Weight-of-Biological Evidence Approach for Assessing Carcinogenicity

  • J. D. Burek
  • D. H. Patrick
  • R. J. Gerson
Chapter
Part of the ILSI Monographs book series (ILSI MONOGRAPHS)

Abstract

Cancer is a complex, multistage, multimechanism phenomenon. Despite this, long-term rodent carcinogenicity studies have been the principal means used to assess the potential carcinogenic effect of compounds. Unfortunately, decades of carcinogenicity testing have failed to provide an unequivocal set of guidelines that determines the true carcinogenic potential of a compound in laboratory animals or humans. Furthermore, there is often considerable debate over what is a biologically significant finding in an individual study. A statistical evaluation helps in assessing the probability that a finding is treatment related, but numerous other factors have an impact on that determination. The data must be evaluated separately and collectively to determine whether the change in question is real.

Keywords

Carcinogenic Effect Phthalate Ester Carcinogenicity Study Toxicol Environ Health Evidence Approach 
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.
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Brand I, Buoen LC, Brand KG (1977). Foreign-body tumors of mice: Strain and sex differences in latency and incidence. J Natl Cancer Inst 58:1443–1447.PubMedGoogle Scholar
  2. Brusick DJ (1977). In vitro mutagenesis assays as predictors of chemical carcinogenesis in mammals. Clin Toxicol 10:79–101.PubMedCrossRefGoogle Scholar
  3. Bucci TJ (1985). Profiles of induced tumors in animals. Toxicol Pathol 13:105–109.PubMedCrossRefGoogle Scholar
  4. Burek JD (1978). Pathology of aging rats. A morphogical and experimental study of the age-associated lesions in aging BN/Bi, WAG/Rij and (WAG X BN) Ft rats. West Palm Beach, CRC Press Inc. Google Scholar
  5. Burek JD, Nitschke KD, Bell TJ, et al. (1984). Methylene chloride: A two-year inhalation toxicity and oncogenicity study in rats and hamsters. Fundam Appl Toxicol 4:30–47.PubMedCrossRefGoogle Scholar
  6. Clayson DB (1985). Dose relationships in experimental carcinogenesis: Dependence on multiple factors including biotransformation. Toxicol Pathol 13:119–127.PubMedCrossRefGoogle Scholar
  7. Di Carlo FJ, Fung VA (1984). Summary of carcinogenicity data generated by the National Cancer Institute/National Toxicology Program. Drug Metab Rev 15: 1251–1273.PubMedCrossRefGoogle Scholar
  8. Digregorio JG, Kotyok BL (1985). Toxicology of asbestos. Clin Pharmacol 32:201–204.Google Scholar
  9. Ekman L, Hansson E, Havu N, Carlsson E, Lundberg C (1985). Toxicological studies on omeprazole. Scand J Gastroenterol (Suppl) 108:53–69.Google Scholar
  10. Gehring PJ, Blau GE (1977). Mechanisms of carcinogenesis: Dose response. J Environ Pathol Toxicol 1:163–179.Google Scholar
  11. Grasso P, Gangolli SD, Golberg L, Hooson J (1971). Physiochemical and other factors determining local sarcoma production by food additives. Food Cosmet Toxicol 9:463–478.PubMedCrossRefGoogle Scholar
  12. Grasso P (1985). Peroxisome proliferation and hepatotoxicity in rodents. Biochem Soc Trans 13:861–862.PubMedGoogle Scholar
  13. Grice HC (1978). The acceptance of risk benefit decisions. In: Gall: CL, Pavletti R, Vettorazzi G (Eds): Chemical Toxicology of Foods Amsterdam, Elsevier/North Holland, pp. 33–45.Google Scholar
  14. Hardisty JF (1985). Factors influencing laboratory animal spontaneous tumor profiles. Toxicol Pathol 13:95–104.PubMedCrossRefGoogle Scholar
  15. Haseman JK (1983). Patterns of tumor incidence in two-year cancer bioassay feeding studies in Fischer 344 rats. Fundam Appl Toxicol 3:1–9.PubMedCrossRefGoogle Scholar
  16. Haseman JK, Crawford DD, Huff JE, Boorman GA, McConnell EE (1984a). Results from 86 two-year carcinogenicity studies conducted by the National Toxicology Program. J Toxicol Environ Health 14:621–639.PubMedCrossRefGoogle Scholar
  17. Haseman HK, Huff J, Boorman CA (1984b). Use of historical control data in carcino-genicity studies in rodents. Toxicol Pathol 12:126–135.PubMedCrossRefGoogle Scholar
  18. Hollander CF, van Rijssel TG (1963). Experimental production of intramandibular carcinoma in mice by mechanical damage. J Natl Cancer Inst 30:337–358.PubMedGoogle Scholar
  19. Hottendorf GH, Pachter IJ (1985). Review and evaluation of the NCI/NTP carcinogenesis bioassays. Toxicol Pathol 13:141–146.PubMedCrossRefGoogle Scholar
  20. International Agency for Research on Cancer (1982). Benzene. In: IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Vol 29. IARL. Some industrial chemicals and dye stuffs. Lyon, International Agency for Research on Cancer, pp. 93–148.Google Scholar
  21. IRGL (Interagency Regulatory Liaison Group) (1979). The scientific basis for identi-fication of potential carcinogens and estimation of risks. Report of the Interagency Regulatory Liaison Group. J Natl Cancer Inst 63:241–268.Google Scholar
