SOT/EUROTOX debate: biomarkers from blood and urine will replace traditional histopathological evaluation to determine adverse responses.

The 2011 SOT/EUROTOX debate addressed the proposition that "Biomarkers From Blood and Urine will Replace Traditional Histopathological Evaluation to Determine Adverse Responses," identifying and comparing the strengths and limitations of histopathology and serum and urine biomarkers. Histopathology has a long and successful history in toxicity testing and a well-defined experience with the technique. Advantages include simplicity and general utility, sensitivity, spatial, and temporal resolution, a recognized role in defining adversity, the ability to use archived samples as a resource, and the ability to adapt to the advent of new molecular pathology tools and endpoints. On the other hand, safety biomarkers can be used to predict, detect, and monitor drug-induced toxicity during both preclinical studies and human trials. Unlike techniques for histopathology, blood and urine biomarkers are noninvasive but remain quantifiable and of translational value. Biomarker measurements reflect the time course of an injury and provide information on the molecular mechanisms of toxicity. After presenting the assenting and dissenting positions on the proposition, this article discusses the uses and the limitations of having a gold standard, how adverse responses are determined, the evolutionary (as opposed to revolutionary) process by which one technology is typically replaced by another, and the overall goal of developing biomarkers which can translate from preclinical safety assessment to clinical utility. The ultimate purpose of this discussion is to help researchers and regulators understand the challenges they face in the development and integration of new and existing biomarkers to determine adverse responses.