THE SUBCHRONIC TOXICITY OF ACRIDINE IN THE RAT

The subchronic toxicity of acridine was investigated in rats following dietary exposure at 0, 1, 10, 100 and 500 ppm for 13 weeks. The growt h rate and food consumption were not affected by treatment and no clin ical signs of toxicity were observed. There was a slight but significa nt decrease in spleen weight, both-in absolute terms and as a percent of body weight, in the 500 ppm males and a slight increase in absolute thymus weight in the females of the same dose group. Both hepatic eth oxyresorufin O-deethylase (EROD) and pentoxyresorufin O-dealkylase (PR OD) activities were slightly, but significantly, elevated in females i n the 500 ppm dose group. No haematological or other biochemical chang es were observed. Females also displayed dose-related increases in ino rganic phosphate and uric acid levels. Treatment-related histopatholog ical changes were seen in the thyroid, liver and kidney and included h epatic anisokaryosis and vesiculation of nuclei and glomerular adhesio ns, reticulin sclerosis and nuclear pyknosis in the kidney. Residue da ta showed a dose-dependent accumulation of aeridine in liver, kidney a nd adipose with the highest concentration being found in the fat of th e 500 ppm dose group. Based on these data, the no observable adverse e ffect level of acridine was judged to be 100 ppm or 12 mg/kg bw/day.