View of the Regulatory Use of Rat Liver Foci Data in the Federal Republic of Germany

Abstract

Altered hepatocellular foci (AHF) are suspected of being phenotypic markers of a stage in the sequential process of tumor development in the liver. A number of short-term and mid-term tests, including some that use AHF as an endpoint, have been reviewed by the Federal Health Office to determine if they are suitable to replace long-term animals experiments for predicting the carcinogenic potential of chemicals. Although regulatory authorities recognize the advantages of short-term tests, including a possible reduction in the number of animals used, it is still premature to make a general recommendation regarding the suitability of these tests for regulatory decision-making. At this time, the Commission of European Communities (CEC) follows a decision-tree approach for regulating chemicals coming to the market. Since it is unrealistic to expect a reasonable number of AHF to evaluate in 28-day or 90-day studies, AHF can only be practically evaluated in the conventional long-term bioassay. There is still insufficient knowledge regarding the biological significance of the various phenotypic forms of AHF to use them as a relevant endpoint for regulatory purposes. However, data on AHF derived from routine hematoxylin and eosin (H&E) work can be used to aid in the interpretation of the study and in recommending additional investigations.