National Academies Press: OpenBook

Issues in Risk Assessment (1993)

Chapter: 8. ACKNOWLEDGEMENTS

« Previous: 7. CONCLUSIONS
Suggested Citation:"8. ACKNOWLEDGEMENTS." National Research Council. 1993. Issues in Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/2078.
×

species concordance depends on carcinogenic potency, and that for weak carcinogens, the maximum possible species concordance may be only about 80%. Lave et al. (1988) suggested that concordance between rats and mice may represent an upper bound on concordance between rodents and humans. Quantitative interspecies extrapolation of carcinogenic potency is therefore done under the presumption that the agent in question will be effective in both species involved.

If progress in carcinogenic risk assessment based on bioassay data is to be made, it seems that additional information beyond that contained in traditional experiments is required. In particular, studies of the mechanisms of chemical carcinogenesis may provide new insights on the estimation of low dose risk (Moolgavkar & Luebeck, 1990). The relative importance of mutation and cell proliferation in carcinogenesis particularly requires further discussion. Cohen & Ellwein (1990) show that proliferation of urinary bladder tissue is essential for the induction of bladder tumors with 2-acetylaminofluorene. Cunningham et al. (1991) recently demonstrated that 2,4-diaminotoluene (2,4-DAT) and 2,6-diaminotoluene (2,6-DAT) are equally mutagenic in Salmonella , yet only 2,4-DAT produces a sufficient increase in cell turnover in rat liver to lead to hepatocarcinogenesis. Ames & Gold (1990) conclude that "without studies of the mechanism of carcinogenesis, the fact that a chemical is a carcinogen at the MTD in rodents provides no information about low dose risk to humans". Physiologically based pharmacokinetic models may afford an opportunity to increase the accuracy of risk estimates through improved tissue dosimetry (Krewski et al., 1991b); measurement of metabolic parameters in different species may also lead to improved interspecies extrapolation (Andersen et al., 1987). More sensitive indicators of effects at very low doses, such as markers of DNA damage suspected to play a role in neoplastic conversion (cf. Lutz, 1990), may also serve to provide improved estimates of risk in the future. All of these considerations suggest a more biologically based approach to cancer risk assessment is needed (Clayson, 1987).

8. Acknowledgements

We are grateful to Drs. David Clayson, Kenny Crump, Lois Gold, Lester Lave, Mary Paxton, and Marvin Schneiderman for helpful com-

Suggested Citation:"8. ACKNOWLEDGEMENTS." National Research Council. 1993. Issues in Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/2078.
×
Page 149
Next: 9. REFERENCES »
Issues in Risk Assessment Get This Book
×
Buy Paperback | $65.00
MyNAP members save 10% online.
Login or Register to save!
Download Free PDF

The scientific basis, inference assumptions, regulatory uses, and research needs in risk assessment are considered in this two-part volume.

The first part, Use of Maximum Tolerated Dose in Animal Bioassays for Carcinogenicity, focuses on whether the maximum tolerated dose should continue to be used in carcinogenesis bioassays. The committee considers several options for modifying current bioassay procedures.

The second part, Two-Stage Models of Carcinogenesis, stems from efforts to identify improved means of cancer risk assessment that have resulted in the development of a mathematical dose-response model based on a paradigm for the biologic phenomena thought to be associated with carcinogenesis.

  1. ×

    Welcome to OpenBook!

    You're looking at OpenBook, NAP.edu's online reading room since 1999. Based on feedback from you, our users, we've made some improvements that make it easier than ever to read thousands of publications on our website.

    Do you want to take a quick tour of the OpenBook's features?

    No Thanks Take a Tour »
  2. ×

    Show this book's table of contents, where you can jump to any chapter by name.

    « Back Next »
  3. ×

    ...or use these buttons to go back to the previous chapter or skip to the next one.

    « Back Next »
  4. ×

    Jump up to the previous page or down to the next one. Also, you can type in a page number and press Enter to go directly to that page in the book.

    « Back Next »
  5. ×

    Switch between the Original Pages, where you can read the report as it appeared in print, and Text Pages for the web version, where you can highlight and search the text.

    « Back Next »
  6. ×

    To search the entire text of this book, type in your search term here and press Enter.

    « Back Next »
  7. ×

    Share a link to this book page on your preferred social network or via email.

    « Back Next »
  8. ×

    View our suggested citation for this chapter.

    « Back Next »
  9. ×

    Ready to take your reading offline? Click here to buy this book in print or download it as a free PDF, if available.

    « Back Next »
Stay Connected!