The role of carcinogenicity studies in risk assessment

  • E. Fröhlich
  • R. Hess
Conference paper


Until recently, most of the controversy about carcinogenicity testing and long-term safety has been concerned with food additives and environmental chemicals rather than with drugs. However, in medicine, cytotoxic drugs or photochemotherapy are used with increasing frequency for the treatment of non-malignant disorders. The occurrence of malignancy in spontaneous or induced immunodeficiency disease has also become a more frequent finding. This has opened the view to possible long-term consequences of certain forms of chemotherapy. Furthermore, for drugs in general which are intended for longer-term use, the question of carcinogenicity has become, from the regulatory point of view, most decisive for the fate of a new product.


Carcinogenic Activity Chemical Carcinogenesis Quantitative Risk Assessment Tumour Occurrence Carcinogenicity Study 
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  1. 1.
    Ames BN, McCann J, Yamasaki E (1975) Methods for Detecting Carcinogens and Mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutat Res 31: 347–364PubMedCrossRefGoogle Scholar
  2. 2.
    Bartsch H, Tomatis L (1983) Comparison between Carcinogenicity and Mutagenicity Based on Chemicals Evaluated in the IARC Monographs. Environ Health Perspec 47: 305–317CrossRefGoogle Scholar
  3. 3.
    Ciminera JL, Heyse JF, Mantel N, Pitot HC (1984) Design of Cancer Assays for Pharmaceutical Agents. Letter to the Editor. Nat Cancer Inst 72: 1212Google Scholar
  4. 4.
    Cox DR (1958) Planning of Experiments. Wiley, New York (Probability and Statistic Series )Google Scholar
  5. 5.
    DeSerres (1976) Prospects for a Revolution in the Methods of Toxicological Evaluation. Mutat Res 38: 165–176CrossRefGoogle Scholar
  6. 6.
    EEC (1983) Council Directive of 26 October 1983 amending Directives 65/65/EEC, 75/318/ EEC and 75/319/EEC on the Approximations of Provisions laid down by law, regulation or administration action relating to proprietary medicinal products (83/570/EEC). Off J Eur Commun L332/1–10Google Scholar
  7. 7.
    Farber E (1982) Chemical carcinogenesis, a biological perspective. Am J Pathol 106: 271–296PubMedGoogle Scholar
  8. 8.
    Fleiss JL (1973) Statistical Methods for Rates and Proportions. Wiley Series in probability and mathematical statistics. Wiley, New YorkGoogle Scholar
  9. 9.
    Food Safety Council (1980). Quantitative Risk Assessment. Food Cosmet. Toxicol 18: 711–734Google Scholar
  10. 10.
    Gart JJ, Chu KC, Tarone RE (1979) Statistical Issues in Interpretation of Chronic Bioassay Tests for Carcinogenicity. J Nat Cancer Inst 62: 957–974PubMedGoogle Scholar
  11. 11.
    Hess R, Waechter F, Bentley P (1981) Zur Thematik des experimentellen Schwellenwertes in der Karzinogenese. AMI-Berichte 2: 219–226Google Scholar
  12. 12.
    Hughes DH, Bruce RD, Hart RW, Fishbein L, Gaylor DW, Carlton WW (1983) A Report on the Workshop on Biological and Statistical Implications of the ED01 Study and Related Data Bases. Fund Appl Toxicol 3: 129–136CrossRefGoogle Scholar
  13. 13.
    IARC (1982) IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Supplement 4, Chemicals, Industrial Processes and Industries Associated with Cancer in humans. IARC Monographs, Volumes 1 to 29. International Agency for Research on Cancer, LyonGoogle Scholar
  14. 14.
    Mantel N (1984) Treatment of Interim Deaths and Low Dose Responses in Bioassay. Letter to the Editor. Risk Analysis 4: 81–82CrossRefGoogle Scholar
  15. 15.
    McCann J, Choi E, Yamasaki E (1975) Detection of Carcinogens as Mutagens in the Salmonella/Microsome Test: Assay of 300 Chemicals. Proc Natl Acad Sci USA 72: 5135–5139PubMedCrossRefGoogle Scholar
  16. 16.
    McCann J, Ames BN (1977) The Salmonella/Microsome Mutagenicity Test: Predictive Value for Animal Carcinogenicity. In: Hiatt HH, Watson JD, Winsten JA (eds) Origins of Human Cancer. Cold Spring Harbor Laboratory, New York, pp 1431–1450Google Scholar
  17. 17.
    Meselson M, Russell K (1977) Comparison of Carcinogenic and Mutagenic Potency. In: Hiatt HH, Watson JD, Winsten JA (eds) Origins of Human Cancer. Cold Spring Harbor Laboratory, New York, pp 1473–1481Google Scholar
  18. 18.
    NTP (1984) Report of the Ad Hoc Panel on Chemical Carcinogenesis Testing and evaluation of the National Toxicology Program. Board of Scientific Counselors, August 17, 1984Google Scholar
  19. 19.
    Peto R, Pike MC, Day NE, Gray RG, Lee PN, Parish S, Peto J, Richards S, Wahrendorf J (1980) Guidelines for Simple, Sensitive Significance Tests for Carcinogenic Effects in Longterm Animal Experiments (Annex). In: Long-Term and Short-Term Screening Assays for Carcinogens: A Critical Appraisal. IARC Monographs, Supplement 2. International Agency for Research on Cancer. Lyon, p 311–425Google Scholar
  20. 20.
    Rinkus SJ, Legator MS (1979) Chemical Characterization of 465 Known or Suspected Carcinogens and Their Correlation with Mutagenic Activity in the Salmonella typhimurium system. Cancer Res 39: 3289–3318PubMedGoogle Scholar
  21. 21.
    Rodricks J, Taylor MR (1983) Application of Risk Assessment to Food Safety Decision Making. Regulat Toxicol Pharmacol 3: 275–307CrossRefGoogle Scholar
  22. 22.
    Salsburg D (1980) The Effects of Lifetime Feeding Studies on Patterns of Senile Lesions in Mice and Rats. Drug Chem Toxicol 3: 1–33PubMedCrossRefGoogle Scholar
  23. 23.
    Staffa JA, Mehlman MA (1980) Innovations in Cancer Risk Assessment (ED01 Study). J Environ Pathol Toxicol (Special Issue) 3: 1–246Google Scholar
  24. 24.
    Theiss JC (1983) The Ranking of Chemicals for Carcinogenic Potency. Regulat Toxicol Pharmacol 3: 220–328CrossRefGoogle Scholar
  25. 25.
    Weinstein IB, Gattoni-Celli S, Kirschmeyer P, Lambert M, Hsiao W, Backer J, Jeffrey A (1984) Molecular Mechanisms in Multistage Chemical Carcinogenesis. In: Greim H, Jung R, Kramer M, Marquardt H (eds) Biochemical Basis of Chemical Carcinogenesis, 13th Workshop Conference HOECHST. Raven Press, New York, pp 193–212Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1985

Authors and Affiliations

  • E. Fröhlich
    • 1
  • R. Hess
  1. 1.Toxicology Ciba-GeigyBaselSwitzerland

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