Chemicals studied and evaluated in long-term carcinogenesis bioassays by both the Ramazzini Foundation and the National Toxicology Program: in tribute to Cesare Maltoni and David Rall

Ann N Y Acad Sci. 2002 Dec;982:208-30. doi: 10.1111/j.1749-6632.2002.tb04935.x.


The Ramazzini Foundation (RF) in Bentivoglio, Italy and the National Toxicology Program (NTP) in Research Triangle Park, North Carolina have carried out several hundred chemical carcinogenesis bioassays: 200 by RF and 500 by NTP. Of these, 21 have been evaluated by both laboratories. The 14 chemicals for which both laboratories have designed, conducted, and reported bioassay results are: acrylonitrile, benzene, chlorine, diesel fuel, ethylbenzene, methylene chloride (dichloromethane), propylene, styrene, styrene oxide, toluene, trichloroethylene, trichlorofluoromethane, vinylidene chloride, and xylenes. The other seven chemicals (two are fibers) were evaluated by both laboratories, but results have not yet been published. Results of these 14 interlaboratory studies were compared both to explore consistency of carcinogenic responses and to identify possible factors that may reveal reasons for any differences observed. Individual carcinogenesis results from each laboratory were duplicated and complementary. Of the 14 chemicals compared, 11 (80%) were either carcinogenic (9 chemicals) or noncarcinogenic (2 chemicals) in both studies. Eight of the paired chemicals had at least one carcinogenic target site in common. The other three were carcinogenic in one laboratory but not in the other. Possible explanations for these differences include dose, method of administration, duration of follow-up, and whether or not total tumors are counted. The collaboration between these two pioneering bioassay laboratory programs contributes greatly to our understanding of chemical carcinogenesis and results in better protection of workers and the general population from chemical diseases, especially cancers.

MeSH terms

  • Animals
  • Biological Assay / methods
  • Carcinogens / administration & dosage
  • Carcinogens / toxicity*
  • Female
  • Foundations
  • Humans
  • Italy
  • Male
  • Mice
  • Mice, Inbred Strains
  • Neoplasms / chemically induced*
  • Neoplasms / prevention & control
  • Neoplasms, Experimental / chemically induced*
  • Neoplasms, Experimental / pathology
  • Rats
  • Rats, Inbred Strains
  • Research Design
  • Species Specificity
  • Time Factors
  • United States


  • Carcinogens