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Risk assessment problems in chemical oncogenesis

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Progress in Drug Research/Fortschritte der Arzneimittelforschung/Progrès des recherches pharmaceutiques

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Abstract

The assessment of the risk to humans represented by positive results obtained in animal oncogenicity bioassays and the associated problems have been reviewed and debated previously [1–8]. Much of the debate has centered on the use of the maximum tolerated dose, application of metabolic and pharmacokinetic parameters, linear versus nonlinear tumor dose response curves and related mathematical modelling, species/strain differences, statistical considerations, the relevance of mutagenic screens and animal to human extrapolations. This review will briefly outline the present status of oncogenicity risk assessment including, where appropriate, brief consideration of some of these problems. The major portion of this discussion, however, will attempt to highlight problems with risk assessment that have not been so thoroughly discussed before. These problems are: the ambiguity of several key terms used in chemical oncogenesis and risk assessment, the dominance of the animal bioassay results over the other data bases available, the lack of validation of the bioassay protocol, oncogenic responses due to the exaggerated pharmacodynamic effects of drugs and risk assessment of antitumor drugs. Recommendations concerning these problems are also offered.

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  1. Medical University of South Carolina, Charleston, South Carolina, 29425, USA

    G. H. Hottendorf

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  1. Basel, Switzerland

    Ernst Jucker  & Urs Meyer  & 

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© 1987 Birkhäuser Verlag Basel

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Hottendorf, G.H. (1987). Risk assessment problems in chemical oncogenesis. In: Jucker, E., Meyer, U. (eds) Progress in Drug Research/Fortschritte der Arzneimittelforschung/Progrès des recherches pharmaceutiques. Progress in Drug Research/Fortschritte der Arzneimittelforschung/Progrès des recherches pharmaceutiques, vol 31. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-9289-6_8

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  • DOI: https://doi.org/10.1007/978-3-0348-9289-6_8

  • Publisher Name: Birkhäuser Basel

  • Print ISBN: 978-3-0348-9981-9

  • Online ISBN: 978-3-0348-9289-6

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