大鼠1,1-二氨基-2,2-二硝基乙烯亚慢性经口毒性研究
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摘要
目的研究1,1-二氨基-2,2-二硝基乙烯(FOX-7)对大鼠的亚慢性经口毒性效应。方法无特定病原体级健康成年SD大鼠随机分为对照组和低、中、高剂量组,每组24只,雌雄各半。3个剂量组分别以10、30和90 mg/(kg·d)体质量FOX-7-水淀粉(水淀粉质量分数为4.0%)混悬液灌胃染毒,1次/d,每周6 d,连续90 d;对照组给予等体积水淀粉溶液灌胃。观察大鼠的中毒表现、体质量、食物利用率、血常规、血液生化指标、脏器系数变化及组织器官的组织病理学改变。结果 1雌性、雄性高剂量组大鼠在染毒第28天后体质量均低于同时间点同性别对照组(P<0.05),在染毒第77和90天食物利用率分别低于同时间点同性别对照组(P<0.05)。2与雌性对照组比较,雌性低、中和高剂量组大鼠红细胞计数、血红蛋白、红细胞压积均下降(P<0.05),雌性高剂量组大鼠血小板计数下降(P<0.05)。与雄性对照组比较,雄性高剂量组大鼠红细胞计数、血红蛋白、红细胞压积和平均红细胞血红蛋白浓度均下降(P<0.05),雄性中和高剂量组大鼠血小板计数均下降(P<0.05)。3与雌性对照组比较,雌性中和高剂量组大鼠血清总胆固醇水平均升高(P<0.05),雌性高剂量组大鼠尿素氮水平升高(P<0.05)。与对照组比较,高剂量组大鼠总蛋白和尿酸水平均升高,而乳酸脱氢酶活力下降(P<0.05)。4雌性高剂量组大鼠脾脏脏器系数高于雌性对照组(P<0.05),雄性中和高剂量组大鼠脾脏脏器系数均高于雄性对照组(P<0.05);高剂量组大鼠肝脏和肾脏的脏器系数均高于对照组(P<0.05);雄性高剂量组大鼠睾丸、附睾的脏器系数均低于雄性对照组(P<0.05),且均出现不同程度的睾丸曲细精管萎缩,精细胞减少。5未观察到有害作用水平在雌性大鼠为小于10.00 mg/(kg·d),雄性大鼠为10.00 mg/(kg·d)。结论在本实验条件下,FOX-7可抑制大鼠的生长发育,引起血液系统及雄鼠的生殖系统损害。
Objective To explore the sub-chronic oral toxicity of 1,1-diamino-2,2-dinitroethene( FOX-7) in rats.Methods Ninety-six specific pathogen free healthy adult SD rats were randomly divided into control group,low-,medium-,and high-dose groups. Each group consisted of 24 rats,half of them were males and the other half were females.The low-,medium-,and high-dose groups of rats were exposed to 10,30,90 mg /( kg·d) body weigh of 1,1-diamino-2,2-dinitroethene by gavage for 90 days,once a day,6 days a week. The control group was given the same volume of 4%water starch solution. The toxic symptoms,the body weight,food utilization,routine blood,blood biochemical indicators,organ coefficients and histopathology changes of the rats were observed or tested. Results a) The body weights of male and female rats in the high-dose group in the 28 th day after exposure were lower than those of the control group for the same time and same sex( P < 0. 05). Food utilization in the male and female high-dose group in the 77 th and 90 th day after exposure were lower than those of the control group for the same time and same sex( P < 0. 05). b) Red blood cell counts,hemoglobin levels,hematocrit levels in the female rats of low-,medium-,and high-dose groups were lower than those of the female control group( P < 0. 05). Platelet counts in the female high-dose group was lower than that of the female control group( P < 0. 05). Red blood cell counts,hemoglobin level,hematocrit level and mean corpuscular hemoglobin concentration in the male high-dose group were lower than those of the male control group( P < 0. 05). The platelet counts in the male medium-,and high-dose group were lower than that of the male control group( P < 0. 05). c) Total cholesterol levels in female medium-,and high-dose group and blood urea nitrogen level in the female high-dose group were higher than those of the female control group( P < 0. 05). In high-dose group,the levels of total protein and uric acid were higher and lactate dehydrogenase level was lower than those of the control group( P < 0. 05). d) The spleen organ coefficients in the female high-dose group were higher and those in male medium- and high-dose groups were higher than those of the control group for same sex( P < 0. 05). The organ coefficients of liver and kidney in high-dose group were higher than those of the control group( P < 0. 05),the organ coefficients of testis and epididym in the male high-dose group were lower than those of the male control group( P < 0. 05). The testis convoluted tubule shrink and seminiferous cells decreased in the male high-dose group. e) The no observed adverse effect level of FOX-7 dinitroethene in female rats were less than10. 00 mg /( kg·d) and it was 10. 00 mg /( kg·d) in the male rats. Conclusion FOX-7 could inhibit the growth of rats and damage the blood system and male reproductive system.
