六苄基六氮杂异伍兹烷亚慢性经口毒性试验研究
|
摘要
目的进行大鼠亚慢性经口毒性试验,获得六苄基六氮杂异伍兹烷(HBIW)的最大无作用剂量水平。方法将80只成年SPF级SD大鼠按体质量随机分为4组,3个染毒组每天的染毒剂量分别为111、333和1 000 mg/kg HBIW,对照组给予相同体积淀粉溶液灌胃,连续给药90 d。实验结束后经腹主动脉采血,分别进行血液生化、血常规和凝血指标分析。对所有动物行大体解剖,取其脏器进行称重,并进行病理组织学检查。结果与对照组相比,1 000 mg/kg染毒组雌、雄性大鼠血小板压积(PCT)[(1.37±0.21)%,(1.40±0.27)%]、PLT[(1 587.56±243.62)109/L,(1 694.40±308.87)109/L]以及雌性大鼠红细胞分布宽度变异系数(RDW-CV)(29.741.24)%明显升高(P<0.05),1 000 mg/kg染毒组雄性大鼠大型血小板比率(P-LCR)(13 37±2 04)%、平均血红蛋白含量(MCH)(16.65±0.44)pg、平均血小板体积(MPV)(8.25±0.27)fl明显降低(P<0.05);333和1 000 mg/kg染毒组雄性大鼠心[(0.34±0.04),(0.34±0.04)]与肝[(2.59±0.13),(2.85±0.37)]脏器系数明显升高(P<0.05),333 mg/kg染毒组雄性大鼠以及111 mg/kg染毒组雌性大鼠肺脏器系数[(0.72±0.22),(0.69±0.10)]明显升高(P<0.05);病理组织学检查结果显示,333和1 000 mg/kg染毒组雄性大鼠分别有2和3只出现肝细胞嗜酸性变,并伴有肝细胞轻度肿胀;333 mg/kg染毒组雄性大鼠肺脏出现炎细胞浸润,1 000 mg/kg染毒组出现肺泡上皮细胞肿胀。结论 HBIW可能造成大鼠免疫力降低和轻度贫血,其对大鼠毒性作用靶器官为肝脏和肺脏,最大无作用剂量为111 mg/kg。
Objective A sub-chronic oral toxicity test of Hexabenzylhexaazaisowurtzitane(HBIW) in rats was conducted to acquire the No\|observed adverse effect level(NOAEL). Methods 80 SPF SD rats were randomly divided into four groups by body weights,and they were administrated by gavage of HBIW for consecutive 90 days with the dosage of 0,111,333 and 1000 mg/kg respectively The animal's blood was collected to conduct clinical biochemistry,hematology and coagulation test, and then the weight of certain organs and histopathological changes were recorded and detected. Results Comparing with the control group,the PCT [(1.37±0.21) %,(1.40±0.27) %] and PLT [(1587.56±243.62) 109/L,(1694.40±308.87) 109/L] in both male and female rats and the RDW\|CV(29.74±1.24) % in the female rats of 1000 mg/kg group increased significantly(P<0.05),while the P\|LCR(13.37±2.04) %,MCH(16.65±0.44) pg and MPV(8.25±0.27) fl in the female rats of 1000 mg/kg group decreased significantly. The organ coefficients of heart [(0.34±0.04),(0.34±0.04)] and liver [(2.59±0.13),(2.85±0.37) in the male rats of 333 mg/kg and 1000 mg/kg group increased significantly,and the lung [(0.72±0.22),(0.69±0.10)] in the female rats of 111 mg/kg and the male rats of333 mg/kg increased significantly. The histopathological examinations revealed that 2 male rats in 333 mg/kg and 3 male rats in1000 mg/kg appeared hepatic cell swelling, acidophilic change respectively, while the lung inflammatory cell infiltration appeared in the male rats of 333 mg/kg,and the alveolar epithelial cell swellings appeared in the male rats of 1000 mg/kg. Conclusions TheHBIW may induce hypoimmunity and slightly anemia of rat,and the target organs are liver and lung,the no-observed adverse effect level is 111 mg/kg as well.
