The Number of Components in a Mixture Determines Whether Synergistic and Antagonistic or Additive Toxicity Predominate: The Funnel Hypothesis

A new hypothesis, the funnel hypothesis, was derived to explain the variation in toxicity of equitoxic multicomponent mixtures of nonspecific toxicants (narcotics). The variation is explained in terms of the volumes associated with solute-solute and solute-solvent interactions. The hypothesis predicts that as the number of components in a mixture increases, the range of deviation from toxic additivity decreases. It also predicts that the toxicity of mixtures measured using biological endpoints that require high toxicant concentrations will deviate more from toxic additivity than endpoints that require low concentrations. Aquatic toxicity data for equitoxic mixtures of narcotic toxicants to a range of aquatic organisms compiled from the literature support the predictions of the funnel hypothesis.