CHRONIC TOXICITY STUDIES OF DIETHYLSTILBESTROL I. ORAL ADMINISTRATION BY STOMACH TUBE TO RATS

Abstract

Stilbestrol dissolved in NaOH soln. or 40% ethyl alc. soln. was given by stomach tube to rats in 4 dose levels, namely, 50[gamma], 250[gamma], 1 mg., and 5 mg., 3 times weekly over periods ranging from 2-14 wks. Complete autopsies were performed on each animal with histological studies of the vital organs and endocrine glands of representative animals in each group. In the 50[gamma] group no significant pathologic changes were found. In the 250[gamma] group hemorrhagic gastric mucosa, traumatic ulcer of the esophagus and hemorrhage into the adrenals were observed, each occurring in 1 animal only; cloudy swelling in kidneys of 4 animals. In the 1 mg. group there was cloudy swelling of the kidneys of 3 and liver damage in 2. In the 5 mg. group adrenal hemorrhage in 3, and an enlarged liver in 1 were found. Microscopic examination showed liver damage in 3. cloudy swelling of the kidneys in 2, toxic changes in adrenals in 3. gastritis in 1 and squamous metaplasia of the endometrium in 1. Blood studies of 2 in this group showed hypoplasia of the bone marrow, leucopenia, neutropenia, thrombocytopenia, achromia and polychromatophilia; these findings were interpreted as aplastic anemia. The dose level per kg. body wt. at which definite pathologic tissue changes were found was 107 times the avg. human therapeutic dose (1 mg. daily for 50 kg. person).