Role of Synergy in Biological Risk Assessment

Abstract

A substantial effort has been made over the past few decades to label toxicological interaction outcomes as synergistic, antagonistic or additive. The mathematical characterizations of “synergism” and “antagonism” are most closely related to the characterization of no interaction, rather than being some intrinsic toxicological property. For now, labels such as “synergism” are useful to regulatory agencies, both for qualitative indications of public health “risk” as well as numerical decision tools for mixture “risk” characterization. Efforts to quantify interaction designations for use in “risk assessment” formulas, however, are highly simplified and carry large uncertainties. Several research directions, such as pharmacokinetic measurements and models as well as toxicogenomics should promote significant improvements; by providing multi-component data to allow these pair-wise interaction labels to be replaced by biologically based mathematical models of joint toxicity in “risk assessment” procedures Synergism is not always dangerous or even significantly more dangerous than the individual toxicities. Statistical analyses do not necessarily indicate any significant impacts on public health. Similarly, antagonism does not necessarily mean the mixture is safe, only that it is less toxic than the no-interaction model would predict [1].