Dose-response assessment radionuclides, stochastic

Given the different approaches to dose-response assessment and the different measures of response normally used for radionuclides and chemicals that cause stochastic effects, estimates of responses from exposure to the two types of substances clearly are not equivalent, and the correspondence of the estimated frequency of responses to the frequency that might actually be experienced differs substantially. Specifically, if the results of experiments indicating chemical-induced stochastic responses in animals are assumed to be indicative of stochastic responses in humans, estimates of responses for chemicals could be considerably more conservative (pessimistic) than estimates for radionuclides. This difference is primarily the result of... 

Stochastic responses from exposure to radionuclides and hazardous chemicals generally are of concern in health protection of the public and in classifying waste. Of the three differences in approaches to dose-response assessment identified above, the most important is the use of a best estimate (MLE) of the dose-response relationship for radionuclides but upper-bound estimates (UCLs) for hazardous chemicals that cause stochastic effects. UCL in the dose-response relationship for chemicals that cause stochastic effects normally exceeds MLE by a factor of 5 to 100 or more. If this difference... 

However, given the current state of knowledge and methods of dose-response assessment for substances that cause stochastic responses, there appear to be important technical and institutional impediments to the use of either incidence or fatalities exclusively. Data on radiation-induced cancer incidence and chemical-induced cancer fatalities for use at the low doses and dose rates relevant to health protection are not readily available, and current regulatory guidance calls for calculation of cancer incidence for hazardous chemicals. Since use of a common measure of response for all substances that cause stochastic responses may not be practical in the near term, both measures (fatalities for radionuclides and incidence for hazardous chemicals) could be used in the interest of expediency. The primary advantage of this approach is that the measures of stochastic response for radionuclides and hazardous chemicals would be based on the best available information from studies in humans and animals, and it would involve the fewest subjective modifying factors. This approach also would be the easiest to implement. 

Dose-Response Relationships. The primary objective of this study is to set forth the foundations of a risk-based waste classification system that applies to hazardous chemicals and radionuclides. Most aspects of the risk assessment process that provide the basis for establishing this system are conceptually the same for chemicals and radionuclides, although the specific data (e.g., solubilities) may differ. One important exception is the assumed relationship of the probability of a response to a unit dose of a substance that causes stochastic effects, which is called the dose-response relationship There are important conceptual differences in the way this relationship has been defined and used for hazardous chemicals and radionuclides, and these differences could pose a major impediment to development of a risk-based waste classification system that applies to both types of substances on a consistent basis. These differences are elucidated in the following section. 

The use of MLEs of probability coefficients for radionuclides but UCLs for chemicals that induce stochastic responses is the most important issue that would need to be resolved to achieve a consistent approach to estimating risks for the purpose of waste classification. For some chemicals, the difference between MLE and UCL can be a factor of 100 or more. The difference between using fatalities or incidence as the measure of response is unlikely to be important. Use of the linearized, multistage model to extrapolate the dose-response relationship for chemicals that induce stochastic effects, as recommended by NCRP, should be reasonably consistent with estimates of the dose-response relationship for radionuclides, and this model has been used widely in estimating probability coefficients in chemical risk assessments. The difference in the number of organs or tissues that are taken into account, although it cannot be reconciled at the present time, should be unimportant. 

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. 

This option does not appear to be advantageous for either radionuclides or chemicals that cause stochastic responses. In radiation protection, total detriment is used mainly to develop the tissue weighting factors in the effective dose (see Section 3.2.2.3.3), but ICRP and NCRP have continued to emphasize fatal responses as the primary health effect of concern in radiation protection and radiation risk assessments. Since total detriment is based on an assumption that fatalities are the primary health effect of concern, the same difficulties described in the previous section would occur if this measure of response were used for chemicals that induce stochastic responses. Other disadvantages of using total detriment include that detriment is not a health-effect endpoint experienced by an exposed individual and the approach to weighting nonfatal responses in relation to fatalities is somewhat arbitrary. Furthermore, total detriment is not as simple and straightforward to understand as either incidence or fatalities. 

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