Estimates of Probability Coefficients for Carcinogens

2 Estimates of Probability Coefficients for Carcinogens. The nominal probabilities of a stochastic response (primarily cancers) per unit dose used in risk assessments, which are referred to in this Report as probability coefficients, normally differ for radionuclides and chemical carcinogens in regard to the degree of conservatism incorporated in the assumed values and the number of organs or tissues at risk that are taken into account. 

The nominal probability coefficient for radionuclides normally used in radiation protection is derived mainly from maximum likelihood estimates (MLEs) of observed responses in the Japanese atomic-bomb survivors. A linear or linear-quadratic dose-response model, which is linear at low doses, is used universally to extrapolate the observed responses at high doses and dose rates to the low doses of concern in radiation protection. The probability coefficient at low doses also includes a small adjustment that takes into account an assumed decrease in the response per unit dose at low doses and dose rates compared with the observed responses at high doses and dose rates. 

In contrast, nominal probability coefficients for chemical carcinogens are derived from upper 95 percent confidence limits of observed responses at high doses, mainly in studies in animals. In some studies, the difference between the upper 95 percent confidence limit and MLE of the observed responses at high doses is an order of magnitude or more. Furthermore, several models have been used to extrapolate the observed responses to the low doses of concern in health protection of the public, with the result that estimated probability coefficients at low doses can differ by several orders of magnitude depending on the extrapolation model chosen. 

the nominal probability coefficients at low doses of chemical carcinogens could be considerably more conservative (more likely to overestimate risk) than the probability coefficient for radionuclides. As a result, potential risks posed by chemical carcinogens could be given a disproportionate weight in classifying waste. 

For the purpose of classifying waste that contains radionuclides, NCRP reaffirms use of the nominal probability coefficient for fatal cancers (i.e., the probability of a fatal cancer per unit effective dose) of 0.05 Sv 1 normally assumed in radiation protection of the public. For chemical carcinogens, NCRP believes that MLEs of probability coefficients obtained from the linearized, multi-stage model should be used in classifying waste, in order to provide reasonable consistency with the probability coefficient for radionuclides. The use of MLEs for chemical carcinogens usually will result in substantially lower probability coefficients than the use of upper 95 percent confidence limits. 

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