D&C Red No. 27 and D&C Red No. 28 are fluorescein-based dyes that were approved in 1982 for use in drugs and cosmetics (except the eye area). Cosmetic retail products containing these dyes are primarily lipsticks and blushers. Dyes physically associated with non-aqueous aluminum or zirconium minerals (lakes) are used in lipsticks, blushers, make-up preparations, hair dyes and colors, rouges and face powders. The toxicological data reviewed by FDA prior to approval of D&C Red No. 27 and D&C Red No. 28 did not include studies of acute phototoxicity or chronic phototoxicity (i.e. photocarcinogenesis). Our current knowledge of the photochemistry and photobiology of D&C Red No. 27 and D&C Red No. 28 raises new concerns about the long-term safety of these colorants. D&C Red No. 28 is now known to be an extremely efficient photodynamic sensitizer whose photo-excitation results in the formation of free radicals and singlet oxygen. These highly reactive species attack cellular components such as lipids, proteins and nucleic acids. Investigators have shown that the genetic damage sensitized by D&C Red No. 28 is mutagenic in bacterial assays. In addition, in vitro studies using mammalian cells have shown that D&C Red No. 28 sensitizes photooxidation of guanine bases in cellular DNA (i.e. 8-oxo-7,8-dihydroguanine), a lesion known to be mutagenic. Clinical data and anecdotal reports indicate that fluorescein, and halogenated derivatives of fluorescein, are phototoxic under certain conditions of exposure. Fluorescein is frequently used in ophthalmic examinations and retinal angiography. There have been a number of anecdotal reports of ocular and cutaneous phototoxicity following intravenous administration of fluorescein for this application. Furthermore, halogenated fluorescein dyes are phototoxic if applied topically to scarified skin, but are not phototoxic if applied to intact skin. These results indicate that delivery of the dye to the skin is an important factor to consider in evaluating the potential phototoxicity and photocarcinogenicity of dyes such as D&C Red No. 27 and D&C Red No.