Food, drug, and cosmetic dyes of the xanthane type (analogs of fluorescein) were applied to isolated molluscan ganglia and changes in the electrophysiological properties of identified neurons were monitored. The synthetic coloring agents increased the resting membrane potential and conductance of the neurons in a dose-dependent manner by increasing the potassium permeability of the membrane relative to that of other ions. The relative activity of these anionic dyes was highly correlated with their lipid solubility. The structure-activity study of the effects of the dyes on molluscan neurophysiology provides a basis for estimating the toxicity and brain uptake of the dyes in vertebrates, and predicting their effects on metabolism and blood clotting.Synthetic dyes have been a constituent of foods, drugs, and cosmetics for more than 100 years, and the safety of such additives has been of concern for almost as long (1). The intended function of these additives has been to enhance the physical appearance of a product, and some proof of their safety, which has in the past been either assumed or ignored, is now required in many countries before they can be incorporated into items intended for human consumption (1-5). Despite such precautions several coloring agents were used for decades before they were ruled unsafe, and the use of other dyes is currently under review because deleterious effects have been discovered or are suspected (1, 5). Interest in the biological activity of artificial colorants has recently been renewed following the claims that a red food dye (FD&C Red No. 2) is carcinogenic (6) and that some food additives, and colorants in particular, may be responsible for producing behavioral changes and learning disabilities in children (e.g., hyperkinesis, minimal brain disfunction) (7-9).The present study was undertaken in order to determine (i) whether some types of synthetic dyes, which are added to foods and drugs purely for cosmetic purposes, are in fact biologically active compounds, and (ii) the physicochemical properties of the compounds responsible for their activity. It was found that xanthane type dyes alter the physiological characteristics of invertebrate neurons and that their biological activity is highly correlated with the compounds' lipid solubility. The structure-activity study of the dyes' effects on neurons provided a basis for estimating their toxicity and brain uptake in vertebrates, and predicting their effects on metabolism and blood clotting.
METHODS AND MATERIALS