Carcinogen dose-response considerations

The 95% confidence limits of the estimate of the linear component of the LMS model, /, can also be calculated. The 95% upper confidence limit is termed qi and is central to the US-EPA s use of the LMS model in quantitative risk assessment, as qi represents an upper bound or worst-case estimate of the dose-response relationship at low doses. It is considered a plausible upper bound, because it is unlikely that the tme dose-response relationship will have a slope higher than qi, and it is probably considerably lower and may even be zero (as would be the case if there was a threshold). Lfse of the qj as the default, therefore, may have considerable conservatism incorporated into it. The values of qi have been considered as estimates of carcinogenic potency and have been called the unit carcinogenic risk or the Carcinogen Potency Factor (CPF). 

Once a chemical s mode(s) of action has been identified, the risk assessor can proceed with the evaluation of carcinogenic potential, including consideration of the relevance of the mode of action to humans. Further consideration of mode of action distinguishes between a genotoxic (or sometimes more rigorously described as DNA-reactive) mode of action, for which there may be some risk at every nonzero dose, and nongenotoxic (or nonmutagenic) modes of action, for which threshold or nonlinear dose-response curves may apply. 

The extent to which hormetic information may be nsefnl in cancer risk assessment deserves consideration. At present, it is nnclear how hormetic dose-responses might influence the MOA information necessary for a departnre from the linearity assnmption. In practice, the hormetic relationships may provide a nsefnl backdrop for nnderstanding that carcinogenic thresholds can exist, bnt it still may not be... 

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