Regulatory Forum Opinion Piece: Thresholds in Toxicologic Pathology

The definition of diagnostic thresholds is an important aspect of identification and recording of histopathologic lesions in toxicology studies. Although the primary goal of the pathology examination is to identify and interpret lesions associated with the administration of the test article, the toxicologic pathologist will encounter many changes in the tissues that are variations in tissue morphology, tissue artifacts, and spontaneous background findings. The pathologist must establish appropriate thresholds to produce a comprehensive record of the findings so that potentially treatment-related lesions may be identified. However, the findings should not be so detailed as to create overly complex data with the appearance of differences when none exist. Care must be taken to be consistent in the identification and recording of background lesions, since they are important for historical control data, which is often used as a reference when interpreting findings in current studies. Insufficient or inconsistent recording of findings may result in a deficiency in the historical control data for the identification and interpretation of a finding in the future.