Time dependence in mixture toxicity with soft electrophiles: 1. Combined effects of selected SN2- and SNAr-reactive agents with a nonpolar narcotic.

Frequently the toxicity of an organic chemical mixture is close to dose-additive, even when the agents are thought to induce toxicity at different molecular sites of action. These findings appear to conflict with the hypothesis that a strictly dose-additive combined effect will be observed for agents sharing a single molecular site of toxic action within the organism. In this study, several SN2-reactive (alpha-halogen) or S(N)Ar-reactive (halogenated dinitrobenzene) soft electrophiles were tested with a model nonpolar narcotic (NPN) to determine the toxicity of the combinations.