沙拉沙星对大鼠生殖毒性和致畸性的研究

本文报道沙拉沙星对Wistar大鼠生殖毒性和致畸性的研究，在孕鼠妊娠经7－15d，分别经口灌服5、50和500mg/kg b.w.剂量沙拉沙星溶液。试验结果显示，沙拉沙星对孕鼠的健康状况、行为和增重均无明显影响；各剂量组受孕鼠的活胎数、死胎数和吸收胎数均无明显影响；除500mg/kg b.w.剂量组胎鼠的体长明显低于对照组外，各组间的胎鼠体重、体长、尾长和胎盘重均未见明显差异；各剂量组和对照组均未出现外观畸形和内脏畸形，仅500mg/kg b.w.剂量组胎鼠的骨骼畸形出现率（36.3%）显著高于对照组（8.7%），但不存在剂量－反应关系。作者认为沙拉沙星对Wistar大鼠无明显的生殖毒性和致畸性。     

马波沙星的致突变性和致畸性研究

选用Wistar大鼠和昆明系小鼠对马波沙星的遗传毒性进行研究。试验结果显示，马波沙星在抑菌剂量之下对鼠伤寒沙门氏菌不产生致突变作用；马波沙星不引起小鼠骨髓有微核多染红细胞率增加；马波沙星不引起雄性小鼠生殖细胞染色体畸变而造成的早期胚胎死亡；20mg／kg b．w．和100mg／kg b．w．剂量马波沙星对母鼠的生殖机能和胎鼠的生长发育无明显影响，对胎鼠不产生致畸作用，500mg／kg b．w．剂量马波沙星对胎鼠体长和骨骼发育有一定影响，但不存在剂量反应关系。上述结果表明，马波沙星无明显的致突变性和致畸性。     

Studies on Mutagenicity and Teratogenicity of Sarafloxacin

Wistar rats and closed Kunming strain mice were selected to study the genetic toxicity of sarafloxacin. The results indicated that sarafloxacin had no significant toxic effect of an excreted mutagen in S. typhimurium strains, and did not induce significantly higher percentages of polyehromatic erythrocytes with micronuclei (MNPCE) in mice. No significant mutagenic activity was observed in dominant lethal assay.At 5 and 50mg/kg b.w. , sarafloxacin did not produce significant effects on the reproductive parameters of litters and fetal growth, and did not induce the teratogenic effects on fetuses. Sarafloxacin induced some toxic effects on body length and skeletal growth in fetuses of 500mg/kg b.w., but had no significant dose - response relationship among the administered dosages of sarafloxacin. The results of the genetic toxicology above indicated that no evidence showing sarafloxacin was mutagenic and potentially teratogenic for animals.     

新型饲料添加剂喹胺醇致突变性及其潜在致癌性预测

 选择Ａｍｅｓ试验、小鼠微核试验和精子畸形试验３种短期试验组合研究了喹胺醇的致突变性,并在获得各 单项试验结果的基础上,利用“致癌性预测和选择试验组合的方法”即 ＣＰＢＳ法对喹胺醇潜在致癌性进行预测。结果表 明：（１）Ａｍｅｓ试验喹胺醇标准掺入不论加与不加Ｓｇ－ｍｉｘ对鼠伤寒沙门氏菌 ＴＡ９８和ＴＡ１００两个标准株都有诱变性,并 有剂量－反应关系。加入 Ｓｇ－ｍｉｘ后,ＴＡ９８和 ＴＡ１００回复突变菌落数均明显下降。（２）小鼠处死前 ３０ｈ和 ６ｈ分别腹腔注 射哇胺醇３０,６０,１２０和２４０ｍｇ／ｋｇ,骨髓嗜多染红细胞（ＰＣＥ）微核率与阴性对照组（５０％ＤＭＳＯ）比较差异均不显著（Ｐ ＞０．０５）。（３）小鼠连续用哇胺醇４５０、７５０、１０００和１５００ ｍｇ／ｋｇ灌胃５ｄ（１次／ｄ）,于第３５天处死,精子畸形率与阴性对 照组（２％吐温－８０）比较差异均不显著（Ｐ＞０．０５）。（４）利用ＣＰＢＳ法预测,喹胺醇θ＝０．２３８,初步定为非致癌物,进一步 的结论还需增加试验组合进行确定。     

