Confronting uncertain causal mechanisms – portfolios of possibilities

Abstract

This chapter returns to smoking and lung cancer risk as a fruitful example of a complex system with many uncertainties (and, as discussed in Chapter 11, nonlinearities) in its input-output (dose-response) relations.These uncertainties, complexities, and nonlinearities raise important challenges for quantitative risk assessment (QRA) modeling. The challenge confronted in this chapter is how to estimate the potential effects on lung cancer of removing a specific constituent, cadmium (Cd), from cigarette smoke, given the very incomplete scientific information available now about its possible modes of carcinogenic action. Not enough is known about how cadmium affects lung cancer to allow useful bounds on risk to be established using biomarkers, as in Chapter 8. A different strategy is needed for QRA