Introduction of Flavor Chemical Eugenol Attenuating the Synergistic Toxicological Interactions of Flavor Mixtures

[Image: see text] The flavor chemicals benzyl alcohol (BEA), phenylethanol (PHA), and cinnamaldehyde (CID) and their binary mixtures have high toxicity sensitivity to the lethal endpoint of Caenorhabditis elegans. Some binary flavor mixtures even have synergistic toxicological interactions. Eugenol (EUG) is closely related to human life and has many special nonlethal effects on organisms. The effect of its introduction on the combined toxicities of flavor mixtures is worth studying. We introduced EUG into three binary (BEA-PHA, BEA-CID, and PHA-CID) and one ternary (BEA-PHA-CID) flavor mixture systems. Five representative mixture rays were selected from each of the four mixture systems using the uniform design ray (UD-Ray) method. The lethal toxicity of each mixture ray to C. elegans was measured at three different exposure volumes (100, 200, and 400 μL), and a dose–effect model was established. The new parameter iSPAN was used to quantitatively characterize the toxicity sensitivity of each chemical and mixture ray. The toxicological interaction of each mixture was evaluated by the toxicological interaction heatmap based on the combination index (CI). It can be seen that all flavor chemicals and their ternary and quaternary mixture rays have high iSPANs, and the highest value is 16.160 (BEA-PHA-CID-EUG-R1 at 400 μL). According to the heatmap and CI, the introduction of EUG attenuates the synergistic toxicological interactions of flavor mixtures, leading to the transformation ofsynergistic interactions in flavor mixtures into additive action and even antagonistic interaction, and the CI value of the antagonistic interaction is up to 1.8494 (BEA-CID-EUG-R4 at 400 μL).