多效唑原药对SD大鼠慢性毒性与致癌性
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摘要
目的探讨多效唑原药对SD大鼠的慢性毒性与致癌作用。方法无特定病原体级刚断乳SD大鼠按体质量随机分为对照组和低、中、高剂量组,每组120只,雌雄各半。采用饲喂法对大鼠进行为期2年的慢性毒性与致癌合并实验,4组雌性大鼠染毒剂量分别为0.0、11.7、48.5、193.9 mg·kg~(-1)·d~(-1),雄性大鼠染毒剂量分别为0.0、13.5、54.2、241.9 mg·kg~(-1)·d~(-1)。实验期间称量大鼠体质量;于染毒结束时进行血常规、血生化、脏器系数和组织病理学检查,计算大鼠死亡率和肿瘤发生率。结果 3个剂量组雌性、雄性大鼠分别在实验1、2周时即可观察到较同时间点同性别大鼠体质量下降(P<0.05)的结果。实验结束时,3个剂量组雌性、雄性大鼠体质量均低于同性别对照组(P<0.05);4组雌性或雄性大鼠死亡率分别比较,差异均无统计学意义(P>0.05)。3个剂量组雌性大鼠脑脏器系数均高于对照组雌性大鼠(P<0.05),高剂量组雌性大鼠肝脏、肾脏和卵巢脏器系数均高于对照组雌性大鼠(P<0.05)。3个剂量组雄性大鼠总胆红素水平均低于对照组雄性大鼠(P<0.05);中、高剂量组雄性大鼠脑和肺脏脏器系数均高于对照组雄性大鼠(P<0.05),高剂量组雄性大鼠肝脏脏器系数高于对照组雄性大鼠(P<0.05)。共有244只大鼠发生402个自发性肿瘤,肿瘤发生率为50.8%(244/480);对照组和低、中、高剂量组大鼠肿瘤发生率分别为61.7%(74/120)、42.5%(51/120)、50.0%(60/120)、49.2%(59/120),3个剂量组大鼠肿瘤发生率均无较对照组出现有统计学意义的升高。结论在本研究设计的染毒剂量条件下,多效唑原药对雌性和雄性SD大鼠慢性毒性的观察到最低有害作用剂量分别为11.7、13.5 mg·kg~(-1)·d~(-1);未见多效唑原药对SD大鼠具有致癌性。
Objective To explore the chronic toxicity and carcinogenicity of paclobutrazol in SD rats. Methods Specific pathogen free SD rats at the age of weaning were randomly divided into control group and low-,medium-,and high-dose groups according the body weight,with 120 rats in each group,half male and half female. The study of combined chronic toxicity and carcinogenicity test in rats was carried out in 2 years by feeding the rats with paclobutrazol. The doses in the 4 groups were 0. 0,11. 7,48. 5 and 193. 9 mg·kg~(-1)·d~(-1) for female rats and 0. 0,13. 5,54. 2 and 241. 9 mg·kg~(-1)·d~(-1) for male rats. The body weight of rats was weighted during the experiment. The blood routine,blood biochemistry,organ coefficient and histopathology examinations were performed at the end of paclobutrazol exposure. The mortality and tumor incidence in rats were calculated. Results The decrease of body weights in female and male rats in dose groups was observed at 1-2 weeks after the experiment,compared with the same sex control group at the same time point( P < 0. 05).At the end of the exposure,the body weights of female and male rats in all three dose groups were lower than that in the same sex rats of control group( P < 0. 05). The mortality rates of female and male rats in the four groups were not significantly different( P > 0. 05). The brain organ coefficients of female rats in the three dose groups were higher than those female rats in the control group( P < 0. 05). The organ coefficients of liver,kidney and ovary of female rats in highdose group were higher than that of female rats in control group( P < 0. 05). The level of total bilirubin in male rats in the three dose groups was lower than that in control group( P < 0. 05). The organ coefficients of brain and lung in male rats in the medium-and high-dose groups were higher than that in the control group( P < 0. 05). The liver organ coefficient in male rats in the high-dose group was higher than that in the control group( P < 0. 05). A total of 244 rats had 402 spontaneous tumors with a tumor incidence rate of 50. 8%(244/480). The incidence of tumor in control,low-,mediumand high-dose groups were 61. 7%( 74/120), 42. 5%( 51/120), 50. 0%( 60/120) and 49. 2%( 59/120)respectively. There was no statistical significance in the incidence of tumors in three dose groups compared with that of the control group. Conclusion Under the dose conditions designed in this study,the lowest observed adverse effect level of paclobutrazol were 11. 7 and 13. 5 mg · kg~(-1)· d~(-1) in females and males respectively. Paclobutrazol was not found carcinogenic to SD rats.
