Scientific Considerations for Evaluating Cancer Bioassays Conducted by the Ramazzini Institute

BACKGROUND: The Ramazzini Institute (RI) has completed nearly 400 cancer bioassays on > 200 compounds. The European Food Safety Authority (EFSA) and others have suggested that study design and protocol differences between the RI and other laboratories may contribute to controversy regarding cancer hazard findings, principally findings on lymphoma/leukemia diagnoses. OBJECTIVE: We aimed to evaluate RI study design, protocol differences, and accuracy of tumor diagnoses for their impact on carcinogenic hazard characterization. METHODS: We analyzed the findings from a recent Pathology Working Group (PWG) review of RI procedures and tumor diagnoses, evaluated consistency of RI and other laboratory findings for chemicals identified by the RI as positive for lymphoma/leukemia, and examined evidence for a number of other issues raised regarding RI bioassays. The RI cancer bioassay design and protocols were evaluated in the context of relevant risk assessment guidance from international authorities. DISCUSSION: Although the PWG identified close agreement with RI diagnoses for most tumor types, it did not find close agreement for lymphoma/leukemia of the respiratory tract or for neoplasms of the inner ear and cranium. Here we discuss a) the implications of the PWG findings, particularly lymphoma diagnostic issues; b) differences between RI studies and those from other laboratories that are relevant to evaluating RI cancer bioassays; and c) future work that may help resolve some concerns. CONCLUSIONS: We concluded that a) issues related to respiratory tract infections have complicated diagnoses at that site (i. e., lymphoma/leukemia), as well as for neoplasms of the inner ear and cranium, and b) there is consistency and value in RI studies for identification of other chemical-related neoplasia.