Abstract
As part of a safety evaluation program for the new synthetic antibacterial agent temafloxacin (TMFX), a 26-week oral toxicity study (0, 100, 200 and 400mg/kg/day) was carried out on rats and followed by a 4-week recovery study. Four rats died during the treatment period and 3 rats receiving 400mg/kg were killed. In the moribund animals, soiled hair, gum, sedation and hypothermia were noted and food consumption and body weight decreased. In the surviving rats, body weight decreased in females receiving 400mg/kg and in males receiving 200mg/kg or more. Water intake increased in rats receiving 400mg/kg. As to clinical pathology, BUN, creatinine and inorganic phosphate were elevated in moribund rats receiving 100mg/kg. Urinary sodium decreased in females receiving 400mg/kg and in males receiving 200mg/kg or more and the serum level of protein decreased in males receiving 200mg/kg or more. The weights of the kidney, adrenal glands and uterus in the 400mg/kg group were higher than those of the control group. Enlarged ceca, atrophy of the thymus and spleen, discoloration of the liver and a white line in the renal medulla were found in rats receiving 400mg/kg. Renal lesions such as tubular dilatation and degeneration or regeneration of the collecting tubular epithelium were observed microscopically. After discontinuation of drug administration, most of the changes detected on clinical observation and laboratory examination disappeared. Thus, the long-term non-toxic dose of TMFX was estimated to be 100mg/kg in rats.
