Reference dose (RfD): the possible impact of hormesis

A fictitious US Environmental Protection Agency Administrator in the year 2 005 is confronted with making a risk management decision on a chemical that exhibits an unambiguous hermetic effect in an animal system. Dose-response curves for average humans and sensitive humans are derived from the animal data. The question is posed: What should the reference dose (RfD) be in th is case? A series of outstanding scientific and policy questions are discus sed that have a bearing on the answer. The concept of the 'regulatory dose (RgD)' is revived to address, if not resolve, the issue.