Objective To explore the sub-chronic oral toxicity of 1,1-diamino-2,2-dinitroethene( FOX-7) in rats.Methods Ninety-six specific pathogen free healthy adult SD rats were randomly divided into control group,low-,medium-,and high-dose groups. Each group consisted of 24 rats,half of them were males and the other half were females.The low-,medium-,and high-dose groups of rats were exposed to 10,30,90 mg /( kg·d) body weigh of 1,1-diamino-2,2-dinitroethene by gavage for 90 days,once a day,6 days a week. The control group was given the same volume of 4%water starch solution. The toxic symptoms,the body weight,food utilization,routine blood,blood biochemical indicators,organ coefficients and histopathology changes of the rats were observed or tested. Results a) The body weights of male and female rats in the high-dose group in the 28 th day after exposure were lower than those of the control group for the same time and same sex( P < 0. 05). Food utilization in the male and female high-dose group in the 77 th and 90 th day after exposure were lower than those of the control group for the same time and same sex( P < 0. 05). b) Red blood cell counts,hemoglobin levels,hematocrit levels in the female rats of low-,medium-,and high-dose groups were lower than those of the female control group( P < 0. 05). Platelet counts in the female high-dose group was lower than that of the female control group( P < 0. 05). Red blood cell counts,hemoglobin level,hematocrit level and mean corpuscular hemoglobin concentration in the male high-dose group were lower than those of the male control group( P < 0. 05). The platelet counts in the male medium-,and high-dose group were lower than that of the male control group( P < 0. 05). c) Total cholesterol levels in female medium-,and high-dose group and blood urea nitrogen level in the female high-dose group were higher than those of the female control group( P < 0. 05). In high-dose group,the levels of total protein and uric acid were higher and lactate dehydrogenase level was lower than those of the control group( P < 0. 05). d) The spleen organ coefficients in the female high-dose group were higher and those in male medium- and high-dose groups were higher than those of the control group for same sex( P < 0. 05). The organ coefficients of liver and kidney in high-dose group were higher than those of the control group( P < 0. 05),the organ coefficients of testis and epididym in the male high-dose group were lower than those of the male control group( P < 0. 05). The testis convoluted tubule shrink and seminiferous cells decreased in the male high-dose group. e) The no observed adverse effect level of FOX-7 dinitroethene in female rats were less than10. 00 mg /( kg·d) and it was 10. 00 mg /( kg·d) in the male rats. Conclusion FOX-7 could inhibit the growth of rats and damage the blood system and male reproductive system.
引文
[1]杨卓.高能材料与高效毁伤技术[M].北京:化学工业出版社,2012:228-229.
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[3]BISHOP M M,VELISAVLJEVIC N,CHELLAPPA R,et al.High pressure-temperature phase diagram of 1,1-Diamino-2,2-dinitroethylene(FOX-7)[J].J Phys Chem A,2015,119(37):9739-9747.
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[9]VRUSHALI P,KANEKER P P,SARNAIK S S.Bioremediation of nitro explosive-diaminodinitroethylene(FOX-7)containing wasterwater[R].India:MACS-Agharker Research Institute,2011.
[10]高俊宏,王鸿,刘志永,等.1,1-二氨基-2,2-二硝基乙烯的急性毒性研究[J].中国工业医学杂志,2015,32(6):120-121.
[11]周宗灿.毒理学教程[M].北京:北京大学医学出版社,2006:163.
[12]程树军,焦红.实验动物替代方法原理与应用[M].北京:科学出版社,2010:345.
[13]王捷.毒性病理学[M].辽宁:辽宁科学技术出版社,2004:118-125.
[14]高永超,王鸿,刘志永,等.1,1-二氨基-2,2-二硝基乙烯对小鼠精子畸形的影响[J].环境与健康杂志,2015,28(3):546-547.
[2]冯晓晶,马会强,张寿忠,等.1,1-二氨基-2,2-二硝基乙烯的合成研究进展[J].化学推进剂与高分子材料,2012,10(2):24-29.
[3]BISHOP M M,VELISAVLJEVIC N,CHELLAPPA R,et al.High pressure-temperature phase diagram of 1,1-Diamino-2,2-dinitroethylene(FOX-7)[J].J Phys Chem A,2015,119(37):9739-9747.
[4]中华人民共和国卫生部.化学品毒性技术鉴定规范[S]北京:中国劳动社会保障出版社,2006.
[5]中华人民共和国国家质量监督检验检疫总局,国家标准化管理委员会.化学品啮齿动物亚慢性经口毒性试验方法:GB/T21763—2008[S].北京:中国标准出版社,2008.
[6]JAI PRAKASH AGRAWAL.High energy materials(propellants,explosives and pyrotechnics)[M].German:Wiley-VCH,2010:103.
[7]BERGLIND R,ANDERSSON A C.Acute toxicity of the explosives CL-20 and FOX-7 in the water flea daphnia magna[R].Sweden:Foersvarets Forskningsanstalt Umea,1999.
[8]BERGLIND R,ANDERSSON A C.On the acute toxicity of four explosives,and FOX-12,Cl20,and FOX-7,in the water flea ceriodaphinia dubia[R].Sweden:Foersvarets Forskningsanstalt Umea,2003.
[9]VRUSHALI P,KANEKER P P,SARNAIK S S.Bioremediation of nitro explosive-diaminodinitroethylene(FOX-7)containing wasterwater[R].India:MACS-Agharker Research Institute,2011.
[10]高俊宏,王鸿,刘志永,等.1,1-二氨基-2,2-二硝基乙烯的急性毒性研究[J].中国工业医学杂志,2015,32(6):120-121.
[11]周宗灿.毒理学教程[M].北京:北京大学医学出版社,2006:163.
[12]程树军,焦红.实验动物替代方法原理与应用[M].北京:科学出版社,2010:345.
[13]王捷.毒性病理学[M].辽宁:辽宁科学技术出版社,2004:118-125.
[14]高永超,王鸿,刘志永,等.1,1-二氨基-2,2-二硝基乙烯对小鼠精子畸形的影响[J].环境与健康杂志,2015,28(3):546-547.