  22. Jack D, Poynter D, Spurling NW (1983). Beta-adenoceptor stimulants and meso-varian leiomyomas in the rat. Toxicology 27:315–320.PubMedCrossRefGoogle Scholar
  23. Koestner A (1985). Prognostic role of cell morphology of animal tumors. Toxicol Pathol 13:90–94.PubMedCrossRefGoogle Scholar
  24. McConnell EE, Solleveld HA, Swenberg JA, Boorman CA (1986). Guidelines for combining neoplasms for evaluation of rodent carcinogenesis studies. J Natl Cancer Inst 76:283–289.PubMedGoogle Scholar
  25. Nelson LW, Kelly WA, Weikel JH (1972). Mesovarial leiomyomas in rats in a chronic toxicity study of mesuprine hydrochloride. Toxicol Appl Pharmacol 23:731–737.PubMedCrossRefGoogle Scholar
  26. Oppenheimer JH, Bernstein G, Surks MI (1968). Increased thyroxine turnover and thyroidal function after stimulation of hepatocellular binding of thyroxine by phenobarbital. J Clin Invest 47:1399–1406.PubMedCrossRefGoogle Scholar
  27. Pessayre D, Mazel P (1976). Induction and inhibition of hepatic drug metabolizing enzymes by rifampin. Biochem Pharmacol 25:943–949.PubMedCrossRefGoogle Scholar
  28. Plaa GL (1986). Toxic responses of the liver. In: Klaassen, Amdur, Doull (Eds): Toxicology, the Basic Science of Poisons, 3rd edit. New York, Macmillan.Google Scholar
  29. Reddy JK, Azarnoft DL, Hignite CE (1980). Hypolipidaemic hepatic peroxisome proliferators form a novel class of chemical carcinogens. Nature 283:397–398.PubMedCrossRefGoogle Scholar
  30. Reddy JK, Rao MS (1986). Peroxisome proliferators and cancer: Mechanisms and implications. Trends Pharmacol Sci 7:438–443.CrossRefGoogle Scholar
  31. Richardson BP, Turkalj I, Fluckiger E (1984). Bromocriptine in Safety Testing of New Drugs. Laurence DR, McLean AEM, Weatherall M (Eds). New York: Academic Press, pp. 19–63. Google Scholar
  32. Ross MH, Bras G (1965). Tumor incidence patterns and nutrition in the rat. J Nutr 87:245–260.PubMedGoogle Scholar
  33. Rustia M, Shubik(1978). Thyroid tumors in rats and hepatomas in mice after griseofulvin treatment. Br J Cancer 38:237–249.PubMedCrossRefGoogle Scholar
  34. Schulte-Hermann R (1974). Induction of liver growth by xenobiotic compounds and other stimuli. CRC Crit Rev Toxicol 3:97–158.PubMedCrossRefGoogle Scholar
  35. Schulte-Hermann R (1985). Tumor promotion in the liver. Arch Toxicol 57:147–158.PubMedCrossRefGoogle Scholar
  36. Shelby MD, Stasiewicz S (1984). Chemicals showing no evidence of carcinogenicity in long-term, two-species rodent studies: The need for short-term test data. Environ Mutagen 6:871–878.PubMedCrossRefGoogle Scholar
  37. Squire RA (1981). Ranking animal carcinogens: A proposed regulatory approach. Science 214:877–880.PubMedCrossRefGoogle Scholar
  38. Tennant RW, Stasiewicz S, Spalding JW (1986). Comparison of multiple parameters of rodent carcinogenicity and in vitro genetic toxicity. Environ Mutagen 8:205–227.PubMedCrossRefGoogle Scholar
  39. Toth B (1985). Methodologies, findings, and implications of chemical carcinogenesis studies: Their significance for hazard assessment. Anticancer Res 5:457–470.PubMedGoogle Scholar
  40. Vainio H, Hemminki K, Wilbour J (1985). Data on the carcinogenicity of chemicals in the IARC Monographs Programme. Carcinogenesis 6:1653–1665.PubMedCrossRefGoogle Scholar
  41. Woo Y, Arcos JC, Argus MF, Griffin GW, Nisghiyama K (1977). Metabolism in vivo of dioxane: Identification of p-dioxane-2-one as the major urinary metabolite. Biochem Pharmacol 26:1535–1538.PubMedCrossRefGoogle Scholar
  42. Woo Y, Argus MF, Arcos JC (1978). Effect of mixed-function oxidase modifiers on metabolism and toxicity of the oncogene dioxane. Cancer Res 38:1621–1625.PubMedGoogle Scholar
  43. Young JD, Braun WH, Gehring PJ (1978). Dose-dependent fate of 1,4-dioxane in rats. J Toxicol Environ Health 4:709–726.PubMedCrossRefGoogle Scholar
  44. Young JD, Braun WH, Gehring PJ, Horvath BS, Daniel RL (1976a). 1,4-dioxane and beta-hydroxyethoxyacetic acid excretion in urine of humans exposed to dioxane vapors. Toxicol Appl Pharmacol 38:643–646.PubMedCrossRefGoogle Scholar
  45. Young JD, Braun WH, LeBeau JE, Gehring PJ (1976b). Saturated metabolism as the mechanism for the dose dependent fate of 1,4 dioxane in rats. Toxicol Appl Pharmacol 37:138 (Abstract). Google Scholar
  46. Young SS, Gries CL (1984). Exploration of the negative correlation between proliferative hepatocellular lesions and lymphoma in rats and mice—establishment and implications. Fundam Appl Toxicol 4:632–640.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1988

Authors and Affiliations

  • J. D. Burek
    • 1
  • D. H. Patrick
    • 1
  • R. J. Gerson
    • 1
  1. 1.Department of Safety AssesmentMerck Sharp and Dohme Research LaboratoriesWest PointUSA

Personalised recommendations