REPRODUCTION STUDIES OF SODIUM COLISTIN METHANESULFONATE (CLM). II TERATOGENICITY STUDY IN MICE

Abstract

Teratogenicity study of sodium colistin methanesulfonate (CLM) was performed with ICR-JCL mice. CLM was administered intravenously at dosage levels of 125, 250 and 500mg/kg/day from day 6 to day 15 of gestation. About two-thirds of pregnant mice in each group were sacrificed on day 18 of gestation and their fetuses were examined. The remaining mothers were allowed to deliver naturally.
Results were obtained as follows;
1. CLM did not affect general behavior, body weight and food consumption in pregnant mice.
2. There were no significant differences between the control group and the treated groups in number of implantations, live fetuses, resorptions in the uterus, body weight of live fetuses, sex ratio and weight of placentas.
3. No significant increase of the prevalence of external, visceral and skeletal anomalies of the fetuses was observed in any treated group.
4. The ossifications of cervical and sacral vertebrae were delayed by treatment with CLM at dosage levels of 250 and 500mg/kg.
5. The were no significant differences between the control and the treated groups of delivery in duration of pregnancy, number and body weight of liveborn, sex ratio, number of implantation sites, delivery rate and nuring rate. Moreover, no stillborn and external anomaly of liveborn were observed in any treated group of delivery.
6. CLM did not affect postnatal growth, development and differentiation in newborn mice.
7. CLM did not affect sensory function of reflex, motor coordination, emotionality and learning ability in newborn mice. But, spontaneous activity of both sexes was reduced by treatment with CLM at dosage levels of 250 and 500mg/kg.
It can be concluded that CLM, in this study, has little unfavorable influence on fetuses and newborn mice, and that the maximum non-toxic level of CLM is 125mg/kg in mice.