ABSTRACT

References ...................................................................................................................................... 129 Routine Techniques ............................................................................................................... 129 Special Techniques ............................................................................................................... 130

Pathologists have been involved in the evaluation of specimens from toxicology studies over the last two centuries. The primary or “routine” responsibility of the pathologist in nonclinical safety assessment is the necropsy of the test animals at the end of the studies and microscopic evaluation of hematoxylin and eosin (H&E)–stained tissue sections on glass slides. Today’s digital and molecular technologies offer an almost limitless possibility of new techniques (many of which are discussed in this chapter) for more sensitive assessment of compound-induced changes. Even so, standard histopathology is still the most commonly used method to assess compound-induced toxicity. This evaluation relies heavily on the extensive anatomical pathology training of pathologists and his or her ability to recognize often subtle microscopic changes, distinguish them from spontaneous (background) changes, and accurately communicate them to non-pathologists. As part of this communication, it is important for pathologists to attempt to describe these changes within the context of pathogenesis, biological and toxicological signicance, and adversity. In addition to the tissue section, the pathologist must be provided with accurate macroscopic observations and organ weights collected at necropsy, to correlate any compound-related macroscopic or organ weight ndings with the microscopic ndings. It is no wonder anatomical pathology is often regarded as a subjective art, and a specialty that is extremely difcult to master.