Proliferative Hepatocellular Lesions of the Rat: Review and Future Use in Risk Assessment
Risk Assessment Forum
The classification of certain experimentally induced proliferative hepatocellular lesions in the rat liver, other than carcinoma, has been the subject of great controversy. This paper addresses three questions that are crucial in the evaluation of such rat tumor data and in the assessment of carcinogenic risk for humans. One question is whether to consider these lesions "hyperplastic" or "neoplastic" in nature, the latter classification being indicative of tumor formation. A second question is to interpret the finding that in some experimental systems, certain nonmalignant proliferative lesions may regress following removal of an inciting, carcinogenic stimulus, with only a small proportion of the lesions persisting. Finally, it is important to know whether any of these lesions may progress to carcinoma.
This paper begins with a composite view of chemically induced hepatocarcinogenesis. Proliferative hepatocellular lesions are described histopathologically, and comparisons among species are made. Discussions are developed on the regression of proliferative lesions following removal of a carcinogenic stimulus, as well as their potential for progression to carcinoma. Current uses of rat liver proliferative lesions in risk assessments by governmental agencies are reviewed, and recommendations are made for the future use of these lesions by EPA in cancer risk assessment.
Note: a complete electronic version of this document that preserves its original appearance (such as in a pdf file format) is not currently available. However, a scanned version is available in image or text format from EPA's National Environmental Publications Information System. Paper copies may be ordered from the National Technical Information Service.
U.S. EPA. Proliferative Hepatocellular Lesions of the Rat: Review and Future Use in Risk Assessment. U.S. Environmental Protection Agency, Risk Assessment Forum, Washington, DC, EPA/625/3-86/011 (NTIS PB87178711), 1986.