Use of joint toxic response to define the primary mode of toxic action for diverse industrial organic chemicals

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Abstract

An important aspect of understanding how multiple toxicants jointly act involves defining the primary mode of toxic action for the chemicals of interest. We have explored the use of 96-h acute toxicity tests with juvenile fathead minnows and primarily binary chemical mixtures to define the primary acute mode of toxic action for diverse industrial organic chemicals. Our investigation mainly considered the two special cases of noninteractive joint action known as concentration (simple similar) and response (independent) addition. The different forms of joint toxicity with binary mixtures were graphically illustrated by isoboie diagrams. Designated as the mode of action-specific reference toxicants were 1-octanol, phenol, and 2,4-dimtrophenol. It was observed from binary isobole diagrams that a chemical with a similar primary mode of toxic action to that of a reference toxicant would display a concentration-addition type of joint action with the reference toxicant over the entire mixture ratio range. Dissimilar chemicals with very steep concentration-response curves generally showed an interaction that was less-than-concentration additive, but consistently demonstrated a joint 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 our experiments.

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