萘丁美酮的生殖毒性实验研究

STUDIES ON THE REPRODUCTIVE TOXICITY OFNABUMETONE

本文选用小鼠睾丸生殖细胞染色体畸变分析试验，和大国发育毒性试验，对萘丁美酮的生殖毒性进行了研究，小鼠睾丸生殖细胞染色体分析试验设三个剂量组：１６７９、８４８．５、４２１，２５１ｍｇ／ｋｇ；和溶剂对照组。连续灌胃染毒５天，第六天取样分析。精原细胞染色体畸变细胞率、间隙率，初级精母细胞第一次减数分裂中期相的畸变细胞率和染色体早＊分离军，以及多倍体细胞率，与熔剂对照组相比较均无显著性差异，ＳＤ大凤的发育毒性试验设三个剂量组：２５０、６２．５和１５．６２５ｍｇ／ｋｇ，和一个敌枯双（１．６ｍｇ／ｋｇ）阳性对照组。分别于妊娠第７—１３天每日空腹灌胃染毒一次，并于妊娠第３、６、９、１２、１５．１８、２０和２１天称体重调整灌胃量，第２１天剖杀孕鼠取胎，观察并记录：孕鼠增重，死胎数，活胎数，胎重，胎鼠外观、内脏及骨骼畸形，以及胎鼠骨骼发育。结果表明：萘丁美酮对孕鼠增重，胎仔发育，胚胎及胎仔存活，胎仔骨骼发育均无影响；也未见引起胎鼠外观、内脏和骨骼畸形。本研究表明，萘丁美酮对雌性小鼠生殖细胞无遗传毒性，对大鼠胚胎及胎仔无发育毒性。

The reproductive toxicity of Nabumetone was studied by two tests,including:chromosomal aberration(CA)test of reproductive cells from the testes of mice, anddevelopmental toxicity test for SD rats. The mice were given daily 3 doses for 5 days,themaximum dose being 1697 mg/kg(1/4 LD50),and samples were taken on the 6th day inCA test.The deferences between the 3 greated troups and sovent control on the frequencesof CA or gap in spermatogonia, and CA, univalents or multivalents in primaryspermtocytes,weren't significant.Three doses(250, 62.5 and l5. 625 mg/kg),a positiveand a negative control were set in the developmental toxicity test.The rats wereadministered daily fromday 7 to day 13, and detected weight at day 3,6,9,12,15,18,20and 21.Litters were collected.Observed and recorded :maternal weight gain,No,earthydeaths ,No。 late deaths, living fetuses ’gross external and internal organs anomalies,andskeletal analysis. Maternal weight gain,fetal development,embryo and fetal survivingand fetal skeletal development weren't effected by Nabumetone; external and internalorgans anomalies and skeletal rnalformation weren't observed,These results indicateneither genotoxicity on the reproductive cells of male mice nor developmental toxicity onthe embryo and fetal of rats for Nabumetone were observed.