METABOLISM AND EXCRETION PATTERNS OF FLUORESCEIN AND CERTAIN HALOGENATED FLUORESCEIN DYES IN RATS

¹ Division of Pharmacology, Bureau of Biological and Physical Sciences, Food and Drug Administration, United States Department of Health, Education, and Welfare, Washington, D. C.

The metabolic behavior and excretory patterns for fluorescein and 11 halogenated fluorescein derivatives in rats have been studied. The materials examined were mainly certified FD&C (Food, Drug, and Cosmetic) or D&C (Drug and Cosmetic) colors or their component dyes.

Paper chromatographic examination of bile and urine specimens showed that the tri- or higher halogenated derivatives were metabolically inert while the monohalogenated derivatives, 4-iodo- and 4-bromofluorescein, were partly dehalogenated. Fluorescein and its mono- and dihalogenated derivatives were partly excreted as glucuronide conjugates. In no instance was the basic fluorescein structure of the dyes degraded.

Studies of the initial 2-hour biliary and urinary excretions of the dyes showed that with increase in halogenation, correspondingly larger proportions of the dyes were excreted in the bile. At the same time there was a trend toward a decreasing amount of dye in the urine. Recoveries, from excreta, of fluorescein and 6 halogenated derivatives ranged from 90 to 100% when the dyes were orally administered to rats.

The point is made that the greater toxicity of the simpler fluoresceins can be related to their metabolism and excretion patterns.