Review article Unexpected tumour findings in lifetime rodent bioassay studies—what to do?

摘要: Currently, the majority of substances tested in lifetime bioassays rodents are not mutagenic and, therefore, at most weakly carcinogenic, generally by epigenetic mechanisms. It thus appears obvious that only marginal increases tumour incidences can be expected and that, every aspect a potential carcinogenic effect must thoroughly evaluated. This paper describes series key factors, which should looked order to exclude bioassay question is flawed for design, technical or qualification reasons. also provides some hints whether there indeed real just variation spontaneous incidences. Tumour findings seen context animal model, pharmcokinetics pharmcodynamics test substance, as well any other observation present studies with including non-tumour and—in particular—potential precursor lesions effects on feed intake survival. The possibility observed may species-specific relevant man discussed. important check what reported similar same pharmacological effect. Data from additional investigations material study and/or mechanistic often needed support final risk assessment. © 2002 Elsevier Science Ireland Ltd. All rights reserved.