Quality assurance of pathology data in GLP complied regulatory toxicology studies

The role of pathology is pivotal in GLP compliant regulatory toxicology studies. Special attention may be given to the killing method and the time of necropsy, since these two together can cause post mortem shift in organ weights. Interpretation of organ weights may be done in conjunction with other data, since organ weight may not provide an accurate measure of toxicity insult. The subjectivity in the histopathology slide reading is an important issue, but it can be minimized by peer reviewing the slides by another pathologist. When interpreting the pathology findings, clear reasons may be given for deciding that specific observations are not related to treatment or are not biologically meaningful. It is recommended that the pathologist should have access to study plan and all the study related data (clinical signs, body weights and food consumption data, clinical pathology data, organ weight data, necropsy observations, the relevant biology of the target molecule, and information about expected activity, known toxicity of the test substance and pharmacokinetic data) prior to the completion of the pathology report so that pathology findings can be interpreted in the context of test article exposure. In the interpretation of long-term rodent carcinogenicity bioassays, historical control tumor data are useful, especially to assess the occurrence of rare tumors and marginally increased tumor incidences. If the data of the treatment group are compared with the historical control data using t test, it should be borne in mind that the number of animals used in these groups is different, being much larger in the latter, since the source of historical control data is several studies. More challenges are emerging for pathologists. In the recent years, in toxicologic pathology, fish models are increasingly being used in carcinogenicity testing and developmental research. Performing experiments using fish models and interpreting the findings of the fish studies are different from the conventional animal studies.