Local and systemic toxicity resulting from large-volume ip administration of doxorubicin in the rat

Doxorubicin was administered to rats in a simulated "belly bath" protocol. Fifty milliliters of various concentrations of drug solution was administered ip and was allowed to remain in situ for either 4 or 36 hours prior to removal. Animals were analyzed at 2, 14, and 60 days after treatment. Doses ranged from lethal (75 and 150 micrograms/ml for 4 hours; 12 and 24 micrograms/ml for 36 hours) to nontoxic (5 micrograms/ml for 4 hours). The most common lesion in surviving animals was chronic fibrosing peritonitis. Grossly, there were large volumes of peritoneal fluid in animals exposed to low concentrations (12 and 24 micrograms/ml) for 36 hours, but peritoneal adhesions were the most commonly observed finding when higher concentrations (20-150 micrograms/ml) were used for 4 hours. Commonly observed systemic toxic effects (bone marrow, gastrointestinal tract, and heart) were not seen in this study. Vehicle-treated control animals were negative for all histologic lesions and gross observations.