甲氧化三丁基锡的急性毒性和遗传毒性研究

目的:研究甲氧化三丁基锡(tributyltin methoxide,TBTMO)对小鼠的急性毒性和遗传毒性。方法:选取昆明种小鼠110只,随机分为11组(TBTMO 420、286、194、180、132、90、73、61、41.5、28 mg/kg及阴性对照组),一次性灌胃给药进行急性毒性测试;另取昆明种小鼠50只随机分成5组(TBTMO 80、40、20 mg/kg组,阴性对照组和阳性对照组),各剂量组和阴性对照组均连续给药2 d,阳性对照组连续给药5 d,均连续观察35d,处死小鼠取双侧附睾制片进行精子畸形试验;并取昆明种小鼠50只随机分成5组(TBTMO 80、40、20 mg/kg组,阴性对照组和阳性对照组),灌胃给药30 h后处死小鼠取胸骨骨髓进行微核试验;取GFP转基因小鼠50只随机分成5组(TBTMO 80、40、20 mg/kg组,阴性对照组和阳性对照组),收集每只小鼠的脾淋巴细胞进行hprt基因突变试验。然后用不同浓度TBTMO(69.4、48.6、34.0、23.8、16.6、0μg/ml)分别处理中国仓鼠肺成纤维细胞(Chinesehamster lung,CHL)进行染色体畸变试验;用不同浓度TBTMO(每皿5×10~5、5×10~4、5×10~3、5×10~2、50、5、0.5、0.05、5×10~-3、5×10~-4μg)分别处理TA97、TA98、TA100、TA102 4种菌株进行Ames试验。结果:TBTMO对小鼠的半数致死量(LD_(50))为98 mg/kg。与阴性对照组比较,TBTMO可致小鼠精子畸形(P0.05或P0.01),且有剂量依赖趋势,其余4项遗传毒性试验结果均为阴性。结论:在本实验条件下,TBTMO对小鼠的急性经口毒性属于中等毒性,可能具有一定的遗传毒性。

Acute toxicity and genetic toxicity of tributyltin methoxide

OBJECTIVE:To investigate the acute toxicity and genetic toxicity of tributyltin methoxide （TBTMO）.METHODS:A total of 110 Kunming mice were randomly divided into 11 groups,then treated orally with various doses of TBTMO（420,286,194,180,132,90,73,61,41.5 and 28 mg/kg） to perform acute toxicity test. A total of 50 Kunming mice were randomly divided into 5 groups（TBTMO 80,40,20 mg/kg,positive control and negative control）.Positive control was treated for five consecutive days.Other four groups were treated for two days.These animals were killed 35 d later,and their bilateral epididymis were removed for sperm shape abnormality test.Another 50 Kunming mice were randomly divided into 5 groups and treated as above mentioned.The animals were killed 30 h after gavage with TBTMO,and their chest bone marrow fluid were obtained for bone marrow mieronueleus test.Another 50 GFP transgenic mice were randomly divided into 5 groups and treated as above.The animals were killed and their spleen lymphocyte was used for hprt gene mutation test.Various doses of TBTMO（69.4,48.6,34.0.23.8,16.6 and 0μg/ml） were used to treat Chinese hamster lung（CHL） cell for chromosome aberration test.Different doses of TBTMO (5×10⁵,5×10⁴,5×10³,5×10²,50,5,0.5,0.05,5×10^-3,5×10^-4μg/dish) were used to deal with TA97, TA98,TA100,TA102 strains for Ames test.RESULTS:The LD₅₀ of TBTMO in mice was 98 mg/kg.TBTMO could induce sperm abnormality in a dose-dependent manner（P < 0.05）.The other four tests showed negative results. CONCLUSION:Under our experimental conditions,TBTMO was classified as moderately-toxic substance.It may produce genetic toxicity.