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Point Estimates of Cancer Risk at Low Doses

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  • David W. Gaylor
  • Ralph L. Kodell
  • James J. Chen
  • Janet A. Springer
  • Ronald J. Lorentzen
  • Robert J. Scheuplein

Abstract

There has been considerable discussion regarding the conservativeness of low‐dose cancer risk estimates based upon linear extrapolation from upper confidence limits. Various groups have expressed a need for best (point) estimates of cancer risk in order to improve risk/benefit decisions. Point estimates of carcinogenic potency obtained from maximum likelihood estimates of low‐dose slope may be highly unstable, being sensitive both to the choice of the dose–response model and possibly to minimal perturbations of the data. For carcinogens that augment background carcinogenic processes and/or for mutagenic carcinogens, at low doses the tumor incidence versus target tissue dose is expected to be linear. Pharmacokinetic data may be needed to identify and adjust for exposure‐dose nonlinearities. Based on the assumption that the dose response is linear over low doses, a stable point estimate for low‐dose cancer risk is proposed. Since various models give similar estimates of risk down to levels of 1%, a stable estimate of the low‐dose cancer slope is provided by ŝ= 0.01/ED01, where ED01 is the dose corresponding to an excess cancer risk of 1%. Thus, low‐dose estimates of cancer risk are obtained by, risk =ŝ× dose. The proposed procedure is similar to one which has been utilized in the past by the Center for Food Safety and Applied Nutrition, Food and Drug Administration. The upper confidence limit, s, corresponding to this point estimate of low‐dose slope is similar to the upper limit, q1 obtained from the generalized multistage model. The advantage of the proposed procedure is that ŝ provides stable estimates of low‐dose carcinogenic potency, which are not unduly influenced by small perturbations of the tumor incidence rates, unlike q̂1.

Suggested Citation

  • David W. Gaylor & Ralph L. Kodell & James J. Chen & Janet A. Springer & Ronald J. Lorentzen & Robert J. Scheuplein, 1994. "Point Estimates of Cancer Risk at Low Doses," Risk Analysis, John Wiley & Sons, vol. 14(5), pages 843-850, October.
    • Handle: RePEc:wly:riskan:v:14:y:1994:i:5:p:843-850
    DOI: 10.1111/j.1539-6924.1994.tb00296.x
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    References listed on IDEAS

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    1. John H. Farmer & Ralph L. Kodell & David W. Gaylor, 1982. "Estimation and Extrapolation of Tumor Probabilities from a Mouse Bioassay with Survival/Sacrifice Components," Risk Analysis, John Wiley & Sons, vol. 2(1), pages 27-34, March.
    2. J. Bowers & B. Brown & J. Springer & L. Tollefson & R. Lorentzen & S. Henry, 1993. "Risk Assessment for Aflatoxin: An Evaluation Based on the Multistage Model," Risk Analysis, John Wiley & Sons, vol. 13(6), pages 637-642, December.
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    Cited by:

    1. Walter W. Piegorsch & R. Webster West, 2005. "Benchmark Analysis: Shopping with Proper Confidence," Risk Analysis, John Wiley & Sons, vol. 25(4), pages 913-920, August.
    2. Ravi P. Subramaniam & Paul White & V. James Cogliano, 2006. "Comparison of Cancer Slope Factors Using Different Statistical Approaches," Risk Analysis, John Wiley & Sons, vol. 26(3), pages 825-830, June.

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