ABSTRACT
Models .............................................................................................. 310 15.2 Nature of Hormesis ....................................................................................... 311
15.2.1 Difculty of Detecting and Measuring Hormesis ............................ 311 15.2.2 Evidence Supports Hormesis as Real ............................................... 312 15.2.3 Apparent Hormesis Arising as an Artifact ....................................... 314
15.3 Biological Stress Responses ......................................................................... 314 15.3.1 Adaptive Responses and Preconditioning ........................................ 314 15.3.2 Parallels between Adaptive Responses and Hormesis...................... 316
15.4 Mechanisms of Hormesis and Stress Responses .......................................... 317 15.5 Prospects for Hormesis in Risk Assessment................................................. 318
15.5.1 Controversy over Assimilating Hormesis into Policy ...................... 318 15.5.2 Precautionary Principle and Scientic Reality ................................. 319 15.5.3 Hormesis and Biomedical Ethics ...................................................... 321
15.6 Challenges of Assimilating Hormesis into Risk Assessment ....................... 321 15.6.1 Default Assumptions for Low-Dose Effects ..................................... 321 15.6.2 Disagreement about the Generalizability of Hormesis .................... 322 15.6.3 Disagreement about the Prevalence of Hormesis ............................. 323 15.6.4 Uncertainties in the Quantication of Hormetic Effects .................. 323 15.6.5 Accounting for Heterogeneity in Susceptibility ............................... 324 15.6.6 Interactions among Agents ............................................................... 326 15.6.7 Hormesis and Concomitant Toxicity ................................................ 326 15.6.8 Feasibility of Hormesis-Based Risk Assessment.............................. 327
15.7 Why an Understanding of Hormesis Is Essential ......................................... 327 15.7.1 Concerns about Hormesis and Risks of Ignoring It ......................... 327 15.7.2 Optimizing the Benets of Mild Stress Responses .......................... 327
Humans are routinely exposed to low doses of toxicants and radiation, but it is extremely difcult or impossible to measure biological effects at the low doses that are of interest. Dose-response models are therefore useful not only in assessing risks associated with measured effects but also in shaping our expectations for effects at dosages below which accurate measurements are impossible or impractical. Figure 15.1 shows threshold and linear nonthreshold (LNT) models that have dominated thought about low doses in toxicology and radiation biology. The curves show the frequency of an adverse effect plotted against dosage. In the threshold model (Figure 15.1a), there is a dosage below which the frequency does not differ from the unexposed control population. This dosage represents a biological threshold, often represented in toxicological studies as a no observed adverse effect level (NOAEL). In contrast, the linear nonthreshold model (Figure 15.1b), often referred to as LNT, extrapolates to the spontaneous frequency on the ordinate.
