Chapter 27 – Carcinogenicity Assessment

In vivo carcinogenicity assessment of chemicals is a long and expensive process, typically including lifetime (2-year) studies in two rodent species. The relevance of these animal data to human cancer risk assessment has been questioned, and there are numerous examples of chemically-induced rodent neoplasms that are not considered applicable to human risk. This chapter summarizes the design, planning, and execution of 2-year rodent carcinogenicity studies as well as the same features in newer alternative (6-month) studies that use mouse models with genetically engineered predispositions to develop xenobiotic-induced cancers (e.g., the rasH2 mouse and p53+/− mouse). Special considerations required when undertaking carcinogenicity assessment of proteins, small nucleic acids, and stem cell-based therapies are also reviewed.