摘要：a c k g r o u n d: Epidemiologists and toxicologists face similar problems when assessing inter actions between exposures, yet they approach the question very differently. The epidemiologic definition of "inter action" leads to the additivity of risk differences (RDA) as the fundamental criterion for causal inference about biological inter actions. Toxicologists define "inter action" as departure from a model based on mode of action: concentration addition (CA; for similarly acting compounds) or indepen-dent action (IA; for compounds that act differently).oB j e c t i v e s: We compared and contrasted theoretical frameworks for inter action in the two fields.Me t h o d s: The same simple thought experiment has been used in both both epidemiology and toxi-cology to develop the definition of "non interaction," with nearly opposite inter pretations. In epide-miology, the "sham combination" leads to a requirement that non interactive dose–response curves be linear, whereas in toxicology, it results in the model of CA. We applied epidemiologic tools to mathematical models of concentration-additive combinations to evaluate their utility.re s u l t s: RDA is equivalent to CA only for linear dose–response curves. Simple models demon-strate that concentration-additive combinations can result in strong synergy or antagonism in the epidemiologic framework at even the lowest exposure levels. For combinations acting through non-similar pathways, RDA approximates IA at low effect levels.co n c l u s i o n s: Epidemiologists have argued for a single logically consistent definition of inter action, but the toxicologic perspective would consider this approach less biologically informative than a comparison with CA or IA. We suggest methods for analysis of concentration-additive epidemiologic data. The two fields can learn a great deal about inter action from each other.
