ASSESSMENT OF THE DEVELOPMENTAL TOXICITY OF DEFEROXAMINE IN MICE

Deferoxamine (DFO), an efficient chelating agent available for the tre atment of iron and aluminium overload, was evaluated for developmental toxicity in Swiss mice. Intraperitoneal injections of DFO were given to pregnant animals at 0, 44, 88, 176, and 352 mg/kg per day on gestat ional days 6 through 15. Maternal clinical status was monitored daily during and after treatment. Fetal parameters, including external, visc eral, and skeletal malformations and variations, were assessed. Mice w ere killed on day 18. No maternal mortality was observed, but dams exh ibited reduced body weight gain during treatment at 88,176, and 352 mg /kg per day. Body weight at termination, corrected body weight, and fo od consumption were reduced in all groups. In contrast, the only signi ficant treatment-related embryo/fetal effect was a decrease in the num ber of live fetuses per litter at 352 mg/kg per day. The no-observable -adverse-effect level (NOAEL) for maternal toxicity of DFO was < 44 mg /kg per day, whereas the NOAEL for developmental toxicity was 176 mg/k g per day. In summary, intraperitoneal administration of DFO to mice d uring organogenesis produced developmental toxicity in the presence of maternal toxicity. Because of the remarkable maternal toxicity of DFO , extreme caution in the use of this drug is recommended during pregna ncy.