Similar phenomena cannot be exclude for foci induced by high doses of carcinogens that elicit significant liver damage. The demonstration of decreased activity of glycogen phosphorylase was the most reliable enzyme histochemical marker in ovo . In addition some foci showed a more violet tinged staining of the reaction product. 4.3 Focal hepatic lesions as endpoints in carcinogenicity testing In rodents, foci of altered hepatocytes are regarded as preneoplastic lesions. These lesions may progress to benign and malignant liver cell tumors without any additional exposure.
Testing based on the induction of tumors in whole animals usually requires more than two years.
Using preneoplastic lesions as end points in carcinogenicity testing may shorten the required time to a few months. Since these experiments are terminated before tumors occur, the animals do not suffer from tumor growth or metastasis. Since foci of altered hepatocytes induced in animal experiments have been successfully used as endpoints in carcinogenicity testing, the occurrence of similar lesions in the IOCA may offer an even more accelerated and convenient approach to carcinogenicity testing. It is generally believed that the long term experiments in carcinogenicity testing are necessary for a sufficiently high sensitivity. However, at least for the detection of the carcinogenic effects of small doses of potent carcinogens, the IOCA based on the induction of focal liver lesions seems to be as sensitive as the chronic rodent bioassay which is based on the occurrence of tumors.