmacology are grounded upon observations that organ functions can be toxicological targets in humans exposed to novel therapeutic agents, and that drug effects on organ functions are not readily detected by standard toxicological testing. Clinical assessment of the gastrointestinal (GI) tract is often limited to measurements of transit time and observations of vomiting or diarrhea, despite the existence of methods and techniques capable of assessing specific changes in GI function at the membrane, cell, and whole animal levels. The core battery of safety pharmacology studies includes the assessment of effects on cardiovascular, central nervous, and respiratory systems, and should generally be conducted before human exposure. Effects on the gastrointestinal tract are not considered to be of primary importance based on a hierarchy of organ systems. Dog model to examine the possible mechanism for the esophageal adverse events has been published and showed that under low pH conditions, alendronate sodium can cause esophageal irritation.