Elucidating the factors contributing to the cell toxicity of pesticides and other environmentally sensitive small molecules is critical for evaluation of their health impacts and for understanding the biological processes that they affect. Disruption and permeation of the plasma membrane, which constitutes the critical interface between the cell and its environment, are recognized initiators of cytotoxicity. We present a new approach for predicting pesticide cytotoxicity through rapid screening of membrane interactions of pesticides using a recently developed live-cell chromatic sensor. The sensing platform comprises living mammalian cells labeled with polydiacetylene (PDA), a chromatic polymer that undergoes intense fluorescence transformations induced by structural perturbations of the membrane bilayer. Within a short time after the addition of membrane-interacting tested compounds to the labeled cells, the PDA patches emit high fluorescence, which can be monitored by conventional spectroscopy and microscopy apparatuses. The chromatic technology facilitates rapid evaluation of membrane activity of pesticide compounds and is capable of distinguishing between toxic effects associated with membrane interactions vs intracellular mechanisms.