ABSTRACT
The notion that “the dose makes the poison” has been a cardinal tenet of toxicology. Modern experimental toxicologists seek for doses and conditions under which a chemical is safe. After identifying an overtly toxic (high) dose level, toxicologists look for the highest dose below that level causing no harm, assuming a monotonic relationship between doses and toxic responses. Dose-response non-monotonicity, on the other hand, means that the slope of a curve, relating doses to the magnitude of the response, changes its sign from positive to negative, or vice versa, at one or more points along the tested range of doses. Along this line, the “low-dose” hypothesis speculates that some compounds, particularly endocrine active chemicals, can bring about biological responses and adverse health effects at low doses either in a monotonic or non-monotonic dose-response curve. This chapter reviews experimental data regarding the concepts of low-dose effects and dose-response non-monotonicity and the existence, or not, of dose-thresholds for adverse effects, which are challenging issues whenever a risk assessment is undertaken and toxicological data are translated into risk management actions.
