Practical implications of nonlinear effects in risk-assessment harmonization.

Cancer and noncancer health effects have traditionally been handled differently in quantitative risk assessment. A threshold (i.e., safe exposure) has been assumed for noncancer health effects, and low-dose linearity without a threshold has been assumed for cancer. "Harmonization" attempts to reconcile these contrasting assumptions under one paradigm. Recent regulatory initiatives suggest that the U.S. Environmental Protection Agency may be leaning toward a harmonized, probabilistic/linear approach for noncancer health effects. Proponents of this approach cite variability in human susceptibility as an argument against thresholds (i.e., some individuals may be exquisitely sensitive at exposures well below threshold levels). They also cite the results of epidemiological models that suggest low-dose linearity for noncancer health effects. We will discuss the implications of these arguments and compare them to what is known about human biological variability in general. We will also touch on the regulatory implications of hormesis within this framework.