Phenolphthalein Laxatives and Risk of Cancer
Patricia F. Coogan · JNCI Journal of the National Cancer Institute · 2000
Phenolphthalein was the main component in numerous over-the-counter laxatives, including Ex-Lax and Feen-A-Mint, for most of the 20th century. The U.S. Food and Drug Administration (FDA) classified phenolphthalein as “safe and effective” in 1975 (1). However, in 1997, the FDA proposed that phenolphthalein be reclassified as “not generally recognized as safe and effective” (2) after a 2-year feeding study in rodents found increased incidences of neoplasms of the ovary, adrenal gland, kidney, and hematopoietic system in treated animals (3). Subsequently, most phenolphthalein-containing laxatives were voluntarily withdrawn from the market in the United States. Phenolphthalein has also been found to be genotoxic (3), to cause oxidative damage (4), and to bind to estrogen receptors (5). The only data on laxative use and human cancers indicate that use is unrelated to the risk of large-bowel cancer (6–12). We used data collected in a hospital-based, case–control surveillance study of medication use to evaluate the relationship between phenolphthalein laxative use and the risk of cancers, both at sites for which animal studies have raised suspicions and at other sites with sufficient numbers for analysis.