Ramazzini Foundation cancer program: history and major projects, life-span carcinogenicity bioassay design, chemicals studied, and results.

The Ramazzini Foundation research program was started over thirty years ago. The features of this program are: (1) systematic and integrated project design; (2) consistency over time; (3) homogeneity of approach: key members of the team remain unchanged; and (4) choice to work on new frontiers of scientific research. The program centers mainly on three projects: Project 1: experimental carcinogenicity bioassays; Project 2: experimental anticarcinogenesis assays to identify factors and active principles (compounds) capable of opposing the onset of tumors while being suitable for preventive/chemopreventive intervention; Project 3: epidemiological studies, both descriptive and analytical, on tumor incidence and mortality in persons professionally and environmentally exposed to industrial carcinogenic risks. The project involving experimental carcinogenicity bioassays for the identification of exogenous carcinogens (environmental and industrial above all) began in 1966. This project has included 398 experimental bioassays on 200 compounds/agents using some 148,000 animals monitored until their spontaneous death. Among the studies already concluded, 47 agents have shown "clear evidence" of carcinogenicity. The results have demonstrated for the first time that (1) vinyl chloride can cause liver angiosarcoma as well as other tumors; (2) benzene is carcinogenic in experimental animals for various tissues and organs; (3) formaldehyde may produce lymphomas and leukemias; and (4) methyl-tert-butyl ether (MTBE), the most common oxygenated additive used in gasolines, can cause lymphomas/leukemias. Many of the results achieved have led to the introduction of norms and measures of primary prevention.