Objective To explore the chronic toxicity and carcinogenicity of paclobutrazol in SD rats. Methods Specific pathogen free SD rats at the age of weaning were randomly divided into control group and low-,medium-,and high-dose groups according the body weight,with 120 rats in each group,half male and half female. The study of combined chronic toxicity and carcinogenicity test in rats was carried out in 2 years by feeding the rats with paclobutrazol. The doses in the 4 groups were 0. 0,11. 7,48. 5 and 193. 9 mg·kg~(-1)·d~(-1) for female rats and 0. 0,13. 5,54. 2 and 241. 9 mg·kg~(-1)·d~(-1) for male rats. The body weight of rats was weighted during the experiment. The blood routine,blood biochemistry,organ coefficient and histopathology examinations were performed at the end of paclobutrazol exposure. The mortality and tumor incidence in rats were calculated. Results The decrease of body weights in female and male rats in dose groups was observed at 1-2 weeks after the experiment,compared with the same sex control group at the same time point( P < 0. 05).At the end of the exposure,the body weights of female and male rats in all three dose groups were lower than that in the same sex rats of control group( P < 0. 05). The mortality rates of female and male rats in the four groups were not significantly different( P > 0. 05). The brain organ coefficients of female rats in the three dose groups were higher than those female rats in the control group( P < 0. 05). The organ coefficients of liver,kidney and ovary of female rats in highdose group were higher than that of female rats in control group( P < 0. 05). The level of total bilirubin in male rats in the three dose groups was lower than that in control group( P < 0. 05). The organ coefficients of brain and lung in male rats in the medium-and high-dose groups were higher than that in the control group( P < 0. 05). The liver organ coefficient in male rats in the high-dose group was higher than that in the control group( P < 0. 05). A total of 244 rats had 402 spontaneous tumors with a tumor incidence rate of 50. 8%(244/480). The incidence of tumor in control,low-,mediumand high-dose groups were 61. 7%( 74/120), 42. 5%( 51/120), 50. 0%( 60/120) and 49. 2%( 59/120)respectively. There was no statistical significance in the incidence of tumors in three dose groups compared with that of the control group. Conclusion Under the dose conditions designed in this study,the lowest observed adverse effect level of paclobutrazol were 11. 7 and 13. 5 mg · kg~(-1)· d~(-1) in females and males respectively. Paclobutrazol was not found carcinogenic to SD rats.
引文
[1]陈润涛,邓莹玉,陈晓燕,等.多效唑原药SD大鼠两代繁殖毒性研究[J].毒理学杂志,2008,22(3):195-196.
[2]郭晶,宋文华,丁峰,等.三唑类杀菌剂对大型蚤急性毒性研究[J].南开大学学报(自然科学版),2009,42(3):76-80.
[3]杨赓,张晓强,钱忠宁,等.多效唑对大型蚤的慢性毒性研究[J].现代农药,2003,2(3):22-25.
[4]熊艳,万丽娟.三唑磷和多效唑及其混合对中华大蟾蜍蝌蚪的急性毒性[J].南昌大学学报,2005,29(5):493-496.
[5]中华人民共和国国家质量监督检验检疫总局,中国国家标准化管理委员会.农药登记毒理学试验方法农药登记毒理学实验方法第28部分:慢性毒性与致癌合并试验:GB/T 15670.28—2017[S].北京:中国标准出版社,2017.
[6]国家环境保护总局.化学品测试方法:慢性毒性与致癌性联合试验[M].北京:中国环境科学出版社,2004:633-638.
[7]Organisation for Economic Co-operation and Development.OECD guidelines for the testing of chemicals,453,Combined chronic toxicity\carcinogenicity studies[S].Paris:OECD,2009:1-20.
[8]钟志勇,刘盛来,郑桂兰,等.慢性毒性联合致癌性试验中SD大鼠血液部分生理生化参考值的研究[J].实验动物科学,2013,30(2):14-19.
[9]周银平,李玲玲,焦茂兴,等.敌草隆原药对大鼠的亚慢性毒性试验[J].毒理学杂志,2007,21(2):157-159.
[10]董延生,尹纪业,陈长,等.SD大鼠脏器重量及脏器系数正常参考值的确立与应用[J].军事医学,2012,36(5):351-353.
[11]张晓鹏,张馨,王伟,等.95%水胺硫磷慢性毒性和致癌性研究[J].中国食品卫生杂志,2010,22(3):229-232.
[12]王海山,孙红梅.植物生长延缓剂提高红茄抗旱性的研究[J].中国农学通报,2012,28(7):126-132.
[13]范志霞,李绍才,孙海龙.多效唑作用下紫穗槐对干旱胁迫的生理响应及抗旱性评价[J].草业学报,2017,26(3):132-141.
[14]KUAI J,YANG Y,SUN Y,et al.Paclobutrazol increases canola seed yield by enhancing lodging and pod shatter resistance in Brassica napus L[J].Field Crops Res,2015,180:10-20.
[15]KUMAR S,GHATTY S,SATYANARAYANA J,et al.Paclobutrazol treatment as a potential strategy for higher seed and oil yield in fieldgrown Camelina sativa L.Crantz[J].BMC Res Notes,2012,5:137.
[16]XU G,LUO R,YAO Y.Paclobutrazol improved the reproductive growth and the quality of seed oil of Jatropha curcas[J].J Plant Growth Regul,2013,32:875-883.
[17]游鸯.汪天.多效唑作用及应用研究进展[J].亚热带植物科学,2013,42(4):361-366.
