USE OF JOINT TOXIC RESPONSE TO DEFINE THE PRIMARY-MODE OF TOXIC ACTION FOR DIVERSE INDUSTRIAL ORGANIC-CHEMICALS

An important aspect of understanding how multiple toxicants jointly ac t involves defining the primary mode of toxic action for the chemicals of interest. We have explored the use of 96-h acute toxicity tests wi th juvenile fathead minnows and primarily binary chemical mixtures to define the primary acute mode of toxic action for diverse industrial o rganic chemicals. Our investigation mainly considered the two special cases of noninteractive joint action known as concentration (simple si milar) and response (independent) addition. The different forms of joi nt toxicity with binary mixtures were graphically illustrated by isobo le diagrams. Designated as the mode of action-specific reference toxic ants were 1-octanol, phenol, and 2,4-dinitrophenol. It was observed fr om binary isobole diagrams that a chemical with a similar primary mode of toxic action to that of a reference toxicant would display a conce ntration-addition type of joint action with the reference toxicant ove r the entire mixture ratio range. Dissimilar chemicals with very steep concentration-response curves generally showed an interaction that wa s less-than-concentration additive, but consistently demonstrated a jo int toxicity that was greater than predicted by the response-addition model. The more-than-concentration additive and complex isoboles that are indicative of interactive toxicity were not commonly observed in o ur experiments.