APM was added to the standard diet, which has been used for > 30 years at the Cesare Maltoni Cancer Research Center (CMCRC
)/ERF, at APM concentrations of 2,000, 400, or 0 ppm to simulate an assumed daily APM intake of 100, 20, or 0 mg/kg bw.
This inadequacy, combined with the general limited knowledge about the safety and potential carcinogenic effects of substances widely present in the industrialized diet, motivated the design of an integrated project of mega-experiments in 1985 at the Cesare Maltoni Cancer Research Center (CMCRC) of the European Ramazzini Foundation (ERF).
For these reasons, and in light of the ever-increasing diffusion of APM in the diet of industrialized countries (particularly in products consumed by young children and pregnant women), we considered it important to perform a mega-experiment following today's internationally recognized good laboratory practices for carcinogenicity bioassays and, more specifically, the life-span carcinogenicity bioassay design followed for many years at the CMCRC and described in previous publications (Soffritri et al.
In fact, previous experiments performed at the CMCRC laboratory have shown that a) methanol administered in drinking water, at doses ranging from 20,000 to 500 ppm, induced a statistically significant increase in the incidence of lymphomas/ leukemias in female rats (Soffritti et al.