Objective A sub-chronic oral toxicity test of Hexabenzylhexaazaisowurtzitane(HBIW) in rats was conducted to acquire the No\|observed adverse effect level(NOAEL). Methods 80 SPF SD rats were randomly divided into four groups by body weights,and they were administrated by gavage of HBIW for consecutive 90 days with the dosage of 0,111,333 and 1000 mg/kg respectively The animal's blood was collected to conduct clinical biochemistry,hematology and coagulation test, and then the weight of certain organs and histopathological changes were recorded and detected. Results Comparing with the control group,the PCT [(1.37±0.21) %,(1.40±0.27) %] and PLT [(1587.56±243.62) 109/L,(1694.40±308.87) 109/L] in both male and female rats and the RDW\|CV(29.74±1.24) % in the female rats of 1000 mg/kg group increased significantly(P<0.05),while the P\|LCR(13.37±2.04) %,MCH(16.65±0.44) pg and MPV(8.25±0.27) fl in the female rats of 1000 mg/kg group decreased significantly. The organ coefficients of heart [(0.34±0.04),(0.34±0.04)] and liver [(2.59±0.13),(2.85±0.37) in the male rats of 333 mg/kg and 1000 mg/kg group increased significantly,and the lung [(0.72±0.22),(0.69±0.10)] in the female rats of 111 mg/kg and the male rats of333 mg/kg increased significantly. The histopathological examinations revealed that 2 male rats in 333 mg/kg and 3 male rats in1000 mg/kg appeared hepatic cell swelling, acidophilic change respectively, while the lung inflammatory cell infiltration appeared in the male rats of 333 mg/kg,and the alveolar epithelial cell swellings appeared in the male rats of 1000 mg/kg. Conclusions TheHBIW may induce hypoimmunity and slightly anemia of rat,and the target organs are liver and lung,the no-observed adverse effect level is 111 mg/kg as well.
引文
[1]庞思平,申帆帆,吕芃浩,等.六硝基六氮杂异伍兹烷合成工艺研究进展[J].兵工学报,2014,35(5):725-732.
[2]刘志永,高俊宏,王鸿,等.六苄基六氮杂异伍兹烷致大鼠急性经口毒性研究[J].中国工业医学杂志,2013,26(6):434-436.
[3]刘志永,高俊宏,王鸿,等.六苄基六氮杂异伍兹烷大鼠28天重复剂量经口毒性[J].中国工业医学杂志,2015,28(3):200-201.
[4]夏洁芳,高俊宏,刘志永,等.六苄基六氮杂异伍兹烷对大鼠的致畸性研究[J].环境卫生学杂志,2016,6(4):259-262.
[5]刘志永,高俊宏,李江平,等.六苄基六氮杂异伍兹烷豚鼠皮肤致敏试验[J].职业与健康,2014,30(11):1468-1470.
[6]刘志永,高俊宏,王鸿,等.四乙酰基六氮杂异伍兹烷致大鼠急性经口毒性研究[J].职业与健康,2014,30(17):1523-1524.
[7]刘志永,王鸿,高俊宏,等.四乙酰基六氮杂异伍兹烷对大鼠的亚急性经口毒性[J].环境与健康杂志,2015,32(3):260-261.
[8]岳红,刘志永,高俊宏,等.四乙酰基二苄基六氮杂异伍兹烷对大鼠亚急性经口毒性研究[J].中国工业医学杂志,2014,27(6):431-433.
[2]刘志永,高俊宏,王鸿,等.六苄基六氮杂异伍兹烷致大鼠急性经口毒性研究[J].中国工业医学杂志,2013,26(6):434-436.
[3]刘志永,高俊宏,王鸿,等.六苄基六氮杂异伍兹烷大鼠28天重复剂量经口毒性[J].中国工业医学杂志,2015,28(3):200-201.
[4]夏洁芳,高俊宏,刘志永,等.六苄基六氮杂异伍兹烷对大鼠的致畸性研究[J].环境卫生学杂志,2016,6(4):259-262.
[5]刘志永,高俊宏,李江平,等.六苄基六氮杂异伍兹烷豚鼠皮肤致敏试验[J].职业与健康,2014,30(11):1468-1470.
[6]刘志永,高俊宏,王鸿,等.四乙酰基六氮杂异伍兹烷致大鼠急性经口毒性研究[J].职业与健康,2014,30(17):1523-1524.
[7]刘志永,王鸿,高俊宏,等.四乙酰基六氮杂异伍兹烷对大鼠的亚急性经口毒性[J].环境与健康杂志,2015,32(3):260-261.
[8]岳红,刘志永,高俊宏,等.四乙酰基二苄基六氮杂异伍兹烷对大鼠亚急性经口毒性研究[J].中国工业医学杂志,2014,27(6):431-433.