Advertisement

The Carcinogenicity Prediction and Battery Selection Approach

  • Julia Pet-Edwards
  • Yacov Y. Haimes
  • Vira Chankong
  • Herbert S. Rosenkranz
  • Fanny K. Ennever

Abstract

Decisions are most often based upon the results of experiments coupled with the knowledge of experts. When sampling or experimental results are available, they often constitute the major factualinformation input into the decision-making process. For example, clinicians and physicians use diagnostic tests and clinical findings along with their expert knowledge to diagnose their patients’ problems. When the physician estimates that the “risk” of a disease is high enough (here we define “risk” as both the probability and the severity), expert knowledge is again used to develop appropriate treatment plans. Toxicologists (in industry, government, and academia) use test results on live animals as well as short-term in vitro tests to study the carcinogenic potential of chemicals. If the risk of carcinogenicity for a particular chemical is high, then a pharmaceutical or chemical company may decide to stop or delay the development of the chemical, a regulatory agency may decide to ban the development or restrict the use of such a chemical, or a researcher in academia may decide to study this chemical further to examine its modes of action. In industry, quality control managers interpret results from multiple “inspectors” (humans or machines) to identify defective parts and to decide whether a defective part should be destroyed or sent to a rework station. Water resources and environmental engineers utilize results from well sampling to decide what type of action is warranted on an aquifer found to be contaminated.

Keywords

Lower Effective Dose National Toxicology Program Defective Part Possible Human Carcinogen Quality Control Manager 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. ACM (Advisory Committee on Mutagenesis), 1986, Guidelines on the Use of Mutagenicity Tests in the Toxicological Evaluation of Chemicals, Minister of National Health and Welfare and Minister of the Environment, Ottawa, Canada.Google Scholar
  2. Ashby, J., 1986, “The prospects for a simplified and internationally harmonized approach to the detection of possible human carcinogens and mutagens,” Mutagenesis, 1:3–16.CrossRefGoogle Scholar
  3. Brusick, D., Ashby, J., de Serres, F., Lohman, P., Matsushima, T., Matter, B., Mendelsohn, M., and Waters, M., 1986, “Weight-of-evidence scheme for evaluation and interpretation of short-term results,” In Genetic Toxicology of Environmental Chemicals, Part B: Genetic Effects and Applied Mutagenesis, C. Ramel, B. Lambert, and J. Magnusson (eds.), Alan R. Liss, New York, pp. 121–129.Google Scholar
  4. Chankong, V., Haimes, Y. Y., Rosenkranz, H. S., and Pet-Edwards, J., 1985, “The carcino-genicity prediction and battery selection (CPBS) method: A Bayesian approach,” Mutation Res., 153:135–166.Google Scholar
  5. Gold, L. S., de Veciana, M., Backman, G. M., Magaw, R., Lopipero, P., Smith, M., Hooper, N. K., Havender, W. R., Bernstein, L., Peto, R., Pike, M. C., and Ames, B. N., 1984, “A carcinogenic potency database of the standardized results of animal bioassays,” Environ. Health Perspect., 58:9–319.CrossRefGoogle Scholar
  6. Gold, L. S., de Veciana, M., Backman, G. M., Magaw, R., Lopipero, P., Smith, M., Blumenthal, M., Levinson, R., Bernstein, L., and Ames, B. N., 1986, “Chronological supplement to the Carcinogenic Potency Database: Standardized results of animal bioassays published through December 1982,” Environ. Health Perspect., 67:161–200.CrossRefGoogle Scholar
  7. Haseman, J. K., Tharrington, E. C., Huff, J. E., and McConnel, E. E., 1986, “Comparison of site-specific and overall tumor incidence analyses for 81 recent National Toxicology Program carcinogenicity studies,” Regul. Toxicol. Pharmcol, 6:155–170.CrossRefGoogle Scholar
  8. Klopman, G., and Rosenkranz, H. S., 1984, “Structural requirements for the mutagenicity of environmental nitroarenes,” Mutation Res., 126:227–238.CrossRefGoogle Scholar
  9. Lave, L. B., and Omenn, G. S., 1986, “Cost-effectiveness of short-term tests for carcinogenicity,” Nature, 324:29–34.CrossRefGoogle Scholar
  10. NAS (National Academy of Sciences, U.S.), 1984, Toxicity Testing: Strategies to Determine Needs and Priorities. The Report of Steering Committee on Identification of Toxic and Potentially Toxic Chemicals for Consideration by the National Toxicology Program, Board on Toxicology and Environmental Health Hazards, Commission on Life Sciences, National Research Council, National Academy Press, Washington, D.C.Google Scholar
  11. Nesnow, S., Argus, M., Bergman, H., Chu, K., Frith, C., Helmes, T., McGaughey, R., Ray, V., Slaga, T. J., Tennant, R., and Weisburger, E., 1987, “Chemical carcinogens: A review and analysis of the literature of selected chemicals and the establishment of the Gene-Tox Carcinogen Data Base,” Mutation Res., 185:1–195.Google Scholar
  12. Pott, P., 1775, “Chirurgical Observations,” Reprinted in Natl. Cancer Inst. Monog., 1963, 10:7.Google Scholar
  13. Rosenkranz, H. S., Klopman, G., Chankong, V., Pet-Edwards, J., and Haimes, Y. Y., 1984, “Prediction of environmental carcinogens: A strategy for the mid-1980’s,” Environ. Mutagen., 6:231–258.CrossRefGoogle Scholar
  14. Shrader-Frechette, K. S., 1985, Risk Analysis and Scientific Method, D. Reidel, Dordrecht.CrossRefGoogle Scholar
  15. Tennant, R. W., Stasiewicz, S., and Spalding, J. W., 1986, “Comparison of multiple parameters of rodent carcinogenicity and in vitro genetic toxicity,” Environ. Mutagen., 8:205–227.CrossRefGoogle Scholar
  16. U.S. Congress, 1981, Office of Technology Assessment, Assessment of Technologies for Determining Cancer Risks from the Environment, U.S. Government Printing Office, Washington, D.C.Google Scholar
  17. Waters, M. D., Stack, H. F., and Brady, A. L., 1986, “Analysis of the spectra of genetic activity in short-term tests,” In Genetic Toxicology of Environmental Chemicals, Part B: Genetic Effects and Applied Mutagenesis, G. Ramel, B. Lambert, and J. Magnusson (eds.), Alan R. Liss, New York, pp. 99–109.Google Scholar
  18. Weisburger, J. H., and Williams, G. M., 1986, “Rational decision points in carcinogenicity bioassays based on mechanisms of mutagenesis and carcinogenesis,” in Genetic Toxicology of Environmental Chemicals, Part B: Genetic Effects and Applied Mutagenesis, C. Ramel, B. Lambert, and J. Magnusson (eds.), Alan R. Liss, New York, pp. 91–98.Google Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Julia Pet-Edwards
    • 1
  • Yacov Y. Haimes
    • 1
  • Vira Chankong
    • 2
  • Herbert S. Rosenkranz
    • 2
  • Fanny K. Ennever
    • 2
  1. 1.University of VirginiaCharlottesvilleUSA
  2. 2.Case Western Reserve UniversityClevelandUSA

Personalised recommendations