PHENOLPHTHALEIN EXPOSURE CAUSES MULTIPLE CARCINOGENIC EFFECTS IN EXPERIMENTAL-MODEL SYSTEMS

Phenolphthalein (a triphenylmethane derivative) has been commonly used as a laxative for most of the twentieth century, but little is known about its long-term carcinogenic potential in experimental studies. In our studies, phenolphthalein administered continuously in the feed fo r 2 ears to F344 rats at doses of 0, 12,500, 25,000, and 50,000 ppm an d to C57BL/ 6 x CB3 F-1 (hereafter called B6C3F(1)) mice at doses of 0 , 3,000, 6,000, and 12,000 ppm caused multiple carcinogenic effects. T reatment-related neoplasms occurred in the kidney and adrenal medulla in male rats, adrenal medulla in female rats, hematopoietic system in male and female mice (histiocytic sarcomas and malignant lymphomas), a nd ovary of female mice. Phenolphthalein has been shown to have estrog enic and clastogenic properties. Previous studies of other estrogenic chemicals (e.g., zearalenone) in the F344 rat and B6C3F(1) mouse have not shown the same spectrum of carcinogenic activity as that found wit h phenolphthalein, suggesting that phenolphthalein: estrogenic activit y alone is not responsible for the spectrum of turners observed. It is more likely that the multiple biological properties of phenolphthalei n, including its ability to form free radicals, its clastogenic activi ty, and its estrogenic activity, contributed to the carcinogenic effec ts observed. These studies show that phenolphthalein is a multisite/mu ltispecies carcinogen. One of the sites for neoplasm that is of partic ular concern is the ovary, and epidemiology studies are under way to i dentify any potential effects of phenolphthalein exposure at this site in humans.