[18]LIN C H,KUO J,WANG Y W,et al.Bacterial diversity in paclobutrazol applied agricultural soils[J].J Environ Sci,2010,45(7):711-718.
[19]SHALINI L,SHARMA D.Persistence and movement of paclobutrazol residues in a mango orchard soil[J].Bull Environ Contam Toxicol,2006,76(6):930-934.
[20]王存.多效唑在植物生产上的应用现状[J].热带农业科学,2009,29(2):67-72.
[21]史晓梅,金芬,黄玉婷,等.水果中常用植物生长调节剂的研究进展[J].食品工业科技,2012,33(4):417-422;426.
[22]朱杰丽,杨柳,柴振林,等.国内外植物生长调节剂限量标准分析研究[J].生物灾害科学,2013,36(2):232-236.
[23]中华人民共和国卫生部.食品中农药最大残留限量:GB 2763—2016[S].北京:中国标准出版社,2014.
[24]申芸萍,郭发新.多效唑在花卉栽培上的应用试验[J].现代农业科技,2008(16):34-35.
[2]郭晶,宋文华,丁峰,等.三唑类杀菌剂对大型蚤急性毒性研究[J].南开大学学报(自然科学版),2009,42(3):76-80.
[3]杨赓,张晓强,钱忠宁,等.多效唑对大型蚤的慢性毒性研究[J].现代农药,2003,2(3):22-25.
[4]熊艳,万丽娟.三唑磷和多效唑及其混合对中华大蟾蜍蝌蚪的急性毒性[J].南昌大学学报,2005,29(5):493-496.
[5]中华人民共和国国家质量监督检验检疫总局,中国国家标准化管理委员会.农药登记毒理学试验方法农药登记毒理学实验方法第28部分:慢性毒性与致癌合并试验:GB/T 15670.28—2017[S].北京:中国标准出版社,2017.
[6]国家环境保护总局.化学品测试方法:慢性毒性与致癌性联合试验[M].北京:中国环境科学出版社,2004:633-638.
[7]Organisation for Economic Co-operation and Development.OECD guidelines for the testing of chemicals,453,Combined chronic toxicity\carcinogenicity studies[S].Paris:OECD,2009:1-20.
[8]钟志勇,刘盛来,郑桂兰,等.慢性毒性联合致癌性试验中SD大鼠血液部分生理生化参考值的研究[J].实验动物科学,2013,30(2):14-19.
[9]周银平,李玲玲,焦茂兴,等.敌草隆原药对大鼠的亚慢性毒性试验[J].毒理学杂志,2007,21(2):157-159.
[10]董延生,尹纪业,陈长,等.SD大鼠脏器重量及脏器系数正常参考值的确立与应用[J].军事医学,2012,36(5):351-353.
[11]张晓鹏,张馨,王伟,等.95%水胺硫磷慢性毒性和致癌性研究[J].中国食品卫生杂志,2010,22(3):229-232.
[12]王海山,孙红梅.植物生长延缓剂提高红茄抗旱性的研究[J].中国农学通报,2012,28(7):126-132.
[13]范志霞,李绍才,孙海龙.多效唑作用下紫穗槐对干旱胁迫的生理响应及抗旱性评价[J].草业学报,2017,26(3):132-141.
[14]KUAI J,YANG Y,SUN Y,et al.Paclobutrazol increases canola seed yield by enhancing lodging and pod shatter resistance in Brassica napus L[J].Field Crops Res,2015,180:10-20.
[15]KUMAR S,GHATTY S,SATYANARAYANA J,et al.Paclobutrazol treatment as a potential strategy for higher seed and oil yield in fieldgrown Camelina sativa L.Crantz[J].BMC Res Notes,2012,5:137.
[16]XU G,LUO R,YAO Y.Paclobutrazol improved the reproductive growth and the quality of seed oil of Jatropha curcas[J].J Plant Growth Regul,2013,32:875-883.
[17]游鸯.汪天.多效唑作用及应用研究进展[J].亚热带植物科学,2013,42(4):361-366.
[18]LIN C H,KUO J,WANG Y W,et al.Bacterial diversity in paclobutrazol applied agricultural soils[J].J Environ Sci,2010,45(7):711-718.
[19]SHALINI L,SHARMA D.Persistence and movement of paclobutrazol residues in a mango orchard soil[J].Bull Environ Contam Toxicol,2006,76(6):930-934.
[20]王存.多效唑在植物生产上的应用现状[J].热带农业科学,2009,29(2):67-72.
[21]史晓梅,金芬,黄玉婷,等.水果中常用植物生长调节剂的研究进展[J].食品工业科技,2012,33(4):417-422;426.
[22]朱杰丽,杨柳,柴振林,等.国内外植物生长调节剂限量标准分析研究[J].生物灾害科学,2013,36(2):232-236.
[23]中华人民共和国卫生部.食品中农药最大残留限量:GB 2763—2016[S].北京:中国标准出版社,2014.
[24]申芸萍,郭发新.多效唑在花卉栽培上的应用试验[J].现代农业科技,2008(16):34-35.