Abstract:

Abstract:Objective To evaluate the safety of a polyoxometalates NCW-6 and clarify  the toxicity and  potential hazard of NCW-6. Methods Orally acute toxicity test and teratogenic sensitivity test of NCW-6 were performed according to the pre-clinical toxicological evaluation for new drugs. In acute toxicity test, the healthy Kunming mice were randomly divided into 7 groups(n=10)   with half of male and female,the maximum dose was 6 000.00 mg•kg^-1 and the minimum dose was 4 000.00 mg•kg^-1 with 400.00 mg•kg^-1 class interval. The  representation of mice was observed 14 d after administered by oral gavage once and  the death number was recorded and the  LD50 was calculated.In teratogenic sensitivity test， the pregnant rats were ramdomly divided into 5 groups and there were  20 rats in each group at least.The NCW-6 doses  were  91.7,366.8 and 1 467.5  mg•kg^-1 in  three treatment groups.5 mL•kg^-1 distilled water was administered in negative control group，continuously by oral gavage 5-16 d after  pregnantcy,once a day;  130  mg•kg^-1 retinoic acid was administered  by oral gavage on the 10th day after pregnancy.The pregnant rats were killed by cervical dislocation on the 20th day, the number of corpus luteum,implantation,live fetuses,resorption fetuses and dead fetuses  were recorded.The  weight,body length,tail length and appearence of fetal rats were observed.The osteological features examination and organ features examination were performed in fetal rats with half of male and female.Results In acute toxicity test,the LD₅₀ of NCW-6 was 5 869.9 mg•kg^-1. The results of teratogenic sensitivity test showed that the body weight and weight gain of pregnant rats in three treatment groups had no significant differences compared with negative control group (P> 0.05);the average fetal weight,body length,tail length and the average birth weight,litter weight of fetal rats in  treatment groups had no significant differences compared with negative control group (P> 0.05);and the appearance,visceral deformity rate and bone malformation rate of fetal rats in treatment groups had no significant differences compared with negative control group(P> 0.05). Conclusion NCW-6 has no toxicity and no teratogenic effects on rats,which deserves further research.

Key words:  polyoxometalates;acute toxicity;teratogenic sensitive period;toxicology