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Phenolphthalein exposure causes multiple carcinogenic effects in experimental model systems

J K Dunnick1, J R Hailey

  • 1National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.

Cancer Research
|November 1, 1996
PubMed
Summary

Phenolphthalein, a former laxative, was found to be a multisite and multispecies carcinogen in long-term rat and mouse studies. Its estrogenic, clastogenic, and free radical-forming properties likely contribute to its cancer-causing effects.

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Area of Science:

  • Toxicology and Carcinogenesis
  • Experimental Pathology

Background:

  • Phenolphthalein, a triphenylmethane derivative, was widely used as a laxative throughout the 20th century.
  • Limited data existed regarding its long-term carcinogenic potential in experimental settings.

Purpose of the Study:

  • To investigate the long-term carcinogenic effects of phenolphthalein in experimental animal models.
  • To determine the spectrum of neoplasms induced by phenolphthalein and explore potential mechanisms.

Main Methods:

  • F344 rats and B6C3F1 mice were administered varying doses of phenolphthalein in their feed for two years.
  • Tumor incidence and types were assessed, and the biological properties of phenolphthalein, including estrogenic and clastogenic activities, were considered.

Main Results:

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  • Phenolphthalein administration resulted in multiple treatment-related neoplasms in both rats and mice.
  • Observed cancers included kidney and adrenal medulla tumors in male rats, adrenal medulla tumors in female rats, hematopoietic system tumors in both sexes of mice, and ovarian tumors in female mice.
  • Phenolphthalein exhibited estrogenic and clastogenic properties, but these alone did not fully explain the observed tumor spectrum.

Conclusions:

  • Phenolphthalein is identified as a multisite and multispecies carcinogen.
  • The carcinogenic effects are likely due to a combination of phenolphthalein's biological properties, including estrogenicity, clastogenicity, and free radical formation.
  • Ovarian neoplasms are a particular concern, prompting ongoing epidemiological studies in humans.