Scientific and Regulatory Policy Committee (SRPC) Review*: Interpretation and Use of Cell Proliferation Data in Cancer Risk Assessment

Authors

Charles E. Wood, U.S. Environmental Protection AgencyFollow
Renee R. Hukkanen, The Dow Chemical Company
Radhakrishna Sura, The Dow Chemical Company
David Jacobson-Kram, U.S. Food and Drug Administration
Thomas Nolte, Boehringer Ingelheim Pharma GmbH & Co.
Marielle Odin, Roche Diagnostics GmbH
Samuel M. Cohen, University of Nebraska Medical CenterFollow

Date of this Version

2015

Citation

Toxicologic Pathology, XX: 1-16, 2015. DOI: 10.1177/0192623315576005

Comments

U.S. government work.

Abstract

Increased cell proliferation is a central key event in the mode of action for many non-genotoxic carcinogens, and quantitative cell proliferation data play an important role in the cancer risk assessment of many pharmaceutical and environmental compounds. Currently, there is limited unified information on assay standards, reference values, targeted applications, study design issues, and quality control considerations for proliferation data. Here, we review issues in measuring cell proliferation indices, considerations for targeted studies, and applications within current risk assessment frameworks. As the regulatory environment moves toward more prospective evaluations based on quantitative pathway-based models, standardization of proliferation assays will become an increasingly important part of cancer risk assessment. To help address this development, we also discuss the potential role for proliferation data as a component of alternative carcinogenicity testing models. This information should improve consistency of cell proliferation methods and increase efficiency of targeted testing strategies.