沙拉沙星的致突变性和致畸性研究

 选用Ｗｉｓｔａｒ大鼠和昆明系小鼠对沙拉沙星的遗传毒性进行研究。试验结果显示，沙拉沙星在抑菌剂量之下对鼠伤寒沙门氏菌不产生致突变作用；沙拉沙星不引起小鼠骨髓有微核多染红细胞率增加；显性致死试验中，沙拉沙星试验结果为阴性；５和 ５０ｍｇ／ｋｇ ｂ．ｗ．剂量沙拉沙星对母鼠的生殖机能和胎鼠的生长发育无明显影响，对胎鼠不产生致畸作用，而 ５００ｍｇ／ｋｇ ｂ．ｗ．剂量沙拉沙星对胎鼠体长和骨骼发育有一定影响，但不存在剂量反应关系。上述结果表明，沙拉沙星无明显的致突变性和致畸性。     

Studies on the Mutagenicity and Teratogenicity of Kuianchun and Its Potential Carcinogenicity Prediction

Kuianchun is a newly synthesized antibacterial and growth-promoting drug. This paper selected a battery of three short-term tests, including Ames test, micronucleus test and sperm abnormality test, to detect the mutagenicity of Kuianchun. The carcinogenicity prediction and battery selection method (CPBS method) was used to determine the probability of carcinogenicity of Kuianchun based upon the results of shortterm tests mentioned above. In addition, traditional teratogenic test was selected to study teratogenicity of Kuianchun. In Ames test, Kuianchun showed mutagenic for Salmonella typhimurium strains TA98 and TA100 in the absence and presence of microsomal metabolic activation system (S9-mix). However, the mutagenicity was reduced by the addition of S9-mix. In micronucleus test, Kuianchun was administered intra-peritoneally to male mouse 30 hours and 6 hours before they were killed respectively. The result indicated that there was no significant difference on the number of micronucleated polychromatic erythrocytes (PCEs) in the mouse bone marrow induced by Kuianchun compared with the negative contrast (50% DMSO) (P ＞ 0.05). In sperm abnormality test, Kuianchun was administered through a gastric incubation to male mouse as a suspension in 2% Tween-80. The dosage levels were 450, 750, 1000 and 1500mg/kg per day for 5 days. The result indicated that the percentage of abnormal sperms induced by Kuianchun was not significant compared with the negative contrast (P＞0.05). In traditional teratogenic test, Kuianchun was given orally to pregnant mouse at 1/30,1/20 and 1/15 LDs0 during 6 - 15days of pregnancy period (the LD50 = 9000mg/kg). No toxicity was found either on mother and embryo in mouse, and teratogenic effects were also not observed at all tested dosages. The probability of carcinogenicity of Kuianchun is 23.8 % (θ = 0.238). The result demonstrated that Kuianchun is a non-carcinogen.     

吡啶酸铬的致突变性和生殖毒性研究

 选用Wistar大鼠和昆明系小鼠对吡啶酸铬的遗传毒性进行研究。结果表明 ,吡啶酸铬在抑菌剂量下对鼠伤寒沙门氏菌TA97、TA98、TA10 0和TA10 2不产生致突变作用 ;吡啶酸铬经口染毒剂量为 5～ 0 .5g·kg-1BW时不引起小鼠骨髓有微核多染红细胞率增加 ;吡啶酸铬对小鼠的显性致死试验结果为阴性 ;饲料中添加 2和 2 0mg·kg-1剂量吡啶酸铬对母鼠的生殖机能和胎鼠的生长发育无明显影响 ,对胎鼠不产生致畸作用 ,而 2 0 0mg·kg-1剂量吡啶酸铬对胎鼠骨骼发育有一定影响 ,但不存在剂量 反应关系。由此得出 ,吡啶酸铬无明显的致突变性和致畸性。