Application of the equivalency factor concept to the phototoxicity and –genotoxicity of furocoumarin mixtures

Furocoumarins (FCs) are natural constituents widely occurring in plants used as food or in phytomedicines, cosmetics, etc. Some FCs exert dermal photo-toxicity and -genotoxicity when combined with UVA irradiation. For a few congeners, skin tumor formation has been described in humans and laboratory animals. Since almost no information is available on the photo-toxic properties of several congeners, we analyzed the photo-cytotoxic, photo-mutagenic, and photo-clastogenic properties in V79 cells for thirteen naturally occurring FCs, and for the coumarin limettin. Furthermore, nine FC mixtures including one mixture based on the FC pattern of an Angelica archangelica extract were tested in the same assays. We found that the concept of relative potency factors for photo-cytotoxic, -mutagenic, and -clastogenicpotencies of FCs, setting the value for 5-methoxypsoralen at 1.00, was applicable to all congeners tested. The concept was used successfully to describe the photo-toxic properties of binary mixtures of 5- and 8-methoxypsoralen. Furthermore, the photo-genotoxic (photo-mutagenic and -clastogenic) properties of complex FC mixtures comprising up to nine different congeners could be predicted. These data suggest that FCs can differ widely in their photo-toxic and photo-genotoxic properties but show relatively strict additivity with respect to their on target-effects when occurring as complex mixtures.