Subchronic (13-Week) Toxicity Studies of Oral Phenolphthalein in Fischer 344 Rats and B6C3F1 Mice

Phenolphthalein is a cathartic agent that is widely used inover-the-counter laxatives. Thirteen-week toxicity studies ofphenolphthalein were performed using F344/N rats and B₆C₃F₁mice. Rats and mice were fed ad libitum with a NIH 07 diet containing0; 3000; 6000; 12,000; 25,000; or 50,000 ppm phenolphthalein.On a milligram per kilogram body weight basis, rats and micefed 50,000 ppm phenolphthalein ingested more drug than wouldbe expected during human laxative abuse. Phenolphthalein producedlittle evidence of toxicity in rats. There was slightly lowerweight gain among the 25,000 and 50,000 ppm groups. Treatedrats showed elevated relative kidney weights (males only) andelevated absolute and relative liver weights at 12,000–50,000ppm phenolphthalein. Rat serum bile acids were depressed early(Days 5 and 6) by phenolphthalein treatment. Several treatment-relatedtoxic effects, however, were identified in mice who receivedmore phenolphthalein per unit body weight than rats. Althoughthere were no effects on body weight gain, elevated liver weightswere noted in female mice receiving 6000–50,000 ppm phenolphthalein.The primary treatment-related findings that occurred duringthe mouse studies involved the reproductive and hematopoieticsystems. Reproductive changes including depressed testis andright epididymal weights and sperm density, an elevated productionof abnormal sperm, and morphologic alterations in seminiferoustubules occurred at all levels of exposure (3000–50,000ppm). Hematopoietic changes included bone marrow hypoplasia(12,000–50,000 ppm), increased splenic hematopoiesis (malesonly, 25,000 and 50,000 ppm), and an elevated incidence of micronucleatederythrocytes (6000–50,000 ppm).