TOLERATED DOSES OF PHENACETIN IN RELATION TO BODY WEIGHT AND ORGAN WEIGHTS

In a study of the clinicopathologic syndrome of toxicity to phenacetin at the range of the acute, oral LD50, Boyd in 1959 (1) used adult female rats and reported the LD50±SE to be 1.65±0.35 g/kg body weight. In 1968, Boyd and Hottenroth (2) studied the toxicity of phenacetin at the range of the oral LD50 (100 days) and reported the acute oral LD50±SE in young male albino rats to be 4.14±0.71 g/kg. Boyd and Hottenroth (2) also reported that female rats were more sensitive to the lethal effects of daily administration of phenacetin than were male rats. In a comparison of the acute oral LD50 in young male and female rats, sex of the animals was found to have no influence on the median lethal dose. To find a reason for these apparently contradictory results, it was decided to measure the clinicopathologic syndrome of toxicity to single oral doses of phenacetin, after methods reviewed by Boyd (3), in male and female albino rats from the age of weaning to that of middle-aged, 1 to 1.5 year old, adults. Over this interval of time, certain organs comprise changing percentages of body weight. Since values for the LD50 are normally expressed as g per kg body weight, it was decided to calculate LD50 values in addition as g/kg organ weights. Any organ in which variation in the LD50 so calculated was less than variation calculated as g/kg body weight, could be concluded to be more concerned with tolerance to lethal doses of phenacetin than is total body weight. © 1969, The Japanese Pharmacological Society. All rights reserved.