Use of rat liver altered focus models for testing chemicals that have completed two-year carcinogenicity studies

Partial hepatectomy (PH) and neonatal rat short-term liver focus models were used to examine the effects of selected chemicals that had been previously tested in the National Toxicology Program (NTP) 2-yr carcinogenicity studies. C.I. Solvent Yellow 14, monuron, chlorendic acid, and 4-hydroxyacetanilide were tested for initiating and promoting activity in the PH model. Chlorendic acid, 4,4'-oxydianiline, 1-amino-2,4-dibromoanthraquinone (ADBAQ), and 4-hydroxyacetanilide were similarly tested in a neonatal rat liver focus model. With the exception of 4-hydroxyacetanilide which was not carcinogenic in the NTP studies, all chemicals tested showed clear evidence of hepatocarcinogenicity. While none of the chemicals showed initiating activity in either the PH or neonatal models, promoting activity, as indicated by increased number, size, or volume fraction of histochemically detected hepatic foci of cellular alteration, was evident for all chemicals with previously demonstrated hepatocarcinogenicity. Liver tumor incidence was documented at 14 months in the PH model and at 300 days in the neonatal model. On the basis of the results obtained from these few chemicals, it is suggested that the use of short-term rat liver focus models may represent a reliable means for identifying chemicals with hepatocarcinogenic potential.