Phenolphthalein has been used for over a century as a laxative, but is now being removed from over-the-counter laxatives over concerns of carcinogenicity. Laxative products formerly containing phenolphthalein have often been reformulated with alternative active ingredients: Feen-a-Mint switched to bisacodyl, and Ex-Lax was switched to a senna extract.
Thymolphthalein is a related laxative made from thymol.
Despite concerns regarding its carcinogenicity based on rodent studies, the use of phenolphthalein as a laxative is unlikely to cause ovarian cancer. Some studies suggest a weak association with colon cancer, while others show none at all.
Phenolphthalein is described as a stimulant laxative. In addition, it has been found to inhibit human cellular calcium influx via store-operated calcium entry (SOCE, see ) in vivo. This is effected by its inhibiting thrombin and thapsigargin, two activators of SOCE that increase intracellular free calcium.
Phenolphthalein has been added to the European Chemicals Agency's candidate list for substance of very high concern (SVHC). It is on the IARC group 2B list for substances "possibly carcinogenic to humans".
The discovery of phenolphthalein's laxative effect was due to an attempt by the Hungarian government to label genuine local white wine with the substance in 1900. Phenolphthalein did not change the taste of the wine and would change color when a base is added, making it a good label in principle. However, it was found that ingestion of the substance led to diarrhea. Max Kiss, a Hungarian-born pharmacist residing in New York, heard about the news and launched Ex-Lax in 1906.