多效唑原药对SD大鼠慢性毒性与致癌性

Chronic toxicity and carcinogenicity of paclobutrazol in SD rats

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.